1-Methyl-7-nitro-5-phenyl-1,3-dihydro-2H-benzo[e][1,4]diazepin-2-one (Nimetazepam)

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Reaxys ID 759813 View in Reaxys

O

1/3 CAS Registry Number: 2011-67-8 Chemical Name: nimetazepam; 1,3-dihydro-1-methyl-7-nitro-5phenyl-2H-1,4-benzodiazepin-2-one; Elimin; 2-methyl-9-nitro-6phenyl-2,5-diazabicyclo[5.4.0]undeca-5,8,10,12-tetraen-3-one; 1-methyl-7-nitro-5-phenyl-1H-benzo[e][1,4]diazepin-2(3H)-one; N-1-Methylnitrazepam; nitrazepam Linear Structure Formula: (C6H3NO2)N(CH3)COCH2NC(C6H5) Molecular Formula: C16H13N3O3 Molecular Weight: 295.298 Type of Substance: heterocyclic InChI Key: GWUSZQUVEVMBPI-UHFFFAOYSA-N Note:

N

N

N

O

O

Substance Label (23) Label References IV

Patent; BUCK INSTITUTE FOR AGE RESEARCH; JOHN, Varghese; BREDESEN, Dale E.; WO2012/24616; (2012); (A1) English, View in Reaxys

1b

Broxton; Sango; Wright; Canadian Journal of Chemistry; vol. 66; nb. 7; (1988); p. 1566 - 1570, View in Reaxys

1c

Broxton, Trevor J.; Wright, Sallyanne; Journal of Organic Chemistry; vol. 51; nb. 15; (1986); p. 2965 2969, View in Reaxys; Broxton; Morrison; Australian Journal of Chemistry; vol. 38; nb. 7; (1985); p. 1037 1043, View in Reaxys

7

Patent; Sumitomo; DE2017060; (1970); Chem.Abstr.; vol. 74; nb. 22904; (1971), View in Reaxys; Paul, H.H.; Sapper, H.; Lohmann, W.; Kalinowski, H. O.; Organic Magnetic Resonance; vol. 21; nb. 5; (1983); p. 319 - 321, View in Reaxys

XIII

Krichevskii, E. S.; Romanova, O. B.; Grinev, A. N.; Chemistry of Heterocyclic Compounds (New York, NY, United States); vol. 19; nb. 12; (1983); p. 1302 - 1305; Khimiya Geterotsiklicheskikh Soedinenii; vol. 19; nb. 12; (1983); p. 1648 - 1651, View in Reaxys

47

Seiler; Zimmermann; Arzneimittel-Forschung/Drug Research; vol. 33; nb. 11; (1983); p. 1519 - 1522, View in Reaxys

9

Kovar; Linden; Breitmaier; Archiv der Pharmazie; vol. 314; nb. 2; (1981); p. 186 - 190, View in Reaxys

2

Sarrazin, Marcel; Faure, Robert; Aubert, Claude; Vincent, Emile-Jean; Journal de Chimie Physique et de Physico-Chimie Biologique; vol. 77; nb. 1; (1980); p. 91 - 94, View in Reaxys

1d

Sugasawa et al.; Journal of Heterocyclic Chemistry; vol. 16; (1979); p. 445,448, View in Reaxys

Bsp. 5

Patent; Sumitomo Chemical Company; CH599175; (1978); DE2508332; Chem.Abstr.; vol. 83; nb. 206341, View in Reaxys

XVII, R1=Me; R2=NO2; R3=R5=H

de Silva et al.; Analytical Chemistry; vol. 48; (1976); p. 10,11, View in Reaxys

3

Sarrazin et al.; Organic Magnetic Resonance; vol. 7; (1975); p. 89,92, View in Reaxys; Patent; Fabr. Med. Terap.; DE2227977; (1973); Chem.Abstr.; vol. 78; nb. 111388; (1973), View in Reaxys

XVII

Inaba et al.; Chemical and Pharmaceutical Bulletin; vol. 19; (1971); p. 722,723,726, View in Reaxys

Beispiel 27 bis 31

Patent; Sumitomo Chem. Comp.; DE1811830; (1971); Chem.Abstr.; vol. 75; nb. 129844; (1971), View in Reaxys

Beisp.4

Patent; Sankyo Co. Ltd.; DE2164154; (1971); Chem.Abstr.; vol. 77; nb. 126704, View in Reaxys

-1,4-benzodiazepin-2-on

Patent; Hoffmann-LaRoche; US3546212; (1970); Chem.Abstr.; vol. 74; nb. 112062, View in Reaxys

XI

Sadée; Archiv der Pharmazie und Berichte der Deutschen Pharmazeutischen Gesellschaft; vol. 302; nb. 10; (1969); p. 769 - 774, View in Reaxys

Beisp.27

Patent; Sumitomo Chem. Comp.; US3770767; (1968); DE1811830; Chem.Abstr.; vol. 75; nb. 129844, View in Reaxys

V

Patent; Hoffmann; US3121114; (1964); Chem.Abstr.; vol. 61; nb. 13332b; (1964), View in Reaxys

IX

Senkowski et al.; Analytical Chemistry; vol. 36; (1964); p. 1991,1992, View in Reaxys

VIIIf

Sternbach,L.H. et al.; Journal of Medicinal Chemistry; vol. 6; (1963); p. 261 - 265, View in Reaxys

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Bsp. 38

Patent; Reeder; Sternbach; US3141890; (1962); Chem.Abstr.; vol. 61; nb. 9514e; (1964), View in Reaxys

V (Z=O, R=Me, X=NO2, X'=H)

Patent; Hoffmann-La Roche Inc.; US3109843; (1962); Chem.Abstr.; vol. 60; nb. 2994a; (1964), View in Reaxys

Patent-Specific Data (2) Location in Patent References Patent; UNIVERSITA' DEGLI STUDI DI FIRENZE; A.I.L. FIRENZE SEZIONE AUTONOMA DI FIRENZE DELL'ASSOCIAZIONE ITALIANA CONTRO LE LEUCEMIE, LINFOMI E MIELOMA - ONLUS; WO2009/81349; (2009); (A1) English, View in Reaxys Claim

Patent; SRCHEM Incorporated; US5288503; (1994); (A1) English, View in Reaxys; Patent; ALTERGON S.A.; EP1273301; (2003); (A2) English, View in Reaxys; Patent; Seth; Pyare; Seth; Pawan; US4721709; (1988); (A1) English, View in Reaxys; Patent; Nippon Shinyaju Co., Ltd.; US5811547; (1998); (A1) English, View in Reaxys; Patent; Sumitomo Chemical Company, Limited; US4044003; (1977); (A1) English, View in Reaxys; Patent; The Procter and Gamble Company; US4557934; (1985); (A1) English, View in Reaxys; Patent; The Arab Company For Drug Industries And Medical Applicances (ACDIMA); US5646131; (1997); (A1) English, View in Reaxys

Druglikeness (1) 1 of 1

LogP

2.188

H Bond Donors

0

H Bond Acceptors

3

Rotatable Bonds

2

TPSA

78.49

Lipinski Number

4

Veber Number

2

Highest Clinical Phase (1) Highest Clinical Phase Marketed Derivative (7) Comment (Derivative)

References

Hydrobromid:F=260-265gr ad

Patent; Sumitomo Kagaku Koge; JP4356500; (1977); Ref. Zh., Khim.; vol. 5; nb. O180P; (1979), View in Reaxys

Hydrochlorid. F: 227-234grad (S. 47)

Patent; Sumitomo Chem. Comp.; DE1811830; (1971); Chem.Abstr.; vol. 75; nb. 129844; (1971), View in Reaxys

Hydrochlorid: F: 243-247grad (Zers.)

Inaba et al.; Chemical and Pharmaceutical Bulletin; vol. 19; (1971); p. 722,723,726, View in Reaxys

HCl*Cr*Salz: F: 186-189grad (Zers.), orange; IR

Inaba et al.; Chemical and Pharmaceutical Bulletin; vol. 19; (1971); p. 722,723,726, View in Reaxys

Hydrobromid: Aus Patent; Sumitomo Chem. Co. Ltd.; DE1817794; (1971); Chem.Abstr.; vol. 75; nb. 63844, View in Reaxys Chromsaeureanhydrid, H2O, 2Benzyloxy-carbonylaminomethyl-1-methyl-5-nitro-3-phenylindolEisessig, HBr; F. 156-157grad, F. 160-165grad (Zers.) Hydrobromid: F. 160-165grad (Zers.)

Patent; Sumitomo Chem. Co.; DE1816046; (1970); Chem.Abstr.; vol. 73; nb. 120690, View in Reaxys

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HCl-Salz: F: 227-234grad (Zers.)

Patent; Sumitomo Chem. Comp.; US3770767; (1968); DE1811830; Chem.Abstr.; vol. 75; nb. 129844, View in Reaxys

Melting Point (7) 1 of 7

Melting Point [°C]

69 - 70

Patent; UNIVERSITA' DEGLI STUDI DI FIRENZE; A.I.L. FIRENZE SEZIONE AUTONOMA DI FIRENZE DELL'ASSOCIAZIONE ITALIANA CONTRO LE LEUCEMIE, LINFOMI E MIELOMA - ONLUS; WO2009/81349; (2009); (A1) English, View in Reaxys 2 of 7

Melting Point [°C]

69 - 70

Location

supporting information

Guandalini; Cellai; Laurenzana; Scapecchi; Paoletti; Romanelli; Bioorganic and Medicinal Chemistry Letters; vol. 18; nb. 18; (2008); p. 5071 - 5074, View in Reaxys 3 of 7

Melting Point [°C]

159 - 161

Sugasawa et al.; Journal of Heterocyclic Chemistry; vol. 16; (1979); p. 445,448, View in Reaxys 4 of 7

Melting Point [°C]

156 - 157

Patent; Hoffmann-La Roche Inc.; US3203990; (1962); Chem.Abstr.; vol. 64; nb. 3576f; (1966), View in Reaxys; Patent; Hoffmann-La Roche Inc.; US3109843; (1962); Chem.Abstr.; vol. 60; nb. 2994a; (1964), View in Reaxys; Patent; Reeder; Sternbach; US3141890; (1962); Chem.Abstr.; vol. 61; nb. 9514e; (1964), View in Reaxys; Patent; Hoffmann-La Roche; US3144439; (1962); Chem.Abstr.; vol. 63; nb. 8385c; (1965), View in Reaxys; Patent; Hoffmann-La Roche; DE1145626; (1963); Chem.Abstr.; vol. 60; nb. 12033h; (1964), View in Reaxys; Patent; Hoffmann-La Roche; DE1136709; (1962); Chem.Abstr.; vol. 59; nb. 12827; (1963), View in Reaxys; Patent; HoffmannLa Roche; US3243427; (1961); Chem.Abstr.; vol. 64; nb. 19647c; (1966), View in Reaxys; Patent; Hoffmann; US3121114; (1964); Chem.Abstr.; vol. 61; nb. 13332b; (1964), View in Reaxys; Patent; Hoffmann-La Roche Inc.; US3131178; (1964); Chem.Abstr.; vol. 61; nb. 4383c; (1964), View in Reaxys; de Silva et al.; Analytical Chemistry; vol. 48; (1976); p. 10,11, View in Reaxys; Patent; Sumitomo Chem. Co.; DE1816046; (1970); Chem.Abstr.; vol. 73; nb. 120690, View in Reaxys; Patent; Hoffmann-La Roche; BE648149; (1964); Chem.Abstr.; vol. 63; nb. 14889h; (1965), View in Reaxys; Patent; Hoffmann-La Roche; CH414652; (1966); US3427304, View in Reaxys; Patent; Hoffmann-La Roche; NL6405644; (1964); Chem.Abstr.; vol. 62; nb. 16137d; (1965), View in Reaxys 5 of 7

Melting Point [°C]

156 - 158

Patent; Sumitomo Chem. Comp.; DE1811830; (1971); Chem.Abstr.; vol. 75; nb. 129844; (1971), View in Reaxys 6 of 7

Melting Point [°C]

157 - 159

Patent; Sankyo Co. Ltd.; DE2164154; (1971); Chem.Abstr.; vol. 77; nb. 126704, View in Reaxys; Inaba et al.; Chemical and Pharmaceutical Bulletin; vol. 19; (1971); p. 722,723,726, View in Reaxys 7 of 7

Melting Point [°C]

156 - 157

Solvent (Melting Point)

ethanol

Sternbach,L.H. et al.; Journal of Medicinal Chemistry; vol. 6; (1963); p. 261 - 265, View in Reaxys Association (MCS) (4) 1 of 4

Description (Association Stability constant of the complex with ... (MCS)) Solvent (Association (MCS))

H2O

Temperature (Association (MCS)) [°C]

37

Partner (Association (MCS))

bovine albumin

Brandys; Negrusz; Pharmazie; vol. 42; nb. 5; (1987); p. 350 - 350, View in Reaxys 2 of 4

Description (Association Stability constant of the complex with ... (MCS)) Solvent (Association (MCS))

H2O

Temperature (Association (MCS)) [°C]

37

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Partner (Association (MCS))

human albumin

Brandys; Negrusz; Pharmazie; vol. 42; nb. 5; (1987); p. 350 - 350, View in Reaxys 3 of 4

Description (Association UV/VIS spectrum of the complex (MCS)) Temperature (Association (MCS)) [°C]

37

Partner (Association (MCS))

aq. HCl

Inotsume; Nakano; Journal of Pharmaceutical Sciences; vol. 69; nb. 11; (1980); p. 1331 - 1334, View in Reaxys 4 of 4

Description (Association UV/VIS spectrum of the complex (MCS)) Solvent (Association (MCS))

CHCl3

Temperature (Association (MCS)) [°C]

37

Partner (Association (MCS))

aq. HCl

Inotsume; Nakano; Journal of Pharmaceutical Sciences; vol. 69; nb. 11; (1980); p. 1331 - 1334, View in Reaxys Conformation (1) Object of Investi- References gation Conformer equilibrium

Sarrazin et al.; Organic Magnetic Resonance; vol. 7; (1975); p. 89,92, View in Reaxys

Crystal Property Description (2) Colour & Other Location Properties yellow

References Patent; UNIVERSITA' DEGLI STUDI DI FIRENZE; A.I.L. FIRENZE SEZIONE AUTONOMA DI FIRENZE DELL'ASSOCIAZIONE ITALIANA CONTRO LE LEUCEMIE, LINFOMI E MIELOMA - ONLUS; WO2009/81349; (2009); (A1) English, View in Reaxys

yellow

supporting information

Guandalini; Cellai; Laurenzana; Scapecchi; Paoletti; Romanelli; Bioorganic and Medicinal Chemistry Letters; vol. 18; nb. 18; (2008); p. 5071 - 5074, View in Reaxys

Dissociation Exponent (1) 1 of 1

Dissociation Exponent (pK)

2.53

Temperature (Dissociation Exponent) [°C]

37

Method (Dissociation Exponent)

spectrophotometric

Type (Dissociation Exponent)

a1/apparent

Inotsume; Nakano; Journal of Pharmaceutical Sciences; vol. 69; nb. 11; (1980); p. 1331 - 1334, View in Reaxys Electrochemical Behaviour (2) Description (Elec- References trochemical Behaviour) Electrolytic dissociation / protonation equilibrium

Inotsume; Nakano; Journal of Pharmaceutical Sciences; vol. 69; nb. 11; (1980); p. 1331 - 1334, View in Reaxys

Polarography

Senkowski et al.; Analytical Chemistry; vol. 36; (1964); p. 1991,1992, View in Reaxys

Further Information (2) Description (Fur- References ther Information)

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Further information

Patent; Sumitomo Chem. Co. Ltd.; DE1817794; (1971); Chem.Abstr.; vol. 75; nb. 63844, View in Reaxys

Further information

Patent; Hoffmann-La Roche; US3144439; (1962); Chem.Abstr.; vol. 63; nb. 8385c; (1965), View in Reaxys

Liquid/Liquid Systems (MCS) (2) 1 of 2

Description (Liquid/ Liquid Systems (MCS))

Distribution between solvent 1 + 2

Temperature (Liquid/ Liquid Systems (MCS)) [°C]

25

Partner (Liquid/Liquid Systems (MCS))

n-octanol, aq. phosphate buffer

Seiler; Zimmermann; Arzneimittel-Forschung/Drug Research; vol. 33; nb. 11; (1983); p. 1519 - 1522, View in Reaxys 2 of 2

Description (Liquid/ Liquid Systems (MCS))

Distribution between solvent 1 + 2

Nakano et al.; Chemical and Pharmaceutical Bulletin; vol. 27; (1979); p. 573,575, View in Reaxys Solubility (MCS) (1) 1 of 1

Nakano et al.; Chemical and Pharmaceutical Bulletin; vol. 27; (1979); p. 573,575, View in Reaxys

NMR Spectroscopy (14) 1 of 14

Nucleus (NMR Spectroscopy)

1H

Solvents (NMR Spectro- chloroform-d1 scopy) Original Text (NMR Spectroscopy)

[1H]-NMR (CDCI3): 3.48 (s, 3H, NCH3); 3.78 (d, J = 10.8 Hz, 1 H, CHH); 4.94 (d, J =10.8 Hz, 1 H, CHH); 7.42-7.46 (m, 2H, aromatic protons); 7.49-7.54 (m, 2H, aromatic protons); 7.58-760 (m, 2H, aromatic protons); 8.22 (d, J = 2.4 Hz, H-6); 8.41 (dd, J = 8.8, 2.4Hz, H-8) ppm.

Comment (NMR Spectroscopy)

Signals given

Patent; UNIVERSITA' DEGLI STUDI DI FIRENZE; A.I.L. FIRENZE SEZIONE AUTONOMA DI FIRENZE DELL'ASSOCIAZIONE ITALIANA CONTRO LE LEUCEMIE, LINFOMI E MIELOMA - ONLUS; WO2009/81349; (2009); (A1) English, View in Reaxys 2 of 14

Description (NMR Spec- Chemical shifts troscopy) Nucleus (NMR Spectroscopy)

1H

Solvents (NMR Spectro- chloroform-d1 scopy) Location

supporting information

Guandalini; Cellai; Laurenzana; Scapecchi; Paoletti; Romanelli; Bioorganic and Medicinal Chemistry Letters; vol. 18; nb. 18; (2008); p. 5071 - 5074, View in Reaxys 3 of 14

Description (NMR Spec- Spectrum troscopy) Nucleus (NMR Spectroscopy)

1H

Solvents (NMR Spectro- CDCl3 scopy) Finner; Zeugner; Archiv der Pharmazie; vol. 320; nb. 2; (1987); p. 179 - 182, View in Reaxys 4 of 14

Description (NMR Spec- Spectrum troscopy) Nucleus (NMR Spectroscopy)

13C

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Solvents (NMR Spectro- CDCl3 scopy) Finner; Zeugner; Archiv der Pharmazie; vol. 320; nb. 2; (1987); p. 179 - 182, View in Reaxys 5 of 14

Description (NMR Spec- Chemical shifts troscopy) Nucleus (NMR Spectroscopy)

13C

Solvents (NMR Spectro- CDCl3 scopy) Finner; Zeugner; Archiv der Pharmazie; vol. 320; nb. 2; (1987); p. 179 - 182, View in Reaxys; Paul, H.-H.; Sapper, H.; Lohmann, W.; Kalinowski, H. O.; Organic Magnetic Resonance; vol. 21; nb. 5; (1983); p. 319 - 321, View in Reaxys 6 of 14

Description (NMR Spec- Chemical shifts troscopy) Nucleus (NMR Spectroscopy)

1H

Solvents (NMR Spectro- CD2Cl2; various solvent(s) scopy) Temperature (NMR Spectroscopy) [°C]

-130

Finner; Zeugner; Archiv der Pharmazie; vol. 320; nb. 2; (1987); p. 179 - 182, View in Reaxys 7 of 14

Description (NMR Spec- Spin-spin coupling constants troscopy) Solvents (NMR Spectro- CDCl3 scopy) Comment (NMR Spectroscopy)

1H-1H, 13C-1H.

Finner; Zeugner; Archiv der Pharmazie; vol. 320; nb. 2; (1987); p. 179 - 182, View in Reaxys 8 of 14

Description (NMR Spec- 2D-NMR troscopy) Finner; Zeugner; Archiv der Pharmazie; vol. 320; nb. 2; (1987); p. 179 - 182, View in Reaxys

9 of 14

Description (NMR Spec- Chemical shifts troscopy) Nucleus (NMR Spectroscopy)

13C

Solvents (NMR Spectro- CDCl3; dimethylsulfoxide-d6 scopy) Temperature (NMR Spectroscopy) [°C]

30

Kovar; Linden; Breitmaier; Archiv der Pharmazie; vol. 314; nb. 2; (1981); p. 186 - 190, View in Reaxys 10 of 14

Description (NMR Spec- Spin-spin coupling constants troscopy) Solvents (NMR Spectro- CDCl3; dimethylsulfoxide-d6 scopy) Temperature (NMR Spectroscopy) [°C]

30

Comment (NMR Spectroscopy)

1H-13C.

Kovar; Linden; Breitmaier; Archiv der Pharmazie; vol. 314; nb. 2; (1981); p. 186 - 190, View in Reaxys 11 of 14

Description (NMR Spec- Chemical shifts troscopy)

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Nucleus (NMR Spectroscopy)

13C

Solvents (NMR Spectro- dimethylsulfoxide-d6 scopy) Temperature (NMR Spectroscopy) [°C]

28

Sarrazin, Marcel; Faure, Robert; Aubert, Claude; Vincent, Emile-Jean; Journal de Chimie Physique et de Physico-Chimie Biologique; vol. 77; nb. 1; (1980); p. 91 - 94, View in Reaxys 12 of 14

Description (NMR Spec- NMR troscopy) Comment (NMR Spectroscopy)

1H

Sarrazin et al.; Organic Magnetic Resonance; vol. 7; (1975); p. 89,92, View in Reaxys 13 of 14

Description (NMR Spec- NMR troscopy) Inaba et al.; Chemical and Pharmaceutical Bulletin; vol. 19; (1971); p. 722,723,726, View in Reaxys

14 of 14

Description (NMR Spec- NMR troscopy) Comment (NMR Spectroscopy)

Tab.1

Sadée; Archiv der Pharmazie und Berichte der Deutschen Pharmazeutischen Gesellschaft; vol. 302; nb. 10; (1969); p. 769 - 774, View in Reaxys IR Spectroscopy (1) 1 of 1

Description (IR Spectroscopy)

IR

Inaba et al.; Chemical and Pharmaceutical Bulletin; vol. 19; (1971); p. 722,723,726, View in Reaxys Mass Spectrometry (1) References Inaba et al.; Chemical and Pharmaceutical Bulletin; vol. 19; (1971); p. 722,723,726, View in Reaxys UV/VIS Spectroscopy (3) 1 of 3

Description (UV/VIS Spectroscopy)

Spectrum

Solvent (UV/VIS Spectroscopy)

aq. NaOH

Comment (UV/VIS Spectroscopy)

200 - 500 nm

Broxton, Trevor J.; Wright, Sallyanne; Journal of Organic Chemistry; vol. 51; nb. 15; (1986); p. 2965 - 2969, View in Reaxys 2 of 3

Description (UV/VIS Spectroscopy)

Absorption maxima

Solvent (UV/VIS Spectroscopy)

dioxane; various solvent(s)

Absorption Maxima (UV/ 280 VIS) [nm] Broxton; Morrison; Australian Journal of Chemistry; vol. 38; nb. 7; (1985); p. 1037 - 1043, View in Reaxys 3 of 3

Description (UV/VIS Spectroscopy)

UV/VIS

Inaba et al.; Chemical and Pharmaceutical Bulletin; vol. 19; (1971); p. 722,723,726, View in Reaxys Use (55) Use Pattern Pharmaceuticals

Location

References

Page/Page column 56; 58; 59;

Patent; THE REGENTS OF THE UNIVERSITY OF CALIFORNIA; ROGAWSKI, Michael A.; PESSAH, Isaac N.; CAO, Zhengyu; LEIN, Pamela J.; WO2014/28398; (2014); (A2) English, View in Reaxys

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60; 61; 62; 66; 67; 68 aura

Page/Page colPatent; THE REGENTS OF THE UNIVERSITY OF CALIFORNIA; ROGAWSKI, Michael umn 56; 58; 59; A.; PESSAH, Isaac N.; CAO, Zhengyu; LEIN, Pamela J.; WO2014/28398; (2014); (A2) 60; 61; 62; 66; 67; English, View in Reaxys 68

clonic seizure

Page/Page colPatent; THE REGENTS OF THE UNIVERSITY OF CALIFORNIA; ROGAWSKI, Michael umn 56; 58; 59; A.; PESSAH, Isaac N.; CAO, Zhengyu; LEIN, Pamela J.; WO2014/28398; (2014); (A2) 60; 61; 62; 66; 67; English, View in Reaxys 68

component of composition comprising a neurosteroid for terminating a seizure

Page/Page colPatent; THE REGENTS OF THE UNIVERSITY OF CALIFORNIA; ROGAWSKI, Michael umn 56; 58; 59; A.; PESSAH, Isaac N.; CAO, Zhengyu; LEIN, Pamela J.; WO2014/28398; (2014); (A2) 60; 61; 62; 66; 67; English, View in Reaxys 68

epilepticus

Page/Page colPatent; THE REGENTS OF THE UNIVERSITY OF CALIFORNIA; ROGAWSKI, Michael umn 56; 58; 59; A.; PESSAH, Isaac N.; CAO, Zhengyu; LEIN, Pamela J.; WO2014/28398; (2014); (A2) 60; 61; 62; 66; 67; English, View in Reaxys 68

for subject suffers Page/Page colPatent; THE REGENTS OF THE UNIVERSITY OF CALIFORNIA; ROGAWSKI, Michael from seizure clus- umn 56; 58; 59; A.; PESSAH, Isaac N.; CAO, Zhengyu; LEIN, Pamela J.; WO2014/28398; (2014); (A2) ters 60; 61; 62; 66; 67; English, View in Reaxys 68 for terminating an impending seizure

Page/Page colPatent; THE REGENTS OF THE UNIVERSITY OF CALIFORNIA; ROGAWSKI, Michael umn 56; 58; 59; A.; PESSAH, Isaac N.; CAO, Zhengyu; LEIN, Pamela J.; WO2014/28398; (2014); (A2) 60; 61; 62; 66; 67; English, View in Reaxys 68

myoclonic epilepsy

Page/Page colPatent; THE REGENTS OF THE UNIVERSITY OF CALIFORNIA; ROGAWSKI, Michael umn 56; 58; 59; A.; PESSAH, Isaac N.; CAO, Zhengyu; LEIN, Pamela J.; WO2014/28398; (2014); (A2) 60; 61; 62; 66; 67; English, View in Reaxys 68

tonic seizure

Page/Page colPatent; THE REGENTS OF THE UNIVERSITY OF CALIFORNIA; ROGAWSKI, Michael umn 56; 58; 59; A.; PESSAH, Isaac N.; CAO, Zhengyu; LEIN, Pamela J.; WO2014/28398; (2014); (A2) 60; 61; 62; 66; 67; English, View in Reaxys 68

Pharmaceuticals

Page/Page column 43; 44; 45

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

SCNIA-related seizure disorders

Page/Page column 43; 44; 45

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

a cardiovascular disease or disorder

Page/Page column 43; 44; 45

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

a disease or disPage/Page colorder associated umn 43; 44; 45 with misregulation of voltage-gated sodium channel alpha subunit activity

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

a disease or disPage/Page colorder associated umn 43; 44; 45 with neuromuscular system

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

a disease or disorder of the genitourinary tract involving sympathetic and parasympathetic innervation

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

Page/Page column 43; 44; 45

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a gastrointestinal tract disease due to dysfunction of the enteric nervous system

Page/Page column 43; 44; 45

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

a neurological disease or disorder

Page/Page column 43; 44; 45

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

ataxia

Page/Page column 43; 44; 45

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

autism

Page/Page column 43; 44; 45

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

benign prostrate hyperplasia

Page/Page column 43; 44; 45

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

colitis

Page/Page column 43; 44; 45

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

congestive heart failure

Page/Page column 43; 44; 45

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

convulsion

Page/Page column 43; 44; 45

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

epilepsy

Page/Page column 43; 44; 45

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

generalized epilepsy with febrile seizure plus (GEFS+)

Page/Page column 43; 44; 45

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

hyperkalemic periodic paralysis

Page/Page column 43; 44; 45

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

hypertension

Page/Page column 43; 44; 45

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

ileitis

Page/Page column 43; 44; 45

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

impaired electrical Page/Page colexcitability involv- umn 43; 44; 45 ing sodium channel dysfunction

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

impotence

Page/Page column 43; 44; 45

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

inflammatory bowel syndrome

Page/Page column 43; 44; 45

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

long Q-T syndrome 3

Page/Page column 43; 44; 45

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

migraine

Page/Page column 43; 44; 45

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

motor endplate disease

Page/Page column 43; 44; 45

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

multiple sclerosis

Page/Page column 43; 44; 45

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

muscular dystrophy

Page/Page column 43; 44; 45

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

pain (including chronic pain)

Page/Page column 43; 44; 45

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

paralysis

Page/Page column 43; 44; 45

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

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paramyotonia congenita

Page/Page column 43; 44; 45

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

potassium-aggravated myotonia

Page/Page column 43; 44; 45

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

preventing or Page/Page coltreating a disease umn 43; 44; 45 associated with at least one sodium channel, voltagegated, type I, alpha subunit (SCN1A) polynucleotide and/or at least one encoded product thereof

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome)

Page/Page column 43; 44; 45

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

sporadic and fam- Page/Page colilial hemiplegic umn 43; 44; 45 migraines

Patent; CuRNA, Inc.; COLLARD, Joseph; KHORKOVA SHERMAN, Olga; HSIAO, Jane H.; WO2013/36403; (2013); (A1) English, View in Reaxys

A reduction in the rate of decline of the clinical dementia rating (CDR) of the mammal

Page/Page column title page; 54-61

Patent; BUCK INSTITUTE FOR AGE RESEARCH; JOHN, Varghese; BREDESEN, Dale E.; WO2012/24616; (2012); (A1) English, View in Reaxys

A stabilization of Page/Page coldecline of the clin- umn title page; ical dementia rat- 54-61 ing (CDR) of the mammal

Patent; BUCK INSTITUTE FOR AGE RESEARCH; JOHN, Varghese; BREDESEN, Dale E.; WO2012/24616; (2012); (A1) English, View in Reaxys

APOE ε4 allele

Page/Page column title page; 54-61

Patent; BUCK INSTITUTE FOR AGE RESEARCH; JOHN, Varghese; BREDESEN, Dale E.; WO2012/24616; (2012); (A1) English, View in Reaxys

Alzheimer's disease

Page/Page column title page; 54-61

Patent; BUCK INSTITUTE FOR AGE RESEARCH; JOHN, Varghese; BREDESEN, Dale E.; WO2012/24616; (2012); (A1) English, View in Reaxys

Amyloidogenic diseases

Page/Page column title page; 54-61

Patent; BUCK INSTITUTE FOR AGE RESEARCH; JOHN, Varghese; BREDESEN, Dale E.; WO2012/24616; (2012); (A1) English, View in Reaxys

Familial Alzheimer's disease (FAD) mutation

Page/Page column title page; 54-61

Patent; BUCK INSTITUTE FOR AGE RESEARCH; JOHN, Varghese; BREDESEN, Dale E.; WO2012/24616; (2012); (A1) English, View in Reaxys

Improvement in Page/Page colthe rate of decline umn title page; of the clinical de- 54-61 mentia rating (CDR) of the mammal

Patent; BUCK INSTITUTE FOR AGE RESEARCH; JOHN, Varghese; BREDESEN, Dale E.; WO2012/24616; (2012); (A1) English, View in Reaxys

Mild cognitive impairment (MCI)

Page/Page column title page; 54-61

Patent; BUCK INSTITUTE FOR AGE RESEARCH; JOHN, Varghese; BREDESEN, Dale E.; WO2012/24616; (2012); (A1) English, View in Reaxys

Mild cognitive impairment (MCI) associated with amyloid deposits in the brain

Page/Page column title page; 54-61

Patent; BUCK INSTITUTE FOR AGE RESEARCH; JOHN, Varghese; BREDESEN, Dale E.; WO2012/24616; (2012); (A1) English, View in Reaxys

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Processing of Page/Page colamyloid precursor umn title page; protein (APP) by 54-61 the non-amyloidogenic pathway

Patent; BUCK INSTITUTE FOR AGE RESEARCH; JOHN, Varghese; BREDESEN, Dale E.; WO2012/24616; (2012); (A1) English, View in Reaxys

Reduction of the Page/Page colplaque load in the umn title page; brain of the mam- 54-61 mal

Patent; BUCK INSTITUTE FOR AGE RESEARCH; JOHN, Varghese; BREDESEN, Dale E.; WO2012/24616; (2012); (A1) English, View in Reaxys

inhibiting, reducPage/Page coling, delaying umn title page; and/or preventing 54-61 the progression of MCI to Alzheimer's disease

Patent; BUCK INSTITUTE FOR AGE RESEARCH; JOHN, Varghese; BREDESEN, Dale E.; WO2012/24616; (2012); (A1) English, View in Reaxys

(0) Medchem (74) 1 of 74

Target Mutant/Chimera Details

5-hydroxytryptamine receptor [Rattus norvegicus]:Wild; Ionotropic Gamma aminobutyric acid A receptor [Rattus norvegicus]:Wild

Target Species (Bioactivity)

Rattus norvegicus; Rattus norvegicus

Target Subunit Proteins

5-hydroxytryptamine receptor [Rattus norvegicus]; Ionotropic Gamma aminobutyric acid A receptor [Rattus norvegicus]

Target Transfection

Non Transfected; Non Transfected

Bioassay Category

In Vivo (Animal models)

Bioassay Name

Specific behaviour

Biological Species/NCBI Sprague Dawley rat ID Substance RN

759813View in Reaxys

Substance Name

Nimetazepam

Substance Dose

10 mg/kg

Substance Route of Adm.

intraperitoneal administration

Substance Dosing Regi- Single men Measurement Parameter

%

Unit

%

Quantitative value

33

Target, Subunit, Species 5-hydroxytryptamine receptor [Rattus norvegicus]; Ionotropic Gamma aminobutyric acid A receptor [Rattus norvegicus] 2 of 74

Target Mutant/Chimera Details

5-hydroxytryptamine receptor [Rattus norvegicus]:Wild; Ionotropic Gamma aminobutyric acid A receptor [Rattus norvegicus]:Wild

Target Species (Bioactivity)

Rattus norvegicus; Rattus norvegicus

Target Subunit Proteins

5-hydroxytryptamine receptor [Rattus norvegicus]; Ionotropic Gamma aminobutyric acid A receptor [Rattus norvegicus]

Target Transfection

Non Transfected; Non Transfected

Bioassay Category

In Vivo (Animal models)

Bioassay Name

Specific behaviour

Biological Species/NCBI Sprague Dawley rat ID

Copyright © 2017 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

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Substance RN

759813View in Reaxys

Substance Name

Nimetazepam

Substance Dose

20 mg/kg

Substance Route of Adm.

intraperitoneal administration

Substance Dosing Regi- Single men Measurement Parameter

%

Unit

%

Quantitative value

40

Target, Subunit, Species 5-hydroxytryptamine receptor [Rattus norvegicus]; Ionotropic Gamma aminobutyric acid A receptor [Rattus norvegicus] 3 of 74

Target Mutant/Chimera Details

5-hydroxytryptamine receptor [Rattus norvegicus]:Wild; Ionotropic Gamma aminobutyric acid A receptor [Rattus norvegicus]:Wild

Target Species (Bioactivity)

Rattus norvegicus; Rattus norvegicus

Target Subunit Proteins

5-hydroxytryptamine receptor [Rattus norvegicus]; Ionotropic Gamma aminobutyric acid A receptor [Rattus norvegicus]

Target Transfection

Non Transfected; Non Transfected

Bioassay Category

In Vivo (Animal models)

Bioassay Name

Specific behaviour

Biological Species/NCBI Sprague Dawley rat ID Substance RN

759813View in Reaxys

Substance Name

Nimetazepam

Substance Dose

30 mg/kg

Substance Route of Adm.

intraperitoneal administration

Substance Dosing Regi- Single men Measurement Parameter

%

Unit

%

Quantitative value

67

Target, Subunit, Species 5-hydroxytryptamine receptor [Rattus norvegicus]; Ionotropic Gamma aminobutyric acid A receptor [Rattus norvegicus] 4 of 74

Target Mutant/Chimera Details

5-hydroxytryptamine receptor [Rattus norvegicus]:Wild; Ionotropic Gamma aminobutyric acid A receptor [Rattus norvegicus]:Wild

Target Species (Bioactivity)

Rattus norvegicus; Rattus norvegicus

Target Subunit Proteins

5-hydroxytryptamine receptor [Rattus norvegicus]; Ionotropic Gamma aminobutyric acid A receptor [Rattus norvegicus]

Target Transfection

Non Transfected; Non Transfected

Bioassay Category

In Vivo (Animal models)

Bioassay Name

Specific behaviour

Biological Species/NCBI Sprague Dawley rat ID Substance RN

759813View in Reaxys

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Substance Name

Nimetazepam

Substance Dose

60 mg/kg

Substance Route of Adm.

intraperitoneal administration

Substance Dosing Regi- Single men Measurement Parameter

%

Unit

%

Quantitative value

38

Target, Subunit, Species 5-hydroxytryptamine receptor [Rattus norvegicus]; Ionotropic Gamma aminobutyric acid A receptor [Rattus norvegicus] 5 of 74

Target Mutant/Chimera Details

5-hydroxytryptamine receptor [Rattus norvegicus]:Wild; Ionotropic Gamma aminobutyric acid A receptor [Rattus norvegicus]:Wild

Target Species (Bioactivity)

Rattus norvegicus; Rattus norvegicus

Target Subunit Proteins

5-hydroxytryptamine receptor [Rattus norvegicus]; Ionotropic Gamma aminobutyric acid A receptor [Rattus norvegicus]

Target Transfection

Non Transfected; Non Transfected

Bioassay Category

In Vivo (Animal models)

Bioassay Name

Specific behaviour

Biological Species/NCBI Sprague Dawley rat ID Substance RN

759813View in Reaxys

Substance Name

Nimetazepam

Substance Dose

10 mg/kg

Substance Route of Adm.

intraperitoneal administration

Substance Dosing Regi- Single men Measurement Parameter

Number

Quantitative value

2.3

Deviation

2.40000

Target, Subunit, Species 5-hydroxytryptamine receptor [Rattus norvegicus]; Ionotropic Gamma aminobutyric acid A receptor [Rattus norvegicus] 6 of 74

Target Mutant/Chimera Details

5-hydroxytryptamine receptor [Rattus norvegicus]:Wild; Ionotropic Gamma aminobutyric acid A receptor [Rattus norvegicus]:Wild

Target Species (Bioactivity)

Rattus norvegicus; Rattus norvegicus

Target Subunit Proteins

5-hydroxytryptamine receptor [Rattus norvegicus]; Ionotropic Gamma aminobutyric acid A receptor [Rattus norvegicus]

Target Transfection

Non Transfected; Non Transfected

Bioassay Category

In Vivo (Animal models)

Bioassay Name

Specific behaviour

Biological Species/NCBI Sprague Dawley rat ID Substance RN

759813View in Reaxys

Substance Name

Nimetazepam

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Substance Dose

20 mg/kg

Substance Route of Adm.

intraperitoneal administration

Substance Dosing Regi- Single men Measurement Parameter

Number

Quantitative value

2

Deviation

1.80000

Target, Subunit, Species 5-hydroxytryptamine receptor [Rattus norvegicus]; Ionotropic Gamma aminobutyric acid A receptor [Rattus norvegicus] 7 of 74

Target Mutant/Chimera Details

5-hydroxytryptamine receptor [Rattus norvegicus]:Wild; Ionotropic Gamma aminobutyric acid A receptor [Rattus norvegicus]:Wild

Target Species (Bioactivity)

Rattus norvegicus; Rattus norvegicus

Target Subunit Proteins

5-hydroxytryptamine receptor [Rattus norvegicus]; Ionotropic Gamma aminobutyric acid A receptor [Rattus norvegicus]

Target Transfection

Non Transfected; Non Transfected

Bioassay Category

In Vivo (Animal models)

Bioassay Name

Specific behaviour

Biological Species/NCBI Sprague Dawley rat ID Substance RN

759813View in Reaxys

Substance Name

Nimetazepam

Substance Dose

30 mg/kg

Substance Route of Adm.

intraperitoneal administration

Substance Dosing Regi- Single men Measurement Parameter

Number

Quantitative value

8

Deviation

2.20000

Target, Subunit, Species 5-hydroxytryptamine receptor [Rattus norvegicus]; Ionotropic Gamma aminobutyric acid A receptor [Rattus norvegicus] 8 of 74

Target Mutant/Chimera Details

5-hydroxytryptamine receptor [Rattus norvegicus]:Wild; Ionotropic Gamma aminobutyric acid A receptor [Rattus norvegicus]:Wild

Target Species (Bioactivity)

Rattus norvegicus; Rattus norvegicus

Target Subunit Proteins

5-hydroxytryptamine receptor [Rattus norvegicus]; Ionotropic Gamma aminobutyric acid A receptor [Rattus norvegicus]

Target Transfection

Non Transfected; Non Transfected

Bioassay Category

In Vivo (Animal models)

Bioassay Name

Specific behaviour

Biological Species/NCBI Sprague Dawley rat ID Substance RN

759813View in Reaxys

Substance Name

Nimetazepam

Substance Dose

60 mg/kg

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Substance Route of Adm.

intraperitoneal administration

Substance Dosing Regi- Single men Measurement Parameter

Number

Quantitative value

7.9

Deviation

0.800000

Target, Subunit, Species 5-hydroxytryptamine receptor [Rattus norvegicus]; Ionotropic Gamma aminobutyric acid A receptor [Rattus norvegicus] 9 of 74

Bioassay Category

Metabolism/Transport

Bioassay Name

Binding

Biological Species/NCBI Human ID Population State

Healthy

Organs/Tissues

plasma

Substance RN

759813View in Reaxys

Substance Name

C-3453

Substance Dose

5 µg/mL

Measurement Parameter

fu

Quantitative value

0.187

Deviation

0.0400000

Lucek; Coutinho; Molecular Pharmacology; vol. 12; nb. 4; (1976); p. 612 - 619, View in Reaxys 10 of 74

Substance Effect

Anticonvulsant

Bioassay Category

In Vivo (Animal models)

Bioassay Name

In vivo Measurement

Bioassay Details

Effect : seizure stage Bioassay : AD: afterdischarge bipolar electrodes implanted into right amygdala of rats; stimulation: 60 Hz, 1 ms and 1 s duration at intensity sufficient to induce AD; stimulation performed 1 h after title comp. administration; amygdaloid kindling classified by Racine method

Biological Species/NCBI Rattus norvegicus ID Substance RN

759813View in Reaxys

Substance Name

89458

Substance Dose

0.500000 mg/kg

Substance Route of Adm.

oral administration

Measurement Parameter

ED50

Unit

mg/kg

Quantitative value

1.26

Fukinaga, Masafumi; Ishizawa, Keisuke; Kamei, Chiaki; Pharmacology; vol. 57; nb. 5; (1998); p. 233 - 241, View in Reaxys 11 of 74

Bioassay Category

In Vitro (Efficacy)

Bioassay Name

In Vitro (others)

Substance RN

759813View in Reaxys

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Substance Name

89458

Qualitative Results

parameters of binding to serum proteins at pH 7.4, obtained from the fluorescence method

Measurement Parameter

Qualitative

Maruyama; Furuie; Hibino; Otagiri; Journal of Pharmaceutical Sciences; vol. 81; nb. 1; (1992); p. 16 - 20, View in Reaxys 12 of 74

Target Mutant/Chimera Details

Ionotropic Gamma aminobutyric acid A receptor [taurine cattle]:Wild

Target Species (Bioactivity)

taurine cattle

Target Subunit Proteins

Ionotropic Gamma aminobutyric acid A receptor [taurine cattle]

Target Transfection

Non Transfected

Bioassay Category

In Vitro (Efficacy)

Bioassay Name

Binding

Biological Species/NCBI taurine cattle ID Organs/Tissues

brain cortex

Cell Fraction

Membrane

Substance RN

759813View in Reaxys

Substance Name

14

Measurement Parameter

IC50

Unit

nM

Quantitative value

64

Measurement pX

7.19

Target, Subunit, Species Ionotropic Gamma aminobutyric acid A receptor [taurine cattle] 13 of 74

Bioassay Category

In Vitro (Efficacy)

Bioassay Name

In Vitro (others)

Bioassay Details

Effect : pro-Alzheimer's disease fragment level; effect on Species : J20 mouse Bioassay : primary neurons derived from hippocampi J20 (PDAPP Mouse Model) Primary Neuronal Cells[0144] This example provides experimental methods for measurement of sAPPalpha, Αβ42 and APPneo in primary neuronal cells.[0145] In vitro primary culture compound testing assay: Primary neuronal cultures were made from embryonic 18 day mice J20

Substance RN

759813View in Reaxys

Substance Name

IV

Qualitative Results

sAPPalpha (% control) = 89 at 1 μmol/l; Abeta42 (% control) = 24 at 1 μmol/l

Measurement Parameter

Qualitative

Patent; BUCK INSTITUTE FOR AGE RESEARCH; JOHN, Varghese; BREDESEN, Dale E.; WO2012/24616; (2012); (A1) English, View in Reaxys 14 of 74

Bioassay Category

Toxicity/Safety Pharmacology

Bioassay Details

Intraperitoneal lethal dose in mouse

Biological Species/NCBI Mus musculus ID Substance RN

759813View in Reaxys

Measurement Parameter

LD50

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Unit

mg/kg

Qualitative value

=

Quantitative value

510

Oyo yakuri; vol. 7; nb. 705; (1973), View in Reaxys 15 of 74

Bioassay Category

Toxicity/Safety Pharmacology

Bioassay Details

Subcutaneous lethal dose in Mouse

Biological Species/NCBI Mus musculus ID Substance RN

759813View in Reaxys

Measurement Parameter

LD50

Unit

mg/kg

Qualitative value

=

Quantitative value

5000

Oyo yakuri; vol. 7; nb. 705; (1973), View in Reaxys 16 of 74

Bioassay Category

Toxicity/Safety Pharmacology

Bioassay Details

Toxic activity of compound in mice upon oral administration was determined

Biological Species/NCBI Mus musculus ID Substance RN

759813View in Reaxys

Substance Route of Adm.

oral administration

Measurement Parameter

LD50

Unit

mg/kg

Qualitative value

=

Quantitative value

750

Esteki, Mahnaz; Khayamian, Taghi; Chemical Biology and Drug Design; vol. 72; nb. 5; (2008); p. 409 - 435, View in Reaxys 17 of 74

Target Mutant/Chimera Details

Peripheral-type benzodiazepine receptor-associated protein 1:Wild

Substance Action on Target

Radioligand (/ligand)

Target Subunit Proteins

Peripheral-type benzodiazepine receptor-associated protein 1

Bioassay Category

In Vitro (Efficacy)

Bioassay Details

Binding affinity of the compound towards benzodiazepine receptor

Substance RN

759813View in Reaxys

Measurement Parameter

Qualitative

Qualitative value

Not Published

Target, Subunit, Species Peripheral-type benzodiazepine receptor-associated protein 1 18 of 74

Bioassay Category

In Vivo (Animal models)

Bioassay Details

Anticonvulsant activity expressed as the dose which prevented convulsions in 50 of the mice tested after subcutaneous administration of 125 mg/kg was measured by metrazole test

Biological Species/NCBI Mus musculus ID

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Substance RN

759813View in Reaxys

Substance Route of Adm.

subcutaneous administration

Measurement Parameter

ED50

Unit

mg/kg

Qualitative value

=

Quantitative value

2.69

Blair; Webb; Journal of Medicinal Chemistry; vol. 20; nb. 9; (1977); p. 1206 - 1210, View in Reaxys 19 of 74

Bioassay Category

In Vitro (Efficacy)

Bioassay Details

Sedation and muscle relaxation effect expressed as dose required to produce relaxation of the body and hind legs when the cats were suspended by the scruff of the neck

Biological Species/NCBI domestic cat ID Substance RN

759813View in Reaxys

Measurement Parameter

MED

Unit

mg/kg

Qualitative value

=

Quantitative value

3.46

Blair; Webb; Journal of Medicinal Chemistry; vol. 20; nb. 9; (1977); p. 1206 - 1210, View in Reaxys 20 of 74

Bioassay Category

In Vitro (Efficacy)

Bioassay Details

Sedative and muscle relaxant effect expressed as dose which caused three out of six mice to slide off a 70 degree inclined screen

Biological Species/NCBI Mus musculus ID Substance RN

759813View in Reaxys

Measurement Parameter

ED50

Unit

mg/kg

Qualitative value

=

Quantitative value

1.46

Blair; Webb; Journal of Medicinal Chemistry; vol. 20; nb. 9; (1977); p. 1206 - 1210, View in Reaxys 21 of 74

Bioassay Category

In Vitro (Efficacy)

Bioassay Details

Taming activity expressed as dose required to tame pairs of fighting mice, their aggression being stimulated by an electrical current applied to their feet using footshock or fighting mice test

Biological Species/NCBI Mus musculus ID Substance RN

759813View in Reaxys

Measurement Parameter

MED

Unit

mg/kg

Qualitative value

=

Quantitative value

2.07

Blair; Webb; Journal of Medicinal Chemistry; vol. 20; nb. 9; (1977); p. 1206 - 1210, View in Reaxys 22 of 74

Target Mutant/Chimera Details

Peripheral-type benzodiazepine receptor-associated protein 1:Wild

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Target Subunit Proteins

Peripheral-type benzodiazepine receptor-associated protein 1

Bioassay Category

In Vitro (Efficacy)

Bioassay Details

Activity of the compound against Benzodiazepine receptor

Substance RN

759813View in Reaxys

Measurement Parameter

Qualitative

Qualitative value

Not Published

Target, Subunit, Species Peripheral-type benzodiazepine receptor-associated protein 1 23 of 74

Bioassay Category

Metabolism/Transport

Bioassay Details

Partition Coefficient of the compound was determined

Substance RN

759813View in Reaxys

Measurement Parameter

Qualitative

Qualitative value

Not Published

Dimitra Hadjipavlou-Litina; Corwin Hansch; Chemical reviews; vol. 94; nb. 6; (1994); p. 1483 - 1505, View in Reaxys 24 of 74

Bioassay Category

Metabolism/Transport

Bioassay Details

Partition Coefficient of the compound was determined

Substance RN

759813View in Reaxys

Measurement Parameter

Qualitative

Qualitative value

Not Published

Dimitra Hadjipavlou-Litina; Corwin Hansch; Chemical reviews; vol. 94; nb. 6; (1994); p. 1483 - 1505, View in Reaxys 25 of 74

Bioassay Category

In Vitro (Efficacy)

Bioassay Details

Anticonvulsant activity of compound was evaluated using anti-pentylenetetrazole test mouse

Biological Species/NCBI Mus musculus ID Substance RN

759813View in Reaxys

Measurement Parameter

pIC50

Quantitative value

2.69

Measurement pX

2.69

Dimitra Hadjipavlou-Litina; Corwin Hansch; Chemical reviews; vol. 94; nb. 6; (1994); p. 1483 - 1505, View in Reaxys 26 of 74

Bioassay Category

In Vitro (Efficacy)

Bioassay Details

Logarithm of effective dose of the compound determined using foot-shock test in mice

Biological Species/NCBI Mus musculus ID Substance RN

759813View in Reaxys

Unit

mM/kg

Qualitative value

=

Quantitative value

2.07

Lukovits; Journal of Medicinal Chemistry; vol. 26; nb. 8; (1983); p. 1104 - 1109, View in Reaxys 27 of 74

Substance Effect

Antiviral

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Bioassay Category

In Vitro (Efficacy)

Bioassay Details

Percent of HEPATITIS C VIRUS infection in HUH-7.5.1-c2 cells at 10 uM compound (dissolved in DMSO) concentration upon incubation at 37 degree C for 3 days relative to control

Biological Species/NCBI Hepatitis C virus ID Cells/Cell Lines

Huh-7.5.1

Substance RN

759813View in Reaxys

Measurement Parameter

%

Unit

%

Qualitative value

=

Quantitative value

123.3

Gastaminza, Pablo; Whitten-Bauer, Christina; Chisari, Francis V.; Proceedings of the National Academy of Sciences of the United States of America; vol. 107; nb. 1; (2010); p. 291 - 296, View in Reaxys 28 of 74

Substance Effect

Toxic

Bioassay Category

Toxicity/Safety Pharmacology

Bioassay Details

Toxicity of the compound was determined by evaluating remaining HUH-7.5.1-c2 cell biomass upon incubation for 72 hours

Cells/Cell Lines

Huh-7.5.1

Substance RN

759813View in Reaxys

Measurement Parameter

Toxicity

Unit

%

Qualitative value

=

Quantitative value

94.9

Gastaminza, Pablo; Whitten-Bauer, Christina; Chisari, Francis V.; Proceedings of the National Academy of Sciences of the United States of America; vol. 107; nb. 1; (2010); p. 291 - 296, View in Reaxys 29 of 74

Bioassay Category

Toxicity/Safety Pharmacology

Bioassay Details

Lethal dose in rat following subcutaneous administration

Biological Species/NCBI Mus musculus ID Substance RN

759813View in Reaxys

Substance Route of Adm.

subcutaneous administration

Qualitative Results

> 5000

Measurement Parameter

LD50

Unit

mg/kg

Quantitative value

5000

Oyo Yakuri. Pharmacometrics, 1973, 7, 705; vol. 7; (1973); p. 705, View in Reaxys 30 of 74

Bioassay Category

Toxicity/Safety Pharmacology

Bioassay Details

Lowest published toxic dose upon oral administration in female 8-14 days rats after conception

Biological Species/NCBI Rattus norvegicus ID Substance RN

759813View in Reaxys

Qualitative Results

700

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Measurement Parameter

TDLo

Unit

mg/kg

Quantitative value

700

Saito; Kobayashi; Takeno; Sakai; Research Communications in Chemical Pathology and Pharmacology; vol. 46; nb. 3; (1984); p. 437 - 447, View in Reaxys 31 of 74

Bioassay Category

Toxicity/Safety Pharmacology

Bioassay Details

Oral lethal dose in mouse

Biological Species/NCBI Mus musculus ID Substance RN

759813View in Reaxys

Substance Route of Adm.

oral administration

Measurement Parameter

LD50

Unit

mg/kg

Qualitative value

=

Quantitative value

750

Sakai; Kitagawa; Yamamoto; Arzneimittel-Forschung; vol. 22; nb. 3; (1972); p. 534 - 539, View in Reaxys 32 of 74

Bioassay Category

Toxicity/Safety Pharmacology

Bioassay Details

Lethal dose upon oral administration in mouse

Biological Species/NCBI Mus musculus ID Substance RN

759813View in Reaxys

Qualitative Results

750

Measurement Parameter

LD50

Unit

mg/kg

Quantitative value

750

Sakai; Kitagawa; Yamamoto; Arzneimittel-Forschung; vol. 22; nb. 3; (1972); p. 534 - 539, View in Reaxys 33 of 74

Bioassay Category

Toxicity/Safety Pharmacology

Bioassay Details

Subcutaneous lethal dose in rat; 1000 mg/Kg

Biological Species/NCBI Rattus norvegicus ID Substance RN

759813View in Reaxys

Substance Route of Adm.

subcutaneous administration

Measurement Parameter

LD50

Unit

mg/kg

Qualitative value

=

Quantitative value

1000

Sakai; Kitagawa; Yamamoto; Arzneimittel-Forschung; vol. 22; nb. 3; (1972); p. 534 - 539, View in Reaxys 34 of 74

Bioassay Category

Toxicity/Safety Pharmacology

Bioassay Details

Lethal dose upon oral administration in rat

Biological Species/NCBI Rattus norvegicus ID

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Substance RN

759813View in Reaxys

Qualitative Results

970

Measurement Parameter

LD50

Unit

mg/kg

Quantitative value

970

Sakai; Kitagawa; Yamamoto; Arzneimittel-Forschung; vol. 22; nb. 3; (1972); p. 534 - 539, View in Reaxys 35 of 74

Bioassay Category

Toxicity/Safety Pharmacology

Bioassay Details

Oral lethal dose in rat

Biological Species/NCBI Rattus norvegicus ID Substance RN

759813View in Reaxys

Substance Route of Adm.

oral administration

Measurement Parameter

LD50

Unit

mg/kg

Qualitative value

=

Quantitative value

970

Sakai; Kitagawa; Yamamoto; Arzneimittel-Forschung; vol. 22; nb. 3; (1972); p. 534 - 539, View in Reaxys 36 of 74

Bioassay Category

Toxicity/Safety Pharmacology

Bioassay Details

Lethal dose in pig following peroral administration causes nausea or vomiting

Biological Species/NCBI Rattus norvegicus ID Substance RN

759813View in Reaxys

Substance Route of Adm.

oral administration

Qualitative Results

> 1000

Measurement Parameter

LD50

Unit

mg/kg

Quantitative value

1000

Sakai; Kitagawa; Yamamoto; Arzneimittel-Forschung; vol. 22; nb. 3; (1972); p. 534 - 539, View in Reaxys 37 of 74

Bioassay Category

Toxicity/Safety Pharmacology

Bioassay Details

Lethal dose upon intraperitoneal administration in mouse

Biological Species/NCBI Mus musculus ID Substance RN

759813View in Reaxys

Qualitative Results

510

Measurement Parameter

LD50

Unit

mg/kg

Quantitative value

510

Oyo Yakuri. Pharmacometrics, 1973, 7, 705; vol. 7; (1973); p. 705, View in Reaxys 38 of 74

Bioassay Category

Toxicity/Safety Pharmacology

Bioassay Details

Intraperitoneal lethal dose in rat

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Biological Species/NCBI Rattus norvegicus ID Substance RN

759813View in Reaxys

Measurement Parameter

LD50

Unit

mg/kg

Qualitative value

=

Quantitative value

970

Sakai; Kitagawa; Yamamoto; Arzneimittel-Forschung; vol. 22; nb. 3; (1972); p. 534 - 539, View in Reaxys 39 of 74

Bioassay Category

Toxicity/Safety Pharmacology

Bioassay Details

Toxic dose required to cause fetotoxicity in rat

Biological Species/NCBI Rattus norvegicus ID Substance RN

759813View in Reaxys

Measurement Parameter

TD

Unit

mg/kg

Qualitative value

=

Quantitative value

100

Saito; Kobayashi; Takeno; Sakai; Research Communications in Chemical Pathology and Pharmacology; vol. 46; nb. 3; (1984); p. 437 - 447, View in Reaxys 40 of 74

Bioassay Category

Toxicity/Safety Pharmacology

Bioassay Details

Lethal dose upon intraperitoneal administration in rat

Biological Species/NCBI Rattus norvegicus ID Substance RN

759813View in Reaxys

Qualitative Results

970

Measurement Parameter

LD50

Unit

mg/kg

Quantitative value

970

Sakai; Kitagawa; Yamamoto; Arzneimittel-Forschung; vol. 22; nb. 3; (1972); p. 534 - 539, View in Reaxys 41 of 74

Bioassay Category

In Vitro (Efficacy)

Bioassay Details

Activity of the compound was determined by using Clined screen test

Substance RN

759813View in Reaxys

Measurement Parameter

Activity

Quantitative value

4.47

Aoyama; Suzuki; Ichikawa; Journal of Medicinal Chemistry; vol. 33; nb. 9; (1990); p. 2583 - 2590, View in Reaxys 42 of 74

Bioassay Category

In Vitro (Efficacy)

Bioassay Details

Anti-pentylenetetrazole effect of the compound was determined

Substance RN

759813View in Reaxys

Measurement Parameter

Activity

Quantitative value

5.62

Aoyama; Suzuki; Ichikawa; Journal of Medicinal Chemistry; vol. 33; nb. 9; (1990); p. 2583 - 2590, View in Reaxys

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43 of 74

Bioassay Category

In Vitro (Efficacy)

Bioassay Details

Anti-fighting behaviour of the compound was determined

Substance RN

759813View in Reaxys

Measurement Parameter

Activity

Quantitative value

5.07

Aoyama; Suzuki; Ichikawa; Journal of Medicinal Chemistry; vol. 33; nb. 9; (1990); p. 2583 - 2590, View in Reaxys 44 of 74

Bioassay Category

Pharmacokinetic

Bioassay Details

Time to reach peak blood levels of desmethyl derivative (nitrazepam) of compound in dog after p.o. administration

Biological Species/NCBI dog ID Substance RN

759813View in Reaxys

Substance Route of Adm.

oral administration

Measurement Parameter

Tmax

Unit

hour

Qualitative value

=

Quantitative value

4

Yanagi; Haga; Endo; Kitagawa; Xenobiotica; vol. 6; nb. 2; (1976); p. 101 - 112, View in Reaxys 45 of 74

Bioassay Category

Pharmacokinetic

Bioassay Details

Peak blood levels of desmethyl derivative (nitrazepam) of compound in dog after p.o. administration

Biological Species/NCBI dog ID Substance RN

759813View in Reaxys

Substance Route of Adm.

oral administration

Qualitative Results

5.2-6.3

Measurement Parameter

Cmax

Unit

µg/mL

Qualitative value

=

Quantitative value

6.3

Yanagi; Haga; Endo; Kitagawa; Xenobiotica; vol. 6; nb. 2; (1976); p. 101 - 112, View in Reaxys 46 of 74

Bioassay Category

Metabolism/Transport

Bioassay Details

Urinary excretion of desmethyl derivative (nitrazepam) of compound in dog after 24-48 h of p.o. administration

Biological Species/NCBI dog ID Substance RN

759813View in Reaxys

Substance Route of Adm.

oral administration

Measurement Parameter

Ue (%)

Unit

%

Qualitative value

=

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Quantitative value

12

Yanagi; Haga; Endo; Kitagawa; Xenobiotica; vol. 6; nb. 2; (1976); p. 101 - 112, View in Reaxys 47 of 74

Bioassay Category

Metabolism/Transport

Bioassay Details

Fecal excretion of compound in dog after 24 h of p.o. administration

Biological Species/NCBI dog ID Substance RN

759813View in Reaxys

Substance Route of Adm.

oral administration

Measurement Parameter

%

Unit

%

Qualitative value

=

Quantitative value

52

Yanagi; Haga; Endo; Kitagawa; Xenobiotica; vol. 6; nb. 2; (1976); p. 101 - 112, View in Reaxys 48 of 74

Bioassay Category

Metabolism/Transport

Bioassay Details

Percent excretion of compound in urine of dog after 48-72 h upon oral administration

Biological Species/NCBI dog ID Substance RN

759813View in Reaxys

Substance Route of Adm.

oral administration

Measurement Parameter

Excretion

Unit

%

Qualitative value

=

Quantitative value

4

Yanagi; Haga; Endo; Kitagawa; Xenobiotica; vol. 6; nb. 2; (1976); p. 101 - 112, View in Reaxys 49 of 74

Bioassay Category

Metabolism/Transport

Bioassay Details

Fecal excretion of desmethyl derivative (nitrazepam)of compound in dog after 24 h of p.o. administration

Biological Species/NCBI dog ID Substance RN

759813View in Reaxys

Substance Route of Adm.

oral administration

Measurement Parameter

%

Unit

%

Qualitative value

=

Quantitative value

71

Yanagi; Haga; Endo; Kitagawa; Xenobiotica; vol. 6; nb. 2; (1976); p. 101 - 112, View in Reaxys 50 of 74

Bioassay Category

Metabolism/Transport

Bioassay Details

Fecal excretion of desmethyl derivative (nitrazepam) of compound in dog after 48-72 h of p.o. administration

Biological Species/NCBI dog ID

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Substance RN

759813View in Reaxys

Substance Route of Adm.

oral administration

Measurement Parameter

%

Unit

%

Qualitative value

=

Quantitative value

3

Yanagi; Haga; Endo; Kitagawa; Xenobiotica; vol. 6; nb. 2; (1976); p. 101 - 112, View in Reaxys 51 of 74

Bioassay Category

Metabolism/Transport

Bioassay Details

Fecal excretion of desmethyl derivative (nitrazepam) of compound in dog after 24-48 h of p.o. administration

Biological Species/NCBI dog ID Substance RN

759813View in Reaxys

Substance Route of Adm.

oral administration

Measurement Parameter

%

Unit

%

Qualitative value

=

Quantitative value

21

Yanagi; Haga; Endo; Kitagawa; Xenobiotica; vol. 6; nb. 2; (1976); p. 101 - 112, View in Reaxys 52 of 74

Bioassay Category

Metabolism/Transport

Bioassay Details

Fecal excretion of compound in dog after 24-48 h of p.o. administration

Biological Species/NCBI dog ID Substance RN

759813View in Reaxys

Substance Route of Adm.

oral administration

Measurement Parameter

%

Unit

%

Qualitative value

=

Quantitative value

34

Yanagi; Haga; Endo; Kitagawa; Xenobiotica; vol. 6; nb. 2; (1976); p. 101 - 112, View in Reaxys 53 of 74

Bioassay Category

Metabolism/Transport

Bioassay Details

Fecal excretion of compound in dog after 48-72 h of p.o. administration

Biological Species/NCBI dog ID Substance RN

759813View in Reaxys

Substance Route of Adm.

oral administration

Measurement Parameter

%

Unit

%

Qualitative value

=

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Quantitative value

6

Yanagi; Haga; Endo; Kitagawa; Xenobiotica; vol. 6; nb. 2; (1976); p. 101 - 112, View in Reaxys 54 of 74

Bioassay Category

Pharmacokinetic

Bioassay Details

Peak blood levels of compound in dog upon p.o. administration

Biological Species/NCBI dog ID Substance RN

759813View in Reaxys

Substance Route of Adm.

oral administration

Qualitative Results

7.7-7.9

Measurement Parameter

Cmax

Unit

µg/mL

Qualitative value

=

Quantitative value

7.9

Yanagi; Haga; Endo; Kitagawa; Xenobiotica; vol. 6; nb. 2; (1976); p. 101 - 112, View in Reaxys 55 of 74

Bioassay Category

In Vivo (Animal models)

Bioassay Details

Blood levels of the compound in dog after 4 h upon oral administration

Biological Species/NCBI dog ID Substance RN

759813View in Reaxys

Substance Route of Adm.

oral administration

Qualitative Results

Range = 5.2-6.3 mug equiv./mL

Measurement Parameter

Qualitative

Yanagi; Haga; Endo; Kitagawa; Xenobiotica; vol. 6; nb. 2; (1976); p. 101 - 112, View in Reaxys 56 of 74

Bioassay Category

Pharmacokinetic

Bioassay Details

Time to reach peak blood level of compound in dog after p.o. administration

Biological Species/NCBI dog ID Substance RN

759813View in Reaxys

Substance Route of Adm.

oral administration

Measurement Parameter

Tmax

Unit

hour

Qualitative value

=

Quantitative value

8

Yanagi; Haga; Endo; Kitagawa; Xenobiotica; vol. 6; nb. 2; (1976); p. 101 - 112, View in Reaxys 57 of 74

Bioassay Category

Metabolism/Transport

Bioassay Details

Urinary excretion of desmethyl derivative (nitrazepam) of compound in dog after 24 h of p.o. administration

Biological Species/NCBI dog ID Substance RN

759813View in Reaxys

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Substance Route of Adm.

oral administration

Measurement Parameter

Ue (%)

Unit

%

Qualitative value

=

Quantitative value

63

Yanagi; Haga; Endo; Kitagawa; Xenobiotica; vol. 6; nb. 2; (1976); p. 101 - 112, View in Reaxys 58 of 74

Bioassay Category

Metabolism/Transport

Bioassay Details

Urinary excretion of desmethyl derivative (nitrazepam) of compound in dog after 48-72 h of p.o. administration

Biological Species/NCBI dog ID Substance RN

759813View in Reaxys

Substance Route of Adm.

oral administration

Measurement Parameter

Ue (%)

Unit

%

Qualitative value

=

Quantitative value

2

Yanagi; Haga; Endo; Kitagawa; Xenobiotica; vol. 6; nb. 2; (1976); p. 101 - 112, View in Reaxys 59 of 74

Bioassay Category

Metabolism/Transport

Bioassay Details

Percent excretion of compound in faeces of dog after 48-72 h upon oral administration

Biological Species/NCBI dog ID Substance RN

759813View in Reaxys

Substance Route of Adm.

oral administration

Measurement Parameter

Excretion

Unit

%

Qualitative value

=

Quantitative value

6

Yanagi; Haga; Endo; Kitagawa; Xenobiotica; vol. 6; nb. 2; (1976); p. 101 - 112, View in Reaxys 60 of 74

Bioassay Category

Metabolism/Transport

Bioassay Details

Urinary excretion of compound in dog after 24 h of p.o. administration

Biological Species/NCBI dog ID Substance RN

759813View in Reaxys

Substance Route of Adm.

oral administration

Measurement Parameter

Ue (%)

Unit

%

Qualitative value

=

Quantitative value

46

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Yanagi; Haga; Endo; Kitagawa; Xenobiotica; vol. 6; nb. 2; (1976); p. 101 - 112, View in Reaxys 61 of 74

Bioassay Category

Metabolism/Transport

Bioassay Details

Urinary excretion of compound in dog after 48-72 h of p.o. administration

Biological Species/NCBI dog ID Substance RN

759813View in Reaxys

Substance Route of Adm.

oral administration

Measurement Parameter

Ue (%)

Unit

%

Qualitative value

=

Quantitative value

4

Yanagi; Haga; Endo; Kitagawa; Xenobiotica; vol. 6; nb. 2; (1976); p. 101 - 112, View in Reaxys 62 of 74

Bioassay Category

Metabolism/Transport

Bioassay Details

Percent excretion of compound in faeces of dog after 24-48 h upon oral administration

Biological Species/NCBI dog ID Substance RN

759813View in Reaxys

Substance Route of Adm.

oral administration

Measurement Parameter

Excretion

Unit

%

Qualitative value

=

Quantitative value

34

Yanagi; Haga; Endo; Kitagawa; Xenobiotica; vol. 6; nb. 2; (1976); p. 101 - 112, View in Reaxys 63 of 74

Bioassay Category

Metabolism/Transport

Bioassay Details

Percent excretion of compound in faeces of dog after 0-24 h upon oral administration

Biological Species/NCBI dog ID Substance RN

759813View in Reaxys

Substance Route of Adm.

oral administration

Measurement Parameter

Excretion

Unit

%

Qualitative value

=

Quantitative value

46

Yanagi; Haga; Endo; Kitagawa; Xenobiotica; vol. 6; nb. 2; (1976); p. 101 - 112, View in Reaxys 64 of 74

Bioassay Category

Metabolism/Transport

Bioassay Details

Percent excretion of compound in faeces of dog after 0-24 h upon oral administration

Biological Species/NCBI dog ID Substance RN

759813View in Reaxys

Substance Route of Adm.

oral administration

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Measurement Parameter

Excretion

Unit

%

Qualitative value

=

Quantitative value

52

Yanagi; Haga; Endo; Kitagawa; Xenobiotica; vol. 6; nb. 2; (1976); p. 101 - 112, View in Reaxys 65 of 74

Bioassay Category

Metabolism/Transport

Bioassay Details

Percent excretion of compound in urine of dog after 24-48 h upon oral administration

Biological Species/NCBI dog ID Substance RN

759813View in Reaxys

Substance Route of Adm.

oral administration

Measurement Parameter

Excretion

Unit

%

Qualitative value

=

Quantitative value

27

Yanagi; Haga; Endo; Kitagawa; Xenobiotica; vol. 6; nb. 2; (1976); p. 101 - 112, View in Reaxys 66 of 74

Bioassay Category

Metabolism/Transport

Bioassay Details

Urinary excretion of compound in dog after 24-48 h of p.o. administration

Biological Species/NCBI dog ID Substance RN

759813View in Reaxys

Substance Route of Adm.

oral administration

Measurement Parameter

Ue (%)

Unit

%

Qualitative value

=

Quantitative value

27

Yanagi; Haga; Endo; Kitagawa; Xenobiotica; vol. 6; nb. 2; (1976); p. 101 - 112, View in Reaxys 67 of 74

Bioassay Category

In Vitro (Efficacy)

Bioassay Details

Anticonvulsant activity of the compound; NC denotes that compound is not classified

Substance RN

759813View in Reaxys

Qualitative Results

NC

Measurement Parameter

Activity

Qualitative value

@

Bruno-Blanch; Galvez; Garcia-Domenech; Bioorganic and Medicinal Chemistry Letters; vol. 13; nb. 16; (2003); p. 2749 - 2754, View in Reaxys 68 of 74

Bioassay Category

In Vitro (Efficacy)

Bioassay Details

Tested for its effect on postnatal survival of Swiss-Webster mice offspring on dietary administration at subneurotoxic doses ; Reduced the survival of the offspring

Biological Species/NCBI Mus musculus ID Substance RN

759813View in Reaxys

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Measurement Parameter

Activity

Qualitative value

ND

William J. Houlihan; Gregory B. Bennett; Annual reports in medicinal chemistry; vol. 13; (1978); p. 21 - 30, View in Reaxys 69 of 74

Bioassay Category

In Vitro (Efficacy)

Bioassay Details

Tested for its activity in an anti-PTZ assay ; Effective

Substance RN

759813View in Reaxys

Measurement Parameter

Activity

Qualitative value

ND

Charles L. Zirkle; Carl Kaiser; Annual reports in medicinal chemistry; vol. 8; (1973); p. 1 - 10, View in Reaxys 70 of 74

Bioassay Category

In Vitro (Efficacy)

Bioassay Details

Tested for its ability to depress motor activity in inclined plane, fighting and rotarod tests in mice ; Effective

Biological Species/NCBI Mus musculus ID Substance RN

759813View in Reaxys

Measurement Parameter

Activity

Qualitative value

ND

Charles L. Zirkle; Carl Kaiser; Annual reports in medicinal chemistry; vol. 8; (1973); p. 1 - 10, View in Reaxys 71 of 74

Bioassay Category

In Vitro (Efficacy)

Bioassay Details

Compound was evaluated for muscle relaxant and anticonvulsant activity; potent

Substance RN

759813View in Reaxys

Measurement Parameter

Activity

Qualitative value

ND

A. D. Rudzik; W. Friis; Annual reports in medicinal chemistry; vol. 8; (1973); p. 29 - 36, View in Reaxys 72 of 74

Bioassay Category

In Vitro (Efficacy)

Bioassay Details

Compound was evaluated for antianxiety activity; Active

Substance RN

759813View in Reaxys

Measurement Parameter

Activity

Qualitative value

ND

A. D. Rudzik; W. Friis; Annual reports in medicinal chemistry; vol. 8; (1973); p. 29 - 36, View in Reaxys 73 of 74

Bioassay Category

In Vitro (Efficacy)

Bioassay Details

Compound was evaluated for hypnotic activity; Active

Substance RN

759813View in Reaxys

Measurement Parameter

Activity

Qualitative value

ND

A. D. Rudzik; W. Friis; Annual reports in medicinal chemistry; vol. 8; (1973); p. 29 - 36, View in Reaxys 74 of 74

Bioassay Category

In Vitro (Efficacy)

Bioassay Details

Tested for its activity in CAR test in rats ; Less active

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Biological Species/NCBI Rattus norvegicus ID Substance RN

759813View in Reaxys

Measurement Parameter

Activity

Qualitative value

ND

Charles L. Zirkle; Carl Kaiser; Annual reports in medicinal chemistry; vol. 8; (1973); p. 1 - 10, View in Reaxys

Reaxys ID 843754 View in Reaxys

O

2/3 CAS Registry Number: 40699-28-3 Chemical Name: 1-methyl-7-nitro-5-phenyl-1,3-dihydro-[5-14 C]benzo[e][1,4]diazepin-2-one; 1,3-Dihydro-1-methyl-7-nitro-5phenyl-2H-1,4-benzodiazepin-2-on-5-14C Linear Structure Formula: C15 (14)CH13N3O3 Molecular Formula: C16H13N3O3 Molecular Weight: 297.287 Type of Substance: heterocyclic InChI Key: GWUSZQUVEVMBPI-VPMSBSONSA-N Note:

N

N 14C

N

O

O

Substance Label (1) Label References I

Yoshitake et al.; Journal of Labelled Compounds; vol. 8; (1972); p. 615,619, View in Reaxys

Druglikeness (1) 1 of 1

LogP

2.188

H Bond Donors

0

H Bond Acceptors

3

Rotatable Bonds

2

TPSA

78.49

Lipinski Number

4

Veber Number

2

Melting Point (1) 1 of 1

Melting Point [°C]

157 - 158

Yoshitake et al.; Journal of Labelled Compounds; vol. 8; (1972); p. 615,619, View in Reaxys

Reaxys ID 6435459 View in Reaxys O

3/3 *H(1+)

Linear Structure Formula: C16H13N3O3 Molecular Formula: C16H13N3O3*H Molecular Weight: 296.305 Type of Substance: heterocyclic InChI Key: GWUSZQUVEVMBPI-UHFFFAOYSA-O Note:

N

N

N

O

H+

O

Substance Label (1) Label References 47*H+

Seiler; Zimmermann; Arzneimittel-Forschung/Drug Research; vol. 33; nb. 11; (1983); p. 1519 - 1522, View in Reaxys

Druglikeness (1)

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1 of 1

LogP

2.188

H Bond Donors

0

H Bond Acceptors

3

Rotatable Bonds

2

TPSA

78.49

Lipinski Number

4

Veber Number

2

Dissociation Exponent (1) 1 of 1

Dissociation Exponent (pK)

2.63

Dissociation Group

N(1+)-H

Temperature (Dissociation Exponent) [°C]

25

Solvent (Dissociation Exponent)

H2O; ethanol

Method (Dissociation Exponent)

spectrophotometric

Type (Dissociation Exponent)

a1/apparent

Comment (Dissociation Exponent)

Ratio of solvents: 98:2

Seiler; Zimmermann; Arzneimittel-Forschung/Drug Research; vol. 33; nb. 11; (1983); p. 1519 - 1522, View in Reaxys Electrochemical Behaviour (1) Description (Elec- References trochemical Behaviour) Electrolytic dissociation / protonation equilibrium

Seiler; Zimmermann; Arzneimittel-Forschung/Drug Research; vol. 33; nb. 11; (1983); p. 1519 - 1522, View in Reaxys

Copyright © 2017 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.

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