Methylecgonidine by Asch

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Date

2 substances in Reaxys

2016-09-15 17h:16m:24s (EST)

O O

Search as: As drawn, No mixtures, No charges, No radicals

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Reaxys ID 83376 View in Reaxys

1/2 CAS Registry Number: 50373-10-9 Chemical Name: methyl ecgonidine; Methyl ecgonidine; R-(−)anhydroecgonine methyl ester; (1R)-(-)-anhydroecgonine methyl ester; (R)-(-)-anhydroecgonine methyl ester; R-(-)-anhydroecognine methyl ester; anhydroecogonine methyl ester Linear Structure Formula: C10H15NO2 Molecular Formula: C10H15NO2 Molecular Weight: 181.235 Type of Substance: heterocyclic InChI Key: MPSNEAHFGOEKBI-VXNVDRBHSA-N Note:

N O O

Substance Label (17) Label References 3

Tamagnan, Gilles; Baldwin, Ronald M.; Kula, Nora S.; Baldessarini, Ross J.; Innis, Robert B.; Bioorganic and Medicinal Chemistry Letters; vol. 10; nb. 16; (2000); p. 1783 - 1785, View in Reaxys; PijarowskaKruszyna; Jaron; Kachniarz; Kasprzak; Kowalska; Malkowski; Demphel; Dolle; Mikolajczak; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 57; nb. 3; (2014); p. 148 - 157, View in Reaxys; Naumiec, Gregory R.; Lincourt, Grace; Clever, Jeremy P.; McGregor, Michael A.; Kovoor, Abraham; Deboef, Brenton; Organic and Biomolecular Chemistry; vol. 13; nb. 9; (2015); p. 2537 - 2540, View in Reaxys

1-1

Patent; Hudson, Edmund C.; US2015/87838; (2015); (A1) English, View in Reaxys

Cashman, John R.; Berkman, Clifford E.; Underiner, Gail; Kolly, Carrie A.; Hunter, Allen D.; Chemical Research in Toxicology; vol. 11; nb. 8; (1998); p. 895 - 901, View in Reaxys; Isomura, Shigeki; Hoffman, Timothy Z.; Wirsching, Peter; Janda, Kim D.; Journal of the American Chemical Society; vol. 124; nb. 14; (2002); p. 3661 - 3668, View in Reaxys; Patent; LAUREN SCIENCES LLC; LINDER, Charles; HELDMAN, Eliahu; GRINBERG, Sarina; WO2014/39501; (2014); (A1) English, View in Reaxys

2; 2a

Rami-Mark, Christina; Bornatowicz, Birgit; Fink, Cornel; Otter, Paul; Ungersboeck, Johanna; Vraka, Chrysoula; Haeusler, Daniela; Nics, Lukas; Spreitzer, Helmut; Hacker, Marcus; Mitterhauser, Markus; Wadsak, Wolfgang; Bioorganic and Medicinal Chemistry; vol. 21; nb. 24; (2013); p. 7562 - 7569, View in Reaxys

Schoenbaechler, Roland; Ametamey, Simon M.; Schubiger, Pius A.; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 42; nb. 5; (1999); p. 447 - 456, View in Reaxys; Tamiz, Amir P.; Smith, Miles P.; Kozikowski, Alan P.; Bioorganic and Medicinal Chemistry Letters; vol. 10; nb. 3; (2000); p. 297 - 300, View in Reaxys; Gu, Xiao-Hui; Zong, Rushi; Kula, Nora S.; Baldessarini, Ross J.; Neumeyer, John L.; Bioorganic and Medicinal Chemistry Letters; vol. 11; nb. 23; (2001); p. 3049 - 3053, View in Reaxys; Patent; ORPHACHEM; WO2008/59349; (2008); (A1) English, View in Reaxys

Carroll, F. Ivy; Blough, Bruce E.; Nie, Zhe; Kuhar, Michael J.; Howell, Leonard L.; Navarro, Hernan A.; Journal of Medicinal Chemistry; vol. 48; nb. 8; (2005); p. 2767 - 2771, View in Reaxys

Sandell; Helfenbein; Halldin; Chou; Emond; Guilloteau; Farde; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 42; nb. SUPPL. 1; (1999); p. S51-S53, View in Reaxys; Chen; Kilts; Camp; Ely; Malveaux; Votaw; Hoffman; Goodman; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 42; nb. SUPPL. 1; (1999); p. S324-S326, View in Reaxys; Chen; Kilts; Camp; Ely; Keil; Malveaux; Votaw; Hoffman; Goodman; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 42; nb. SUPPL. 1; (1999); p. S400-S402, View in Reaxys; Sandell, Johan; Halldin, Christer; Helfenbein, Julie; Chou, YuanHwa; Vercouillce, Johnny; Emond, Patrick; Swahn, Carl-Gunnar; Guilloteau, Denis; Farde, Lars; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 43; nb. 10; (2000); p. 1033 - 1046, View in Reaxys; Meltzer, Peter C.; Blundell, Paul; Madras, Bertha K.; Medicinal Chemistry Research; vol. 8; nb. 1-2; (1998); p. 12 - 34, View in Reaxys; Plisson, Christophe; McConathy, Jonathan; Martarello, Laurent; Malveaux, Eugene J.; Camp, Vernon M.; Williams, Larry; Votaw, John R.; Goodman, Mark M.; Journal of Medicinal Chemistry; vol. 47; nb. 5; (2004); p. 1122 - 1135, View in Reaxys

Chung, Kyoo-Hyun; Lim, Choong Hwan; Lee, Dong Reyoul; Jin, Changbae; Chi, Dae Yoon; Bioorganic and Medicinal Chemistry Letters; vol. 11; nb. 23; (2001); p. 3077 - 3080, View in Reaxys; Bois, Frederic; Baldwin, Ronald M.; Kula, Nora S.; Baldessarini, Ross J.; Innis, Robert B.; Tamagnan, Gilles; Bioorganic and Medicinal Chemistry Letters; vol. 14; nb. 9; (2004); p. 2117 - 2120, View in Reaxys

Paula, Stefan; Tabet, Michael R.; Farr, Carol D.; Norman, Andrew B.; Ball Jr., W. James; Journal of Medicinal Chemistry; vol. 47; nb. 1; (2004); p. 133 - 142, View in Reaxys

Cheng, Jie; Izenwasser, Sari; Zhang, Chunming; Zhang, Suhong; Wade, Dean; Trudell, Mark L.; Bioorganic and Medicinal Chemistry Letters; vol. 14; nb. 7; (2004); p. 1775 - 1778, View in Reaxys

AEME

Kintz, Pascal; Sengler, Catherine; Cirimele, Vincent; Mangin, Patrice; Human and Experimental Toxicology; vol. 16; nb. 2; (1997); p. 123 - 127, View in Reaxys; Erzouki, H. K.; Allen, A. C.; Newman, A. H.; Goldberg, S. R.; Schindler, C. W.; Life Sciences; vol. 57; nb. 20; (1995); p. 1861 - 1868, View in Reaxys; Xia, Yang; Wang, Pingping; Bartlett, Michael G.; Solomon, Harvey M.; Busch, Kenneth L.; Analytical Chem-

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istry; vol. 72; nb. 4; (2000); p. 764 - 771, View in Reaxys; Fandino, Anabel S.; Karas, Michael; Toennes, Stefan W.; Kauert, Gerold; Journal of Mass Spectrometry; vol. 37; nb. 5; (2002); p. 525 - 532, View in Reaxys; Fandino, Anabel S.; Toennes, Stefan W.; Kauert, Gerold F.; Chemical Research in Toxicology; vol. 15; nb. 12; (2002); p. 1543 - 1548, View in Reaxys MEG

El-Fawal; Wood; Journal of Pharmacology and Experimental Therapeutics; vol. 272; nb. 3; (1995); p. 991 996, View in Reaxys; Xiao, Yong-Fu; Morgan, James P.; Journal of Pharmacology and Experimental Therapeutics; vol. 284; nb. 1; (1998); p. 10 - 18, View in Reaxys; Yang, Yinke; Ke, Qingen; Cai, Jingbo; Xiao, Yong-Fu; Morgan, James P.; British Journal of Pharmacology; vol. 132; nb. 2; (2001); p. 451 - 460, View in Reaxys

Zou; Kopajtic; Katz; Wirtz; Justice Jr.; Newman; Journal of Medicinal Chemistry; vol. 44; nb. 25; (2001); p. 4453 - 4461, View in Reaxys

(-)-3

Node, Manabu; Nakamura, Soichi; Nakamura, Daisaku; Katoh, Takahiro; Nishide, Kiyoharu; Tetrahedron Letters; vol. 40; nb. 29; (1999); p. 5357 - 5360, View in Reaxys

EDME

Neudorfl, Pavel; Hupe, Michel; Pilon, Pierre; Lawrence, Andre H.; Analytical Chemistry; vol. 69; nb. 20; (1997); p. 4283 - 4285, View in Reaxys

MEG base

Willetts, J.; Chen, L. C.; Graefe, J. F.; Wood, R. W.; Life Sciences; vol. 57; nb. 15; (1995); p. P225 - P230, View in Reaxys

MEG (Merck XII.Ed.3540)

Chen; Graefe; Shojaie; Willetts; Wood; Life Sciences; vol. 56; nb. 1; (1995); p. PL7-P12, View in Reaxys

Boiling Point (2) Boiling Point [°C]

Pressure (Boiling Point) [Torr]

References

124 - 126

Zaugg et al.; Journal of Organic Chemistry; vol. 23; (1958); p. 847,850, View in Reaxys

107

Ugrjumow; Zhurnal Obshchei Khimii; vol. 14; (1944); p. 997,1001; Chem.Abstr.; (1945); p. 4616, View in Reaxys

Refractive Index (2) Refractive Index Wavelength (Refractive Index) [nm]

Temperature (Refractive Index) [°C]

References

1.5006

589

Zaugg et al.; Journal of Organic Chemistry; vol. 23; (1958); p. 847,850, View in Reaxys

1.504

656.3

Ugrjumow; Zhurnal Obshchei Khimii; vol. 14; (1944); p. 997,1001; Chem.Abstr.; (1945); p. 4616, View in Reaxys

Density (1) 1 of 1

Density [g·cm-3]

1.0921

Reference Temperature [°C]

Measurement Temperature [°C]

Ugrjumow; Zhurnal Obshchei Khimii; vol. 14; (1944); p. 997,1001; Chem.Abstr.; (1945); p. 4616, View in Reaxys Crystal Property Description (2) Colour & Other Location Properties colourless

supporting information

yellow

References Rami-Mark, Christina; Bornatowicz, Birgit; Fink, Cornel; Otter, Paul; Ungersboeck, Johanna; Vraka, Chrysoula; Haeusler, Daniela; Nics, Lukas; Spreitzer, Helmut; Hacker, Marcus; Mitterhauser, Markus; Wadsak, Wolfgang; Bioorganic and Medicinal Chemistry; vol. 21; nb. 24; (2013); p. 7562 - 7569, View in Reaxys Schoenbaechler, Roland; Ametamey, Simon M.; Schubiger, Pius A.; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 42; nb. 5; (1999); p. 447 - 456, View in Reaxys

Optical Rotatory Power (5) 1 of 5

Patent; Nihon Medi-Physics Co., Ltd.; US6486323; (2002); (B1) English, View in Reaxys

2 of 5

Type (Optical Rotatory Power)

[alpha]

Concentration (Optical Rotatory Power)

0.80 g/100ml

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Solvent (Optical Rotatory Power)

methanol

Optical Rotatory Power [deg]

-41

Wavelength (Optical Ro- 589 tatory Power) [nm] Temperature (Optical Rotatory Power) [°C]

Node, Manabu; Nakamura, Soichi; Nakamura, Daisaku; Katoh, Takahiro; Nishide, Kiyoharu; Tetrahedron Letters; vol. 40; nb. 29; (1999); p. 5357 - 5360, View in Reaxys 3 of 5

Type (Optical Rotatory Power)

[alpha]

Concentration (Optical Rotatory Power)

1.22 g/100ml

Length of Path [cm]

Solvent (Optical Rotatory Power)

CHCl3

Optical Rotatory Power [deg]

-35.1

Wavelength (Optical Ro- 589 tatory Power) [nm] Holmquist; Parham; Holleman; Carroll; Organic Preparations and Procedures International; vol. 29; nb. 3; (1997); p. 308 - 311, View in Reaxys 4 of 5

Type (Optical Rotatory Power)

[alpha]

Concentration (Optical Rotatory Power)

1.50 g/100ml

Solvent (Optical Rotatory Power)

methanol

Optical Rotatory Power [deg]

-41.7

Wavelength (Optical Ro- 589 tatory Power) [nm] Temperature (Optical Rotatory Power) [°C]

Davies, Huw M. L.; Matasi, Julius J.; Mark Hodges; Huby, Nicholas J. S.; Thornley, Craig; Kong, Norman; Houser, Jeffrey H.; Journal of Organic Chemistry; vol. 62; nb. 4; (1997); p. 1095 - 1105, View in Reaxys 5 of 5

Type (Optical Rotatory Power)

[alpha]

Solvent (Optical Rotatory Power)

neat (no solvent)

Optical Rotatory Power [deg]

-54.96

Wavelength (Optical Ro- 589 tatory Power) [nm] Temperature (Optical Rotatory Power) [°C]

Ugrjumow; Zhurnal Obshchei Khimii; vol. 14; (1944); p. 997,1001; Chem.Abstr.; (1945); p. 4616, View in Reaxys Vapour Pressure (1) Comment (VaReferences pour Pressure) Equation: log P = 16.6 - (3.64E3/T),

Neudorfl, Pavel; Hupe, Michel; Pilon, Pierre; Lawrence, Andre H.; Analytical Chemistry; vol. 69; nb. 20; (1997); p. 4283 - 4285, View in Reaxys

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T = 253.0-293.0 K, P in ppb NMR Spectroscopy (7) 1 of 7

Description (NMR Spec- COSY (Correlation Spectroscopy); HMQC (Heteronuclear Multiple Quantum Coherence); troscopy) Spectrum Nucleus (NMR Spectroscopy)

Location

Sheet 6

Patent; LAUREN SCIENCES LLC; LINDER, Charles; HELDMAN, Eliahu; GRINBERG, Sarina; WO2014/39501; (2014); (A1) English, View in Reaxys 2 of 7

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

Solvents (NMR Spectro- CDCl3 scopy) Frequency (NMR Spectroscopy) [MHz]

400

Isomura, Shigeki; Hoffman, Timothy Z.; Wirsching, Peter; Janda, Kim D.; Journal of the American Chemical Society; vol. 124; nb. 14; (2002); p. 3661 - 3668, View in Reaxys 3 of 7

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

13C

Solvents (NMR Spectro- CDCl3 scopy) Isomura, Shigeki; Hoffman, Timothy Z.; Wirsching, Peter; Janda, Kim D.; Journal of the American Chemical Society; vol. 124; nb. 14; (2002); p. 3661 - 3668, View in Reaxys 4 of 7

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

Solvents (NMR Spectro- CDCl3 scopy) Meltzer, P. C.; Liang, A. Y.; Brownell, A.-L.; Elmaleh, D. R.; Madras, B. K.; Journal of Medicinal Chemistry; vol. 36; nb. 7; (1993); p. 855 - 862, View in Reaxys; Kozikowski, Alan P.; Saiah, M. K. Eddine; Johnson, Kenneth M.; Bergmann, John S.; Journal of Medicinal Chemistry; vol. 38; nb. 16; (1995); p. 3086 - 3093, View in Reaxys; Majewski; Lazny; Journal of Organic Chemistry; vol. 60; nb. 18; (1995); p. 5825 - 5830, View in Reaxys; Holmquist; Parham; Holleman; Carroll; Organic Preparations and Procedures International; vol. 29; nb. 3; (1997); p. 308 311, View in Reaxys; Emond; Boazi; Duchene; Chalon; Besnard; Guilloteau; Frangin; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 39; nb. 9; (1997); p. 757 - 772, View in Reaxys; Zou; Kopajtic; Katz; Wirtz; Justice Jr.; Newman; Journal of Medicinal Chemistry; vol. 44; nb. 25; (2001); p. 4453 - 4461, View in Reaxys 5 of 7

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

Solvents (NMR Spectro- CDCl3 scopy) Frequency (NMR Spectroscopy) [MHz]

300

Schoenbaechler, Roland; Ametamey, Simon M.; Schubiger, Pius A.; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 42; nb. 5; (1999); p. 447 - 456, View in Reaxys 6 of 7

Description (NMR Spec- Chemical shifts troscopy)

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Nucleus (NMR Spectroscopy)

13C

Solvents (NMR Spectro- CDCl3 scopy) Emond; Boazi; Duchene; Chalon; Besnard; Guilloteau; Frangin; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 39; nb. 9; (1997); p. 757 - 772, View in Reaxys 7 of 7

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

1H-1H

Majewski; Lazny; Journal of Organic Chemistry; vol. 60; nb. 18; (1995); p. 5825 - 5830, View in Reaxys; Holmquist; Parham; Holleman; Carroll; Organic Preparations and Procedures International; vol. 29; nb. 3; (1997); p. 308 - 311, View in Reaxys IR Spectroscopy (1) 1 of 1

Description (IR Spectroscopy)

Bands

Original Text (IR Spectroscopy)

The FT-JR shows the presence of the ester group (COOCH3) at 1711 cm1•

Location

Paragraph 00399

Patent; LAUREN SCIENCES LLC; LINDER, Charles; HELDMAN, Eliahu; GRINBERG, Sarina; WO2014/39501; (2014); (A1) English, View in Reaxys Mass Spectrometry (3) Description (Mass Location Spectrometry)

References

gas chromatogra- Paragraph 00398 phy mass spectrometry (GCMS); spectrum

Patent; LAUREN SCIENCES LLC; LINDER, Charles; HELDMAN, Eliahu; GRINBERG, Sarina; WO2014/39501; (2014); (A1) English, View in Reaxys

spectrum; electron impact (EI); fragmentation pattern

Fandino, Anabel S.; Karas, Michael; Toennes, Stefan W.; Kauert, Gerold; Journal of Mass Spectrometry; vol. 37; nb. 5; (2002); p. 525 - 532, View in Reaxys

spectrum; fragmentation pattern

Paul, Buddha D.; McWhorter, Lisa K.; Smith, Michael L.; Journal of Mass Spectrometry; vol. 34; nb. 6; (1999); p. 651 - 660, View in Reaxys

Pharmacological Data (25) 1 of 25

Comment (Pharmacological Data)

Bioactivities present

Patent; Research Biochemicals Limited Partnership; US5310912; (1994); (A1) English, View in Reaxys; Patent; Research Triangle Institute; US5736123; (1998); (A1) English, View in Reaxys; Patent; New York University Medical Center; US5552407; (1996); (A1) English, View in Reaxys; Patent; Nihon Medi-Physics Co., Ltd.; US6486323; (2002); (B1) English, View in Reaxys; Patent; Research Biochemicals Limited Paternership; EP703791; (2002); (B1) English, View in Reaxys; Zaugg et al.; Journal of Organic Chemistry; vol. 23; (1958); p. 847,850, View in Reaxys; Ugrjumow; Zhurnal Obshchei Khimii; vol. 14; (1944); p. 997,1001; Chem.Abstr.; (1945); p. 4616, View in Reaxys; Matchett; Levine; Journal of the American Chemical Society; vol. 63; (1941); p. 2444, View in Reaxys; Milius, Richard A.; Saha, Jayanta K.; Madras, Bertha K.; Neumeyer, John L.; Journal of Medicinal Chemistry; vol. 34; nb. 5; (1991); p. 1728 - 1731, View in Reaxys; Neumeyer; Wang; Milius; Baldwin; ZeaPonce; Hoffer; Sybirska; Al-Tikriti; Charney; Malison; Laruelle; Innis; Journal of Medicinal Chemistry; vol. 34; nb. 10; (1991); p. 3144 - 3146, View in Reaxys; Davies, Huw M. L.; Huby, Nicholas J. S.; Tetrahedron Letters; vol. 33; nb. 46; (1992); p. 6935 - 6938, View in Reaxys; Kozikowski, Alan P.; Roberti, Marinella; Xiang, Li; Bergmann, John S.; Callahan, Patrick M.; et al.; Journal of Medicinal Chemistry; vol. 35; nb. 25; (1992); p. 4764 4766, View in Reaxys; Meltzer, P. C.; Liang, A. Y.; Brownell, A.-L.; Elmaleh, D. R.; Madras, B. K.; Journal of Medicinal Chemistry; vol. 36; nb. 7; (1993); p. 855 - 862, View in Reaxys; Jindal; Lutz; Journal of Pharmaceutical Sciences; vol. 78; nb. 12; (1989); p. 1009 - 1014, View in Reaxys; Boja; Kuhar; Kopajtic; Yang; Abraham; Lewin; Carroll; Journal of medicinal chemistry; vol. 37; nb. 8; (1994); p. 1220 - 1223, View in Reaxys; Goodman; Kung; Kabalka; Switzer; Journal of Medicinal Chemistry; vol. 37; nb. 10; (1994); p. 1535 - 1542, View in Reaxys; Muller; Halldin; Swahn; Foged; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 34; nb. 11; (1994); p. 1031 - 1040, View in Reaxys; Carroll, F. Ivy; Mascarella, S. Wayne; Kuzemko, Michael A.; Gao, Yigong; Abra-

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ham, Philip; et al.; Journal of Medicinal Chemistry; vol. 37; nb. 18; (1994); p. 2865 - 2873, View in Reaxys; Keverline, Kathryn I.; Abraham, Philip; Lewin, Anita H.; Carroll, F. Ivy; Tetrahedron Letters; vol. 36; nb. 18; (1995); p. 3099 - 3102, View in Reaxys; Kozikowski, Alan P.; Saiah, M. K. Eddine; Johnson, Kenneth M.; Bergmann, John S.; Journal of Medicinal Chemistry; vol. 38; nb. 16; (1995); p. 3086 - 3093, View in Reaxys 2 of 25

Comment (Pharmacological Data)

Bioactivities present

Majewski; Lazny; Journal of Organic Chemistry; vol. 60; nb. 18; (1995); p. 5825 - 5830, View in Reaxys; Davies, Huw M. L.; Matasi, Julius J.; Mark Hodges; Huby, Nicholas J. S.; Thornley, Craig; Kong, Norman; Houser, Jeffrey H.; Journal of Organic Chemistry; vol. 62; nb. 4; (1997); p. 1095 - 1105, View in Reaxys; Xu; Trudell; Journal of Heterocyclic Chemistry; vol. 33; nb. 6; (1996); p. 2037 - 2039, View in Reaxys; Holmquist; Parham; Holleman; Carroll; Organic Preparations and Procedures International; vol. 29; nb. 3; (1997); p. 308 - 311, View in Reaxys; Thiruvazhi; Abraham; Kuhar; Carroll; Chemical Communications; nb. 6; (1997); p. 555 - 556, View in Reaxys; Thompson, Philip E.; Hearn, Milton T. W.; Tetrahedron Letters; vol. 38; nb. 16; (1997); p. 2907 - 2910, View in Reaxys; Sakurai, Mitsuya; Wirsching, Peter; Janda, Kim D.; Tetrahedron Letters; vol. 37; nb. 31; (1996); p. 5479 - 5482, View in Reaxys; Emond; Boazi; Duchene; Chalon; Besnard; Guilloteau; Frangin; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 39; nb. 9; (1997); p. 757 - 772, View in Reaxys; Lieske, Spencer F.; Journal of Medicinal Chemistry; vol. 41; nb. 6; (1998); p. 864 - 876, View in Reaxys; Pei; Gupta; Badio; Padgett; Daly; Journal of medicinal chemistry; vol. 41; nb. 12; (1998); p. 2047 - 2055, View in Reaxys; Willetts, J.; Chen, L. C.; Graefe, J. F.; Wood, R. W.; Life Sciences; vol. 57; nb. 15; (1995); p. P225 - P230, View in Reaxys; Chen; Graefe; Shojaie; Willetts; Wood; Life Sciences; vol. 56; nb. 1; (1995); p. PL7-P12, View in Reaxys; Neudorfl, Pavel; Hupe, Michel; Pilon, Pierre; Lawrence, Andre H.; Analytical Chemistry; vol. 69; nb. 20; (1997); p. 4283 - 4285, View in Reaxys; Schoenbaechler, Roland; Ametamey, Simon M.; Schubiger, Pius A.; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 42; nb. 5; (1999); p. 447 - 456, View in Reaxys; Kintz, Pascal; Sengler, Catherine; Cirimele, Vincent; Mangin, Patrice; Human and Experimental Toxicology; vol. 16; nb. 2; (1997); p. 123 - 127, View in Reaxys; Node, Manabu; Nakamura, Soichi; Nakamura, Daisaku; Katoh, Takahiro; Nishide, Kiyoharu; Tetrahedron Letters; vol. 40; nb. 29; (1999); p. 5357 - 5360, View in Reaxys; Erzouki, H. K.; Allen, A. C.; Newman, A. H.; Goldberg, S. R.; Schindler, C. W.; Life Sciences; vol. 57; nb. 20; (1995); p. 1861 1868, View in Reaxys; Sandell; Helfenbein; Halldin; Chou; Emond; Guilloteau; Farde; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 42; nb. SUPPL. 1; (1999); p. S51-S53, View in Reaxys; Chen; Kilts; Camp; Ely; Malveaux; Votaw; Hoffman; Goodman; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 42; nb. SUPPL. 1; (1999); p. S324-S326, View in Reaxys; Chen; Kilts; Camp; Ely; Keil; Malveaux; Votaw; Hoffman; Goodman; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 42; nb. SUPPL. 1; (1999); p. S400S402, View in Reaxys 3 of 25

Comment (Pharmacological Data)

Bioactivities present

El-Fawal; Wood; Journal of Pharmacology and Experimental Therapeutics; vol. 272; nb. 3; (1995); p. 991 - 996, View in Reaxys; Cashman, John R.; Berkman, Clifford E.; Underiner, Gail; Kolly, Carrie A.; Hunter, Allen D.; Chemical Research in Toxicology; vol. 11; nb. 8; (1998); p. 895 - 901, View in Reaxys; Xia, Yang; Wang, Pingping; Bartlett, Michael G.; Solomon, Harvey M.; Busch, Kenneth L.; Analytical Chemistry; vol. 72; nb. 4; (2000); p. 764 - 771, View in Reaxys; Xiao, Yong-Fu; Morgan, James P.; Journal of Pharmacology and Experimental Therapeutics; vol. 284; nb. 1; (1998); p. 10 - 18, View in Reaxys; Tamiz, Amir P.; Smith, Miles P.; Kozikowski, Alan P.; Bioorganic and Medicinal Chemistry Letters; vol. 10; nb. 3; (2000); p. 297 - 300, View in Reaxys; Tamagnan, Gilles; Baldwin, Ronald M.; Kula, Nora S.; Baldessarini, Ross J.; Innis, Robert B.; Bioorganic and Medicinal Chemistry Letters; vol. 10; nb. 16; (2000); p. 1783 - 1785, View in Reaxys; Sandell, Johan; Halldin, Christer; Helfenbein, Julie; Chou, Yuan-Hwa; Vercouillce, Johnny; Emond, Patrick; Swahn, Carl-Gunnar; Guilloteau, Denis; Farde, Lars; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 43; nb. 10; (2000); p. 1033 - 1046, View in Reaxys; Meltzer, Peter C.; Blundell, Paul; Madras, Bertha K.; Medicinal Chemistry Research; vol. 8; nb. 1-2; (1998); p. 12 - 34, View in Reaxys; Gu, Xiao-Hui; Zong, Rushi; Kula, Nora S.; Baldessarini, Ross J.; Neumeyer, John L.; Bioorganic and Medicinal Chemistry Letters; vol. 11; nb. 23; (2001); p. 3049 - 3053, View in Reaxys; Chung, Kyoo-Hyun; Lim, Choong Hwan; Lee, Dong Reyoul; Jin, Changbae; Chi, Dae Yoon; Bioorganic and Medicinal Chemistry Letters; vol. 11; nb. 23; (2001); p. 3077 - 3080, View in Reaxys; Paul, Buddha D.; McWhorter, Lisa K.; Smith, Michael L.; Journal of Mass Spectrometry; vol. 34; nb. 6; (1999); p. 651 - 660, View in Reaxys; Zou; Kopajtic; Katz; Wirtz; Justice Jr.; Newman; Journal of Medicinal Chemistry; vol. 44; nb. 25; (2001); p. 4453 - 4461, View in Reaxys; Yang, Yinke; Ke, Qingen; Cai, Jingbo; Xiao, Yong-Fu; Morgan, James P.; British Journal of Pharmacology; vol. 132; nb. 2; (2001); p. 451 - 460, View in Reaxys; Isomura, Shigeki; Hoffman, Timothy Z.; Wirsching, Peter; Janda, Kim D.; Journal of the American Chemical Society; vol. 124; nb. 14; (2002); p. 3661 - 3668, View in Reaxys; Fandino, Anabel S.; Karas, Michael; Toennes, Stefan W.; Kauert, Gerold; Journal of Mass Spectrometry; vol. 37; nb. 5; (2002); p. 525 - 532, View in Reaxys; Paula, Stefan; Tabet, Michael R.; Farr, Carol D.; Norman, Andrew B.; Ball Jr., W. James; Journal of Medicinal Chemistry; vol. 47; nb. 1; (2004); p. 133 - 142, View in Reaxys; Plisson, Christophe; McConathy, Jonathan; Martarello, Laurent; Malveaux, Eugene J.; Camp, Vernon M.; Williams, Larry; Votaw, John R.; Goodman, Mark M.; Journal of Medicinal Chemistry; vol. 47; nb. 5; (2004); p. 1122 - 1135, View in Reaxys; Bois, Frederic; Baldwin, Ronald M.; Kula, Nora S.; Baldessarini, Ross J.; Innis, Robert B.; Tamagnan, Gilles; Bioorganic and Medicinal Chemistry Letters; vol. 14; nb. 9; (2004); p. 2117 - 2120, View in Reaxys; Cheng, Jie; Izenwasser, Sari; Zhang, Chunming; Zhang, Suhong; Wade, Dean; Trudell, Mark L.; Bioorganic and Medicinal Chemistry Letters; vol. 14; nb. 7; (2004); p. 1775 1778, View in Reaxys; Fandino, Anabel S.; Toennes, Stefan W.; Kauert, Gerold F.; Chemical Research in Toxicology; vol. 15; nb. 12; (2002); p. 1543 - 1548, View in Reaxys

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4 of 25

Comment (Pharmacological Data)

Bioactivities present

Carroll, F. Ivy; Blough, Bruce E.; Nie, Zhe; Kuhar, Michael J.; Howell, Leonard L.; Navarro, Hernan A.; Journal of Medicinal Chemistry; vol. 48; nb. 8; (2005); p. 2767 - 2771, View in Reaxys; Coi, Alessio; Massarelli, Ilaria; Murgia, Laura; Saraceno, Marilena; Calderone, Vincenzo; Bianucci, Anna Maria; Bioorganic and Medicinal Chemistry; vol. 14; nb. 9; (2006); p. 3153 - 3159, View in Reaxys; Ekins, Sean; Balakin, Konstantin V.; Savchuk, Nikolay; Ivanenkov, Yan; Journal of Medicinal Chemistry; vol. 49; nb. 17; (2006); p. 5059 - 5071, View in Reaxys; Ferreira, Scott; Crumb Jr., William J.; Carlton, Carol G.; Clarkson, Craig W.; Journal of Pharmacology and Experimental Therapeutics; vol. 299; nb. 1; (2001); p. 220 - 226, View in Reaxys; Patent; Neuro Imaging Technologies, LLC; US5698179; (1997); (A1) English, View in Reaxys; Patent; ORPHACHEM; WO2008/59349; (2008); (A1) English, View in Reaxys; Coi, Alessio; Massarelli, Ilaria; Testai, Lara; Calderone, Vincenzo; Bianucci, Anna Maria; European Journal of Medicinal Chemistry; vol. 43; nb. 11; (2008); p. 2479 - 2488, View in Reaxys; Riss, Patrick Johannes; Hummerich, Rene; Schloss, Patrick; Organic and Biomolecular Chemistry; vol. 7; nb. 13; (2009); p. 2688 - 2698, View in Reaxys; Jin, Chunyang; Navarro, Hernan A.; Carroll, F. Ivy; Journal of Medicinal Chemistry; vol. 51; nb. 24; (2008); p. 8048 - 8056, View in Reaxys; Jin, Chunyang; Navarro, Hernan A.; Ivy Carroll; Bioorganic and Medicinal Chemistry; vol. 17; nb. 14; (2009); p. 5126 - 5132, View in Reaxys; Riss, Patrick J.; Hooker, Jacob M.; Alexoff, David; Kim, Sung-Won; Fowler, Joanna S.; Roesch, Frank; Bioorganic and Medicinal Chemistry Letters; vol. 19; nb. 15; (2009); p. 4343 - 4345, View in Reaxys; Cordova, Armando; Lin, Shuangzheng; Tseggai, Abrehet; Advanced Synthesis and Catalysis; vol. 354; nb. 7; (2012); p. 1363 - 1372, View in Reaxys; Cavalli, Andrea; Buonfiglio, Rosa; Ianni, Cristina; Masetti, Matteo; Ceccarini, Luisa; Caves, Rachel; Chang, Michael W. Y.; Mitcheson, John S.; Roberti, Marinella; Recanatini, Maurizio; Journal of Medicinal Chemistry; vol. 55; nb. 8; (2012); p. 4010 - 4014, View in Reaxys; Nisius, Britta; Goeller, Andreas H.; Bajorath, Juergen; Chemical Biology and Drug Design; vol. 73; nb. 1; (2009); p. 17 - 25, View in Reaxys; Bains, William; Basman, Antranig; White, Cat; Progress in Biophysics and Molecular Biology; vol. 86; nb. 2; (2004); p. 205 - 233, View in Reaxys; Erzouki; Allen; Newman; Goldberg; Schindler; Life Sciences; vol. 57; nb. 20; (1995); p. 1861 - 1868, View in Reaxys; Rami-Mark, Christina; Bornatowicz, Birgit; Fink, Cornel; Otter, Paul; Ungersboeck, Johanna; Vraka, Chrysoula; Haeusler, Daniela; Nics, Lukas; Spreitzer, Helmut; Hacker, Marcus; Mitterhauser, Markus; Wadsak, Wolfgang; Bioorganic and Medicinal Chemistry; vol. 21; nb. 24; (2013); p. 7562 - 7569, View in Reaxys; Patent; LAUREN SCIENCES LLC; LINDER, Charles; HELDMAN, Eliahu; GRINBERG, Sarina; WO2014/39501; (2014); (A1) English, View in Reaxys; Pijarowska-Kruszyna; Jaron; Kachniarz; Kasprzak; Kowalska; Malkowski; Demphel; Dolle; Mikolajczak; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 57; nb. 3; (2014); p. 148 - 157, View in Reaxys; Patent; Hudson, Edmund C.; US2015/87838; (2015); (A1) English, View in Reaxys 5 of 25

Comment (Pharmacological Data)

Bioactivities present

Naumiec, Gregory R.; Lincourt, Grace; Clever, Jeremy P.; McGregor, Michael A.; Kovoor, Abraham; Deboef, Brenton; Organic and Biomolecular Chemistry; vol. 13; nb. 9; (2015); p. 2537 - 2540, View in Reaxys; Castrignanò, Erika; Lubben, Anneke; Kasprzyk-Hordern, Barbara; Journal of Chromatography A; vol. 1438; (2016); p. 84 - 99, View in Reaxys 6 of 25

Effect (Pharmacological Data)

protein binding

Species or Test-System (Pharmacological Data)

human anticocaine monoclonal antibody 2E2

Method (Pharmacological Data)

relative binding affinity (RBA) measured by competition ELISA using biotinylated goat antihuman IgG

Further Details (Pharmacological Data)

RBA: IC50 value for title comp./ IC50 value for cocaine

Results

RBA: 21000

Paula, Stefan; Tabet, Michael R.; Farr, Carol D.; Norman, Andrew B.; Ball Jr., W. James; Journal of Medicinal Chemistry; vol. 47; nb. 1; (2004); p. 133 - 142, View in Reaxys 7 of 25

Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat liver microsomes

Sex

male

Concentration (Pharmacological Data)

150 μmol/l

Kind of Dosing (Pharmacological Data)

title comp. dissolved in acetonitrile at conc. of 1 mg/ml

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Method (Pharmacological Data)

0.75 mg of protein; 0.1 mol/l phosph. buffer (pH 7.4); 1.2 mmol/l NADP; 2 units of isocitrate dehydrogenase; 5 mmol/l isocitrate; 5 mmol/l MgCl2; incubated with title comp. for 60 min at 37 deg C; GC/MS; detection of thermolabile metabolites: nanoESI-MS

Further Details (Pharmacological Data)

incubations without substrate or without microsomes were used as control; incub. in presence of 200 mmol/l NaF (esterase inhibitor) served as control for nonenzymatic hydrolysis; pooled organs of 3 animals

Results

esterase activity was 748 pmol anhydroecgonine formed/min/mg; nonenzymatic hydrolysis was 1.1 percent (0.83 nmol/incubation); N-demethylation of title comp. could be increased in presence of NaF

Metabolite XRN (Pharmacological Data)

82843; 7687323; 9259642

Metabolite (Pharmacological Data)

ecgonidine; noranhydroecgonine methyl ester; anhydroecgonine methyl ester N-oxide

Fandino, Anabel S.; Toennes, Stefan W.; Kauert, Gerold F.; Chemical Research in Toxicology; vol. 15; nb. 12; (2002); p. 1543 - 1548, View in Reaxys 8 of 25

Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat lung microsomes

Sex

male

Concentration (Pharmacological Data)

150 μmol/l

Kind of Dosing (Pharmacological Data)

title comp. dissolved in acetonitrile at conc. of 1 mg/ml

Method (Pharmacological Data)

0.75 mg of protein; 0.1 mol/l phosph. buffer (pH 7.4); 1.2 mmol/l NADP; 2 units of isocitrate dehydrogenase; 5 mmol/l isocitrate; 5 mmol/l MgCl2; incub. with title comp. for 60 min at 37 deg C; GC/MS; detection of thermolabile metabolites: nanoESI-MS

Further Details (Pharmacological Data)

Results

esterase activity was 139 pmol anhydroecgonine formed/min/mg; nonenzymatic hydrolysis was 1.1 percent (0.83 nmol/incubation); N-demethylation was observed only in presence of NaF

Metabolite XRN (Pharmacological Data)

82843; 7687323; 9259642

Metabolite (Pharmacological Data)

ecgonidine; noranhydroecgonine methyl ester; anhydroecgonine methyl ester N-oxide

Fandino, Anabel S.; Toennes, Stefan W.; Kauert, Gerold F.; Chemical Research in Toxicology; vol. 15; nb. 12; (2002); p. 1543 - 1548, View in Reaxys 9 of 25

Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat kidney microsomes

Sex

male

Concentration (Pharmacological Data)

150 μmol/l

Kind of Dosing (Pharmacological Data)

title comp. dissolved in acetonitrile at conc. of 1 mg/ml

Method (Pharmacological Data)

Further Details (Pharmacological Data)

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Results

esterase activity was 30 pmol anhydroecgonine formed/min/mg; nonenzymatic hydrolysis was 1.1 percent (0.83 nmol/incubation); no metabolites of oxidative pathways were detected

Metabolite XRN (Pharmacological Data)

82843

Metabolite (Pharmacological Data)

ecgonidine

Fandino, Anabel S.; Toennes, Stefan W.; Kauert, Gerold F.; Chemical Research in Toxicology; vol. 15; nb. 12; (2002); p. 1543 - 1548, View in Reaxys 10 of 25

Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat brain microsomes

Sex

male

Concentration (Pharmacological Data)

150 μmol/l

Kind of Dosing (Pharmacological Data)

title comp. dissolved in acetonitrile at conc. of 1 mg/ml

Method (Pharmacological Data)

Further Details (Pharmacological Data)

Results

esterase activity was 9 pmol anhydroecgonine formed/min/mg; nonenzymatic hydrolysis was 1.1 percent (0.83 nmol/incubation); no metabolites of oxidative pathways were detected

Metabolite XRN (Pharmacological Data)

82843

Metabolite (Pharmacological Data)

ecgonidine

Fandino, Anabel S.; Toennes, Stefan W.; Kauert, Gerold F.; Chemical Research in Toxicology; vol. 15; nb. 12; (2002); p. 1543 - 1548, View in Reaxys 11 of 25

Effect (Pharmacological Data)

biotransformation

Species or Test-System (Pharmacological Data)

Sprague-Dawley rat liver microsomes

Sex

male

Concentration (Pharmacological Data)

5 mmol/l

Kind of Dosing (Pharmacological Data)

title comp. dissolved in acetonitrile at conc. of 1 mg/ml

Method (Pharmacological Data)

0.75 mg of protein; 0.1 mol/l phosphate buffer (pH 7.4); 1.2 mmol/l NADP; 2 units of isocitrate dehydrogenase; 5 mmol/l isocitrate; 5 mmol/l MgCl2; incub. in presence of 250 mmol/l ethanol for 60 min at 37 deg C; metabolites were identified with GC/MS

Further Details (Pharmacological Data)

in presence and absence of 200 mmol/l NaF (esterase inhibitor); incubation in presence of NaF was the control for nonenzymatic hydrolysis; pooled organs of 3 animals

Results

in presence of NaF anhydroecgonine and anhydroecgonine ethyl ester were hardly detectable

Comment (Pharmacological Data)

Further metabolite(s)

Metabolite XRN (Pharmacological Data)

82843; 7687323; 83629

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Metabolite (Pharmacological Data)

ecgonidine; noranhydroecgonine methyl ester; anhydroecgonine ethyl ester

Fandino, Anabel S.; Toennes, Stefan W.; Kauert, Gerold F.; Chemical Research in Toxicology; vol. 15; nb. 12; (2002); p. 1543 - 1548, View in Reaxys 12 of 25

Effect (Pharmacological Data)

agonist

Species or Test-System (Pharmacological Data)

human embryonic lung (HEL299) cell

Concentration (Pharmacological Data)

0.01 - 10 μmol/l

Method (Pharmacological Data)

cells incubated with title comp. for 24 h

Further Details (Pharmacological Data)

title comp. is an acetylcholine M2 muscarinic receptor agonist; Western blotting analysis; cyclic AMP and cyclic GMP assays using enzyme immunoassay kits

Results

title comp. significantly enhanced cyclic GMP production and reduced cyclic AMP content in concentration-dependent manner (concentration-response curves shown)

Yang, Yinke; Ke, Qingen; Cai, Jingbo; Xiao, Yong-Fu; Morgan, James P.; British Journal of Pharmacology; vol. 132; nb. 2; (2001); p. 451 - 460, View in Reaxys 13 of 25

Effect (Pharmacological Data)

membrane current; inhibition of

Species or Test-System (Pharmacological Data)

human embryonic kidney 293 cell

Concentration (Pharmacological Data)

100 - 300 μmol/l

Kind of Dosing (Pharmacological Data)

dissolved in deionized water

Method (Pharmacological Data)

HERG potassium currents elicited in patch-clamped cells stably transfected with HERG by step depolarization to voltage between -70 and +60 mV from -80 mV, followed by repolarization to -60 mV in presence of title comp.; changes in tail currents recorded

Further Details (Pharmacological Data)

HERG: human ether-a-go-go-related gene

Results

title comp. concentration-dependently blocked HERG potassium currents; blockade was increased significantly over voltage range where HERG activated, but became constant at voltages where HERG activation was maximal (figure, table)

Ferreira, Scott; Crumb Jr., William J.; Carlton, Carol G.; Clarkson, Craig W.; Journal of Pharmacology and Experimental Therapeutics; vol. 299; nb. 1; (2001); p. 220 - 226, View in Reaxys 14 of 25

Effect (Pharmacological Data)

membrane current; inhibition of

Species or Test-System (Pharmacological Data)

human embryonic kidney 293 cell

Concentration (Pharmacological Data)

Ca. 10 - 1000 μmol/l

Kind of Dosing (Pharmacological Data)

dissolved in deionized water

Method (Pharmacological Data)

cells stably transfected with HERG patch-clamped in whole-cell configuration; HERG potassium currents elicited by 5-s step depolarization from -80 mV, followed by repolarization to -60 mV in presence of title comp.; changes in tail currents recorded

Further Details (Pharmacological Data)

HERG: human ether-a-go-go-related gene

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

171.7 μmol/l

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Results

title comp. concentration-dependently blocked HERG potassium currents (figure)

Ferreira, Scott; Crumb Jr., William J.; Carlton, Carol G.; Clarkson, Craig W.; Journal of Pharmacology and Experimental Therapeutics; vol. 299; nb. 1; (2001); p. 220 - 226, View in Reaxys 15 of 25

Effect (Pharmacological Data)

membrane current; effect on

Species or Test-System (Pharmacological Data)

human atrial myocyte

Concentration (Pharmacological Data)

100 μmol/l

Kind of Dosing (Pharmacological Data)

dissolved in deionized water

Method (Pharmacological Data)

cells patch-clamped in whole-cell configuration; sodium currents elicited during train of pulses to -20 mV from -140 mV in presence of title comp.; changes in current recorded

Comment (Pharmacological Data)

No effect

Ferreira, Scott; Crumb Jr., William J.; Carlton, Carol G.; Clarkson, Craig W.; Journal of Pharmacology and Experimental Therapeutics; vol. 299; nb. 1; (2001); p. 220 - 226, View in Reaxys 16 of 25

Effect (Pharmacological Data)

membrane current; inhibition of

Species or Test-System (Pharmacological Data)

human embryonic kidney 293 cell

Concentration (Pharmacological Data)

200 μmol/l

Kind of Dosing (Pharmacological Data)

dissolved in deionized water

Method (Pharmacological Data)

cells stably transfected with HERG patch-clamped in whole-cell configuration; potassium currents elicited by 5-s step depolarization to +60 mv from -80 mV, followed by repolarization to -60 mV in presence of title comp.; tail current kinetics analyzed

Further Details (Pharmacological Data)

HERG: human ether-a-go-go-related gene

Results

title comp. only reduced amplitude of HERG potassium current without significant effect on tail current kinetics (figure, table)

Ferreira, Scott; Crumb Jr., William J.; Carlton, Carol G.; Clarkson, Craig W.; Journal of Pharmacology and Experimental Therapeutics; vol. 299; nb. 1; (2001); p. 220 - 226, View in Reaxys 17 of 25

Comment (Pharmacological Data)

affinity for muscarinic (M1, M2, M3, M4) receptors in membranes from transfected CHO cells; affinity for nicotinic (α4β2) and muscarinic (M1) receptors in rat celebral cortical membranes

Pei; Gupta; Badio; Padgett; Daly; Journal of medicinal chemistry; vol. 41; nb. 12; (1998); p. 2047 - 2055, View in Reaxys 18 of 25

Effect (Pharmacological Data)

antagonist

Species or Test-System (Pharmacological Data)

Ferret atrial myocytes

Sex

male

Concentration (Pharmacological Data)

20 μmol/l

Method (Pharmacological Data)

Hearts removed from animals (6-10 w); atrial myocytes enzymatically isolated and dispersed in Tyrode's solution; 22-23 deg C; myocytes superfused using external solution with carbachol and title comp.; suppressant effect of title comp. measured

Further Details (Pharmacological Data)

IK(ACh): acetylcholine (ACh)-activated muscarinic K+ current; muscarinic receptors investigation; carbachol (1 μmol/l) activated atrial myocytes to IK(ACh) 231 pA (holding potential 0 mV); nystatin-perforated patch-clamp method of measurements

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Results

Current-time relationship for perfusion period for carbachol alone and carbachol plus title comp.; IK(ACh) was markedly reduced in the presence of title comp.; extracellular application of title comp. produced 53 percent inhibition of IK(ACh) in myocytes

Xiao, Yong-Fu; Morgan, James P.; Journal of Pharmacology and Experimental Therapeutics; vol. 284; nb. 1; (1998); p. 10 - 18, View in Reaxys 19 of 25

Effect (Pharmacological Data)

antagonist

Species or Test-System (Pharmacological Data)

Ferret atrial myocytes

Sex

male

Concentration (Pharmacological Data)

0.1 - 100 μmol/l

Method (Pharmacological Data)

Hearts removed from animals (6-10 w); atrial myocytes enzymatically isolated and dispersed in Tyrode's solution; 22-23 deg C; myocytes superfused using external solution with carbachol plus various conc. of title comp.; suppression effect assessed

Further Details (Pharmacological Data)

Type (Pharmacological Data)

IC50

Value of Type (Pharmacological Data)

12 μmol/l

Results

Dose-response curve for title comp.-induced suppression of IK(ACh); inhibition of IK(ACh) is concentration-dependent

Xiao, Yong-Fu; Morgan, James P.; Journal of Pharmacology and Experimental Therapeutics; vol. 284; nb. 1; (1998); p. 10 - 18, View in Reaxys 20 of 25

Effect (Pharmacological Data)

lung injury

Species or Test-System (Pharmacological Data)

guinea pig

Sex

male

Route of Application

inhalation

Exposure Period (Pharmacological Data)

24 h

Method (Pharmacological Data)

nebulized title compound (conc. 4.32-16.12 mg/l air) was administered for 1 min

Further Details (Pharmacological Data)

animals were exsanguinated, their lungs lavaged and lavage fluid assayed for protein and lactate dehydrogenase

Results

aerosol of title compound induced lung damage, evidenced by presence of blood and higher level of protein and lactate dehydrogenase in the lung lavage fluid

Willetts, J.; Chen, L. C.; Graefe, J. F.; Wood, R. W.; Life Sciences; vol. 57; nb. 15; (1995); p. P225 - P230, View in Reaxys 21 of 25

Effect (Pharmacological Data)

bronchoconstrictive

Species or Test-System (Pharmacological Data)

Guinea pig

Sex

male

Route of Application

inhalation

Kind of Dosing (Pharmacological Data)

condensation aerosol (13 mg/l of air) inhalatio, 1 min

Exposure Period (Pharmacological Data)

1 - 40 min

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Method (Pharmacological Data)

pig weight 250-350 g; atmospheres 5 l/min; condensation aerosol; inhaled volume and airway conductance measured on pneumotachograph

Further Details (Pharmacological Data)

6 pig per test; 1 min of exposure; change of airflow and box pressure signal; specific airway conductance (SGaw)

Results

SGaw reduced to 24.0 percent of baseline; 1 pig died within 10 min of exposure; 2 pig recovery to baseline within 20 min of exposure, 1 pig within 40 min of exposure; associated with bronchoconstriction observed in crack smokers

Chen; Graefe; Shojaie; Willetts; Wood; Life Sciences; vol. 56; nb. 1; (1995); p. PL7-P12, View in Reaxys 22 of 25

Effect (Pharmacological Data)

respiratory

Species or Test-System (Pharmacological Data)

rabbit

Sex

male and female

Concentration (Pharmacological Data)

3 mg

Exposure Period (Pharmacological Data)

7 min

Method (Pharmacological Data)

anesthetized adult rabbits (2.5-3.5 kg) cannulated and connected to a respiratory monitor; arterial catheter connected to a blood pressure transducer; bolus dose inj. of title comp.

Further Details (Pharmacological Data)

baseline values for all measures 10, 5 and 2.5 min prior to drug adm. into the vertebral artery

Results

produced decreases in blood pressure and heart rate (2-4 min); peak effect of 5-7 min; duration of 20-30 min; increased respiratory rate

Erzouki, H. K.; Allen, A. C.; Newman, A. H.; Goldberg, S. R.; Schindler, C. W.; Life Sciences; vol. 57; nb. 20; (1995); p. 1861 - 1868, View in Reaxys 23 of 25

Effect (Pharmacological Data)

respiratory

Species or Test-System (Pharmacological Data)

rabbit

Sex

male and female

Route of Application

intravenous

Concentration (Pharmacological Data)

3 mg

Exposure Period (Pharmacological Data)

7 min

Method (Pharmacological Data)

anesthetized adult rabbits (2.5-3.5 kg) cannulated and connected to a respiratory monitor; arterial catheter connected to a blood pressure transducer; bolus dose inj. of title comp.

Further Details (Pharmacological Data)

baseline values for all measures 10, 5 and 2.5 min prior to drug adm.

Results

produced decreases in blood pressure and heart rate (2-4 min); peak effect of 5-7 min; duration of 20-30 min; increased respiratory rate

Erzouki, H. K.; Allen, A. C.; Newman, A. H.; Goldberg, S. R.; Schindler, C. W.; Life Sciences; vol. 57; nb. 20; (1995); p. 1861 - 1868, View in Reaxys 24 of 25

Effect (Pharmacological Data)

antagonist

Species or Test-System (Pharmacological Data)

guinea pig tracheal rings

Concentration (Pharmacological Data)

1E-09 - 0.001 mol/l

Kind of Dosing (Pharmacological Data)

as fumarate

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Method (Pharmacological Data)

in vitro; tracheal rings from male Hartley guinea pigs (250-350 g); organ bath containing Krebs-Henseleit solution; 37 deg C; 95 percent O2 - 5 percent CO2; also in the presence of acetylcholine (ACh), histamine, carbachol, KCl, BaCl2, and 4-DAMP

Further Details (Pharmacological Data)

incubation time 5 min; tension generated by tissue contraction measured

Results

did not induce contraction of isolated tracheal rings; dose-dependently relaxed tissue precontracted with ACh; reduced magnitude of contractions induced by ACh, carbachol, histamine, and KCl but not by BaCl2

El-Fawal; Wood; Journal of Pharmacology and Experimental Therapeutics; vol. 272; nb. 3; (1995); p. 991 - 996, View in Reaxys 25 of 25

Effect (Pharmacological Data)

antagonist

Species or Test-System (Pharmacological Data)

chicken biventer cervicis muscle

Concentration (Pharmacological Data)

1E-07 - 0.001 mol/l

Kind of Dosing (Pharmacological Data)

as fumarate

Method (Pharmacological Data)

in vitro; isolated striated tissue from adult White Leghorn hens (1.5-2.0 kg); organ bath containing Krebs-Henseleit solution; 37 deg C; 95 percent O2 - 5 percent CO2; contraction induced by electrical stimulation or by acetylcholine (ACh)

Further Details (Pharmacological Data)

tension generated by tissue measured

Results

ineffective in altering amplitude of contraction produced by supramaximal electrical stimulation or by exogenously applied ACh; drug alone did not contract or relax tissue

El-Fawal; Wood; Journal of Pharmacology and Experimental Therapeutics; vol. 272; nb. 3; (1995); p. 991 - 996, View in Reaxys Concentration in the Environment (5) 1 of 5

Species (Concentration in the Environment)

meconium of neonates

Contamination Concentration

0 - 0.4194 mg/kg

Method, Remarks (Concentration in the Environment)

newborn infants whose mothers' urine screened positive for benzoylecgonine; 22 screened samples, 21 positive; approved by Human Investigations Committee of Emory University, School of Medicine, Atlanta, GA; mean value: 0.0475 mg/kg; LC-MS-MS method

Xia, Yang; Wang, Pingping; Bartlett, Michael G.; Solomon, Harvey M.; Busch, Kenneth L.; Analytical Chemistry; vol. 72; nb. 4; (2000); p. 764 - 771, View in Reaxys 2 of 5

Media (Concentration in the Environment)

human urine

Contamination Concentration

5 - 1477 μg/l

Method, Remarks (Concentration in the Environment)

urine collect. from 489 specimen (cocaine smoking, clinical and forensic cases) during 18 months; test. comp. detected in 89 cases; urine extracted, derivatized, GC-MS analyzed; selective ion monitoring

Kintz, Pascal; Sengler, Catherine; Cirimele, Vincent; Mangin, Patrice; Human and Experimental Toxicology; vol. 16; nb. 2; (1997); p. 123 - 127, View in Reaxys 3 of 5

Media (Concentration in the Environment)

human saliva

Contamination Concentration

5 - 18 μg/l

Method, Remarks (Concentration in the Environment)

saliva collect. from 6 specimen (cocaine smoking, clinical and forensic cases) during 18 months; test. comp. detected in 6 cases; saliva extracted, derivatized, GC-MS analyzed; selective ion monitoring

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Kintz, Pascal; Sengler, Catherine; Cirimele, Vincent; Mangin, Patrice; Human and Experimental Toxicology; vol. 16; nb. 2; (1997); p. 123 - 127, View in Reaxys 4 of 5

Media (Concentration in the Environment)

human hair

Contamination Concentration

0.20 - 21.56 ng/mg

Method, Remarks (Concentration in the Environment)

hair collect. from 158 specimen (cocaine smoking, clinical and forensic cases; mother and newborn premature baby) during 18 months; test. comp. detected in 32 cases; GC-MS analyzed; selective ion monitoring

Kintz, Pascal; Sengler, Catherine; Cirimele, Vincent; Mangin, Patrice; Human and Experimental Toxicology; vol. 16; nb. 2; (1997); p. 123 - 127, View in Reaxys 5 of 5

Media (Concentration in the Environment)

human sweat

Contamination Concentration

53 ng/patch

Method, Remarks (Concentration in the Environment)

sweat collect. from 87 specimen (cocaine smoking, clinical and forensic cases) during 18 months; test. comp. detected in 1 case; sweat patch isolated; test comp. extracted; derivatized, GC-MS analyzed; selective ion monitoring

Kintz, Pascal; Sengler, Catherine; Cirimele, Vincent; Mangin, Patrice; Human and Experimental Toxicology; vol. 16; nb. 2; (1997); p. 123 - 127, View in Reaxys Isolation from Natural Product (1) Isolation from References Natural Product Isolierung aus Sa- Matchett; Levine; Journal of the American Chemical Society; vol. 63; (1941); p. 2444, View in Reaxys men von Erythroxylum coca und Erythroxylum novogranatense

Reaxys ID 147226 View in Reaxys

2/2 CAS Registry Number: 127379-24-2 Chemical Name: (+/-)-Ecgonidine methyl ester; 8-methyl-8aza-bicyclo[3.2.1]oct-2-ene-2-carboxylic acid methyl ester; anhydroecgonine methyl ester; ecgonidine methylate; 8-methylnortrop-2-ene-2-carboxylic acid methyl ester; methyl (1RS)-8methyl-8-azabicyclo-[3.2.1]oct-2-ene-2-carboxylate Linear Structure Formula: C10H15NO2 Molecular Formula: C10H15NO2 Molecular Weight: 181.235 Type of Substance: heterocyclic InChI Key: MPSNEAHFGOEKBI-UHFFFAOYSA-N Note:

N O O

Substance Label (4) Label References 3

Stehouwer, Jeffrey S.; Jarkas, Nachwa; Zeng, Fanxing; Voll, Ronald J.; Williams, Larry; Owens, Michael J.; Votaw, John R.; Goodman, Mark M.; Journal of Medicinal Chemistry; vol. 49; nb. 23; (2006); p. 6760 - 6767, View in Reaxys; Hultsch, Christina; Blank, Olga; Wester, Hans-Juergen; Heinrich, Markus R.; Tetrahedron Letters; vol. 49; nb. 11; (2008); p. 1881 - 1883, View in Reaxys

Newman, Amy Hauck; Cha, Joo Hwan; Cao, Jianjing; Kopajtic, Theresa; Katz, Jonathan L.; Parnas, M. Laura; Vaughan, Roxanne; Lever, John R.; Journal of Medicinal Chemistry; vol. 49; nb. 22; (2006); p. 6621 - 6625, View in Reaxys

5, R=R'=Me

Wyatt, Emma E.; Fergus, Suzanne; Galloway, Warren R. J. D.; Bender, Andreas; Fox, David J.; Plowright, Alleyn T.; Jessiman, Alan S.; Welch, Martin; Spring, David R.; Chemical Communications; nb. 31; (2006); p. 3296 - 3298, View in Reaxys

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3. intermed. to 2 Boiling Point (2) Boiling Point [°C]

Hoepping; George; Flippen-Anderson; Kozikowski; Tetrahedron Letters; vol. 41; nb. 39; (2000); p. 7427 7432, View in Reaxys Pressure (Boiling Point) [Torr]

References

67 - 74

0.1

Clarke et al.; Journal of Medicinal Chemistry; vol. 16; (1973); p. 1260,1262, View in Reaxys

135 - 137

Zirkle et al.; Journal of Organic Chemistry; vol. 27; (1962); p. 1269,1277, View in Reaxys

Refractive Index (2) Refractive Index Wavelength (Refractive Index) [nm]

Temperature (Refractive Index) [°C]

References

1.5011

589

Clarke et al.; Journal of Medicinal Chemistry; vol. 16; (1973); p. 1260,1262, View in Reaxys

1.4996

589

24.5

Zirkle et al.; Journal of Organic Chemistry; vol. 27; (1962); p. 1269,1277, View in Reaxys

Crystal Property Description (1) Colour & Other References Properties yellow

Further Information (1) Description (Fur- References ther Information) Further information

Bainowa et al.; Doklady Chemistry; vol. 157; (1964); p. 703; Doklady Akademii Nauk SSSR; vol. 157; (1964); p. 599, View in Reaxys

Optical Rotatory Power (1) 1 of 1

Type (Optical Rotatory Power)

[alpha]

Optical Rotatory Power [deg]

38.3

Wavelength (Optical Ro- 589 tatory Power) [nm] Temperature (Optical Rotatory Power) [°C]

Clarke et al.; Journal of Medicinal Chemistry; vol. 16; (1973); p. 1260,1262, View in Reaxys NMR Spectroscopy (12) 1 of 12

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

13C

Solvents (NMR Spectro- CDCl3 scopy) Frequency (NMR Spectroscopy) [MHz]

90.6

Hultsch, Christina; Blank, Olga; Wester, Hans-Juergen; Heinrich, Markus R.; Tetrahedron Letters; vol. 49; nb. 11; (2008); p. 1881 - 1883, View in Reaxys 2 of 12

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

Solvents (NMR Spectro- CDCl3 scopy)

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Frequency (NMR Spectroscopy) [MHz]

360

Hultsch, Christina; Blank, Olga; Wester, Hans-Juergen; Heinrich, Markus R.; Tetrahedron Letters; vol. 49; nb. 11; (2008); p. 1881 - 1883, View in Reaxys 3 of 12

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

13C

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

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

13C

Solvents (NMR Spectro- dimethylsulfoxide-d6 scopy) Frequency (NMR Spectroscopy) [MHz]

125

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

Solvents (NMR Spectro- dimethylsulfoxide-d6 scopy) Frequency (NMR Spectroscopy) [MHz]

400

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

Solvents (NMR Spectro- CDCl3 scopy) Davies; Saikali; Young; Journal of Organic Chemistry; vol. 56; nb. 19; (1991); p. 5696 - 5700, View in Reaxys 8 of 12

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

13C

Solvents (NMR Spectro- CDCl3 scopy)

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Davies; Saikali; Young; Journal of Organic Chemistry; vol. 56; nb. 19; (1991); p. 5696 - 5700, View in Reaxys 9 of 12

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

1H-1H

Davies; Saikali; Young; Journal of Organic Chemistry; vol. 56; nb. 19; (1991); p. 5696 - 5700, View in Reaxys 10 of 12

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

Solvents (NMR Spectro- dimethylsulfoxide-d6 scopy) Kline Jr.; Wright; Fox; Eldefrawi; Journal of Medicinal Chemistry; vol. 33; nb. 7; (1990); p. 2024 - 2027, View in Reaxys 11 of 12

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

13C

Solvents (NMR Spectro- dimethylsulfoxide-d6 scopy) Kline Jr.; Wright; Fox; Eldefrawi; Journal of Medicinal Chemistry; vol. 33; nb. 7; (1990); p. 2024 - 2027, View in Reaxys 12 of 12

Description (NMR Spec- Spin-spin coupling constants troscopy) Solvents (NMR Spectro- dimethylsulfoxide-d6 scopy) Comment (NMR Spectroscopy)

1H-1H

Kline Jr.; Wright; Fox; Eldefrawi; Journal of Medicinal Chemistry; vol. 33; nb. 7; (1990); p. 2024 - 2027, View in Reaxys IR Spectroscopy (5) 1 of 5

Description (IR Spectroscopy)

Bands

Solvent (IR Spectroscopy)

neat liquid

Description (IR Spectroscopy)

Bands

Solvent (IR Spectroscopy)

CDCl3

Comment (IR Spectroscopy)

2940 - 1630 cm**(-1)

Davies; Saikali; Young; Journal of Organic Chemistry; vol. 56; nb. 19; (1991); p. 5696 - 5700, View in Reaxys 3 of 5

Description (IR Spectroscopy)

Bands

Solvent (IR Spectroscopy)

neat (no solvent)

Comment (IR Spectroscopy)

2950 - 1049 cm**(-1)

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Kline Jr.; Wright; Fox; Eldefrawi; Journal of Medicinal Chemistry; vol. 33; nb. 7; (1990); p. 2024 - 2027, View in Reaxys 4 of 5

Description (IR Spectroscopy)

Zirkle et al.; Journal of Organic Chemistry; vol. 27; (1962); p. 1269,1277, View in Reaxys; Clarke et al.; Journal of Medicinal Chemistry; vol. 16; (1973); p. 1260,1262, View in Reaxys 5 of 5

Description (IR Spectroscopy)

Spectrum

Bainowa et al.; Doklady Chemistry; vol. 157; (1964); p. 703; Doklady Akademii Nauk SSSR; vol. 157; (1964); p. 599, View in Reaxys Mass Spectrometry (1) Description (Mass References Spectrometry) electron impact (EI); spectrum

Davies; Saikali; Young; Journal of Organic Chemistry; vol. 56; nb. 19; (1991); p. 5696 - 5700, View in Reaxys

Pharmacological Data (2) 1 of 2

Comment (Pharmacological Data)

Bioactivities present

Patent; NeuroSearch A/S; US5369113; (1994); (A1) English, View in Reaxys; Patent; NeuroSearch A/S; US2001/18444; (2001); (A1) English, View in Reaxys; Patent; Okano, Kyoko; Itoh, Osamu; US2001/20096; (2001); (A1) English, View in Reaxys; Zirkle et al.; Journal of Organic Chemistry; vol. 27; (1962); p. 1269,1277, View in Reaxys; Bainowa et al.; Doklady Chemistry; vol. 157; (1964); p. 703; Doklady Akademii Nauk SSSR; vol. 157; (1964); p. 599, View in Reaxys; Clarke et al.; Journal of Medicinal Chemistry; vol. 16; (1973); p. 1260,1262, View in Reaxys; Kline Jr.; Wright; Fox; Eldefrawi; Journal of Medicinal Chemistry; vol. 33; nb. 7; (1990); p. 2024 2027, View in Reaxys; Davies; Saikali; Young; Journal of Organic Chemistry; vol. 56; nb. 19; (1991); p. 5696 5700, View in Reaxys; Meegalla, S. K.; Ploessl, K.; Kung, M.-P.; Mu, M.; Kung, H. F.; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 40; (1997); p. 434 - 436, View in Reaxys; Zheng, Qi-Huang; Mulholland, G. Keith; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 40; (1997); p. 551 - 553, View in Reaxys; Pei; Gupta; Badio; Padgett; Daly; Journal of medicinal chemistry; vol. 41; nb. 12; (1998); p. 2047 - 2055, View in Reaxys; Hoepping; George; Flippen-Anderson; Kozikowski; Tetrahedron Letters; vol. 41; nb. 39; (2000); p. 7427 - 7432, View in Reaxys; Stehouwer, Jeffrey S.; Jarkas, Nachwa; Zeng, Fanxing; Voll, Ronald J.; Williams, Larry; Owens, Michael J.; Votaw, John R.; Goodman, Mark M.; Journal of Medicinal Chemistry; vol. 49; nb. 23; (2006); p. 6760 - 6767, View in Reaxys; Newman, Amy Hauck; Cha, Joo Hwan; Cao, Jianjing; Kopajtic, Theresa; Katz, Jonathan L.; Parnas, M. Laura; Vaughan, Roxanne; Lever, John R.; Journal of Medicinal Chemistry; vol. 49; nb. 22; (2006); p. 6621 - 6625, View in Reaxys; Hultsch, Christina; Blank, Olga; Wester, Hans-Juergen; Heinrich, Markus R.; Tetrahedron Letters; vol. 49; nb. 11; (2008); p. 1881 - 1883, View in Reaxys; Wyatt, Emma E.; Fergus, Suzanne; Galloway, Warren R. J. D.; Bender, Andreas; Fox, David J.; Plowright, Alleyn T.; Jessiman, Alan S.; Welch, Martin; Spring, David R.; Chemical Communications; nb. 31; (2006); p. 3296 - 3298, View in Reaxys; Sinha, Nandita; Sen, Srikanta; European Journal of Medicinal Chemistry; vol. 46; nb. 2; (2011); p. 618 - 630, View in Reaxys; Coi, Alessio; Massarelli, Ilaria; Saraceno, Marilena; Carli, Niccolo; Testai, Lara; Calderone, Vincenzo; Bianucci, Anna Maria; Chemical Biology and Drug Design; vol. 74; nb. 4; (2009); p. 416 - 433, View in Reaxys; Fred M.Hershenson; John G. Marriott; Walter H.Moos; Annual reports in medicinal chemistry; vol. 21; (1986); p. 31 - 40, View in Reaxys; Patent; Jensen Leif Helth; Moldt Peter; Scheel-Kruger Jorgen; EP604355; (B1); (1994), View in Reaxys 2 of 2

Comment (Pharmacological Data)

Bioactivities present

Patent; Moldt Peter; Scheel-Kruger Jorgen; Jensen Leif Helth; EP604352; (B1); (1994), View in Reaxys; Patent; MOLDT Peter; WATJEN Frank; SCHEEL-KRUGER Joergen; EP885220; (B1); (2001), View in Reaxys; Patent; Jorgen Scheel-Kruger; Peter Moldt; Frank Watjen; US2002/128284; (A1); (2002), View in Reaxys; Patent; SCHEEL-KRUGER Jorgen; MOLDT Peter; WATJEN FrankA; WO1997/30997; (A1); (1997), View in Reaxys

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