4-Methyl-5-phenyl-4,5-dihydrooxazol-2-amine (4-MAR) by Asch

Reaxys

PubChem

eMolecules

Reactions (13)

Substances (10)

Structure

Citations (15)

Structure/Compound Data Chemical Name: trans-4S,5S-4-methylaminorex Reaxys Registry Number: 4946439

CAS Registry Number: 27780-30-9 Type of Substance: heterocyclic Molecular Formula: C10H12N2O Linear Structure Formula: C10H12N2O Molecular Weight: 176.218 InChI Key: LJQBMYDFWFGESC-IONNQARKSA-N

N° of preparations All Preps | All Reactions

Available Data

2 prep out of 2 reactions.

Identification Physical Data (1) Bioactivity (8)

Synthesize | Hide Details Find similar Chemical Names and Synonyms trans-4S,5S-4-methylaminorex, trans-4S,5S-2-amino-4-methyl-5-phenyl-Δ2-oxazoline, 4S,5S-methylaminorex, (4S)-4r-methyl-5t-phenyl-4,5-dihydrooxazol-2-ylamine, trans-4-methyl-5-phenyl-4,5-dihydro-2-oxazolamine, (+)-trans-2-Amino-4-methyl-5-phenyl-2-oxazolin Identification Substance Label (2) Label

Reference

trans-4S,5S

Kankaanpaa, Aino; Ellermaa, Satu; Meririnne, Esa; Hirsjarvi, Paula; Seppala, Timo

Journal of Pharmacology and Experimental Therapeutics, 2002 , vol. 300, # 2 p. 450 - 459 Title/Abstract Full Text Show Details

(+)-Va

Poos,G.I. et al.

Journal of Medicinal Chemistry, 1963 , vol. 6, p. 266 - 272 Full Text View citing articles Show Details

Physical Data

N° of ref. 7

Melting Point (1) Melting Point

Solvent (Melting Point)

Reference

177.5 - 179.5 °C

benzene

Poos,G.I. et al.

Journal of Medicinal Chemistry, 1963 , vol. 6, p. 266 - 272 Full Text View citing articles Show Details

Bioactivity Pharmacological Data (8) 1 of 8

Comment (Pharmacological Data)

Bioactivities present

Reference

E. R. Squibb and Sons, Inc.

Patent: US4311840 A1, 1982 ; Title/Abstract Full Text Show Details

Poos,G.I. et al.

Journal of Medicinal Chemistry, 1963 , vol. 6, p. 266 - 272 Full Text View citing articles Show Details

Wollweber; Hiltman; Stoepel; Kroneberg

European Journal of Medicinal Chemistry, 1980 , vol. 15, # 2 p. 111 - 117 Title/Abstract Full Text View citing articles Show Details

Zheng, Yiwen; Russell, Bruce; Schmierer, David; Laverty, Richard

Journal of Pharmacy and Pharmacology, 1997 , vol. 49, # 1 p. 89 - 96 Title/Abstract Full Text View citing articles Show Details

Kankaanpaa, Aino; Ellermaa, Satu; Meririnne, Esa; Hirsjarvi, Paula; Seppala, Timo

Journal of Pharmacology and Experimental Therapeutics, 2002 , vol. 300, # 2 p. 450 - 459 Title/Abstract Full Text Show Details

Meririnne, Esa; Ellermaa, Satu; Kankaanpaeae, Aino; Bardy, Ali; Seppaelae, Timo

Journal of Pharmacology and Experimental Therapeutics, 2004 , vol. 309, # 3 p. 1198 - 1205 Title/Abstract Full Text View citing articles Show Details

Brunner, Friedrich; Wolkart, Gerald; Haleen, Stephen

Journal of Pharmacology and Experimental Therapeutics, 2002 , vol. 300, # 2 p. 450 - 459 Title/Abstract Full Text View citing articles Show Details

2 of 8

3 of 8

Effect (Pharmacological Data)

pharmacokinetics

Species or TestSystem (Pharmacological Data)

Han:Wistar rat

Sex

male

Route of Application

intravenous

Concentration (Pharmacological Data)

2 mg/kg

Kind of Dosing (Pharmacological Data)

single bolus over 30 s

Method (Pharmacological Data)

adult rats weighing 250 to 350 g used; after title comp. administration blood samples drawn at various time points up to 240 min; conc. of title comp. determined with GC/MS

Further Details (Pharmacological Data)

data analyzed by model-independent methods, using non-linear least squares fitting; t1/2di: distribution half-life

Half-life Time (Pharmacological Data)

34.5 min

Results

t1/2di = 5.3 min, Vdss = 1.7 l/kg, AUC0-240 = 51.1 μg/ml*min (graph, table)

Reference

Meririnne, Esa; Ellermaa, Satu; Kankaanpaeae, Aino; Bardy, Ali; Seppaelae, Timo

Journal of Pharmacology and Experimental Therapeutics, 2004 , vol. 309, # 3 p. 1198 - 1205 Title/Abstract Full Text View citing articles Show Details

Effect (Pharmacological Data)

pharmacokinetics

Species or Test-

Han:Wistar rat

System (Pharmacological Data)

4 of 8

5 of 8

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

2 mg/kg

Kind of Dosing (Pharmacological Data)

single bolus

Method (Pharmacological Data)

adult rats weighing 250 to 350 g used; after title comp. administration blood samples drawn at various time points up to 240 min; conc. of title comp. determined with GC/MS

Further Details (Pharmacological Data)

data analyzed by model-independent methods, using non-linear least squares fitting; t1/2ab: absorption half-life; Fbioav: bioavailability

Half-life Time (Pharmacological Data)

41.9 min

Results

Cmax = 0.33 μg/ml, Tmax = 17.5 min, t1/2ab = 4.8 min, Fbioav = 32.4 percent, AUC0-240 = 16.6 μg/ml*min (graph, table)

Reference

Meririnne, Esa; Ellermaa, Satu; Kankaanpaeae, Aino; Bardy, Ali; Seppaelae, Timo

Journal of Pharmacology and Experimental Therapeutics, 2004 , vol. 309, # 3 p. 1198 - 1205 Title/Abstract Full Text View citing articles Show Details

Effect (Pharmacological Data)

pharmacokinetics

Species or TestSystem (Pharmacological Data)

Han:Wistar rat

Sex

male

Route of Application

peroral

Concentration (Pharmacological Data)

2 mg/kg

Kind of Dosing (Pharmacological Data)

oral gavage with syringe after at least 4 h fasting

Method (Pharmacological Data)

adult rats weighing 250 to 350 g used; after title comp. administration blood samples drawn at various time points up to 240 min; conc. of title comp. determined with GC/MS

Further Details (Pharmacological Data)

data analyzed by model-independent methods, using non-linear least squares fitting; Fbioav: bioavailability

Results

Cmax = 0.08 μg/ml, Tmax = 18 min, Fbioav = 6.2 percent, AUC0-240 = 3.2 μg/ml*min (graph, table)

Reference

Meririnne, Esa; Ellermaa, Satu; Kankaanpaeae, Aino; Bardy, Ali; Seppaelae, Timo

Journal of Pharmacology and Experimental Therapeutics, 2004 , vol. 309, # 3 p. 1198 - 1205 Title/Abstract Full Text View citing articles Show Details

Effect (Pharmacological Data)

pharmacokinetics

Species or TestSystem (Pharmacological Data)

Han:Wistar rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

5 mg/kg

6 of 8

Kind of Dosing (Pharmacological Data)

single bolus

Method (Pharmacological Data)

adult rats weighing 300 to 400 g used; after title comp. inj. rats decapitated at various time points up to 280 min; trunk blood (bl) collected, brain (br), liver (li), left kidney(ki), samples of pectoral muscle (mu) and subcutaneous fat (fa) dissected

Further Details (Pharmacological Data)

conc. of title comp. in tissues quantified using extraction and GC/MS

Results

AUC30-150 (μg/(ml or g)*min): 76.7 (bl), 474.7 (br), 59.8 (fa), 215.7 (mu), 541.2 (li), 1578.8 (ki); elimination half-lives (min): 38.5 (bl), 43.3 (br), 53.3 (fa), 35.5 (mu), 51.7 (li), 51.7 (ki); low level of metabolite in blood and brain

Metabolite (Pharmacological Data)

(1S,2S)-2-amino-1-phenylpropanol [Reaxys RN: 2802895]

Reference

Meririnne, Esa; Ellermaa, Satu; Kankaanpaeae, Aino; Bardy, Ali; Seppaelae, Timo

Journal of Pharmacology and Experimental Therapeutics, 2004 , vol. 309, # 3 p. 1198 - 1205 Title/Abstract Full Text View citing articles Show Details

Effect (Pharmacological Data)

behavioural symptoms

Species or TestSystem (Pharmacological Data)

Wistar rat

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

2.5 - 10 mg/kg

Kind of Dosing (Pharmacological Data)

dissolved in saline, pH adjusted to physiological level with 2 M NaOH

Method (Pharmacological Data)

behavioral changes (locomotor activity, onset, frequency and/or duration of different behaviors) of rats monitored; extracellular dopamine and 5-HT levels in nucleus accumbens determined by HPLC, samples taken by in vivo microdialysis

Further Details (Pharmacological Data)

7 of 8

5-HT = 5-hydroxytryptamine; concentration of title comp. in dialysate also determined; D = dopamine

Results

significantly elevated D (at 5-10 mg/kg) and 5-HT (10 mg/kg) levels; at 5-10 mg/kg biphasic pattern with rapid initial rise, then rapid decline and stereotyped behavior (sniffing, head bobbing, weaving) and backward walking, ataxia or catatonia observed

Reference

Kankaanpaa, Aino; Ellermaa, Satu; Meririnne, Esa; Hirsjarvi, Paula; Seppala, Timo

Journal of Pharmacology and Experimental Therapeutics, 2002 , vol. 300, # 2 p. 450 - 459 Title/Abstract Full Text Show Details

Effect (Pharmacological Data)

neurochemical, acute

Species or TestSystem (Pharmacological Data)

CBA mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

15 mg/kg

Kind of Dosing (Pharmacological Data)

single dose; dissolved by drop of 60 percent H2SO4 and adjusted to pH 6.0 with Na2HPO4

Exposure Period (Pharmacological Data)

6 h

Method (Pharmacological

body weight 20-25 g; food and water ad libitum; administration of drug; killed at 1, 3 or 6 h after administration; samples of striatum, cortex and hippocampus removed

Data)

8 of 8

Further Details (Pharmacological Data)

tissue levels of 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), dopamine, and 3,4-dihydroxyphenylacetic acid (DOPAC); HPLC analysis

Results

5-HT: initial increase, return to control by 6 h; 5-HIAA: decrease at 1 h followed by increase; dopamine in striatum: no change by 3 h, marked increase at 6 h; DOPAC in striatum: decrease at first and increase later

Reference

Zheng, Yiwen; Russell, Bruce; Schmierer, David; Laverty, Richard

Journal of Pharmacy and Pharmacology, 1997 , vol. 49, # 1 p. 89 - 96 Title/Abstract Full Text View citing articles Show Details

Effect (Pharmacological Data)

neurochemical, long-term

Species or TestSystem (Pharmacological Data)

CBA mouse

Sex

male

Route of Application

intraperitoneal

Concentration (Pharmacological Data)

15 mg/kg

Kind of Dosing (Pharmacological Data)

doses repeted 3 times in 24 h period (usually 17:00, 09:00, 17:00); dissolved in drop of 60 percent H2SO4 and adjusted to pH 6.0 with NaH2PO4

Exposure Period (Pharmacological Data)

8 d

Method (Pharmacological Data)

body weight 20-25 g; food and water ad libitum; administration of drug; killed 7 d after last dose; samples of striatum removed

Further Details (Pharmacological Data)

striatal levels of 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC); HPLC analysis

Results

levels ( percent of control) of: DOPAC 138.0 (P<0.01), dopamine 105.8, 5-HIAA 99.7, and 5-HT 96.9

Reference

Zheng, Yiwen; Russell, Bruce; Schmierer, David; Laverty, Richard

Journal of Pharmacy and Pharmacology, 1997 , vol. 49, # 1 p. 89 - 96 Title/Abstract Full Text View citing articles Show Details

Chemical Name: 4-methylaminorex Reaxys Registry Number: 515250

CAS Registry Number: 3568-94-3 Type of Substance: heterocyclic Molecular Formula: C10H12N2O Linear Structure Formula: C10H12N2O Molecular Weight: 176.218 InChI Key: LJQBMYDFWFGESC-UHFFFAOYSA-N

Synthesize | Hide Details Find similar Chemical Names and Synonyms 4-methylaminorex, 2-Amino-4-methyl-5-phenyl-oxazolin, 2-Amino-4-methyl-5-phenyloxazolin Identification Substance Label (1) Label

Reference

I R=Ph, R1=Me, R2=H

Mc. Neil lab. Inc.,

Patent: US3278382 , 1959 ;

1 prep out of 1 reactions.

Identification Physical Data (3) Bioactivity (1)

Chem.Abstr., 1966 , vol. 65, # 18592a Full Text Show Details

Physical Data Melting Point (2) Melting Point

Reference

154.5 - 156 °C

McNeil Laboratories Inc.

Patent: US3161650 , 1963 ; Chem.Abstr., 1965 , vol. 62, # 10439e Full Text Show Details

McNeil Lab.

Patent: FR2448BE628803 , 19631963 ; Chem.Abstr., 1964 , vol. 61, # 9500h Full Text Show Details

154 - 156 °C

Mc. Neil lab. Inc.,

Patent: US3278382 , 1959 ; Chem.Abstr., 1966 , vol. 65, # 18592a Full Text Show Details

Partition octan-1-ol/water (MCS) (1) log POW

Location

Reference

1.63

supporting information

Adachi, Shinya; Liew, Sean K.; Lee, C. Frank; Lough, Alan; He, Zhi; Denis, Jeffrey D. St.; Poda, Gennady; Yudin, Andrei K.

Organic Letters, 2015 , vol. 17, # 22 p. 5594 - 5597 Title/Abstract Full Text View citing articles Show Details

Bioactivity Pharmacological Data (1) 1 of 1

Comment (Pharmacological Data)

Bioactivities present

Reference

McNeil Laboratories Inc.

Patent: US3161650 , 1963 ; Chem.Abstr., 1965 , vol. 62, # 10439e Full Text Show Details

McNeil Lab.

Patent: FR2448BE628803 , 19631963 ; Chem.Abstr., 1964 , vol. 61, # 9500h Full Text Show Details

Mc. Neil lab. Inc.,

Patent: US3278382 , 1959 ; Chem.Abstr., 1966 , vol. 65, # 18592a Full Text Show Details

POOS; CARSON; ROSENAU; ROSZKOWSKI; KELLEY; MCGOWIN

Journal of medicinal chemistry, 1963 , vol. 6, p. 266 - 272 Title/Abstract Full Text Show Details

Nizar, Hisham; Dargan, Paul I.; Wood, David M.

Journal of Medical Toxicology, 2015 , vol. 11, # 1 p. 80 - 84 Title/Abstract Full Text View citing articles Show Details

Adachi, Shinya; Liew, Sean K.; Lee, C. Frank; Lough, Alan; He, Zhi; Denis, Jeffrey D. St.; Poda, Gennady; Yudin, Andrei K.

Organic Letters, 2015 , vol. 17, # 22 p. 5594 - 5597 Title/Abstract Full Text View citing articles Show Details

Chemical Name: cis-4R,5S-4-methylaminorex Reaxys Registry Number: 8139250

Type of Substance: heterocyclic Molecular Formula: C10H12N2O Linear Structure Formula: C10H12N2O Molecular Weight: 176.218 InChI Key: LJQBMYDFWFGESC-VXNVDRBHSA-N

Synthesize | Hide Details

1 prep out of 1 reactions.

Identification Spectra (4) Bioactivity (7)

Find similar Chemical Names and Synonyms cis-4R,5S-4-methylaminorex, cis-4R,5S-2-amino-4-methyl-5-phenyl-Δ2-oxazoline, (4R,5S)-4-methyl-5-phenyloxazolin-2-amine, 4R,5Smethylaminorex Identification Substance Label (2) Label

Reference

9b-(c)

Cruz, Alejandro; Padilla-Martinez, Itzia Irene; Garcia-Baez, Efren V.; Contreras, Rosalinda

Tetrahedron Asymmetry, 2007 , vol. 18, # 1 p. 123 - 130 Title/Abstract Full Text View citing articles Show Details

cis-4R,5S

Kankaanpaa, Aino; Ellermaa, Satu; Meririnne, Esa; Hirsjarvi, Paula; Seppala, Timo

Journal of Pharmacology and Experimental Therapeutics, 2002 , vol. 300, # 2 p. 450 - 459 Title/Abstract Full Text Show Details

Spectra NMR Spectroscopy (3) Description (NMR Spectroscopy)

Nucleus (NMR Spectroscopy)

Chemical shifts

Solvents (NMR Spectroscopy)

Frequency (NMR Spectroscopy)

13C

CDCl3

75.46 MHz

Cruz, Alejandro; Padilla-Martinez, Itzia Irene; GarciaBaez, Efren V.; Contreras, Rosalinda

Tetrahedron Asymmetry, 2007 , vol. 18, # 1 p. 123 - 130 Title/Abstract Full Text View citing articles Show Details

CDCl3

300.08 MHz

Cruz, Alejandro; Padilla-Martinez, Itzia Irene; GarciaBaez, Efren V.; Contreras, Rosalinda

Tetrahedron Asymmetry, 2007 , vol. 18, # 1 p. 123 - 130 Title/Abstract Full Text View citing articles Show Details

CDCl3

300.08 MHz

Cruz, Alejandro; Padilla-Martinez, Itzia Irene; GarciaBaez, Efren V.; Contreras, Rosalinda

Tetrahedron Asymmetry, 2007 , vol. 18, # 1 p. 123 - 130 Title/Abstract Full Text View citing articles Show Details

Coupling Nuclei

Reference

IR Spectroscopy (1) Description (IR Spectroscopy)

Solvent (IR Spectroscopy)

Reference

Bands

KBr

Cruz, Alejandro; Padilla-Martinez, Itzia Irene; Garcia-Baez, Efren V.; Contreras, Rosalinda

Tetrahedron Asymmetry, 2007 , vol. 18, # 1 p. 123 - 130 Title/Abstract Full Text View citing articles Show Details

Bioactivity Pharmacological Data (7) 1 of 7

2 of 7