NDLI: In vivo Evaluation of Substituted 3-Amino-1,4-benzodiazepines as Anti-depressant, Anxiolytic and Anti-nociceptive Agents

Please wait, while we are loading the content...

In vivo Evaluation of Substituted 3-Amino-1,4-benzodiazepines as Anti-depressant, Anxiolytic and Anti-nociceptive Agents

Content Provider	Scilit
Author	Lattmann, Eric Lattmann, Pornthip Boonprakob, Yodchai Airarat, Wanchai Singh, Harjit Offel, Michael Sattayasai, Jintana
Copyright Year	2009
Description	Oxazepam (CAS 604-75-1) 4a served as building block in the synthesis of substituted 3-amino-1,4-benzodiazepines, which were subsequently tested in various CNS animal models. The hydroxy group of oxazepam was either activated as a chloride (Method A) or as a phosphor-oxy derivative (Method B) giving the desired 3-amino-1,4-benzodiapines 6a–6r in high yields with primary and secondary amines in a typical nucleophilic substitution reaction. Eighteen 3-substituted 1,4-benzodiazepines were prepared and served as new chemical entities and for lead structure discovery. The mixed cholecystokinin (CCK) antagonist 6e showed anxiolytic and antidepressant effects from 10 μg/kg in mice in the elevated x-maze test and the forced swimming test. The $CCK_{1}$ antagonist 6 g has shown antidepressant effects from the same dose, but lacked anxiolytic properties. Both compounds potentiated at a dose of 0.5 mg/kg morphine antinociception with a maximum possible effect (MPE) about 35%. By assessing initially the MPE of antinocipection for the 18 newly synthesised benzodiazepines in the tail-flick test, 4 other benzodiazepines were found active. In further in vivo evaluation the cyclohexyl derivative 6i displayed anxiolytic, antidepressant and antinociceptive properties as single agent at a dose of 5 mg/kg without toxicity. The benzodiazepines 6i and 6p, which initially showed a higher MPE in terms of morphine potentiation (43/44%) showed analgesic effects as single agents, without having anxiolytic or antidepressant properties. The amino-piperidinyl derivative 6p displayed a similar dose-response relationship to morphine, but was 3 times more potent.
Related Links	http://www.thieme-connect.de/products/ejournals/pdf/10.1055/s-0031-1296366.pdf
Ending Page	71
Page Count	11
Starting Page	61
ISSN	00044172
e-ISSN	16167066
DOI	10.1055/s-0031-1296366
Journal	Arzneimittelforschung
Issue Number	02
Volume Number	59
Language	English
Publisher	Georg Thieme Verlag KG
Publisher Date	2009-02-01
Access Restriction	Open
Subject Keyword	Journal: Arzneimittelforschung Medicinal Chemistry 3-amino-5-phenyl-l 4-benzodiazepinone 4-benzodiazepines Cholecystokinin Antagonists
Content Type	Text
Resource Type	Article
Subject	Drug Discovery

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Synthesis and Preliminary Biological Evaluation of Novel N-Substituted 1-Amino-3-[1-methyl(phenyl)-1H-indazol-4-yloxy]-propan-2-ols Interesting as Potential Antiarrhythmic, Local Anaesthetic and Analgesic Agents

Synthesis and Evaluation of N-(5-Methyl-3-oxo-1,2-diphenyl-2,3-dihydro-1H-pyrazol-4-yl)-N’-phenylureas as Cholecystokinin Antagonists

Pharmacological Effects of Triazolo[4,3-d] and Tetrazolo[1,5-a][1,4]benzodiazepines on the Central Nervous System

Design, Synthesis and Histamine H1-Receptor Antagonistic Activity of Some Novel 4-Amino-2-(substituted)-5-(substituted) aryl-6-[(substituted aryl)amino]pyrimidines

Anti-depressant and anti-nociceptive effects of 1,4-benzodiazepine-2-ones based cholecystokinin (CCK(2)) antagonists.

Design, Synthesis and Pharmacological Evaluation of a Series of 5-Carbethoxy-4-chloro-6-(substituted amino)pyrimidines as Potential Analgesic and Anti-flammatory Agents with Very Low Ulcerogenic Potential

Synthesis of 3-Substituted-5-(4-carboxycyclohexylmethyl)-tetrahydro-2H-1,3,5-thiadiazine-2-thione Derivatives as Antifibrinolytic and Antimicrobial Agents

Synthesis and Antifungal and Antioxidant Properties of some New 5-Substituted-4-amino(or aryl)-3-mercapto-4(H)-1,2,4-triazoles

New 4(1H)-Pyridinone Derivatives as Analgesic Agents

In vivo Evaluation of Substituted 3-Amino-1,4-benzodiazepines as Anti-depressant, Anxiolytic and Anti-nociceptive Agents

Similar Documents

Synthesis and Preliminary Biological Evaluation of Novel N-Substituted 1-Amino-3-[1-methyl(phenyl)-1H-indazol-4-yloxy]-propan-2-ols Interesting as Potential Antiarrhythmic, Local Anaesthetic and Analgesic Agents

Synthesis and Evaluation of N-(5-Methyl-3-oxo-1,2-diphenyl-2,3-dihydro-1H-pyrazol-4-yl)-N’-phenylureas as Cholecystokinin Antagonists

Pharmacological Effects of Triazolo[4,3-d] and Tetrazolo[1,5-a][1,4]benzodiazepines on the Central Nervous System

Design, Synthesis and Histamine H1-Receptor Antagonistic Activity of Some Novel 4-Amino-2-(substituted)-5-(substituted) aryl-6-[(substituted aryl)amino]pyrimidines

Anti-depressant and anti-nociceptive effects of 1,4-benzodiazepine-2-ones based cholecystokinin (CCK(2)) antagonists.

Design, Synthesis and Pharmacological Evaluation of a Series of 5-Carbethoxy-4-chloro-6-(substituted amino)pyrimidines as Potential Analgesic and Anti-flammatory Agents with Very Low Ulcerogenic Potential

Synthesis of 3-Substituted-5-(4-carboxycyclohexylmethyl)-tetrahydro-2H-1,3,5-thiadiazine-2-thione Derivatives as Antifibrinolytic and Antimicrobial Agents

Synthesis and Antifungal and Antioxidant Properties of some New 5-Substituted-4-amino(or aryl)-3-mercapto-4(H)-1,2,4-triazoles

New 4(1H)-Pyridinone Derivatives as Analgesic Agents

In vivo Evaluation of Substituted 3-Amino-1,4-benzodiazepines as Anti-depressant, Anxiolytic and Anti-nociceptive Agents