Biomaterial Database

Discovery of a series of aminopiperidines as novel iNOS inhibitors. 2008

Bertrand Le Bourdonnec, and Lara K Leister, and Christopher A Ajello, and Joel A Cassel, and Pamela R Seida, and Heather O'Hare, and Minghua Gu, and Guo-Hua Chu, and Paul A Tuthill, and Robert N DeHaven, and Roland E Dolle

Department of Chemistry, Adolor Corporation, 700 Pennsylvania Drive, Exton, PA 19341, USA. blebourdonnec@adolor.com

Nitric oxide (NO), a mediator of various physiological and pathophysiological processes, is synthesized by three isozymes of nitric oxide synthase (NOS). Potential candidate clinical drugs should be devoid of inhibitory activity against endothelial NOS (eNOS), since eNOS plays an important role in maintaining normal blood pressure and flow. A new series of aminopiperidines as potent inhibitors of iNOS were identified from a HTS lead. From this study, we identified compound 33 as a potent iNOS inhibitor, with >25-fold selectivity over eNOS and 16-fold selectivity over nNOS.

UI	MeSH Term	Description	Entries
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D010880	Piperidines	A family of hexahydropyridines.
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000588	Amines	A group of compounds derived from ammonia by substituting organic radicals for the hydrogens. (From Grant & Hackh's Chemical Dictionary, 5th ed)	Amine
D001665	Binding Sites	The parts of a macromolecule that directly participate in its specific combination with another molecule.	Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015195	Drug Design	The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include PHARMACOKINETICS, dosage analysis, or drug administration analysis.	Computer-Aided Drug Design,Computerized Drug Design,Drug Modeling,Pharmaceutical Design,Computer Aided Drug Design,Computer-Aided Drug Designs,Computerized Drug Designs,Design, Pharmaceutical,Drug Design, Computer-Aided,Drug Design, Computerized,Drug Designs,Drug Modelings,Pharmaceutical Designs
D052247	Nitric Oxide Synthase Type II	A CALCIUM-independent subtype of nitric oxide synthase that may play a role in immune function. It is an inducible enzyme whose expression is transcriptionally regulated by a variety of CYTOKINES.	INOS Enzyme,Inducible NOS Protein,Inducible Nitric Oxide Synthase,NOS-II,Nitric Oxide Synthase II,Nitric Oxide Synthase, Type II,NOS II
D052248	Nitric Oxide Synthase Type I	A CALCIUM-dependent, constitutively-expressed form of nitric oxide synthase found primarily in NERVE TISSUE.	NCNOS Enzyme,NOS1 Protein,Neural Constitutive Nitric Oxide Synthase,Neuronal Nitric Oxide Synthase,Nitric Oxide Synthase, Type I,nNOS Enzyme