Disubstituted 1-aryl-4-aminopiperidine library synthesis using computational drug design and high-throughput batch and flow technologies.
A platform that incorporates computational library design, parallel solution-phase synthesis, continuous flow hydrogenation, and automated high throughput purification and reformatting technologies was applied to the production of a 120-member library of 1-aryl-4-aminopiperidine analogues for drug discovery screening. The application described herein demonstrates the advantages of computational library design coupled with a flexible, modular approach to library synthesis. The enabling technologies described can be readily adopted by the traditional medicinal chemist without extensive training and lengthy process development times.
Medicinal Chemistry Research Technologies, ‡Molecular Structure and Characterization, and §Pharmacokinetics and Drug Metabolism, Therapeutic Discovery, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.
Marian C
MC
Bryan
Christopher D
CD
Hein
Hua
H
Gao
Xiaoyang
X
Xia
Heather
H
Eastwood
Bernd A
BA
Bruenner
Steven W
SW
Louie
Elizabeth M
EM
Doherty
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D000465:Algorithms; D000818:Animals; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects* / Q000502:physiology; D015195:Drug Design; D057166:High-Throughput Screening Assays; D006801:Humans; D008861:Microsomes / Q000737:chemistry / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012995:Solubility; D013552:Swine
C481395:4-aminopiperidine; C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D010880:Piperidines; D054852:Small Molecule Libraries