Heterocyclic aminopyrrolidine derivatives as melatoninergic agents.
A series of chiral heterocyclic aminopyrrolidine derivatives was synthesized as novel melatoninergic ligands. Binding affinity assays were performed on cloned human MT(1) and MT(2) receptors, stably expressed in NIH3T3 cells. Compound 16 was identified as an orally bioavailable agonist at MT(1) and MT(2) melatonin receptors with low vasoconstrictive activity.
Sun
Li-Qiang
LQ
Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA. sunl@bms.com
Chen
Jie
J
Mattson
Ronald J
RJ
Epperson
James R
JR
Deskus
Jeffrey A
JA
Li
Wen Sen
WS
Takaki
Katherine
K
Hodges
Donald B
DB
Iben
Lawrence
L
Mahle
Cathy D
CD
Ortiz
Astrid
A
Molstad
David
D
Ryan
Elaine
E
Yeleswaram
Krishnaswamy
K
Xu
Cen
C
Luo
Guanglin
G
D016475:3T3 Cells; D000634:Aminoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D003001:Cloning, Molecular; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008550:Melatonin / Q000819:agonists* / Q000494:pharmacology; D051379:Mice; D044122:Receptor, Melatonin, MT1 / Q000187:drug effects / Q000378:metabolism; D044123:Receptor, Melatonin, MT2 / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship
D000634:Aminoquinolines; D006571:Heterocyclic Compounds; D008024:Ligands; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D011994:Recombinant Proteins; D005576:Colforsin; D000242:Cyclic AMP; D008550:Melatonin