Diphenyl sulfoxides as selective antagonists of the muscarinic M2 receptor.
Structure activity studies on [4-(phenylsulfonyl)phenyl]methylpiperazine led to the discovery of 4-cyclohexyl-alpha-[4-[[4-methoxyphenyl(S)-sufinyl]phenyl]-1-pi perazineacetonitrile, 1, an M2 selective muscarinic antagonist. Affinity at the cloned human M2 receptor was 2.7 nM; the M1/M2 selectivity is 40-fold.
Kozlowski
J A
JA
Schering-Plough Research Institute, Kenilworth, NJ 07033-0539, USA. joseph.kozlowski@spcorp.com
Lowe
D B
DB
Guzik
H S
HS
Zhou
G
G
Ruperto
V B
VB
Duffy
R A
RA
McQuade
R
R
Crosby
G
G
Taylor
L A
LA
Billard
W
W
Binch
H
H
Lachowicz
J E
JE
D000109:Acetylcholine / Q000378:metabolism; D000284:Administration, Oral; D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001555:Benzene Derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003984:Dibenzazepines / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D005663:Furans; D006801:Humans; D018727:Muscarinic Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009281:Naphthalenes; D010880:Piperidines; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000502:physiology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
D000470:Alkaloids; D001555:Benzene Derivatives; D003984:Dibenzazepines; D005663:Furans; D018727:Muscarinic Antagonists; D009281:Naphthalenes; D010880:Piperidines; D011725:Pyridines; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D011994:Recombinant Proteins; C079888:BIBN 99; C048860:diphenyl sulfoxide; C048172:himbacine; D000109:Acetylcholine