Synthesis and structure-activity relationship of some 5-[[[(dialkylamino)alkyl]-1-piperidinyl]acetyl]-10,11-dihydro-5H- benzo[b,e][1,4]diazepin-11-ones as M2-selective antimuscarinics.
A series of 5-[[[(dialkylamino)alkyl]-1-piperidinyl]acetyl]- 10,11-dihydro-5H-dibenzo[b,e][1,4]-diazepin-11-ones were prepared as potential M2-selective ligands. The compounds were evaluated for their affinity and selectivity for the muscarinic cholinergic receptor. The best M2-selective antimuscarinic agent studied is 5-[[4-[4-diethylamino)butyl]-1- piperidinyl]acetyl]-10,11-dihydro-5H-dibenzo[b,e][1,4]diazepin-11- one, which is approximately 10 times more potent at M2 receptors than previously known compounds such as 11-[[4-[4-(diethylamino)butyl]- 1-piperidinyl]acetyl]-5,11-dihydro-6H- pyrido[2,3-b][1,4]benzodiazepin-6-one (AQ-RA 741).
Cohen
V I
VI
Section of Radiopharmaceutical Chemistry, George Washington University Medical Center, Washington, D.C. 20037.
Baumgold
J
J
Jin
B
B
De La Cruz
R
R
Rzeszotarski
W J
WJ
Reba
R C
RC
D000818:Animals; D001570:Benzodiazepinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010276:Parasympatholytics / Q000138:chemical synthesis*; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship
D001570:Benzodiazepinones; D010276:Parasympatholytics; D010880:Piperidines; D011976:Receptors, Muscarinic; C069054:AQ-RA 741; C077351:5-((4-(4-(diethylamino)butyl)-1-piperidinyl)acetyl)-10,11-dihydrobenzo(b,e)(1,4)diazepine-11-one; D010890:Pirenzepine; C048593:otenzepad