Synthesis and SAR of analogs of the M1 allosteric agonist TBPB. Part II: Amides, sulfonamides and ureas--the effect of capping the distal basic piperidine nitrogen.
This letter describes the further synthesis and SAR, developed through an iterative analog library approach, of analogs of the highly selective M1 allosteric agonist TBPB by deletion of the distal basic piperidine nitrogen by the formation of amides, sulfonamides and ureas. Despite the large change in basicity and topology, M1 selectivity was maintained.
Miller
Nicole R
NR
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Daniels
R Nathan
RN
Bridges
Thomas M
TM
Brady
Ashley E
AE
Conn
P Jeffrey
PJ
Lindsley
Craig W
CW
D000494:Allosteric Regulation; D000495:Allosteric Site; D000577:Amides / Q000737:chemistry*; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D008956:Models, Chemical; D009584:Nitrogen / Q000737:chemistry*; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry*; D043643:Receptor, Muscarinic M1 / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry*; D014508:Urea / Q000737:chemistry*
C532626:1-(1'-(2-methylbenzyl)-1,4'-bipiperidin-4-yl)-1H-benzo(d)imidazol-2-(3H)-one; D000577:Amides; D001562:Benzimidazoles; D010880:Piperidines; D043643:Receptor, Muscarinic M1; D013449:Sulfonamides; C032727:piperidine; D014508:Urea; D009584:Nitrogen