725233-19-2Relevant articles and documents
HETEROCYCLIC COMPOUNDS CONTAINING A PYRROLOPYRIDINE OR BENZIMIDAZOLE CORE
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Page/Page column 68-69, (2011/06/26)
The present invention relates to compounds of Formula (I) and pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5 and n are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.
Synthesis and structure-activity studies on N-[5-(1H-imidazol-4-yl)-5,6,7,8-tetrahydro-1-naphthalenyl]methanesulfonamide, an imidazole-containing α1A-adrenoceptor agonist
Altenbach, Robert J.,Khilevich, Albert,Kolasa, Teodozyj,Rohde, Jeffrey J.,Bhatia, Pramila A.,Patel, Meena V.,Searle, Xenia B.,Yang, Fan,Bunnelle, William H.,Tietje, Karin,Bayburt, Erol K.,Carroll, William A.,Meyer, Michael D.,Henry, Rodger,Buckner, Steven A.,Kuk, Jane,Daza, Anthony V.,Milicic, Ivan V.,Cain, John C.,Kang, Chae H.,Ireland, Lynne M.,Carr, Tracy L.,Miller, Thomas R.,Hancock, Arthur A.,Nakane, Masaki,Esbenshade, Timothy A.,Brune, Michael E.,O'Neill, Alyssa B.,Gauvin, Donna M.,Katwala, Sweta P.,Holladay, Mark W.,Brioni, Jorge D.,Sullivan, James P.
, p. 3220 - 3235 (2007/10/03)
Structure-activity studies were performed on the α 1A-adrenoceptor (AR) selective agonist N-[5-(1H-imidazol-4-yl)-5,6,7,8-tetrahydro-1-naphthalenyl]methanesulfonamide (4). Compounds were evaluated for binding activity at the α1A, α1b, α1d, α2a, and α2B subtypes. Functional activity in tissues containing the α1A (rabbit urethra), α1B (rat spleen), α1D (rat aorta), and α2A (rat prostatic vas deferens) was also evaluated. A dog in vivo model simultaneously measuring intraurethral pressure (IUP) and mean arterial pressure (MAP) was used to assess the uroselectivity of the compounds. Many of the compounds that were highly selective in vitro for the α1A-AR subtype were also more uroselective in vivo for increasing IUP over MAP than the nonselective α1-agonists phenylpropanolamine (PPA) (1) and ST-1059 (2, the active metabolite of midodrine), supporting the hypothesis that greater α1A selectivity would reduce cardiovascular side effects. However, the data also support a prominent role of the α1A-AR subtype in the control of MAP.