14347-25-2Relevant articles and documents
Development of an enabling route to PF-00610355: A novel inhaled β2-adrenoreceptor agonist
De Koning, Pieter D.,Gladwell, Iain R.,Moses, Ian B.,Panesar, Maninder S.,Pettman, Alan J.,Thomson, Nicholas M.
experimental part, p. 1247 - 1255 (2012/01/19)
The initial route used to prepare PF-00610355 (8) for early clinical development is described. Through careful choice of solvent, an efficient, telescoped route to carboxylic acid 23 was developed, affording this late-stage intermediate in 80% yield over 4 steps. Deprotection of 23 to give sodium salt 24a and coupling with amine 6·HCl afforded the desired API. Effective synthetic routes to two of the starting materials, chiral bromide 1 and amine 6, are also described.
4-Aminopiperidine ureas as potent selective agonists of the human β3-Adrenergic receptor
Ashwell, Mark A,Solvibile Jr., William R,Han, Stella,Largis, Elwood,Mulvey, Ruth,Tillet, Jeffrey
, p. 3123 - 3127 (2007/10/03)
The preparation and structure-activity relationships (SARs) of potent agonists of the human β3-adrenergic receptor (AR) derived from a 4-aminopiperidine scaffold are described. Examples combine human β3-AR potency with selectivity over human β1-AR and/or human β2-AR agonism. Compound 29s was identified as a potent (EC50 = 1 nM) and selective (greater than 400-fold over β1- with no β2-AR agonism) full β3-AR agonist with in vivo activity in a transgenic mouse model of thermogenesis.
Catecholamine surrogates useful as β3 agonists
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, (2008/06/13)
Compounds of the formula STR1 or pharmaceutically acceptable salts thereof wherein: A is a bond, --(CH 2) n -- or --CH(B)--, where n is an integer of 1 to 3 and B is --CN, --CON(R 9)R 9'' or --CO 2 R 7 ;R 1 is lower alkyl, aryl or arylalkyl;R 2 is hydrogen, hydroxy, alkoxy, --CH 2 OH, cyano, --C(O)OR 7, --CO 2 H, --CONH 2, tetrazole, --CH 2 NH 2 or halogen; STR2 R 3 is hydrogen, alkyl, heterocycle or R 4 is hydrogen, alkyl or B;R 5, R 5'', R 8, R 8'' or R 8"" are independently hydrogen, alkoxy, lower alkyl, halogen, --OH, --CN, --(CH 2) n NR 6 COR 7, --CON(R 6)R 6'', --CON(R 6)OR 6'', --CO 2 R 6, --SR 7, --SOR 7, --SO 2 R 7, --N(R 6)SO 2 R 1, --N(R 6)R 6'', --NR 6 COR 7, --OCH 2 CON(R 6)R 6'', --OCH 2 CO 2 R 7 or aryl; orR 5 and R 5'' or R 8 and R 8'' may together with the carbon atoms to which they are attached form an aryl or heterocycle;R 6 and R 6'' are independently hydrogen or lower alkyl; andR 7 is lower alkyl;R 9 is hydrogen, lower alkyl, alkyl, cycloalkyl, arylalkyl, aryl, heteroaryl; or R 9 and R 9'' may together with the nitrogen atom to which they are attached form a heterocycle; with the proviso that when A is a bond or --(CH 2) n and R 3 is hydrogen or unsubstituted alkyl, then R 4 is B or substituted alkyl. These compounds are beta 3 adrenergic receptor agonists and are useful, therefore for example, in the treatment of diabetes, obesity and gastrointestinal diseases.
