246262-39-5

Upstream product

• 994-30-9 triethylsilyl chloride 
• 170687-75-9 (R)-2-iodo-1-[4-(phenylmethoxy)-3-[(methylsulfonyl)amino]phenyl]ethanol 
• 288-32-4 1H-imidazole 
• 7732-18-5 water 
• 170687-82-8 N-{2-(benzyloxy)-5-[(1R)-2-bromo-1-hydroxyethyl]phenyl}methane sulfonamide 

Downstream Products

• 170688-90-1 N-{2-Benzyloxy-5-[(R)-2-((R)-1-naphthalen-1-yl-2-phenyl-ethylamino)-1-triethylsilanyloxy-ethyl]-phenyl}-methanesulfonamide 
• 639083-01-5 2-(3-{(2R)-2-[2-(4-benzyloxy-3-methanesulfonylaminophenyl)-(2R)-2-hydroxyethylamino]propyl}-1H-indol-7-yloxy)-N,N-diethylacetamide 
• 639083-38-8 3-{(2R)-2-[2-(4-benzyloxy-3-methanesulfonylaminophenyl)-(2R)-2-(triethylsilyloxy)ethylamino]propyl}-1H-indole-6-carboxylic acid diethylamide 
• 340756-75-4 N-[5-((1R)-2-amino-1-hydroxy-ethyl)-2-hydroxy-phenyl]-methanesulfonamide 
• 300345-78-2 N-[2-benzyloxy-5-(2-amino-(1R)-1-hydroxy-ethyl)-phenyl]-methanesulfonamide 
• 246261-44-9 N-[2-benzyloxy-5-[(1R)-1-hydroxy-2-(3-methoxy-6,7,8,9-tetrahydro-5H-benzo-cyclohepten-6-ylamino)ethyl]phenyl]methanesulfonamide 
• 259799-15-0 N-[2-benzyloxy-5-[(1R)-2-[(1S)-3,3-bis(4-methoxyphenyl)-1-methylpropyl]-amino-1-hydroxyethyl]phenyl]methanesulfonamide 
• 259799-55-8 N-[5-[(1R)-2-[N-benzyl-[(1RS)-3,3-bis(4-methoxyphenyl)-1-methylpropyl]amino]-1-(triethylsilyloxy)-ethyl]-2-(benzyloxy)phenyl]methanesulfonamide 
• 259798-72-6 (1R)-1-[4-benzyloxy-3-(methanesulfonylamino)phenyl]-2-[3,3-bis(4-methoxyphenyl)-propyl]aminoethanol 
• 851336-70-4 ethyl 4'-{(R)-2-[(R)-2-(4-benzyloxy-3-methanesulfonylaminophenyl)-2-triethylsilanyloxyethyl-amino]propyloxy}biphenyl-4-carboxylate 

Relevant academic research and scientific papers

INDOLE, INDAZOLE, AND BENZAZOLE DERIVATIVE

The compound of the formula (I): wherein W is a group of the following formula (VIII) binding to any possible position on the Q: Q is, together with W, a group of the formula: -C(M=C(R3A)-N(R3)-, etc.; R3A is H or optionally substituted lower alkyl; R4, R5, R6, and R7 are independently H or optionally substituted lower alkyl; R1 is optionally substituted lower alkyl, etc.; R2 is H, etc.; R3 is H, etc.; Ar is phenyl, etc., or a pharmaceutically acceptable salt thereof, where these compounds exhibiting β3-adrenoceptor-stimulating activity and being useful as a medicament for treatment of obesity, etc.

Beta 3 agonists. Part 1: Evolution from inception to BMS-194449

Screening of the BMS collection identified 4-hydroxy-3-methylsulfonanilidoethanolamines as full beta 3 agonists. Substitution of the ethanolamine nitrogen with a benzyl group bearing a para hydrogen bond acceptor promoted β3 selectivity. SAR elucidation established that highly selective β3 agonists were generated upon substitution of Cα with either benzyl to form (R)-1,2-diarylethylamines or with aryl to generate 1,1-diarylmethylamines. This latter subset yielded a clinical candidate, BMS-194449 (35).

Catecholamine surrogates useful as β3 agonists

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.