化合物 T30502 | 170686-12-1

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 石蒜科生物碱
• 中文名称: 化合物 T30502
• 英文名称: BMS-194449
• 英文别名: (R)-N-[5-[2-[[bis-(4-difluoromethoxyphenyl)methyl]amino]-1-hydroxyethyl]-2-hydroxyphenyl]methanesulfonamide；Methanesulfonamide, N-(5-((1R)-2-((bis(4-(difluoromethoxy)phenyl)methyl)amino)-1-hydroxyethyl)-2-hydroxyphenyl)-；N-[5-[(1R)-2-[bis[4-(difluoromethoxy)phenyl]methylamino]-1-hydroxyethyl]-2-hydroxyphenyl]methanesulfonamide
• CAS: 170686-12-1
• 化学式: C₂₄H₂₄F₄N₂O₆S
• 分子量: 544.524
• InChiKey: FUKHGCVTMAEHRG-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  37
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  126
• 氢给体数：
  4
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  4,4'-二羟基二苯甲酮 在 palladium on activated charcoal 氟化铵 、 sodium hydroxide 、 氢气 、 羟胺 、 溶剂黄146 、 N,N-二异丙基乙胺 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 异丙醇 为溶剂， 生成 化合物 T30502
  参考文献：
  名称：

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

  摘要：

  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 beta (3) selectivity. SAR elucidation established that highly selective beta (3) agonists were generated upon substitution of C-alpha 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).(1) (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00628-x

文献信息

• Catecholamine surrogates useful as B3 agonists
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：EP0659737A2

  公开（公告）日：1995-06-28

  Compounds of the formula or pharmaceutically acceptable salts thereof wherein: A is a bond, -(CH2)n- or -CH(B)-, where n is an integer of 1 to 3 and B is -CN, -CON(R9)R9' or -C02R7; R1 is lower alkyl, aryl or arylalkyl; R2 is hydrogen, hydroxy, alkoxy, -CH20H, cyano, -C(O)OR7 , -C02H, -CONH2, tetrazole, -CH2NH2 or halogen; R3 is hydrogen, alkyl, heterocycle or R4 is hydrogen, alkyl or B; R5, R5', R8, R8' or R8'' are independently hydrogen, alkoxy, lower alkyl, halogen, -OH, -CN, -(CH2)-nNR6COR7, -CON(R6)R6', -CON(R6)OR6', -C02R6, -SR7, -SOR7, -S02R7, -N(R6)SO2R1, -N(R6)R6', -NR6COR7, -OCH2CON(R6)R6', -OCH2CO2R7 or aryl; or R5 and R5' or R8 and R8' may together with the carbon atoms to which they are attached form an aryl or heterocycle; R6 and R6' are independently hydrogen or lower alkyl; and R7 is lower alkyl; R9 is hydrogen, lower alkyl, alkyl, cycloalkyl, arylalkyl, aryl, heteroaryl; or R9 and R9' may together with the nitrogen atom to which they are attached form a hetocycle; with the proviso that when A is a bond or -(CH2)n and R3 is hydrogen or unsubstituted alkyl, then R4 is B or substituted alkyl. These compounds are beta3 adrenergic receptor agonists and are useful, therefore for example, in the treatment of diabetes, obesity and gastrointestinal diseases.

  式中的化合物 或其药学上可接受的盐类，其中 A 是键、-(CH2)n- 或 -CH(B)-，其中 n 是 1 至 3 的整数，B 是 -CN、-CON(R9)R9' 或 -C02R7； R1 是低级烷基、芳基或芳烷基； R2 是氢、羟基、烷氧基、- 0H、氰基、-C(O)OR7、-C02H、-CONH2、四唑、- NH2 或卤素； R3 是氢、烷基、杂环或卤素。 R4 是氢、烷基或 B； R5、R5'、R8、R8' 或 R8'' 独立地为氢、烷氧基、低级烷基、卤素、-OH、-CN、-( )-nNR6COR7、-CON(R6)R6'、-C02R6、-SR7、-SOR7、-S02R7、-N(R6)SO2R1、-N(R6)R6'、-NR6COR7、-O CON(R6)R6'、-O CO2R7 或芳基；或 R5 和 R5' 或 R8 和 R8'可与它们所连接的碳原子一起形成芳基或杂环； R6 和 R6'独立地为氢或低级烷基；以及 R7 是低级烷基； R9是氢、低级烷基、烷基、环烷基、芳烷基、芳基、杂芳基；或 R9和R9'可与它们所连接的氮原子一起形成一个杂环；但当A是键或-( )n且R3是氢或未取代的烷基时，则R4是B或取代的烷基。这些化合物是β3肾上腺素能受体激动剂，因此可用于治疗糖尿病、肥胖症和胃肠道疾病等。
• Catecholamine surrogates useful as beta 3 agonists
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：EP0659737B1

  公开（公告）日：2003-03-26