N-methoxy-N-methyl-2-[3-(2-pyridinyl)phenyl]acetamide | 215947-45-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: N-methoxy-N-methyl-2-[3-(2-pyridinyl)phenyl]acetamide
• 英文别名: N-methyl-N-methoxy-3-(2-pyridyl)-phenylacetamide；N-methoxy-N-methyl-2-(3-pyridin-2-ylphenyl)acetamide
• CAS: 215947-45-8
• 化学式: C₁₅H₁₆N₂O₂
• 分子量: 256.304
• InChiKey: KRQUXJURVLBBJR-UHFFFAOYSA-N

物化性质

• 沸点：
  386.5±44.0 °C(predicted)
• 密度：
  1.141±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  42.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-methoxy-N-methyl-2-[3-(2-pyridinyl)phenyl]acetamide 在 正丁基锂 、 sodium hydride 作用下， 以 四氢呋喃 、 正己烷 、 甲苯 、 mineral oil 为溶剂， 反应 6.5h， 生成
  参考文献：
  名称：

  Synthesis and evaluation of γ-lactam analogs of PGE2 as EP4 and EP2/EP4 agonists

  摘要：

  To identify topically effective EP4 agonists and EP2/EP4 dual agonists with excellent subtype selectivity, further optimization of the 16-phenyl omega-chain moiety of the gamma-lactam 5-thia prostaglandin E analog and the 2-mercaptothiazole-4-carboxylic acid analog were undertaken. Rat in vivo evaluation of these newly identified compounds as their poly (lactide-co-glycolide) microsphere formulation, from which sustained release of the test compound is possible, led us to discover compounds that showed efficacy in a rat bone fracture healing model after its topical administration without serious influence on blood pressure and heart rate. A structure-activity relationship study is also presented. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.04.008
• 作为产物：
  描述：

  3-羟基苯乙酸 在 吡啶 、 potassium phosphate 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 乙二醇二甲醚 、 二氯甲烷 、 乙腈 为溶剂， 反应 36.25h， 生成 N-methoxy-N-methyl-2-[3-(2-pyridinyl)phenyl]acetamide
  参考文献：
  名称：

  Synthesis and evaluation of γ-lactam analogs of PGE2 as EP4 and EP2/EP4 agonists

  摘要：

  To identify topically effective EP4 agonists and EP2/EP4 dual agonists with excellent subtype selectivity, further optimization of the 16-phenyl omega-chain moiety of the gamma-lactam 5-thia prostaglandin E analog and the 2-mercaptothiazole-4-carboxylic acid analog were undertaken. Rat in vivo evaluation of these newly identified compounds as their poly (lactide-co-glycolide) microsphere formulation, from which sustained release of the test compound is possible, led us to discover compounds that showed efficacy in a rat bone fracture healing model after its topical administration without serious influence on blood pressure and heart rate. A structure-activity relationship study is also presented. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.04.008

文献信息

• Protease inhibitors
  申请人：SmithKline Beecham Corporation

  公开号：US06369077B1

  公开（公告）日：2002-04-09

  This invention relates to compounds of formula (I): wherein: Y is Ar or NR1R2; R1 is R″, R″C(O), R″C(S), R″SO2, R″OC(O), R″R′NC(O), or R″R′NC(S); R2 is H, C1-6alkyl, C2-6alkenyl, Ar-C0-6alkyl, or Het-C0-6alkyl; R3 is H, C2-6alkenyl, C2-6alkynyl, Het, Ar or C1-6alkyl optionally substituted by OR′, SR′, NR′2, N(R′)C(O)OR″, CO2R′, CO2NR′2, N(C═NH)NH2, Het or Ar; R4 is H, C1-6alkyl, C2-6alkenyl, Ar-C0-6alkyl, or Het-C0-6alkyl; R5 is  Ar-C0-6alkyl, Het-C0-6alkyl, adamantyl-C(O)—, Ar-C(O)—, Het-C(O)— or; R6 is R″, R″C(O), R″C(S), R″SO2, R″OC(O), R″R′NC(O), R″R′NC(S), or R″OC(O)NR′CH(R*)C(O); R7 is C3-6cycloalkyl-C0-6alkyl, Ar-C0-6alkyl, Het-C0-6alkyl, Ar-C0-6alkoxy, Het-C0-6alkoxy, or C1-6alkyl optionally substituted by OR′, SR′, NR′2, N(R′)C(O)OR″, CO2R′, CO2NR′2, N(C═NH)NH2, Het or Ar; R* is H, C1-6alkyl, C2-6alkenyl, C3-6cycloalkyl-C0-6-alkyl, Ar-C0-6alkyl, Het-C0-6alkyl; each R′ independently is H, C1-6alkyl, C2-6alkenyl, Ar-C0-6alkyl, or Het-C0-6alkyl; each R″ independently is C1-6alkyl, C3-6cycloalkyl-C0-6-alkyl, Ar-C0-6alkyl, or Het-C0-6alkyl; R′″ is H, C1-6alkyl, C3-6cycloalkyl-C0-6alkyl, Ar-C0-6alkyl, or Het-C0-6alkyl; Z is C(O) or CH2; and n is 1, 2 or 3; or a pharmaceutically acceptable salt thereof, which are inhibitors of cysteine proteases, particularly cathepsin K, and are useful in the treatment of diseases in which inhibition of bone loss is a factor.

  本发明涉及式（I）的化合物：其中：Y是Ar或NR1R2；R1是R″，R″C（O），R″C（S），R″SO2，R″OC（O），R″R′NC（O）或R″R′NC（S）；R2是H，C1-6烷基，C2-6烯基，Ar-C0-6烷基或Het-C0-6烷基；R3是H，C2-6烯基，C2-6炔基，Het，Ar或C1-6烷基，可选地被OR′，SR′，NR′2，N（R′）C（O）OR″，CO2R′，CO2NR′2，N（C═NH）NH2，Het或Ar取代；R4是H，C1-6烷基，C2-6烯基，Ar-C0-6烷基或Het-C0-6烷基；R5是Ar-C0-6烷基，Het-C0-6烷基，金刚烷基-C（O）—，Ar-C（O）—，Het-C（O）—或；R6是R″，R″C（O），R″C（S），R″SO2，R″OC（O），R″R′NC（O），R″R′NC（S）或R″OC（O）NR′CH（R*）C（O）；R7是C3-6环烷基-C0-6烷基，Ar-C0-6烷基，Het-C0-6烷基，Ar-C0-6烷氧基，Het-C0-6烷氧基或C1-6烷基，可选地被OR′，SR′，NR′2，N（R′）C（O）OR″，CO2R′，CO2NR′2，N（C═NH）NH2，Het或Ar取代；R*是H，C1-6烷基，C2-6烯基，C3-6环烷基-C0-6-烷基，Ar-C0-6烷基或Het-C0-6烷基；每个R′独立地是H，C1-6烷基，C2-6烯基，Ar-C0-6烷基或Het-C0-6烷基；每个R″独立地是C1-6烷基，C3-6环烷基-C0-6-烷基，Ar-C0-6烷基或Het-C0-6烷基；R′″是H，C1-6烷基，C3-6环烷基-C0-6烷基，Ar-C0-6烷基或Het-C0-6烷基；Z是C（O）或CH2；n为1、2或3；或其药学上可接受的盐，它们是半胱氨酸蛋白酶的抑制剂，特别是卡特普西 K，并且在抑制骨质流失是一个因素的疾病的治疗中有用。
• US6369077B1
  申请人：——

  公开号：US6369077B1

  公开（公告）日：2002-04-09
• Synthesis and evaluation of γ-lactam analogs of PGE2 as EP4 and EP2/EP4 agonists
  作者：Tohru Kambe、Toru Maruyama、Yoshihiko Nakai、Hiroji Oida、Takayuki Maruyama、Nobutaka Abe、Akio Nishiura、Hisao Nakai、Masaaki Toda

  DOI：10.1016/j.bmc.2012.04.008

  日期：2012.6

  To identify topically effective EP4 agonists and EP2/EP4 dual agonists with excellent subtype selectivity, further optimization of the 16-phenyl omega-chain moiety of the gamma-lactam 5-thia prostaglandin E analog and the 2-mercaptothiazole-4-carboxylic acid analog were undertaken. Rat in vivo evaluation of these newly identified compounds as their poly (lactide-co-glycolide) microsphere formulation, from which sustained release of the test compound is possible, led us to discover compounds that showed efficacy in a rat bone fracture healing model after its topical administration without serious influence on blood pressure and heart rate. A structure-activity relationship study is also presented. (C) 2012 Elsevier Ltd. All rights reserved.