tert-butyl 4-((3-bromo-2-chloropyridin-4-ylamino)methyl)-5,6-dihydropyridine-1(2H)-carboxylate | 857730-22-4

• 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: tert-butyl 4-((3-bromo-2-chloropyridin-4-ylamino)methyl)-5,6-dihydropyridine-1(2H)-carboxylate
• 英文别名: 4-[(3-bromo-2-chloro-pyridin-4-ylamino)-methyl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester；4-[(3-Bromo-2-chloro-pyridin-4-ylamino)-methyl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester；tert-butyl 4-[[(3-bromo-2-chloropyridin-4-yl)amino]methyl]-3,6-dihydro-2H-pyridine-1-carboxylate
• CAS: 857730-22-4
• 化学式: C₁₆H₂₁BrClN₃O₂
• 分子量: 402.719
• InChiKey: FXVMHULTOXVPSY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  54.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-((3-bromo-2-chloropyridin-4-ylamino)methyl)-5,6-dihydropyridine-1(2H)-carboxylate 在 4-二甲氨基吡啶 、 四丁基溴化铵 、 palladium diacetate 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 为溶剂， 反应 24.0h， 生成 tert-butyl 4'-chloro-1',2,2',3-tetrahydro-1H-spiro[pyridine-4,3'-pyrrolo[3,2-c]pyridine]-1-carboxylate
  参考文献：
  名称：

  Conformationally Constrained ortho-Anilino Diaryl Ureas: Discovery of 1-(2-(1′-Neopentylspiro[indoline-3,4′-piperidine]-1-yl)phenyl)-3-(4-(trifluoromethoxy)phenyl)urea, a Potent, Selective, and Bioavailable P2Y₁ Antagonist

  摘要：

  Preclinical antithrombotic efficacy and bleeding models have demonstrated that P2Y(1) antagonists are efficacious as antiplatelet agents and may offer a safety advantage over P2Y(12) antagonists in terms of reduced bleeding liabilities. In this article, we describe the structural modification of the tert-butyl phenoxy portion of lead compound 1 and the subsequent discovery of a novel series of conformationally constrained ortho-anilino diaryl ureas. In particular, spiropiperidine indoline-substituted diaryl ureas are described as potent, orally bioavailable small-molecule P2Y(1) antagonists with improved activity in functional assays and improved oral bioavailability in rats. Homology modeling and rat PK/PD studies on benchmark compound 31 will also be presented. Compound 31 was our first P2Y(1) antagonist to demonstrate a robust oral antithrombotic effect with mild bleeding liability in the rat thrombosis and hemostasis models.

  DOI：

  10.1021/jm4013906
• 作为产物：
  描述：

  N-Boc-4-(羟甲基)-1,2,3,6-四氢吡啶 在 2,6-二甲基吡啶 、 氯化亚砜 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 41.0h， 生成 tert-butyl 4-((3-bromo-2-chloropyridin-4-ylamino)methyl)-5,6-dihydropyridine-1(2H)-carboxylate
  参考文献：
  名称：

  Conformationally Constrained ortho-Anilino Diaryl Ureas: Discovery of 1-(2-(1′-Neopentylspiro[indoline-3,4′-piperidine]-1-yl)phenyl)-3-(4-(trifluoromethoxy)phenyl)urea, a Potent, Selective, and Bioavailable P2Y₁ Antagonist

  摘要：

  Preclinical antithrombotic efficacy and bleeding models have demonstrated that P2Y(1) antagonists are efficacious as antiplatelet agents and may offer a safety advantage over P2Y(12) antagonists in terms of reduced bleeding liabilities. In this article, we describe the structural modification of the tert-butyl phenoxy portion of lead compound 1 and the subsequent discovery of a novel series of conformationally constrained ortho-anilino diaryl ureas. In particular, spiropiperidine indoline-substituted diaryl ureas are described as potent, orally bioavailable small-molecule P2Y(1) antagonists with improved activity in functional assays and improved oral bioavailability in rats. Homology modeling and rat PK/PD studies on benchmark compound 31 will also be presented. Compound 31 was our first P2Y(1) antagonist to demonstrate a robust oral antithrombotic effect with mild bleeding liability in the rat thrombosis and hemostasis models.

  DOI：

  10.1021/jm4013906

文献信息

• [EN] SPIROPIPERIDINE DERIVATIVES FOR CONTROLLING PESTS<br/>[FR] DÉRIVÉS DE SPIROPIPÉRIDINE POUR LUTTER CONTRE LES NUISIBLES
  申请人：SYNGENTA PARTICIPATIONS AG

  公开号：WO2005061500A1

  公开（公告）日：2005-07-07

  The use of a compound of Formula (I), Y is a single bond, C=O, C=S or S(O)m where m is 0, 1 or 2; the ring represented by T is a 5 or 6 membered heteroaromatic and R1, R2, R3, R8 and Ra are specified organic groups and p is 0, 1, 2, 3, 4, 5 or 6; p+q is 1, 2, 3, 4, 5 or 6; or salts or N-oxides thereof or compositions containing them in controlling insects, acarines, nematodes or molluscs; novel compounds are also provided.

  使用Formula（I）中的化合物，其中Y是单键，C=O，C=S或S（O）m，其中m为0、1或2；T表示的环是5或6个成员的杂芳族，R1、R2、R3、R8和Ra是指定的有机基团，p为0、1、2、3、4、5或6；p+q为1、2、3、4、5或6；或其盐或N-氧化物或含有它们的组合物在控制昆虫、螨虫、线虫或软体动物方面；还提供了新化合物。
• Spiropiperidine derivatives for controlling pests
  申请人：Cassayre Jerome

  公开号：US20070135408A1

  公开（公告）日：2007-06-14

  The use of a compound of Formula (I), Y is a single bond, C═O, C═S or S(O)m where m is 0, 1 or 2; the ring represented by T is a 5 or 6 membered heteroaromatic and R 1 , R 2 , R 3 , R 8 and Ra are specified organic groups and p is 0, 1, 2, 3, 4, 5 or 6; p+q is 1, 2, 3, 4, 5 or 6; or salts or N-oxides thereof or compositions containing them in controlling insects, acarines, nematodes or molluscs; novel compounds are also provided.

  使用式（I）化合物，其中Y为单键，C═O，C═S或S（O）m，其中m为0、1或2；所表示的环T为5或6成员的杂环芳香族，并且R1、R2、R3、R8和Ra是指定的有机基团，p为0、1、2、3、4、5或6；p+q为1、2、3、4、5或6；或其盐或N-氧化物或含有它们的组合物，在控制昆虫、螨、线虫或软体动物方面提供了新的化合物。
• SPIROPIPERIDINE DERIVATIVES FOR CONTROLLING PESTS
  申请人：Syngenta Participations AG

  公开号：EP1694677A1

  公开（公告）日：2006-08-30
• US7960401B2
  申请人：——

  公开号：US7960401B2

  公开（公告）日：2011-06-14