ethyl α-(3-chloro-4-aminophenyl)-propionate | 26406-97-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl α-(3-chloro-4-aminophenyl)-propionate
• 英文别名: ethyl 2-(4-amino-3-chlorophenyl)propionate；ethyl α-(4-amino-3-chlorophenyl)-propionate；ethyl α-(4-amino-3-chlorophenyl)propionate；ethyl alpha-(3-chloro-4-aminophenyl)-propionate；α-(4-Amino-3-chlorphenyl)-propionsaeureaethylester；ethyl 2-(4-amino-3-chlorophenyl)propanoate
• CAS: 26406-97-3
• 化学式: C₁₁H₁₄ClNO₂
• 分子量: 227.691
• InChiKey: WPTJMBKBIFEFTA-UHFFFAOYSA-N

物化性质

• 溶解度：
  可溶于氯仿、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl α-(3-chloro-4-aminophenyl)-propionate 在 吡啶 、 lithium hydroxide monohydrate 、 1-羟基苯并三唑 、 1,2-二氯乙烷 、 三乙胺 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 2-[3-chloro-4-(methanesulfonamido)phenyl]-N-[[2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl]methyl]propanamide
  参考文献：
  名称：

  Discovery of 2-(3,5-difluoro-4-methylsulfonaminophenyl)propanamides as potent TRPV1 antagonists

  摘要：

  A series of A-region analogues of 2-(3-fluoro-4-methylsufonamidophenyl)propanamide 1 were investigated as TRPV1 antagonists. The analysis of structure-activity relationship indicated that a fluoro group at the 3-(or/and) 5-position and a methylsulfonamido group at the 4-position were optimal for antagonism of TRPV1 activation by capsaicin. The most potent antagonist 6 not only exhibited potent antagonism of activation of hTRPV1 by capsaicin, low pH and elevated temperature but also displayed highly potent antagonism of activation of rTRPV1 by capsaicin. Further studies demonstrated that antagonist 6 blocked the hypothermic effect of capsaicin in vivo, consistent with its in vitro mechanism, and it showed promising analgesic activity in the formalin animal model.

  DOI：

  10.1016/j.bmcl.2018.05.043
• 作为产物：
  描述：

  2-氯丙酸乙酯 在 potassium tert-butylate 、 铁粉 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.19h， 生成 ethyl α-(3-chloro-4-aminophenyl)-propionate
  参考文献：
  名称：

  N-4-t-Butylbenzyl 2-(4-methylsulfonylaminophenyl) propanamide TRPV1 antagonists: Structure–activity relationships in the A-region

  摘要：

  Structure-activity relationships for the A-region in a series of N-4-t-butylbenzyl 2-(4-methylsulfonylaminophenyl) propanamides as TRPV1 antagonists have been investigated. Among them, the 3-fluoro analogue 54 showed high binding affinity and potent antagonism for both rTRPV1 and hTRPV1 in CHO cells. Its stereospecific activity was demonstrated with marked selectivity for the (S)-configuration (54S versus 54R). A docking study of 54S with our hTRPV1 homology model highlighted crucial hydrogen bonds between the ligand and the receptor contributing to its potency. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.11.008

文献信息

• Tertiary aminoacids
  申请人：Ciba-Geigy Corporation

  公开号：US03997669A1

  公开（公告）日：1976-12-14

  New .alpha.-(cyclic tert. aminophenyl)-aliphatic acids, e.g. those of the formula ##STR1## AND FUNCTIONAL DERIVATIVES THEREOF, ARE ANTI-INFLAMMATORY AGENTS.

  新的.alpha.-(环状叔丁基氨基苯基)-脂肪酸，例如式##STR1##及其功能衍生物，是抗炎药物。
• 1,2 Dihydro- and 1,2,3,4-tetrahydro quinolylacetic acids and analgesic
  申请人：Nippon Zoki Pharmaceutical Co.

  公开号：US04555513A1

  公开（公告）日：1985-11-26

  Novel quinolylacetic acid compounds of the formula (I): ##STR1## wherein R.sub.1 is a member selected from the group consisting of hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, and a lower alkyl group having 1 to 4 carbon atoms substituted with an aromatic group having a substituent; R.sub.2 is a member selected from the group consisting of hydrogen atom and a lower alkyl group having 1 to 4 carbon atoms; R.sub.3 is a member selected from the group consisting of hydrogen, a halogen atom, an alkyl group having 1 to 8 carbon atoms, and an alkenyl group having 2 to 8 carbon atoms; R.sub.4 and R.sub.5, carpable of cyclization, are each a member selected from the group consisting of hydrogen atom and a lower alkyl group having 1 to 4 carbon atoms; R.sub.6 is a member selected from the group consisting of hydrogen atom an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 5 carbon atoms, an alkynyl group having 3 to 8 carbon atoms, an aralkyl group, a substituted aralkyl group, an aliphatic or aromatic acyl group, and a substituted aliphatic or aromatic acyl group; and A is a member selected from the group consisting of hydrogen atom and an oxo group; the broken line denoting a second bond or no bond when A is a hydrogen atom and denoting no bond when A is an oxo group, and pharmaceutically acceptable salts thereof.

  化合物的结构式 (I)：##STR1## 其中 R.sub.1 是从氢原子、具有 1 到 4 个碳原子的较低烷基基团，以及具有取代基的芳基的 1 到 4 个碳原子的较低烷基基团中选择的成员；R.sub.2 是从氢原子和具有 1 到 4 个碳原子的较低烷基基团中选择的成员；R.sub.3 是从氢、卤素原子、具有 1 到 8 个碳原子的烷基基团和具有 2 到 8 个碳原子的烯基基团中选择的成员；R.sub.4 和 R.sub.5，可进行环化，分别是从氢原子和具有 1 到 4 个碳原子的较低烷基基团中选择的成员；R.sub.6 是从氢原子、具有 1 到 8 个碳原子的烷基基团、具有 2 到 5 个碳原子的烯基基团、具有 3 到 8 个碳原子的炔基基团、芳基烷基基团、取代芳基烷基基团、脂肪或芳香族酰基团以及取代脂肪或芳香族酰基团中选择的成员；A 是从氢原子和氧代基中选择的成员；断线表示第二键或当 A 是氢原子时无键，并且当 A 是氧代基时表示无键，以及其药用盐。
• Certain pyrrolylphenyl-substituted hydroxamic acid derivatives
  申请人：CIBA-GEIGY AG

  公开号：EP0378991A1

  公开（公告）日：1990-07-25

  Disclosed are the pyrrolylphenyl-substituted hydroxamic acid derivatives of the formula wherein R represents hydrogen, lower alkyl, halogen or lower alkoxy; R₁ and R₂ indepen­dently represent hydrogen, lower alkyl or aryl; Y represents a direct bond, lower alkylene, lower alkenylene, lower alkadienylene, (thio, sulfinyl or sulfonyl)-lower alkylene or oxy-­lower alkylene; Z represents wherein R₃ represents hydrogen or acyl; R₄ represents lower alkyl, C₃-C₇-cycloalkyl, aryl or aryl-lower alkyl; or Z represents wherein R₃ represents hydrogen or acyl; R₅ represents lower alkyl, C₃-C₇-cycloalkyl, aryl, aryl-lower alkyl, amino or N-(mono- or di-lower alkyl)-amino; R₆ and R₇ represent hydrogen or lower alkyl; and pharmaceutically acceptable salts thereof provided that R₃ represents hydrogen; which are useful as selective lipoxygenase inhibitors, methods for preparation thereof, pharmaceutical compositions comprising said compounds, and a method of inhibiting lipoxygenase and of treating diseases in mammals which are respon­sive to lipoxygenase inhibition using said compounds and pharmaceutical compositions comprising said compounds of the invention.

  所公开的是式中的吡咯基苯基取代的羟肟酸衍生物 其中 R 代表氢、低级烷基、卤素或低级烷氧基；R₁ 和 R₂ 独立地代表氢、低级烷基或芳基；Y 代表直接键、低级亚烷基、低级亚烯基、低级亚烷基二烯基、（硫代、亚砜基或磺酰基）-低级亚烷基或氧基-低级亚烷基；Z 代表 其中 R₃ 代表氢或酰基； R₄ 代表低级烷基、C₃-C₇-环烷基、芳基或芳基-低级烷基；或 Z 代表 其中 R₃ 代表氢或酰基；R₅ 代表低级烷基、C₃-C₇-环烷基、芳基、芳基-低级烷基、氨基或 N-(单-或二-低级烷基)-氨基；R₆ 和 R₇ 代表氢或低级烷基；及其药学上可接受的盐，条件是 R₃ 代表氢；可用作选择性脂氧合酶抑制剂、其制备方法、包含所述化合物的药物组合物，以及使用所述化合物和包含本发明所述化合物的药物组合物抑制脂氧合酶和治疗对脂氧合酶抑制有反应的哺乳动物疾病的方法。
• Stereospecific High-affinity TRPV1 Antagonists: Chiral <i>N</i>-(2-Benzyl-3-pivaloyloxypropyl) 2-[4-(methylsulfonylamino)phenyl]propionamide Analogues
  作者：HyungChul Ryu、Mi-Kyoung Jin、Su Yeon Kim、Hyun-Kyung Choi、Sang-Uk Kang、Dong Wook Kang、Jeewoo Lee、Larry V. Pearce、Vladimir A. Pavlyukovets、Matthew A. Morgan、Richard Tran、Attila Toth、Daniel J. Lundberg、Peter M. Blumberg

  DOI：10.1021/jm701049p

  日期：2008.1.1

  Previously, we reported the thiourea antagonists 2a and 2b as potent and high affinity TRPV1 antagonists. For further optimization of the lead compounds, a series of their amide and alpha-substituted amide surrogates were investigated and novel chiral N-(2-benzyl-3-pivaloyloxypropyl) 2-[4-(methylsulfonylamino)phenyl]propionamide analogues were characterized as potent and stereospecific rTRPV1 antagonists. In particular, compounds 72 and 73 displayed high binding affinities, with K-i values of 4.12 and 1.83 nM and potent antagonism with Ki values of 0.58 and 5.2 nM, respectively, in rTRPV1/CHO cells. These values are comparable or more potent than those of 5-iodoRTX under the same assay conditions. A distinctive binding model that includes two hydrophobic pockets is proposed for this series of compounds based on docking studies of 57 and 72 with a homology model of the TM3/4 region of TRPV1.
• Picciola; Ravenna; Carenini, Farmaco, Edizione Scientifica, 1981, vol. 36, # 12, p. 1037 - 1056
  作者：Picciola、Ravenna、Carenini、Gentili、Riva

  DOI：——

  日期：——