5-(4-methyl-1-piperazinyl)-2-pentynoic acid | 877201-54-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 5-(4-methyl-1-piperazinyl)-2-pentynoic acid
• 英文别名: 5-(4-methylpiperazin-1-yl)pent-2-ynoic acid
• CAS: 877201-54-2
• 化学式: C₁₀H₁₆N₂O₂
• 分子量: 196.249
• InChiKey: IEGBVKHULYTOHO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(4-methyl-1-piperazinyl)-2-pentynoic acid 、 6-amino-4-[(3-bromo-4-fluorophenyl)amino]pyrido[3,4-d]pyrimidine 在 吡啶 、 吡啶盐酸盐 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以35%的产率得到5-(4-Methyl-piperazin-1-yl)-pent-2-ynoic acid [4-(3-bromo-4-fluoro-phenylamino)-pyrido[3,4-d]pyrimidin-6-yl]-amide
  参考文献：
  名称：

  Tyrosine Kinase Inhibitors. 19. 6-Alkynamides of 4-Anilinoquinazolines and 4-Anilinopyrido[3,4-d]pyrimidines as Irreversible Inhibitors of the erbB Family of Tyrosine Kinase Receptors

  摘要：

  Structure-activity relationships for inhibition of erbB1, erbB2, and erbB4 were determined for a series of alkynamide analogues of quinazoline- and pyrido[3,4-d]pyrimidine-based compounds. The compounds were prepared by coupling the appropriate 6-aminoquinazolines or 6-aminopyrido[3,4-d]pyrimidines with alkynoic acids, using EDCI center dot HCl in pyridine. The compounds showed pan-erbB enzyme inhibition but were on average about 10-fold more potent against erbB1 than against erbB2 and erbB4. For cellular inhibition, the nature of the alkylating side chains was an important determinant, with 5-dialkylamino-2-pentynamide type Michael acceptors providing the highest potency. This is suggested to be due to an improved ability of the amine to participate in an autocatalysis of the Michael reaction with enzyme cysteine residues. Pyrido[3,4-d]pyrimidine analogue 39 was selected for in vivo evaluation and achieved tumor regressions at 10 mg/kg in the A431 human epidermoid carcinoma and at 40 mg/kg for the SF767 human glioblastoma and the SKOV3 human ovarian carcinoma. Complete stasis was observed at 40 mg/kg in the BXPC3 human pancreatic carcinoma as well as in the H125 human non-small-cell lung carcinoma.

  DOI：

  10.1021/jm050936o
• 作为产物：
  描述：

  二氧化碳 、 1-(3-丁炔-1-基)-4-甲基哌嗪 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 3.0h， 以67%的产率得到5-(4-methyl-1-piperazinyl)-2-pentynoic acid
  参考文献：
  名称：

  Tyrosine Kinase Inhibitors. 19. 6-Alkynamides of 4-Anilinoquinazolines and 4-Anilinopyrido[3,4-d]pyrimidines as Irreversible Inhibitors of the erbB Family of Tyrosine Kinase Receptors

  摘要：

  Structure-activity relationships for inhibition of erbB1, erbB2, and erbB4 were determined for a series of alkynamide analogues of quinazoline- and pyrido[3,4-d]pyrimidine-based compounds. The compounds were prepared by coupling the appropriate 6-aminoquinazolines or 6-aminopyrido[3,4-d]pyrimidines with alkynoic acids, using EDCI center dot HCl in pyridine. The compounds showed pan-erbB enzyme inhibition but were on average about 10-fold more potent against erbB1 than against erbB2 and erbB4. For cellular inhibition, the nature of the alkylating side chains was an important determinant, with 5-dialkylamino-2-pentynamide type Michael acceptors providing the highest potency. This is suggested to be due to an improved ability of the amine to participate in an autocatalysis of the Michael reaction with enzyme cysteine residues. Pyrido[3,4-d]pyrimidine analogue 39 was selected for in vivo evaluation and achieved tumor regressions at 10 mg/kg in the A431 human epidermoid carcinoma and at 40 mg/kg for the SF767 human glioblastoma and the SKOV3 human ovarian carcinoma. Complete stasis was observed at 40 mg/kg in the BXPC3 human pancreatic carcinoma as well as in the H125 human non-small-cell lung carcinoma.

  DOI：

  10.1021/jm050936o

文献信息

• [EN] IRREVERSIBLE INHIBITORS OF TYROSINE KINASES<br/>[FR] INHIBITEURS IRREVERSIBLES DE TYROSINE KINASES
  申请人：WARNER-LAMBERT COMPANY

  公开号：WO1997038983A1

  公开（公告）日：1997-10-23

  (EN) The present invention provides compounds that are irreversible inhibitors of tyrosine kinases. Also provided is a method of treating cancer, restenosis, atherosclerosis, endometriosis, and psoriasis and a pharmaceutical composition that comprises a compound that is an irreversible inhibitor of tyrosine kinases.(FR) La présente invention concerne des composés qui sont des inhibiteurs irréversibles de tyrosine kinases. L'invention, qui concerne également un traitement du cancer, de la resténose, de l'athérosclérose, de l'endométriose et du psoriasis, concerne en outre une spécialité pharmaceutique comprenant un composé qui est un inhibiteur irréversible de tyrosine kinases.

  (中文)本发明提供了一些不可逆酪氨酸激酶抑制剂化合物。还提供了一种治疗癌症、再狭窄、动脉粥样硬化、子宫内膜异位症和牛皮癣的方法，以及包含一种不可逆酪氨酸激酶抑制剂化合物的制药组合物。
• Irreversible inhibitors of tyrosine kinases
  申请人：——

  公开号：US20030229051A1

  公开（公告）日：2003-12-11

  The present invention provides compounds that are irreversible inhibitors of tyrosine kinases. Also provided is a method of treating cancer, restenosis, atherosclerosis, endometriosis, and psoriasis and a pharmaceutical composition that comprises a compound that is an irreversible inhibitor of tyrosine kinases.

  本发明提供了一些不可逆酪氨酸激酶抑制剂化合物。同时提供了一种治疗癌症、再狭窄、动脉硬化、子宫内膜异位症和牛皮癣的方法，以及一种包含不可逆酪氨酸激酶抑制剂化合物的药物组合物。
• Use of a composition comprising a retinoid and an erb inhibitor in the preparation of a medicament for the treatment of retinoid skin damage
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP1230919A2

  公开（公告）日：2002-08-14

  Erb inhibitors used in combination with retinoids are effective to prevent skin injury otherwise caused by retinoids alone. A method of treating skin aging and similar skin disorders comprises administering retinoids in combination with erb inhibitors of the general formula where E1, E2, and E3 include halo, aryl is an alkylcarbonyl or alkenylcarbonyl, and alkoxy is lower alkoxy optionally substituted with amino groups.

  Erb 抑制剂与维甲酸类药物结合使用，可有效防止维甲酸类药物单独使用造成的皮肤损伤。一种治疗皮肤老化和类似皮肤病的方法包括将维甲酸与通式为 Erb 的抑制剂联合使用 其中 E1、E2 和 E3 包括卤代，芳基是烷基羰基或烯基羰基，烷氧基是任选被氨基取代的低级烷氧基。
• Method for inhibiting retinoid skin damage
  申请人：——

  公开号：US20020169176A1

  公开（公告）日：2002-11-14

  Erb inhibitors used in combination with retinoids are effective to prevent skin injury otherwise caused by retinoids alone. A method of treating skin aging and similar skin disorders comprises administering retinoids in combination with erb inhibitors of the general formula 1 where E 1 , E 2 , and E 3 include halo, aryl is an alkylcarbonyl or alkenylcarbonyl, and alkoxy is lower alkoxy optionally substituted with amino groups.

  Erb 抑制剂与维甲酸类药物结合使用，可有效防止维甲酸类药物单独使用造成的皮肤损伤。一种治疗皮肤老化和类似皮肤疾病的方法包括将维甲酸与通式为 1 式中 E 1 , E 2 和 E 3 包括卤素，芳基是烷基羰基或烯基羰基，烷氧基是可选被氨基取代的低级烷氧基。
• IRREVERSIBLE INHIBITORS OF TYROSINE KINASES
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0892789B1

  公开（公告）日：2002-02-27