[4-(3-Pyridylcarbonylamino)-2-(2-methylphenyl)benzoyl]methionine Methyl Ester | 191102-18-8

• 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: [4-(3-Pyridylcarbonylamino)-2-(2-methylphenyl)benzoyl]methionine Methyl Ester
• 英文别名: methyl (2S)-2-[[2-(2-methylphenyl)-4-(pyridine-3-carbonylamino)benzoyl]amino]-4-methylsulfanylbutanoate
• CAS: 191102-18-8
• 化学式: C₂₆H₂₇N₃O₄S
• 分子量: 477.584
• InChiKey: YPADVAAQZOLKOZ-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  123
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [4-(3-Pyridylcarbonylamino)-2-(2-methylphenyl)benzoyl]methionine Methyl Ester 在 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以59%的产率得到[4-(3-Pyridylcarbonylamino)-2-(2-methylphenyl)benzoyl]methionine
  参考文献：
  名称：

  Potent and Selective Non-Cysteine-Containing Inhibitors of Protein Farnesyltransferase

  摘要：

  Potent and selective non-thiol-containing inhibitors of protein farnesyltransferase are described. FTI-276 (1) was transformed into pyridyl ether analogue 19. The potency of pyridyl ether 19 was improved by modification of the biphenyl core to that of an o-tolyl substituted biphenyl core to give 29. In addition to 0.4 nM in vitro potency, 29 displayed 350 nM potency in whole cells as the parent carboxylic acid. The o-tolyl biphenyl core dramatically and unexpectedly enhanced the potency of other compounds as exemplified by 46, 47, 48, and 49.

  DOI：

  10.1021/jm980298s
• 作为产物：
  描述：

  烟酸 在 草酰氯 、 碳酸氢钠 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 [4-(3-Pyridylcarbonylamino)-2-(2-methylphenyl)benzoyl]methionine Methyl Ester
  参考文献：
  名称：

  Potent and Selective Non-Cysteine-Containing Inhibitors of Protein Farnesyltransferase

  摘要：

  Potent and selective non-thiol-containing inhibitors of protein farnesyltransferase are described. FTI-276 (1) was transformed into pyridyl ether analogue 19. The potency of pyridyl ether 19 was improved by modification of the biphenyl core to that of an o-tolyl substituted biphenyl core to give 29. In addition to 0.4 nM in vitro potency, 29 displayed 350 nM potency in whole cells as the parent carboxylic acid. The o-tolyl biphenyl core dramatically and unexpectedly enhanced the potency of other compounds as exemplified by 46, 47, 48, and 49.

  DOI：

  10.1021/jm980298s

文献信息

• Inhibitors of protein isoprenyl transferases
  申请人：University of Pittsburgh

  公开号：US20020193596A1

  公开（公告）日：2002-12-19

  Compounds having the formula 1 or a pharmaceutically acceptable salt thereof wherein R 1 is (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkoxy, (e) thioalkoxy, (f) halo, (g) haloalkyl, (h) aryl-L 2 —, and (i) heterocyclic-L 2 —; R 2 is selected from (a) 2 (b) —C(O)NH—CH(R 14 )—C(O)OR 15 , (c) 3 (d) —C(O)NH—CH(R 14 )—C(O)NHSO 2 R 16 (e) —C(O)NH—CH(R 14 )-tetrazolyl, (f) —C(O)NH-heterocyclic, and (g) —C(O)NH—CH(R 14 )—C(O)NR 17 R 18 ; R 3 is heterocyclic, aryl, substituted or unsubstituted cycloalkyl; R 4 is hydrogen, lower alkyl, haloalkyl, halogen, aryl, arylakyl, heterocyclic, or (heterocyclic)alkyl; L 1 is absent or is selected from (a) —L 4 —N(R 5 )—L 5 —, (b) —L 4 —O—L 5 —, (c) —L 4 —S(O) n —L 5 — (d) —L 4 -L 6 —C(W)—N(R 5 )—L 5 —, (e) —L 4 -L 6 —S(O) m —N(R 5 )—L 5 —, (f) —L 4 —N(R 5 )—C(W)—L 7 -L 5 —, (g) —L 4 —N(R 5 )—S(O) p —L 7 —L 5 —, (h) optionally substituted alkylene, (i) optionally substituted alkenylene, and (j) optionally substituted alkynylene are inhibitors of protein isoprenyl transferases. Also disclosed are protein isoprenyl transferase inhibiting compositions and a method of inhibiting protein isoprenyl transferases.

  具有公式1或其药学上可接受的盐的化合物，其中R1为(a)氢，(b)较低的烷基，(c)烯基，(d)烷氧基，(e)硫代烷氧基，(f)卤素，(g)卤素烷基，(h)芳基-L2-，(i)杂环-L2-; R2选择自(a)2(b) -C(O)NH-CH(R14)-C(O)OR15，(c)3(d) -C(O)NH-CH(R14)-C(O)NHSO2R16(e) -C(O)NH-CH(R14)-四唑基，(f) -C(O)NH-杂环，和(g) -C(O)NH-CH(R14)-C(O)NR17R18; R3是杂环，芳基，取代或未取代的环烷基; R4为氢，较低的烷基，卤素烷基，卤素，芳基，芳基烷基，杂环或(杂环)烷基; L1不存在或选择自(a) -L4-N(R5)-L5-，(b) -L4-O-L5-，(c) -L4-S(O)n-L5-，(d) -L4-L6-C(W)-N(R5)-L5-，(e) -L4-L6-S(O)m-N(R5)-L5-，(f) -L4-N(R5)-C(W)-L7-L5-，(g) -L4-N(R5)-S(O)p-L7-L5-，(h) 可选取代的烷基，(i) 可选取代的烯基，和(j) 可选取代的炔基是蛋白质异戊烯基转移酶的抑制剂。还公开了蛋白质异戊烯基转移酶抑制组合物和一种抑制蛋白质异戊烯基转移酶的方法。
• INHIBITORS OF PROTEIN ISOPRENYL TRANSFERASES
  申请人：UNIVERSITY OF PITTSBURGH

  公开号：EP0873123B1

  公开（公告）日：2003-04-09
• US6693123B2
  申请人：——

  公开号：US6693123B2

  公开（公告）日：2004-02-17
• Potent and Selective Non-Cysteine-Containing Inhibitors of Protein Farnesyltransferase
  作者：David J. Augeri、Stephen J. O'Connor、Dave Janowick、Bruce Szczepankiewicz、Gerry Sullivan、John Larsen、Douglas Kalvin、Jerry Cohen、Edward Devine、Haichao Zhang、Sajeev Cherian、Badr Saeed、Shi-Chung Ng、Saul Rosenberg

  DOI：10.1021/jm980298s

  日期：1998.10.1

  Potent and selective non-thiol-containing inhibitors of protein farnesyltransferase are described. FTI-276 (1) was transformed into pyridyl ether analogue 19. The potency of pyridyl ether 19 was improved by modification of the biphenyl core to that of an o-tolyl substituted biphenyl core to give 29. In addition to 0.4 nM in vitro potency, 29 displayed 350 nM potency in whole cells as the parent carboxylic acid. The o-tolyl biphenyl core dramatically and unexpectedly enhanced the potency of other compounds as exemplified by 46, 47, 48, and 49.