7-(2-chloroethoxy)-4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-3-quinolinecarbonitrile | 380844-42-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 7-(2-chloroethoxy)-4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-3-quinolinecarbonitrile
• 英文别名: 7-[2-Chloroethoxy]-4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-3-quinolinecarbonitrile；7-(2-chloroethoxy)-4-(2,4-dichloro-5-methoxyanilino)-6-methoxyquinoline-3-carbonitrile
• CAS: 380844-42-8
• 化学式: C₂₀H₁₆Cl₃N₃O₃
• 分子量: 452.724
• InChiKey: CTPFVVJNDXWGGI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  76.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  吗啉 、 7-(2-chloroethoxy)-4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-3-quinolinecarbonitrile 在 sodium iodide 作用下， 以 乙二醇二甲醚 为溶剂， 以45%的产率得到4-Phenylamino 3-quinolinecarbonitrile deriv. 26
  参考文献：
  名称：

  Optimization of 4-Phenylamino-3-quinolinecarbonitriles as Potent Inhibitors of Src Kinase Activity

  摘要：

  Subsequent to the discovery of 4-[(2,4-dichlorophenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile (1a) as an inhibitor of Src kinase activity (IC50 = 30 nM), several additional analogues were prepared. Optimization of the C-4 anilino group of la led to le, which contains a 2,4-dichloro-5-methoxy-substituted aniline. Replacement of the methoxy group at C-7 of le with a 3-(morpholin-4-yl)propoxy group provided 2c, resulting in increased inhibition of both Src kinase activity and Src-mediated cell proliferation. Analogues of 2c, with other trisubstituted anilines at C-4 were also potent Src inhibitors, and the propoxy group of 2c was preferred over ethoxy, butoxy, or pentoxy. Replacement of the morpholine group of 2c with a 4-methylpiperazine group provided 31a, which had an IC50 of 1.2 nM in the Src enzymatic assay, an IC50 of 100 nM for the inhibition of Src-dependent cell proliferation and was selective for Src over non-Src family kinases. Compound 31a, which had higher 1 and 4 h plasma levels than 2c, effectively inhibited tumor growth in xenograft models.

  DOI：

  10.1021/jm0102250
• 作为产物：
  描述：

  4-氯-7-羟基-6-甲氧基喹啉-3-甲腈 在 吡啶盐酸盐 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙二醇乙醚 为溶剂， 反应 4.25h， 生成 7-(2-chloroethoxy)-4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-3-quinolinecarbonitrile
  参考文献：
  名称：

  Optimization of 4-Phenylamino-3-quinolinecarbonitriles as Potent Inhibitors of Src Kinase Activity

  摘要：

  Subsequent to the discovery of 4-[(2,4-dichlorophenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile (1a) as an inhibitor of Src kinase activity (IC50 = 30 nM), several additional analogues were prepared. Optimization of the C-4 anilino group of la led to le, which contains a 2,4-dichloro-5-methoxy-substituted aniline. Replacement of the methoxy group at C-7 of le with a 3-(morpholin-4-yl)propoxy group provided 2c, resulting in increased inhibition of both Src kinase activity and Src-mediated cell proliferation. Analogues of 2c, with other trisubstituted anilines at C-4 were also potent Src inhibitors, and the propoxy group of 2c was preferred over ethoxy, butoxy, or pentoxy. Replacement of the morpholine group of 2c with a 4-methylpiperazine group provided 31a, which had an IC50 of 1.2 nM in the Src enzymatic assay, an IC50 of 100 nM for the inhibition of Src-dependent cell proliferation and was selective for Src over non-Src family kinases. Compound 31a, which had higher 1 and 4 h plasma levels than 2c, effectively inhibited tumor growth in xenograft models.

  DOI：

  10.1021/jm0102250

文献信息

• [EN] 4-ANILINO-3-QUINOLINECARBONITRILES FOR THE TREATMENT OF CHRONIC MYELOGENOUS LEUKEMIA (CML)<br/>[FR] 4-ANILINO-3-QUINOLINECARBONITRILES DESTINES AU TRAITEMENT DE LEUCEMIE MYELOGENE CHRONIQUE (CML)
  申请人：WYETH CORP

  公开号：WO2005047259A1

  公开（公告）日：2005-05-26

  Compounds of the formula (I): wherein: n is an integer from 0-3; X is N, CH; R is alkyl of 1 to 3 carbon atoms; R' is 2,4-diCl, 5-OMe in para, ortho, or meta position; 2,4-diCl in para position; 3,4,5­tri-OMe in para position; 2-Cl, 5-OMe in para position; 2-Me, 5-OMe in para position; 2,4-di-Me in para position; 2,4-diMe-5-OMe in para position; 2,4-diCl, 5-OEt in para position; and R2 is alkyl of 1 to 3 carbon atoms, and pharmaceutically acceptable salts thereof.

  式(I)的化合物：其中：n是0-3之间的整数；X是N，CH；R是1至3个碳原子的烷基；R'是对位、邻位或间位的2,4-二氯，5-甲氧基；对位的2,4-二氯；对位的3,4,5-三甲氧基；对位的2-氯，5-甲氧基；对位的2-甲基，5-甲氧基；对位的2,4-二甲基；对位的2,4-二甲基-5-甲氧基；对位的2,4-二氯，5-乙氧基；以及R2是1至3个碳原子的烷基，及其药用可接受的盐。
• [EN] 4-[(2,4-DICHLORO-5-METHOXYPHENYL)AMINO]-6-ALKOXY-3-QUINOLINECARBONITRILES FOR THE TREATMENT OF ISCHEMIC INJURY<br/>[FR] 4-[(2,4-DICHLORO-5-METHOXYPHENYL)AMINO]-6-ALCOXY-3-QUINOLINECARBONITRILES POUR LE TRAITEMENT DES LESIONS ISCHEMIQUES
  申请人：WYETH CORP

  公开号：WO2004075898A1

  公开（公告）日：2004-09-10

  Compounds of the Formula (I), wherein X is N, CH n is an integer from 1-3; and R' and R are independently, alkyl of 1 to 3 carbon atoms, and pharmaceutically acceptable salts thereof, with the proviso that when n is 1, X is not N; are useful for inhibiting vascular permeability caused by disease, injury, or other trauma.

  公式（I）的化合物，其中X为N，CHn为1-3的整数；R'和R分别独立地表示1到3个碳原子的烷基，以及其药学上可接受的盐，但当n为1时，X不是N。这些化合物可用于抑制疾病、损伤或其他创伤引起的血管通透性。
• 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-alkoxy-3-quinolinecarbonitriles for the treatment of ischemic injury
  申请人：Wyeth

  公开号：US20040229880A1

  公开（公告）日：2004-11-18

  Compounds of the formula: 1 wherein: X is N, CH n is an integer from 1-3; and R′ and R are independently, alkyl of 1 to 3 carbon atoms, and pharmaceutically acceptable salts thereof, with the proviso that when n is 1, X is not N; are useful for inhibiting vascular permeability caused by disease, injury, or other trauma.

  公式为1的化合物，其中： X为N，CHn为1-3的整数； R'和R分别为1至3个碳原子的烷基，以及其药学上可接受的盐。 但当n为1时，X不是N。 这些化合物可用于抑制由疾病、损伤或其他创伤引起的血管通透性。
• 4- (2,4-DICHLORO-5-METHOXYPHENYL)AMINO -6-ALKOXY-3-QUINOLINECARBONITRILES FOR THE TREATMENT OF ISCHEMIC INJURY
  申请人：Wyeth

  公开号：EP1594502A1

  公开（公告）日：2005-11-16
• Optimization of 4-Phenylamino-3-quinolinecarbonitriles as Potent Inhibitors of Src Kinase Activity
  作者：Diane H. Boschelli、Fei Ye、Yanong D. Wang、Minu Dutia、Steve L. Johnson、Biqi Wu、Karen Miller、Dennis W. Powell、Deanna Yaczko、Mairead Young、Mark Tischler、Kim Arndt、Carolyn Discafani、Carlo Etienne、Jay Gibbons、Janet Grod、Judy Lucas、Jennifer M. Weber、Frank Boschelli

  DOI：10.1021/jm0102250

  日期：2001.11.1

  Subsequent to the discovery of 4-[(2,4-dichlorophenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile (1a) as an inhibitor of Src kinase activity (IC50 = 30 nM), several additional analogues were prepared. Optimization of the C-4 anilino group of la led to le, which contains a 2,4-dichloro-5-methoxy-substituted aniline. Replacement of the methoxy group at C-7 of le with a 3-(morpholin-4-yl)propoxy group provided 2c, resulting in increased inhibition of both Src kinase activity and Src-mediated cell proliferation. Analogues of 2c, with other trisubstituted anilines at C-4 were also potent Src inhibitors, and the propoxy group of 2c was preferred over ethoxy, butoxy, or pentoxy. Replacement of the morpholine group of 2c with a 4-methylpiperazine group provided 31a, which had an IC50 of 1.2 nM in the Src enzymatic assay, an IC50 of 100 nM for the inhibition of Src-dependent cell proliferation and was selective for Src over non-Src family kinases. Compound 31a, which had higher 1 and 4 h plasma levels than 2c, effectively inhibited tumor growth in xenograft models.