[4-(6-Chloro-naphthalene-2-sulfonyl)-piperazin-1-yl]-(5-methyl-4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridin-2-yl)-methanone | 724706-32-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: [4-(6-Chloro-naphthalene-2-sulfonyl)-piperazin-1-yl]-(5-methyl-4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridin-2-yl)-methanone
• 英文别名: [4-(6-chloronaphthalen-2-yl)sulfonylpiperazin-1-yl]-(5-methyl-6,7-dihydro-4H-[1,3]thiazolo[5,4-c]pyridin-2-yl)methanone
• CAS: 724706-32-5
• 化学式: C₂₂H₂₃ClN₄O₃S₂
• 分子量: 491.035
• InChiKey: AAYCSPVJCQPYHO-UHFFFAOYSA-N

物化性质

• 沸点：
  684.3±65.0 °C(Predicted)
• 密度：
  1.446±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  32
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  110
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  碘甲烷 、 [4-(6-Chloro-naphthalene-2-sulfonyl)-piperazin-1-yl]-(5-methyl-4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridin-2-yl)-methanone 以 N,N-二甲基甲酰胺 为溶剂， 以56%的产率得到[4-(6-chloronaphthalen-2-yl)sulfonylpiperazin-1-yl]-(5,5-dimethyl-6,7-dihydro-4H-[1,3]thiazolo[5,4-c]pyridin-5-ium-2-yl)methanone;iodide
  参考文献：
  名称：

  Orally active factor Xa inhibitors: 4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine derivatives

  摘要：

  In our investigation of factor Xa inhibitors, a series of 1-(6-chloronaphthalen-2-yl)sulfonyl-4-(4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carbonyl)piperazines 3a-i were synthesized. In vitro inhibitory activities of the compounds against factor Xa and coagulation are summarized. Among the compounds, 3c and 3d, possessing a carbamoyl or N-methylcarbamoyl moiety, showed potent inhibitory activities when administered orally to rats. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.03.036
• 作为产物：
  描述：

  2-氯萘 在 N-甲基吗啉 、 盐酸 、 氯化亚砜 、 硫酸 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.05h， 生成 [4-(6-Chloro-naphthalene-2-sulfonyl)-piperazin-1-yl]-(5-methyl-4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridin-2-yl)-methanone
  参考文献：
  名称：

  Synthesis and Conformational Analysis of a Non-Amidine Factor Xa Inhibitor That Incorporates 5-Methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine as S4 Binding Element

  摘要：

  Our exploratory study was based on the concept that a non-amidine factor Xa (fXa) inhibitor is suitable for an orally available anticoagulant. We synthesized and evaluated a series of N-(6-chloronaphthalen-2-yl)sulfonylpiperazine derivatives incorporating various fused-bicyclic rings containing an aliphatic amine expected to be S4 binding element. Among this series, 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine type 61 displayed orally potent anti-fXa activity and evident prolongation of prothrombin time (PT) with the moderate bioavailability in rats. The X-ray crystal analysis afforded an obvious binding mode that 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine and 6-chloronaphthalene respectively bound to S4 and S1 subsites. In this X-ray study, we discovered a novel intramolecular S-O close contact. Ab initio energy calculations of model compounds deduced that conformers with the most close S-O proximity were most stable. The Mulliken population analysis proposed that this energy profile was caused by both of electrostatic S-O affinity and N-O repulsion. The results of these calculations and X-ray analysis suggested a possibility that the restricted conformation effected the affinity to S4 subsite of fXa.

  DOI：

  10.1021/jm049884d

文献信息

• US7756674B2
  申请人：——

  公开号：US7756674B2

  公开（公告）日：2010-07-13
• US7970580B2
  申请人：——

  公开号：US7970580B2

  公开（公告）日：2011-06-28
• US7970581B2
  申请人：——

  公开号：US7970581B2

  公开（公告）日：2011-06-28
• Orally active factor Xa inhibitors: 4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine derivatives
  作者：Noriyasu Haginoya、Syozo Kobayashi、Satoshi Komoriya、Yumiko Hirokawa、Taketoshi Furugori、Takayasu Nagahara

  DOI：10.1016/j.bmcl.2004.03.036

  日期：2004.6

  In our investigation of factor Xa inhibitors, a series of 1-(6-chloronaphthalen-2-yl)sulfonyl-4-(4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carbonyl)piperazines 3a-i were synthesized. In vitro inhibitory activities of the compounds against factor Xa and coagulation are summarized. Among the compounds, 3c and 3d, possessing a carbamoyl or N-methylcarbamoyl moiety, showed potent inhibitory activities when administered orally to rats. (C) 2004 Elsevier Ltd. All rights reserved.
• Synthesis and Conformational Analysis of a Non-Amidine Factor Xa Inhibitor That Incorporates 5-Methyl-4,5,6,7-tetrahydrothiazolo[5,4-<i>c</i>]pyridine as S4 Binding Element
  作者：Noriyasu Haginoya、Syozo Kobayashi、Satoshi Komoriya、Toshiharu Yoshino、Makoto Suzuki、Takashi Shimada、Kengo Watanabe、Yumiko Hirokawa、Taketoshi Furugori、Takayasu Nagahara

  DOI：10.1021/jm049884d

  日期：2004.10.1

  Our exploratory study was based on the concept that a non-amidine factor Xa (fXa) inhibitor is suitable for an orally available anticoagulant. We synthesized and evaluated a series of N-(6-chloronaphthalen-2-yl)sulfonylpiperazine derivatives incorporating various fused-bicyclic rings containing an aliphatic amine expected to be S4 binding element. Among this series, 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine type 61 displayed orally potent anti-fXa activity and evident prolongation of prothrombin time (PT) with the moderate bioavailability in rats. The X-ray crystal analysis afforded an obvious binding mode that 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine and 6-chloronaphthalene respectively bound to S4 and S1 subsites. In this X-ray study, we discovered a novel intramolecular S-O close contact. Ab initio energy calculations of model compounds deduced that conformers with the most close S-O proximity were most stable. The Mulliken population analysis proposed that this energy profile was caused by both of electrostatic S-O affinity and N-O repulsion. The results of these calculations and X-ray analysis suggested a possibility that the restricted conformation effected the affinity to S4 subsite of fXa.