1,5-bis(tert-butoxycarbonyl)-2-(tert-butyldiphenylsiloxy)methyl-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine | 259809-52-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: 1,5-bis(tert-butoxycarbonyl)-2-(tert-butyldiphenylsiloxy)methyl-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine
• 英文别名: 1,5-Bis(t-butoxycarbonyl)-2-(t-butyldiphenylsiloxy)methyl-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine；ditert-butyl 2-[[tert-butyl(diphenyl)silyl]oxymethyl]-6,7-dihydro-4H-pyrrolo[3,2-c]pyridine-1,5-dicarboxylate
• CAS: 259809-52-4
• 化学式: C₃₄H₄₆N₂O₅Si
• 分子量: 590.835
• InChiKey: RYTVOUBLWBOXTK-UHFFFAOYSA-N

物化性质

• 沸点：
  629.4±65.0 °C(Predicted)
• 密度：
  1.07±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.64
• 重原子数：
  42
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  70
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1,5-bis(tert-butoxycarbonyl)-2-(tert-butyldiphenylsiloxy)methyl-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine 在 sodium dihydrogenphosphate 、 2-甲基-2-丁烯 、 sodium perchlorate 、 戴斯-马丁氧化剂 、 氟化氢吡啶 作用下， 以 吡啶 、 二氯甲烷 、 叔丁醇 为溶剂， 反应 23.0h， 生成 1,5-bis(tert-butoxycarbonyl)-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid
  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
• 作为产物：
  描述：

  2-(tert-butoxycarbonylamino)-3-(tert-butyldiphenylsiloxy)propanol 在 盐酸 、 正丁基锂 、 戴斯-马丁氧化剂 、 二异丙胺 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 17.0h， 生成 1,5-bis(tert-butoxycarbonyl)-2-(tert-butyldiphenylsiloxy)methyl-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine
  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

• Novel sulfonyl derivatives
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：US20040082611A1

  公开（公告）日：2004-04-29

  Described in the present invention are a sulfonyl derivative represented by the following formula (I): Q 1 -Q 2 -T 1 -Q 3 -SO 2 -Q A (I) [wherein Q 1 represents a saturated or unsaturated 5- or 6-membered cyclic hydrocarbon group, 5- or 6-membered heterocyclic group, dicyclic fused ring or tricyclic fused ring group which may have a substituent; Q 2 represents a single bond, an oxygen atom, a sulfur atom, a linear or branched C 1-6 alkylene group or the like; Q A represents an arylalkenyl group which may have a substituent or a heteroarylalkenyl group which may have a substituent; and T 1 represents a carbonyl group or the like] and a medicament comprising the same. The compound has strong FXa inhibitory action, provides prompt, sufficient and long-lasting anti-thrombus effects when orally administered, and has low side effects and is therefore useful as an excellent anticoagulant.

  本发明描述了一种由以下式(I)表示的磺酰基衍生物： Q1-Q2-T1-Q3-SO2-QA(I) [其中，Q1表示饱和或不饱和的5-或6-环烃基、5-或6-杂环基、二环融合环或三环融合环基，可能具有取代基；Q2表示单键、氧原子、硫原子、线性或支链的C1-6烷基等；QA表示可能具有取代基的芳基烯基或杂芳基烯基；T1表示羰基基团或类似物]，以及包含该化合物的药物。该化合物具有强烈的FXa抑制作用，口服后提供快速、充分和持久的抗血栓效果，并且具有低副作用，因此可用作优秀的抗凝剂。
• Sulfonyl derivatives
  申请人：Daiichi Pharmaceutical Co., Ltd.

  公开号：US06747023B1

  公开（公告）日：2004-06-08

  Described in the present invention are a sulfonyl derivative represented by the following formula (I): Q1—Q2—T1—Q3—SO2—QA  (I) [wherein Q1 represents a saturated or unsaturated 5- or 6-membered cyclic hydrocarbon group, 5- or 6-membered heterocyclic group, dicyclic fused ring or tricyclic fused ring group which may have a substituent; Q2 represents a single bond, an oxygen atom, a sulfur atom, a linear or branched C1-6 alkylene group or the like; QA represents an arylalkenyl group which may have a substituent or a heteroarylalkenyl group which may have a substituent; and T1 represents a carbonyl group or the like] and a medicament comprising the same. The compound has strong FXa inhibitory action, provides prompt, sufficient and long-lasting anti-thrombus effects when orally administered, and has low side effects and is therefore useful as an excellent anticoagulant.

  本发明涉及一种磺酰基衍生物，其由以下式（I）表示：Q1-Q2-T1-Q3-SO2-QA（I）[其中，Q1代表饱和或不饱和的5-或6-成员环烃基，5-或6-成员杂环基，二环融合环或三环融合环基，可以有取代基；Q2代表单键，氧原子，硫原子，线性或支链C1-6烷基或类似物；QA代表芳基烯基，可以有取代基，或杂环芳基烯基，可以有取代基；T1代表羰基或类似物]，以及包含该化合物的药物。该化合物具有强烈的FXa抑制作用，在口服时提供迅速，充分和持久的抗血栓效果，并且副作用低，因此是一种优秀的抗凝剂。
• 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.