(2S)-3-[(6-chloronaphthalen-2-yl)sulfonyl]-2-hydroxypropanoic acid | 701299-82-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (2S)-3-[(6-chloronaphthalen-2-yl)sulfonyl]-2-hydroxypropanoic acid
• 英文别名: (2S)-3-((6-chloronaphthalen-2-yl)sulfonyl)-2-hydroxypropanoic acid；(2S)-3-[(6-chloronaphthalen-2-yl)sulfonyl]-2-hydroxypropionic acid；(2S)-3-[(6-chloro-2-naphthyl)sulfonyl]-2-hydroxypropionic acid；(2S)-3-(6-chloronaphthalen-2-yl)sulfonyl-2-hydroxypropanoic acid
• CAS: 701299-82-3
• 化学式: C₁₃H₁₁ClO₅S
• 分子量: 314.746
• InChiKey: ZBBROOUDWAFZRO-GFCCVEGCSA-N

物化性质

• 沸点：
  627.9±55.0 °C(Predicted)
• 密度：
  1.551±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  100
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S)-3-[(6-chloronaphthalen-2-yl)sulfonyl]-2-hydroxypropanoic acid 、 1-(4-哌啶基)-2-咪唑啉酮 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 以46%的产率得到1-(1-{(2S)-3-[(6-chloronaphthalen-2-yl)sulfonyl]-2-hydroxypropanoyl}piperidin-4-yl)imidazolidin-2-one
  参考文献：
  名称：

  Discovery of a Tetrahydropyrimidin-2(1H)-one Derivative (TAK-442) as a Potent, Selective, and Orally Active Factor Xa Inhibitor

  摘要：

  Coagulation enzyme factor Xa (FXa) is a particularly promising target for the development of new anticoagulant agents. We previously reported the imidazo[1,5-c]imidazol-3-one derivative 1 as a potent and orally active FXa inhibitor. However, it was found that 1 predominantly undergoes hydrolysis upon incubation with human liver microsomes, and the human specific metabolic pathway made it difficult to predict the human pharmacokinetics. To address this issue, our synthetic efforts were focused on modification of the imidazo[1,5-c]imidazol-3-one moiety of the active metabolite 3a, derived from 1, which resulted in the discovery of the tetrahydropyrimidin-2(1H)-one derivative 5k as a highly potent and selective FXa inhibitor. Compound 5k showed no detectable amide bond cleavage in human liver microsomes, exhibited a good pharmacokinetic profile in monkeys, and had a potent antithrombotic efficacy in a rabbit model without prolongation of bleeding time. Compound 5k is currently under clinical development with the code name TAK-442.

  DOI：

  10.1021/jm901699j
• 作为产物：
  描述：

  (2S)-3-[(6-chloronaphthalen-2-yl)thio]-2-hydroxypropanoic acid 在 Oxone 作用下， 以 丙酮 为溶剂， 反应 5.0h， 以82%的产率得到(2S)-3-[(6-chloronaphthalen-2-yl)sulfonyl]-2-hydroxypropanoic acid
  参考文献：
  名称：

  合成和2-代谢物的生物评价（1- {3 - [（6-氯萘-2-基）磺酰基]丙酰基}哌啶-4-基）-5-甲基-1,2-二氢-3 ħ -咪唑并[1,5 - c ]咪唑-3-一

  摘要：

  我们最近发现了咪唑并[1,5 - c ]咪唑-3-酮衍生物1作为有效，选择性和口服生物利用因子Xa（FXa）抑制剂。在这项研究中，我们合成了1的代谢物并评估了它们的生物活性。结果，我们确定了活性代谢物S -5和6具有与FX 1相当的有效FXa抑制活性，并且在猴子中具有良好的药代动力学特征。

  DOI：

  10.1016/j.bmc.2009.10.009

文献信息

• [EN] CYCLIC AMIDE DERIVATIVES, AND THEIR PRODUCTION AND USE AS ANTITHROMBOTIC AGENTS<br/>[FR] DÉRIVÉS D'AMIDES CYCLIQUES ET LEUR PRODUCTION ET UTILISATION COMME AGENTS ANTITHROMBOTIQUES
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2005113504A1

  公开（公告）日：2005-12-01

  The present invention provides a cyclic amide derivative useful as a drug for treating thrombosis, which is represented by the formula (I): wherein R1 represents an optionally substituted cyclic hydrocarbon group or an optionally substituted heterocyclic group, W represents a bond or an optionally substituted divalent chain hydrocarbon group, a represents 0, 1, or 2, X1 represents an optionally substituted lower alkylene or an optionally substituted lower alkenylene, Y1 represents -C(O)-, -S(O)- or -S(O)2-, A represents a piperazine ring which may be further substituted or a piperidine ring which may be further substituted, X2 represents a bond or an optionally substituted lower alkylene, Y2 represents -C(O)-, -S(O)-, -S(O)2- or -C(=NR7)-, X3 represents an optionally substituted C1-4 alkylene or an optionally substituted C2-4 alkenylene, Z3 represents -N(R4)-, -O- or a bond, Z1 represents -C(R2)(R2')-, -N(R2)-, etc., and Z2 represents -C(R3)(R3')-, -N(R3)-, etc., or a salt thereof.

  本发明提供了一种环酰胺衍生物，可用作治疗血栓症的药物，其化学式为（I）：其中R1代表一个可选择取代的环烃基或一个可选择取代的杂环基，W代表一个键或一个可选择取代的双价链烃基，a代表0、1或2，X1代表一个可选择取代的较低碳烷基或一个可选择取代的较低烯烃基，Y1代表-C（O）-、-S（O）-或-S（O）2-，A代表可能进一步取代的哌嗪环或可能进一步取代的哌啶环，X2代表一个键或一个可选择取代的较低碳烷基，Y2代表-C（O）-、-S（O）-、-S（O）2-或-C（=NR7）-，X3代表一个可选择取代的C1-4烷基或一个可选择取代的C2-4烯烃基，Z3代表-N（R4）-、-O-或一个键，Z1代表-C（R2）（R2'）-、-N（R2）-等，Z2代表-C（R3）（R3'）-、-N（R3）-等，或其盐。
• Cyclic Amide Derivative, and Its Production and Use
  申请人：Kubo Keiji

  公开号：US20070244118A1

  公开（公告）日：2007-10-18

  The present invention provides a cyclic amide derivative useful as a drug for treating thrombosis, which is represented by the formula (I)-: wherein R 1 represents an optionally substituted cyclic hydrocarbon group or an optionally substituted heterocyclic group, W represents a bond or an optionally substituted divalent chain hydrocarbon group, a represents 0, 1, or 2, X 1 represents an optionally substituted lower alkylene or an optionally substituted lower alkenylene, Y 1 represents —C(O)—, —S(O)— or —S(O) 2 —, A represents a piperazine ring which may be further substituted or a piperidine ring which may be further substituted, X 2 represents a bond or an optionally substituted lower alkylene, Y 2 represents —C(O)—, —S(O)—, —S(O) 2 — or —C(═NR 7 )—, X 3 represents an optionally substituted C 1-4 alkylene or an optionally substituted C 2-4 alkenylene, Z 3 represents —N(R 4 )—, —O— or a bond, Z 1 represents —C(R 2 )(R 2′ )—, —N(R 2 )—, etc., and Z 2 represents —C(R 3 )(R 3′ )—, —N(R 3 )—, etc., or a salt thereof.

  本发明提供了一种环酰胺衍生物，用作治疗血栓的药物，其化学式表示为(I)-:其中R1表示可选取代的环烃基或可选取代的杂环基，W表示键或可选取代的二价链烃基，a表示0、1或2，X1表示可选取代的较低烷基或可选取代的较低烯基，Y1表示—C(O)—、—S(O)—或—S(O)2—，A表示可进一步取代的哌嗪环或可进一步取代的哌啶环，X2表示键或可选取代的较低烷基，Y2表示—C(O)—、—S(O)—、—S(O)2—或—C(═NR7)—，X3表示可选取代的C1-4烷基或可选取代的C2-4烯基，Z3表示—N(R4)—、—O—或键，Z1表示—C(R2)(R2′)—、—N(R2)—等，Z2表示—C(R3)(R3′)—、—N(R3)—等，或其盐。
• Imidazole derivative, process for producing the same, and use
  申请人：Kubo Keiji

  公开号：US20070004736A1

  公开（公告）日：2007-01-04

  There is provided an imidazole derivative useful as a thrombosis treating agent, which is represented by the formula (I): wherein R represents an optionally substituted cyclic hydrocarbon group or an optionally substituted heterocyclic group, W represents a bond or an optionally substituted divalent linear hydrocarbon group, X represents an optionally substituted divalent hydrocarbon group, Y represents —CO—, —S(O)—, —S(O) 2 — or a bond, ring A represents an optionally substituted pyrrolidine ring, an optionally substituted piperidine ring or an optionally substituted perhydroazepine ring, Z 1 and Z 3 independently represent a bond or an optionally substituted divalent linear hydrocarbon group, Z 2 represents —N(R 1 )—, —O—, —S(O)—, —S(O) 2 —, —CO—, —CH(R 1 )— or a bond, ring B represents an optionally substituted imidazole ring, wherein a substituent which the optionally substituted imidazole ring represented by ring B may have may be taken together with R 1 to form an optionally substituted ring, and a represents 0, 1 or 2.

  提供了一种咪唑衍生物，用作治疗血栓的药物，其化学式表示为(I)式：其中R代表可选取代的环烃基或可选取代的杂环基，W代表键或可选取代的二价直链烃基，X代表可选取代的二价烃基，Y代表-CO-、-S(O)-、-S(O)2-或键，环A代表可选取代的吡咯烷环、可选取代的哌啶环或可选取代的过氢杂环己烷环，Z1和Z3独立地代表键或可选取代的二价直链烃基，Z2代表-N(R1)-、-O-、-S(O)-、-S(O)2-、-CO-、-CH(R1)-或键，环B代表可选取代的咪唑环，其中可选取代的咪唑环所具有的取代基可以与R1一起形成可选取代的环，a代表0、1或2。
• Thiazoline derivative and use of the same
  申请人：Kubo Keiji

  公开号：US20070010528A1

  公开（公告）日：2007-01-11

  A thiazoline derivative represented by Formula (I): wherein R is a cyclic hydrocarbon group which may be substituted, or a heterocyclic group which may be substituted; X is a bond or a divalent chain hydrocarbon group which may be substituted; X′ is a bond or —N(R 5 )—; Y is a divalent hydrocarbon group which may be substituted; Y′ is a bond or —C(═O)—; ring A is a nitrogen-containing heterocycle which may be substituted; Z 1 and Z 3 are each independently a bond or a divalent chain hydrocarbon group which may be substituted; Z 2 is a bond or —N(R 6 )—; and B is a group represented by the formula: which is useful as a therapeutic drug for thrombosis, is provided.

  提供一种由式（I）表示的噻唑啉衍生物：其中R是环烃基，可以被取代，或者是可以被取代的杂环基; X是键或二价链烃基，可以被取代; X'是键或-N(R5)-; Y是二价烃基，可以被取代; Y'是键或-C(═O)-; 环A是含氮杂环，可以被取代; Z1和Z3各自独立地是键或二价链烃基，可以被取代; Z2是键或-N(R6)-; B是下式表示的基团：该化合物可用作治疗血栓症的药物。
• Cyclic amide derivative, and its production and use
  申请人：Kubo Keiji

  公开号：US20080255352A1

  公开（公告）日：2008-10-16

  The present invention provides a cyclic amide derivative useful as a drug for treating thrombosis, which is represented by the formula (I): wherein R 1 represents an optionally substituted cyclic hydrocarbon group or an optionally substituted heterocyclic group, W represents a bond or an optionally substituted divalent chain hydrocarbon group, a represents 0, 1, or 2, X 1 represents an optionally substituted lower alkylene or an optionally substituted lower alkenylene, Y 1 represents —C(O)—, —S(O)— or —S(O) 2 —, A represents a piperazine ring which may be further substituted or a piperidine ring which may be further substituted, X 2 represents a bond or an optionally substituted lower alkylene, Y 2 represents —C(O)—, —S(O)—, —S(O) 2 — or —C(═NR 7 )—, X 3 represents an optionally substituted C 1-4 alkylene or an optionally substituted C 2-4 alkenylene, Z 3 represents —N(R 4 )—, —O— or a bond, Z 1 represents —C(R 2 )(R 2′ )—, —N(R 2 )—, etc., and Z 2 represents —C(R 3 )(R 3′ )—, —N(R 3 )—, etc., or a salt thereof.

  本发明提供了一种用于治疗血栓症的环酰胺衍生物，其化学式表示为(I)：其中，R1代表可选取代的环烃基或可选取代的杂环基，W代表键或可选取代的双价链烃基，a代表0、1或2，X1代表可选取代的较低烷基烯基或可选取代的较低烷基，Y1代表—C（O）—、—S（O）—或—S（O）2—，A代表可进一步取代的哌嗪环或可进一步取代的吡啶环，X2代表键或可选取代的较低烷基，Y2代表—C（O）—、—S（O）—、—S（O）2—或—C（═NR7）—，X3代表可选取代的C1-4烷基或可选取代的C2-4烯基，Z3代表—N（R4）—、—O—或键，Z1代表—C（R2）（R2′）—、—N（R2）—等，Z2代表—C（R3）（R3′）—、—N（R3）—等，或其盐。