(5-amino-3-chloro-4-methyl-thiophen-2-yl)-morpholin-4-yl-methanone | 778611-41-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: (5-amino-3-chloro-4-methyl-thiophen-2-yl)-morpholin-4-yl-methanone
• 英文别名: (3-chloro-4-methyl-5-aminothiophen-2-yl)morpholin-4-ylmethanone；(5-amino-3-chloro-4-methylthiophen-2-yl)-morpholin-4-ylmethanone
• CAS: 778611-41-9
• 化学式: C₁₀H₁₃ClN₂O₂S
• 分子量: 260.744
• InChiKey: RPFNEXIPWYAHJM-UHFFFAOYSA-N

物化性质

• 沸点：
  497.8±45.0 °C(Predicted)
• 密度：
  1.405±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  83.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (5-amino-3-chloro-4-methyl-thiophen-2-yl)-morpholin-4-yl-methanone 在 劳森试剂 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 42.0h， 生成 1-[5-tert-butyl-2-(4-fluoro-phenyl)-2H-pyrazol-3-yl]-3-[4-chloro-3-methyl-5-(morpholine-4-carbothioyl)-thiophen-2-yl]urea
  参考文献：
  名称：

  [EN] 5-MORPHOLINYLMETHYLTHIOPHENYL PHARMACEUTIAL COMPOUNDS AS P38 MAP KINASE MODULATORS
  [FR] COMPOSES PHARMACEUTIQUES DE 5-MORPHOLINYLMETHYLTHIOPHENYLE UTILISES COMME MODULATEURS DE LA P38 MAP KINASE

  摘要：

  该发明提供了化合物的结构式(I)或其盐、溶剂合物或N-氧化物，其中：R1和R2相同或不同，每个都选择自氢、饱和的C1-3烃基、卤素和氰基；X选择自C=O、C=S、C(=O)NH、C(=S)NH、C(=O)O、C(=O)S、C(=S)O和C(=S)S；R3选择自芳香族和杂环芳基，每个有5到12个环成员，并且未取代或通过一个或多个在权利要求中定义的取代基R10取代；R4和R5相同或不同，选择自氢和甲基；或者R4和R5中的一个选择自羟甲基和乙基，另一个为氢；R6和R7相同或不同，选择自氢和甲基。该结构式(I)的化合物具有作为p38 MAP激酶和Taf激酶抑制剂的活性。

  公开号：

  WO2005100338A1
• 作为产物：
  描述：

  3-氯-4-甲基-2-硫代苯羧酸 在 nitronium tetrafluoborate 、 铁粉 、 1-羟基苯并三唑 、 iron(II) sulfate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 22.0h， 生成 (5-amino-3-chloro-4-methyl-thiophen-2-yl)-morpholin-4-yl-methanone
  参考文献：
  名称：

  [EN] 5-MORPHOLINYLMETHYLTHIOPHENYL PHARMACEUTIAL COMPOUNDS AS P38 MAP KINASE MODULATORS
  [FR] COMPOSES PHARMACEUTIQUES DE 5-MORPHOLINYLMETHYLTHIOPHENYLE UTILISES COMME MODULATEURS DE LA P38 MAP KINASE

  摘要：

  该发明提供了化合物的结构式(I)或其盐、溶剂合物或N-氧化物，其中：R1和R2相同或不同，每个都选择自氢、饱和的C1-3烃基、卤素和氰基；X选择自C=O、C=S、C(=O)NH、C(=S)NH、C(=O)O、C(=O)S、C(=S)O和C(=S)S；R3选择自芳香族和杂环芳基，每个有5到12个环成员，并且未取代或通过一个或多个在权利要求中定义的取代基R10取代；R4和R5相同或不同，选择自氢和甲基；或者R4和R5中的一个选择自羟甲基和乙基，另一个为氢；R6和R7相同或不同，选择自氢和甲基。该结构式(I)的化合物具有作为p38 MAP激酶和Taf激酶抑制剂的活性。

  公开号：

  WO2005100338A1

文献信息

• [EN] 5-AMINO-2-CARBONYLTHIOPHENE DERIVATIVES FOR USE AS P38 MAP KINASE INHIBITORS IN THE TREATMENT OF INFLAMMATORY DISEASES<br/>[FR] DERIVES DE 5-AMINO-2-CARBONYLTHIOPHENE UTILISES EN TANT QU'INHIBITEURS DE LA P38 MAP KINASE DANS LE TRAITEMENT DES MALADIES INFLAMMATOIRES
  申请人：ASTEX TECHNOLOGY LTD

  公开号：WO2004089929A1

  公开（公告）日：2004-10-21

  The invention provides the use of a compound for the manufacture of a medicament for the prophylaxis or treatment of a disease state or condition mediated by a p38 MAP kinase; the compound being defined by formula (I): wherein: R1 and R2 are the same or different and each is selected from hydrogen, C1-4 hydrocarbyl, halogen and cyano; X is selected from C=O, C=S, C(=O)NH, C(=S)NH, C(=O)O, C(=O)S, C(=S)O and C(=S)S; R3 is selected from aryl and heteroaryl groups each having from 5 to 12 ring members, the aryl and heteroaryl groups each being unsubstituted or substituted by one or more substituent groups R7 selected from halogen, hydroxy, trifluoromethyl, cyano, nitro, carboxy, amino, carbocyclic and heterocyclic groups having from 3 to 12 ring members; a group Ra-Rb wherein Ra is a bond, 0, CO, X1C(X2), C(X2)X1, X1C(X2)X1, S, SO, SO2, NRc, SO2NRc or NRcSO2; and Rb is selected from hydrogen, carbocyclic and heterocyclic groups having from 3 to 7 ring members, and a C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from hydroxy, oxo, halogen, cyano, nitro, amino, mono- or di-C1-4 hydrocarbylamino, carbocyclic and heterocyclic groups having from 3 to 12 ring members and wherein one or more carbon atoms of the C1-8 hydrocarbyl group may optionally be replaced by 0, S, SO, SO2, NRc, X1C(X2), C(X2)X1 or X1C(X2)X1; X1 is 0, S or NRc and X2 is =0, =S or =NRc; Rc is hydrogen or C1-4 hydrocarbyl; R4 is a group YR5 or a group R6; Y is is NH, 0 or S; R5 is selected from (a) carbocyclic and heterocyclic groups having from 3 to 12 ring members; and (b) C1-8 hydrocarbyl groups optionally substituted by one or more substituents selected from hydroxy, oxo, halogen, cyano, amino, mono- or di- C1-4 hydrocarbylamino, and carbocyclic and heterocyclic groups having from 3 to 12 ring members, wherein one or more carbon atoms of the C1-8 hydrocarbyl group may optionally be replaced by 0, S, SO, SO2, NRc, X1C(X2), C(X2)X1 or X1C(X2)X1, provided that when Y is 0, a carbon atom adjacent to the group Y is not replaced by 0; and R6 is a heterocyclic group having from 4 to 12 ring members and containing at least one ring nitrogen atom through which R6 is linked to the adjacent carbonyl group; wherein the carbocyclic and heterocyclic groups of substituents R5 and R6 are each unsubstituted or substituted by one or more substituent groups R7 as hereinbefore defined. Also provided are novel compounds, pharmaceutical compositions containing the compounds and methods for their preparation.

  本发明提供了一种化合物的用途，用于制备用于预防或治疗由p38 MAP激酶介导的疾病状态或病况的药物；该化合物由以下式（I）定义：其中：R1和R2相同或不同，每个均选择自氢、C1-4烃基、卤素和氰基；X选择自C=O、C=S、C(=O)NH、C(=S)NH、C(=O)O、C(=O)S、C(=S)O和C(=S)S；R3选择自含有5至12个环成员的芳基和杂环芳基，芳基和杂环芳基未取代或通过一个或多个取代基R7取代，所述取代基R7选择自卤素、羟基、三氟甲基、氰基、硝基、羧基、氨基、具有3至12个环成员的碳环和杂环基；一个基团Ra-Rb，其中Ra为键，0，CO，X1C(X2)，C(X2)X1，X1C(X2)X1，S，SO，SO2，NRc，SO2NRc或NRcSO2；Rb选择自氢、具有3至7个环成员的碳环和杂环基，以及一个C1-8烃基，可选地通过一个或多个取代基选择自羟基、酮基、卤素、氰基、硝基、氨基、单或双C1-4烃基氨基、具有3至12个环成员的碳环和杂环基取代，并且C1-8烃基的一个或多个碳原子可选地被0、S、SO、SO2、NRc、X1C(X2)、C(X2)X1或X1C(X2)X1替代；X1为0、S或NRc，X2为=0、=S或=NRc；Rc为氢或C1-4烃基；R4为一个基团YR5或一个基团R6；Y为NH、0或S；R5选择自（a）具有3至12个环成员的碳环和杂环基；和（b）可选地通过一个或多个取代基选择自羟基、酮基、卤素、氰基、氨基、单或双C1-4烃基氨基、具有3至12个环成员的碳环和杂环基取代的C1-8烃基，其中C1-8烃基的一个或多个碳原子可选地被0、S、SO、SO2、NRc、X1C(X2)、C(X2)X1或X1C(X2)X1替代，但是当Y为0时，与基团Y相邻的碳原子不被0替代；R6为具有4至12个环成员的杂环基，并且通过其中一个环氮原子与相邻的羰基连接；取代基R5和R6的碳环和杂环基各自未取代或通过一个或多个取代基R7取代，如前所述。还提供了新的化合物、含有该化合物的制剂以及其制备方法。
• [EN] THIOPHENE AMIDE COMPOUNDS FOR USE IN THE TREATMENT OR PROPHYLAXIS OF CANCERS<br/>[FR] COMPOSES D'AMIDE THIOPHENIQUE DESTINES A ETRE UTILISES DANS LE TRAITEMENT OU LA PROPHYLAXIE DU CANCER
  申请人：ASTEX THERAPEUTICS LTD

  公开号：WO2006040569A1

  公开（公告）日：2006-04-20

  The invention provides the use of a compound for the manufacture of a medicament for the prophylaxis or treatment of a cancer or a para-neoplastic effect associated with a cancer, the para-neoplastic effect being other than cachexia, and the compound being a compound of the formula (I), or a salt, solvate or N-oxide thereof, wherein: R1 and R2 are the same or different and each is selected from hydrogen, C1-4 hydrocarbyl, halogen and cyano; X is selected from C=O, C=S, C(=O)NH, C(=S)NH, C(=O)O, C(=O)S, C(=S)O and C(=S)S; R3 is an aryl or heteroaryl group of 5 to 12 ring members optionally substituted by one or more substituent groups R7 wherein R7 is as defined in the claims; R4 is a group YR5 or a group R6; Y is NH, O or S; R5 is selected from (a) optionally substituted carbocyclic and heterocyclic groups having from 3 to 12 ring members; and (b) optionally substituted C1-8 hydrocarbyl 20 groups; and R6 is an optionally substituted heterocyclic group having from 4 to 12 ring members and containing at least one ring nitrogen atom through which R6 is linked to the adjacent carbonyl group.

  该发明提供了一种化合物的用途，用于制造用于预防或治疗癌症或与癌症相关的癌前病变效应的药物，其中癌前病变效应不包括虚弱症，该化合物为式(I)的化合物，或其盐、溶剂合物或N-氧化物，其中：R1和R2相同或不同，每个均选自氢、C1-4烃基、卤素和氰基；X选自C=O、C=S、C(=O)NH、C(=S)NH、C(=O)O、C(=O)S、C(=S)O和C(=S)S；R3为含有5至12个环成员的芳基或杂芳基，可以选择地被一个或多个取代基R7取代，其中R7如索引中定义；R4为一个基团YR5或一个基团R6；Y为NH、O或S；R5选自(a)从3到12个环成员的可选择取代的碳环和杂环基团；以及(b)可选择取代的C1-8烃基基团；R6为一个含有从4到12个环成员的可选择取代的杂环基团，并且至少包含一个环氮原子，通过该环氮原子，R6与相邻的酰基基团连接。
• 5 Amino-2-carbonylthiophene derivatives for use as p38 map kinase inhibitors in the treatment of inflammatory diseases
  申请人：Gill Liam Adrian

  公开号：US20070082898A1

  公开（公告）日：2007-04-12

  The invention provides the use of a compound for the manufacture of a medicament for the prophylaxis or treatment of a disease state or condition mediated by a p38 MAP kinase; the compound being defined by formula (I): wherein: R 1 and R 2 are the same or different and each is selected from hydrogen, C 1-4 hydrocarbyl, halogen and cyano; X is selected from C═O, C═S, C(═O)NH, C(═S)NH, C(═O)O, C(═O)S, C(═S)O and C(═S)S; R 3 is selected from aryl and hetcroaryl groups each having from 5 to 12 ring members, the aryl and heteroaryl groups each being unsubstituted or substituted by one or more substituent groups R 7 selected from halogen, hydroxy, trifluoromethyl, cyano, nitro, carboxy, amino, carbocyclic and heterocyclic groups having from 3 to 12 ring members; a group R a —R b wherein R a is a bond, 0, CO, X 1 C(X 2 ), C(X 2 )X 1 , X 1 C(X 2 )X 1 , S, SO, SO 2 , NR c , SO 2 NR c or NR c SO 2 ; and R b is selected from hydrogen, carbocyclic and heterocyclic groups having from 3 to 7 ring members, and a C 1-8 hydrocarbyl group optionally substituted by one or more substituents selected from hydroxy, oxo, halogen, cyano, nitro, amino, mono- or di-C 1-4 hydrocarbylamino, carbocyclic and heterocyclic groups having from 3 to 12 ring members and wherein one or more carbon atoms of the C 1-8 hydrocarbyl group may optionally be replaced by O, S, SO, SO 2 , NR c , X 1 C(X 2 ), C(X 2 )X 1 or X 1 C(X 2 )X 1 ; X 1 is O, S or NR c and X 2 is ═O, ═S or ═NR c ; R c is hydrogen or C 1-4 hydrocarbyl; R 4 is a group YR 5 or a group R 6 ; Y is is NH, O or S; R 5 is selected from (a) carbocyclic and heterocyclic groups having from 3 to 12 ring members; and (b) C 1-8 hydrocarbyl groups optionally substituted by one or more substituents selected from hydroxy, oxo, halogen, cyano, amino, mono- or di- C 1-4 hydrocarbylamino, and carbocyclic and heterocyclic groups having from 3 to 12 ring members, wherein one or more carbon atoms of the C 1-8 hydrocarbyl group may optionally be replaced by O, S, SO, SO 2 , NR c , X 1 C(X 2 ), C(X 2 )X 1 or X 1 C(X 2 )X 1 , provided that when Y is O, a carbon atom adjacent to the group Y is not replaced by O; and R 6 is a heterocyclic group having from 4 to 12 ring members and containing at least one ring nitrogen atom through which R 6 is linked to the adjacent carbonyl group; wherein the carbocyclic and heterocyclic groups of substituents R 5 and R 6 are each unsubstituted or substituted by one or more substituent groups R 7 as hereinbefore defined. Also provided are novel compounds, pharmaceutical compositions containing the compounds and methods for their preparation.

  本发明提供了一种化合物的使用，用于制造预防或治疗由p38 MAP激酶介导的疾病状态或病情的药物；该化合物由公式（I）定义：其中：R1和R2相同或不同，分别选自氢，C1-4烃基，卤素和氰基；X选自C═O，C═S，C（═O）NH，C（═S）NH，C（═O）O，C（═O）S，C（═S）O和C（═S）S；R3选自含有5至12个环成员的芳基和杂环芳基基团，芳基和杂环芳基基团均未取代或取代了一个或多个取代基R7，所述取代基R7选自卤素，羟基，三氟甲基，氰基，硝基，羧基，氨基，碳环和含有3至12个环成员的杂环基团；Ra-Rb基团，其中Ra为键，0，CO，X1C（X2），C（X2）X1，X1C（X2）X1，S，SO，SO2，NRc，SO2NRc或NRcSO2；Rb选自氢，含有3至7个环成员的碳环和杂环基团，以及C1-8烃基，可选地取代一个或多个取代基，所述取代基选自羟基，氧代基，卤素，氰基，硝基，氨基，单或双C1-4烃基氨基，碳环和含有3至12个环成员的杂环基团，其中C1-8烃基的一个或多个碳原子可以选为O，S，SO，SO2，NRc，X1C（X2），C（X2）X1或X1C（X2）X1；X1为O，S或NRc，X2为═O，═S或═NRc；Rc为氢或C1-4烃基；R4为基团YR5或基团R6；Y选自NH，O或S；R5选自（a）含有3至12个环成员的碳环和杂环基团；和（b）可选地取代一个或多个取代基的C1-8烃基，所述取代基选自羟基，氧代基，卤素，氰基，氨基，单或双C1-4烃基氨基，以及含有3至12个环成员的碳环和杂环基团，其中C1-8烃基的一个或多个碳原子可以选为O，S，SO，SO2，NRc，X1C（X2），C（X2）X1或X1C（X2）X1，但当Y为O时，与基团Y相邻的碳原子不被O取代；R6为含有4至12个环成员的杂环基团，且通过至少一个环氮原子与相邻的羰基基团连接，其中取代基R5和R6的碳环和杂环基团均未取代或取代了一个或多个取代基R7，如前所述。还提供了新的化合物，含有该化合物的制药组合物以及其制备方法。
• 5-Morpholinylmethylthiophenyl Pharmaceutical Compounds As P38 MAP Kinase Modulators
  申请人：Gill Liam Adrian

  公开号：US20070208015A1

  公开（公告）日：2007-09-06

  The invention provides compounds of the formula (I) or a salt, solvate or N-oxide thereof, wherein: R 1 and R 2 are the same or different and each is selected from hydrogen, saturated C 1-3 hydrocarbyl, halogen and cyano; X is selected from C═O, C═S, C(═O)NH, C(═S)NH, C(═O)O, C(═O)S, C(═S)O and C(═S)S; R 3 is selected from aryl and heteroaryl groups each having from 5 to 12 ring members and being unsubstituted or substituted by one or more substituent groups R 10 as defined in the claims; R 4 and R 5 are the same or different and are selected from hydrogen and methyl; or one of R 4 and R 5 is selected from hydroxymethyl and ethyl and the other is hydrogen; and R 6 and R 7 are the same or different and are selected from hydrogen and methyl. The compounds of the formula (I) hayed activity as p38 MAP kinase and Taf kinase inhibitors.

  本发明提供公式（I）的化合物或其盐，溶剂化合物或N-氧化物，其中：R1和R2相同或不同，每个都从氢，饱和的C1-3烃基，卤素和氰中选择；X从C═O，C═S，C（═O）NH，C（═S）NH，C（═O）O，C（═O）S，C（═S）O和C（═S）S中选择；R3从芳基和杂环基中选择，每个具有从5到12个环成员，未取代或被一个或多个R10取代，如权利要求所定义；R4和R5相同或不同，选择从氢和甲基中选择；或者R4和R5中的一个选择从羟甲基和乙基中选择，另一个是氢；R6和R7相同或不同，选择从氢和甲基中选择。公式（I）的化合物具有作为p38 MAP激酶和Taf激酶抑制剂的活性。
• EP1615907A1
  申请人：——

  公开号：EP1615907A1

  公开（公告）日：2006-01-18