5-(cyclopropylmethyl)-1,3,4-thiadiazole-2-amine | 299937-30-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(cyclopropylmethyl)-1,3,4-thiadiazole-2-amine
• 英文别名: 5-cyclopropylmethyl-[1,3,4]thiadiazol-2-ylamine；5-(cyclopropylmethyl)-1,3,4-thiadiazol-2-amine
• CAS: 299937-30-7
• 化学式: C₆H₉N₃S
• 分子量: 155.224
• InChiKey: WBXJSQZWPQDHJY-UHFFFAOYSA-N

物化性质

• 沸点：
  318.2±25.0 °C(Predicted)
• 密度：
  1.414±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  80
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(cyclopropylmethyl)-1,3,4-thiadiazole-2-amine 在 N-甲基吗啉 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 2-((1-((5-(Cyclopropylmethyl)-1,3,4-thiadiazol-2-yl)carbamoyl)cyclopentyl)methyl)pentanoic acid
  参考文献：
  名称：

  Novel Selective Inhibitors of Neutral Endopeptidase for the Treatment of Female Sexual Arousal Disorder. Synthesis and Activity of Functionalized Glutaramides

  摘要：

  Female sexual arousal disorder (FSAD) is a highly prevalent sexual disorder affecting up to 40% of women. We describe herein our efforts to identify a selective neutral endopeptidase (NEP) inhibitor as a potential treatment for FSAD. The rationale for this approach, together with a description of the medicinal chemistry strategy, lead compounds, and SAR investigations are detailed. In particular, the strategy of starting with the clinically precedented selective NEP inhibitor, Candoxatrilat, and targeting low molecular weight and relatively polar mono-carboxylic acids is described. This led ultimately to the prototype development candidate R-13, for which detailed pharmacology and pharmacokinetic parameters are presented.(1)

  DOI：

  10.1021/jm060133g
• 作为产物：
  描述：

  环丙乙腈 、 氨基硫脲 在 三氟乙酸 作用下， 反应 2.0h， 以536 mg的产率得到5-(cyclopropylmethyl)-1,3,4-thiadiazole-2-amine
  参考文献：
  名称：

  NITROGEN-CONTAINING HETEROCYCLIC COMPOUND OR SALT THEREOF

  摘要：

  由式[1]表示的化合物（在该式中，Z表示N、CH或类似物；X表示NH或类似物；R表示杂环烷基或类似物；R2、R3和R4中的每一个表示氢原子、卤原子、烷氧基或类似物；R5表示杂环烷基或类似物）或其盐。

  公开号：

  US20150322063A1

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。
• [EN] CYCLOPENTYL-SUBSTITUTED GLUTARAMIDE DERIVATIVES AS INHIBITORS OF NEUTRAL ENDOPEPTIDASE<br/>[FR] DERIVES DE GLUTARAMIDE SUBSTITUES PAR DU CYCLOPENTYL UTILISES COMME INHIBITEURS DE L'ENDOPEPTIDASE NEUTRE
  申请人：PFIZER LTD

  公开号：WO2002002513A1

  公开（公告）日：2002-01-10

  The invention provides compounds of formula I wherein R1 is optionally substituted C¿1?-6alkyl, optionally substituted C3-7 cycloalkyl, optionally substituted aryl or optionally substituted heterocyclyl; n is 0, 1 or 2; and Y is -NR?18S(O)¿uR19 or a group shown below.

  该发明提供了公式I的化合物，其中R1是可选取代的C1-6烷基，可选取代的C3-7环烷基，可选取代的芳基或可选取代的杂环基；n为0，1或2；Y为-NR?18S(O)uR19或下图所示的基团。
• Cyclopentyl-substituted glutaramide derivatives as inhibitors of neutral endopeptidase
  申请人：——

  公开号：US20020052370A1

  公开（公告）日：2002-05-02

  The invention provides compounds of formula I wherein R 1 is optionally substituted C 1-6 alkyl, optionally substituted C 3-7 cycloalkyl, optionally substituted aryl or optionally substituted heterocyclyl; n is 0, 1 or 2; and Y is —NR 18 S(O) u R 19 or a group shown below. 1

  本发明提供了式I的化合物，其中R1是可选取代的C1-6烷基，可选取代的C3-7环烷基，可选取代的芳基或可选取代的杂环基；n为0、1或2；Y为—NR18S(O)uR19或下图所示的基团1。
• 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。