1-benzoyl-2-[2-(2-guanidinothiazol-4-ylmethylthio)ethyl]-3-[2-(imidazol-4-yl)ethyl]guanidine

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-benzoyl-2-[2-(2-guanidinothiazol-4-ylmethylthio)ethyl]-3-[2-(imidazol-4-yl)ethyl]guanidine
• 英文别名: N-[N'-[2-[(diaminomethylideneamino)-(1,3-thiazol-4-yl)methyl]sulfanylethyl]-N-[2-(1H-imidazol-5-yl)ethyl]carbamimidoyl]benzamide
• 化学式: C₂₀H₂₅N₉OS₂
• 分子量: 471.61
• InChiKey: SVZZKSZERRUMLF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  32
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  213
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-benzoyl-3-[2-(2-guanidinothiazol-4-ylmethylthio)ethyl]thiourea 、 histamine dichloride 、 N,N-二甲基甲酰胺 在 silver nitrate 、 三乙胺 作用下， 生成 1-benzoyl-2-[2-(2-guanidinothiazol-4-ylmethylthio)ethyl]-3-[2-(imidazol-4-yl)ethyl]guanidine
  参考文献：
  名称：

  Antisecretory guanidine derivatives and pharmaceutical compositions

  摘要：

  该发明涉及公式I的胍基衍生物：Het.sup.1 -(CH.sub.2).sub.m -Y.sup.1 -(CH.sub.2).sub.n -NR.sup.1 -A-NR.sup.2 -(CH.sub.2).sub.q -Y.sup.2 -(CH.sub.2).sub.p -Het.sup.2 I，其中Y.sup.1和Y.sup.2为O、S、直链键、CH.sub.2或SO；m和p为0至4，n和q为1至4，前提是当Y.sup.1或Y.sup.2为O、S或SO时，m或p为1至4，并且当Y.sup.1或Y.sup.2为O或SO时，n或q为2至4；R.sup.1和R.sup.2中的一个为氢，另一个为氢或C.sub.(1-6)烷基；A为3,4-二氧代环丁烷-1,2-二基或C.dbd.Z，其中Z为S、O、NCN、NNO.sub.2、CHNO.sub.2、NCONH.sub.2、C(CN).sub.2、NCOR.sup.3、NCO.sub.2 R.sup.3 NSO.sub.2 R.sup.3或NR.sup.4，其中R.sup.3为C.sub.(1-6)烷基或C.sub.(6-12)芳基，R.sup.4为氢或C.sub.(1-6)烷基或当R.sup.1和R.sup.2为氢时，A为-A.sup.1 -E.sup.1 -G-E.sup.2 -A.sup.2 - II，其中A.sup.1和A.sup.2为3,4-二氧代环丁烷-1,2-二基或C.dbd.Z.sup.1和C.dbd.Z.sup.2，其中Z.sup.1和Z.sup.2与Z相同，E.sup.1和E.sup.2为O或S或NH，可选择地被C.sub.(1-10)烷基、C.sub.(3-10)烯基、C.sub.(3-10)炔基、C.sub.(3-8)环烷基、C.sub.(2-6)（一次羟基）烷基、C.sub.(3-10)烷氧基烷基、C.sub.(3-10)烷基氨基或C.sub.(3-10)二烷基氨基取代，G为C.sub.(2-12)烷基、C.sub.(4-12)烯基、C.sub.(4-12)炔基或C.sub.(3-12)羟基烷基；Het.sup.1为噁唑-4-基、噻唑-4-基或咪唑-4-基，在2-位被取代为：##STR1##或Het.sup.1为1,2,4-噻二唑-3-基或1,2,4-氧二唑-3-基，在5-位被基团III取代，其中R.sup.5为氢、C.sub.(1-10)烷基、C.sub.(1-6)醇酰基或C.sub.(7-11)芳酰基；Het.sup.2与Het.sup.1相同或由C.sub.(1-6)烷基、C.sub.(1-6)烷氧基、OH、CF.sub.3、HOCH.sub.2、NH.sub.2或卤素取代的未融合的含N的5-或6-成员单环杂环，或Het.sup.2为##STR2##其中B为直链或支链C.sub.(1-6)烷基，R.sup.6和R.sup.7为氢、C.sub.(1-8)烷基、C.sub.(3-10)烷氧基烷基、C.sub.(3-10)烷基氨基烷基、C.sub.(3-10)二烷基氨基烷基或C.sub.(7-12)苯基烷基，可选择地在苯环上取代为C.sub.(1-6)烷基、C.sub.(1-6)烷氧基或卤素，或R.sup.6和R.sup.7连接形成含O或N的5-或6-成员饱和环，N被氢或C.sub.(1-6)烷基取代；前提是当R.sup.1和R.sup.2为氢且A为C.dbd.NH时，Y.sup.1和/或Y.sup.2为S，当R.sup.1和R.sup.2为氢、A为C.dbd.NH且Het.sup.2为咪唑时，链中的原子数：(CH.sub.2).sub.q -Y.sup.2 -(CH.sub.2).sub.p V至少为4；及其盐。

  公开号：

  US04309435A1

文献信息

• Antisecretory guanidine derivatives, processes for their manufacture and pharmaceutical compositions containing them
  申请人：IMPERIAL CHEMICAL INDUSTRIES PLC

  公开号：EP0010418B1

  公开（公告）日：1984-03-07
• US4309435A
  申请人：——

  公开号：US4309435A

  公开（公告）日：1982-01-05
• US4493840A
  申请人：——

  公开号：US4493840A

  公开（公告）日：1985-01-15
• Antisecretory guanidine derivatives and pharmaceutical compositions
  申请人：Imperial Chemical Industries Ltd.

  公开号：US04309435A1

  公开（公告）日：1982-01-05

  The invention relates to a guanidine derivative of the formula I: Het.sup.1 -(CH.sub.2).sub.m -Y.sup.1 -(CH.sub.2).sub.n -NR.sup.1 -A-NR.sup.2 -(CH.sub.2).sub.q -Y.sup.2 -(CH.sub.2).sub.p -Het.sup.2 I in which Y.sup.1 and Y.sup.2 are O, S, direct bonds, CH.sub.2 or SO; m and p are 0 to 4, n and q are 1 to 4, provided that when Y.sup.1 or Y.sup.2 is O, S or SO, m or p is 1 to 4 and provided that when Y.sup.1 or Y.sup.2 is O or SO, n or q is 2 to 4; one of R.sup.1 and R.sup.2 is hydrogen and the other is hydrogen or C.sub.(1-6) alkyl; A is 3,4-dioxocyclobuten-1,2-diyl or C.dbd.Z in which Z is S, O, NCN, NNO.sub.2, CHNO.sub.2, NCONH.sub.2, C(CN).sub.2, NCOR.sup.3, NCO.sub.2 R.sup.3 NSO.sub.2 R.sup.3 or NR.sup.4 in which R.sup.3 is C.sub.(1-6) alkyl or C.sub.(6-12) aryl and R.sup.4 is hydrogen or C.sub.(1-6) alkyl or when R.sup.1 and R.sup.2 are hydrogen A is -A.sup.1 -E.sup.1 -G-E.sup.2 -A.sup.2 - II in which A.sup.1 and A.sup.2 are 3,4-dioxocyclobuten-1,2-diyl or C.dbd.Z.sup.1 and C.dbd.Z.sup.2 in which Z.sup.1 and Z.sup.2 are the same as Z, E.sup.1 and E.sup.2 are O or S or NH optionally substituted by C.sub.(1-10) alkyl, C.sub.(3-10) alkenyl, C.sub.(3-10) alkynyl, C.sub.(3-8) cycloalkyl, C.sub.(2-6) (primary hydroxy)alkyl, C.sub.(3-10) alkoxyalkyl, C.sub.(3-10) alkylamino or C.sub.(3-10) dialkylamino and G is C.sub.(2-12) alkylene, C.sub.(4-12) alkenylene, C.sub.(4-12) alkynylene or C.sub.(3-12) hydroxyalkylene; Het.sup.1 is oxazol-4-yl, thiazol-4-yl or imidazol-4-yl substituted in the 2-position by: ##STR1## or Het.sup.1 is 1,2,4-thiadiazol-3-yl or 1,2,4-oxadiazol-3-yl substituted in the 5-position by radical III in which R.sup.5 is hydrogen, C.sub.(1-10) alkyl, C.sub.(1-6) alkanoyl or C.sub.(7-11) aroyl; Het.sup.2 is same as Het.sup.1 or an unfused N-containing 5- or 6-membered monocyclic heterocyclic ring optionally substituted by C.sub.(1-6) alkyl, C.sub.(1-6) alkoxy, OH, CF.sub.3, HOCH.sub.2, NH.sub.2 or halogen or Het.sup.2 is ##STR2## in which B is a straight or branched chain C.sub.(1-6) alkylene and R.sup.6 and R.sup.7 are hydrogen, C.sub.(1-8) alkyl, C.sub.(3-10) -alkoxyalkyl, C.sub.(3-10) alkylaminoalkyl, C.sub.(3-10) dialkylaminoalkyl, or C.sub.(7-12) phenylalkyl optionally substituted on the phenyl ring by C.sub.(1-6) alkyl, C.sub.(1-6) alkoxy, or halogen or R.sup.6 and R.sup.7 are joined to form a 5- or 6-membered saturated ring optionally containing O or N, the N substituted by hydrogen or C.sub.(1-6) alkyl; provided that when R.sup.1 and R.sup.2 are hydrogen and A is C.dbd.NH, Y.sup.1 and/or Y.sup.2 is S, and that when R.sup.1 and R.sup.2 are hydrogen, A is C.dbd.NH and Het.sup.2 is imidazole, the number of atoms in the chain: (CH.sub.2).sub.q -Y.sup.2 -(CH.sub.2).sub.p V is at least 4; and the salts thereof.

  该发明涉及公式I的胍基衍生物：Het.sup.1 -(CH.sub.2).sub.m -Y.sup.1 -(CH.sub.2).sub.n -NR.sup.1 -A-NR.sup.2 -(CH.sub.2).sub.q -Y.sup.2 -(CH.sub.2).sub.p -Het.sup.2 I，其中Y.sup.1和Y.sup.2为O、S、直链键、CH.sub.2或SO；m和p为0至4，n和q为1至4，前提是当Y.sup.1或Y.sup.2为O、S或SO时，m或p为1至4，并且当Y.sup.1或Y.sup.2为O或SO时，n或q为2至4；R.sup.1和R.sup.2中的一个为氢，另一个为氢或C.sub.(1-6)烷基；A为3,4-二氧代环丁烷-1,2-二基或C.dbd.Z，其中Z为S、O、NCN、NNO.sub.2、CHNO.sub.2、NCONH.sub.2、C(CN).sub.2、NCOR.sup.3、NCO.sub.2 R.sup.3 NSO.sub.2 R.sup.3或NR.sup.4，其中R.sup.3为C.sub.(1-6)烷基或C.sub.(6-12)芳基，R.sup.4为氢或C.sub.(1-6)烷基或当R.sup.1和R.sup.2为氢时，A为-A.sup.1 -E.sup.1 -G-E.sup.2 -A.sup.2 - II，其中A.sup.1和A.sup.2为3,4-二氧代环丁烷-1,2-二基或C.dbd.Z.sup.1和C.dbd.Z.sup.2，其中Z.sup.1和Z.sup.2与Z相同，E.sup.1和E.sup.2为O或S或NH，可选择地被C.sub.(1-10)烷基、C.sub.(3-10)烯基、C.sub.(3-10)炔基、C.sub.(3-8)环烷基、C.sub.(2-6)（一次羟基）烷基、C.sub.(3-10)烷氧基烷基、C.sub.(3-10)烷基氨基或C.sub.(3-10)二烷基氨基取代，G为C.sub.(2-12)烷基、C.sub.(4-12)烯基、C.sub.(4-12)炔基或C.sub.(3-12)羟基烷基；Het.sup.1为噁唑-4-基、噻唑-4-基或咪唑-4-基，在2-位被取代为：##STR1##或Het.sup.1为1,2,4-噻二唑-3-基或1,2,4-氧二唑-3-基，在5-位被基团III取代，其中R.sup.5为氢、C.sub.(1-10)烷基、C.sub.(1-6)醇酰基或C.sub.(7-11)芳酰基；Het.sup.2与Het.sup.1相同或由C.sub.(1-6)烷基、C.sub.(1-6)烷氧基、OH、CF.sub.3、HOCH.sub.2、NH.sub.2或卤素取代的未融合的含N的5-或6-成员单环杂环，或Het.sup.2为##STR2##其中B为直链或支链C.sub.(1-6)烷基，R.sup.6和R.sup.7为氢、C.sub.(1-8)烷基、C.sub.(3-10)烷氧基烷基、C.sub.(3-10)烷基氨基烷基、C.sub.(3-10)二烷基氨基烷基或C.sub.(7-12)苯基烷基，可选择地在苯环上取代为C.sub.(1-6)烷基、C.sub.(1-6)烷氧基或卤素，或R.sup.6和R.sup.7连接形成含O或N的5-或6-成员饱和环，N被氢或C.sub.(1-6)烷基取代；前提是当R.sup.1和R.sup.2为氢且A为C.dbd.NH时，Y.sup.1和/或Y.sup.2为S，当R.sup.1和R.sup.2为氢、A为C.dbd.NH且Het.sup.2为咪唑时，链中的原子数：(CH.sub.2).sub.q -Y.sup.2 -(CH.sub.2).sub.p V至少为4；及其盐。