2-guanidino-4-[(2-aminoethyl)thiomethyl]thiazole dihydrochloride

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-guanidino-4-[(2-aminoethyl)thiomethyl]thiazole dihydrochloride
• 英文别名: 2-<4-<<(2-aminoethyl)thio>methyl>-2-thiazolyl>guanidine dihydrochloride；tiotidine dihydrochloride；2-(4-((2-aminoethylthio)methyl)thiazol-2-yl)guanidine dihydrochloride；[4-[[(2-aminoethyl)thio]methyl]-2-thiazolyl]guanidine dihydrochloride；2-[(2-guanidino-4-thiazolyl)methylthio]ethylamine dihydrochloride；2-[(2-guanidinothiazol-4-yl)methylthio]ethylamine dihydrochloride；2-[[2-(Diaminomethylideneamino)-1,3-thiazol-4-yl]methylsulfanyl]ethylazanium;chloride
• 化学式: C₇H₁₃N₅S₂*2ClH
• 分子量: 304.268
• InChiKey: ALUADPCVKGLEJH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.66
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  157
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-guanidino-4-[(2-aminoethyl)thiomethyl]thiazole dihydrochloride 在 水 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 3.0h， 生成 N-[2-[[2-(diaminomethylideneamino)-1,3-thiazol-4-yl]methylsulfanyl]ethyl]-2-hydroxyacetamide
  参考文献：
  名称：

  NOVEL COMPOUND, ORGANIC CATION TRANSPORTER 3 DETECTION AGENT, AND ORGANIC CATION TRANSPORTER 3 ACTIVITY INHIBITOR

  摘要：

  公开号：

  EP3018125B1
• 作为产物：
  描述：

  半胱胺盐酸盐 、 2-胍基-4-氯甲基噻唑盐酸盐 在 sodium ethanolate 、 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 18.25h， 以79.5%的产率得到2-guanidino-4-[(2-aminoethyl)thiomethyl]thiazole dihydrochloride
  参考文献：
  名称：

  NOVEL COMPOUND, ORGANIC CATION TRANSPORTER 3 DETECTION AGENT, AND ORGANIC CATION TRANSPORTER 3 ACTIVITY INHIBITOR

  摘要：

  公开号：

  EP3018125B1

文献信息

• Synthesis and Pharmacology of Combined Histamine H1-/H2-Receptor Antagonists Containing Diphenhydramine and Cyproheptadine Derivatives
  作者：Cornelia Wolf、Walter Schunack

  DOI：10.1002/ardp.19963290206

  日期：——

  The classical histamine H1‐receptor antagonists diphenhydramine (3a) and cyproheptadine (9) and their derivatives (3b—d, 10) were connected with a 2‐guanidinothiazole containing structure (28) derived from the H2‐receptor antagonist tiotidine in order to obtain combined H1‐/H2‐receptor antagonists. The two moieties were not directly linked together, but were separated by a polymethylene spacer and

  经典的组胺 H1 受体拮抗剂苯海拉明 (3a) 和赛庚啶 (9) 及其衍生物 (3b — d, 10) 与 H2 受体拮抗剂噻替丁衍生的含有 2-胍基噻唑的结构 (28) 连接以获得联合 H1/H2 受体拮抗剂。这两个部分没有直接连接在一起，而是由一个聚亚甲基间隔基和一个极性基团（硝基乙二胺或尿素）隔开。由此获得了 12 种化合物，它们分别在离体豚鼠回肠 (H1) 和离体豚鼠右心房 (H2) 处分别具有高 H1 和 H2 受体拮抗剂活性。苯海拉明和赛庚啶组分的掺入提供了对 H1 受体的高亲和力。然而，三环赛庚啶及其 10,11-二氢衍生物 (30–32, 34)，与苯海拉明 (29a-d, 33a-d) 相比，导致 H2-受体拮抗剂效力降低。使用硝基乙二胺作为极性基团显然更有利于 H1 和 H2 受体亲和力作为尿素功能。所有化合物都引起竞争性和非竞争性拮抗的双重模式。在新化合物中，具有 4-氟-或
• Sulfonamidines, process for the production thereof and pharmaceutical
  申请人：Ferrer Internacional S.A.

  公开号：US04728655A1

  公开（公告）日：1988-03-01

  Sulfonamidine is disclosed of the general formula (I): R--NH--CH.dbd.N--SO.sub.2 --R.sub.1 (I) wherein R is a group selected from 2-[[(5-methyl-1H-imidazole-4-yl)methyl]thio]ethyl], 2-[[[5-[(dimethylamino)methyl]-2-furanyl]methyl]thio]ethyl, 2-[[[2-[(aminoiminomethyl)amino]-4-thiazolyl]methyl]thio]ethyl] or 3-[3-(1-piperidinylmethyl)phenoxy] propyl and R.sub.1 is alkyl; or a phenyl group optionally substituted by alkyl, halogen, nitro, alkoxy, alkanoylamino, carboxylic acid, alkoxycarbonyl, dialkylamino, alkylsulphonyl, alkylsulphonylamino or alkylthio; or 1,3,4-thiadiazole-2-yl substituted by alkanoylamino, and the pharmaceutically acceptable salts thereof, as well as a process for preparing these compounds and pharmaceutical compositions containing the same. These compounds have antiulcer activity and can be used in the treatment of peptic ulcers and other pathologies caused or stimulated by gastric acidity.

  Sulfonamidine揭示了一般式(I)：R--NH--CH.dbd.N--SO.sub.2 --R.sub.1 (I)，其中R是从2-[[(5-甲基-1H-咪唑-4-基)甲基]硫基]乙基，2-[[[5-[(二甲氨基)甲基]-2-呋喃基]甲基]硫基]乙基，2-[[[2-[(氨基亚甲基)氨基]-4-噻唑基]甲基]硫基]乙基或3-[3-(1-哌啶基甲基)苯氧基]丙基中选择的基团，而R.sub.1是烷基；或者是苯基，可以选择地被烷基，卤素，硝基，烷氧基，烷酰胺基，羧酸，烷氧羰基，二烷基氨基，烷基磺酰基，烷基磺酰胺基或烷基硫基取代；或者是被烷酰胺基取代的1,3,4-噻二唑-2-基；以及其药学上可接受的盐，以及制备这些化合物的方法和含有这些化合物的药物组合物。这些化合物具有抗溃疡活性，可用于治疗消化性溃疡和其他由胃酸引起或刺激的病理。
• Anti-ulcer urea compounds
  申请人：G. D. Searle & Co.

  公开号：US04386211A1

  公开（公告）日：1983-05-31

  The invention relates to certain urea derivatives of the formula R.sub.1 CH.sub.2 S(CH.sub.2).sub.2 NHCONHR.sub.2 where R.sub.1 are certain furanyls, imidazoles and thiazolyls and R.sub.2 are certain imidazoles and thiazolyls. These compounds are H-2 histamine receptor inhibitors and therefore useful in the treatment of ulcers.

  该发明涉及一些尿素衍生物，其化学式为R.sub.1 CH.sub.2 S(CH.sub.2).sub.2 NHCONHR.sub.2，其中R.sub.1为某些呋喃基、咪唑基和噻唑基，R.sub.2为某些咪唑基和噻唑基。这些化合物是H-2组胺受体抑制剂，因此在溃疡治疗中具有用途。
• Synthese und kombinierte H1-/H2-antagonistische Aktivität von Mepyramin-, Pheniramin- und Cyclizin-Derivaten mit Cyanoguanidin-, Harnstoff- und Nitroethendiamin-Partialstrukturen
  作者：Frank R. Schulze、Rudi A. Alisch、Armin Buschauer、Walter Schunack

  DOI：10.1002/ardp.19943270708

  日期：——

  Durch die Verknüpfung typischer Partialstrukturen von H1 und H2‐Antagonisten über eine Cyanoguanidin‐, Harnstoff‐ oder Nitroethendiamin‐gruppe wurden Substanzen mit kombinierter H1‐/H2‐antihistaminischer Wirkung synthetisiert. Der Verlust des basischen Seitenketten‐Stickstoffs führt am H1‐Rezeptor des Meerschweinchenileums zu einem Abfall der Aktivität im Vergleich zu den betreffenden Referenzsubstanzen

  通过氰基胍、尿素或硝基乙二胺基团连接 H1 和 H2 拮抗剂的典型部分结构，合成了具有联合 H1/H2 抗组胺作用的物质。与具有相同 H1 部分结构的相关参考物质相比，碱性侧链氮的损失导致豚鼠回肠 H1 受体的活性降低。在豚鼠钠（H2 受体模型）上，还发现具有美吡胺和环嗪结构元件的化合物不如参考 H2 拮抗剂（噻替丁、雷尼替丁、拉米替丁）有效。相比之下，与苯那敏结构单元的连接产生了高效的 H2 拮抗剂，其活性高达西咪替丁的 27 倍。
• 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。