4-[2-(2,2,2-trifluoroethyl)-guanidino]-2-(3-aminopropylthio)pyrimidine

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 4-[2-(2,2,2-trifluoroethyl)-guanidino]-2-(3-aminopropylthio)pyrimidine
• 英文别名: 4-[2-(2,2,2-Trifluoroethyl)guanidino]-2-(3-aminopropylthio)pyrimidine；1-[2-(3-aminopropylsulfanyl)pyrimidin-4-yl]-2-(2,2,2-trifluoroethyl)guanidine
• 化学式: C₁₀H₁₅F₃N₆S
• 分子量: 308.331
• InChiKey: INGPHSZPCRSYLB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  128
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-[2-(2,2,2-trifluoroethyl)-guanidino]-2-(3-aminopropylthio)pyrimidine 、 甲酸乙酯 在 盐酸 、 乙酸乙酯 作用下， 以 乙醇 为溶剂， 反应 48.0h， 以to give N-[3-(4-[2-(2,2,2-trifluoroethyl)guanidino]pyrimid-2-ylthio)propyl]formamide (0.2 g.), m.p. 165°-166°的产率得到N-[3-(4-[2-(2,2,2-trifluoroethyl)guanidino]pyrimid-2-ylthio)propyl]formamide
  参考文献：
  名称：

  Carbonyl derivatives

  摘要：

  本发明涉及一种卡那霉素衍生物，其为组胺H-2受体拮抗剂并抑制胃酸分泌。根据本发明提供了式I的胍衍生物：##STR1## 其中R.sup.1和R.sup.2，相同或不同，为氢或1-10C烷基，3-8C环烷基或4-14C环烷基烷基，每个烷基，环烷基或环烷基烷基可以携带一个或多个F，Cl或Br原子，前提是R.sup.1和R.sup.2中的一个被卤素取代，或R.sup.2为氢且R.sup.1为R.sup.5-E-W，其中W为2-6C烷基，可选地被1或2个1-4C烷基取代，E为O，S，SO，SO.sub.2或NR.sup.6，其中R.sup.6为H或1-6C烷基，R.sup.5为H或1-6C烷基，可选地被1或2个1-4C烷基取代，或R.sup.5和R.sup.6结合形成吡咯烷，哌嗪，吗啉，哌嗪或N-甲基哌嗪环，或R.sup.2为H且R.sup.1为H，1-10C烷基，3-8C环烷基，4-14C环烷基烷基，3-6C烯基，3-6C炔基，1-6C烷酰基，6-10C芳基，7-11C芳基烷基或7-11C芳基酰基; 环X为规范中定义的杂环；A为苯基或5-7C环烷基，或可选地插入一或两个基团的1-8C烷基；D为O或S；R.sup.4为H或1-6C烷基；R.sup.3为H或规范中描述的多种基团；以及其药学上可接受的酸加成盐。同时还描述了制造工艺和制药组合物。

  公开号：

  US04657908A1
• 作为产物：
  描述：

  4-[3-(2,2,2-trifluoroethyl)thioureido]-2-[(3-phthalimido)propylthio]pyrimidine 、 氧化汞(II)红 、 N,N-二甲基甲酰胺 在 盐酸 、 一水合肼 作用下， 以 乙醇 为溶剂， 生成 4-[2-(2,2,2-trifluoroethyl)-guanidino]-2-(3-aminopropylthio)pyrimidine
  参考文献：
  名称：

  Haloguanidine compounds, pharmaceutical compositions and methods of use

  摘要：

  用于抑制胃酸分泌和治疗由胃酸引起或加重的消化性溃疡的化合物具有以下结构式（I）：##STR1##其中R.sup.1和R.sup.2为H，C.sub.1-10烷基，C.sub.3-8环烷基或环烷基烷基，其中烷基部分为C.sub.1-6，环烷基部分为C.sub.3-8，每个烷基，环烷基和环烷基烷基可选择地被来自F、Cl和Br的一个或多个卤素取代，前提是R.sup.1和R.sup.2中至少有一个是卤素取代的烷基，环烷基或环烷基烷基，并且直接连接到氮的碳上没有卤素取代物；X，m，Y，n和R.sup.3如规范中所述；以及其药用可接受的酸加盐。还描述了制备结构式（I）化合物的方法，含有它们的药物组合物，利用这种组合物的方法以及用于合成结构式（I）化合物的中间体。

  公开号：

  US04362728A1

文献信息

• Histamine H2-antagonists
  申请人：ICI Americas Inc.

  公开号：US04496571A1

  公开（公告）日：1985-01-29

  The invention relates to carbonyl derivatives which are histamine H-2 antagonists and which inhibit gastric acid secretion. According to the invention where is provided a guanidine derivative of the formula I: ##STR1## in which R.sup.1 and R.sup.2, same or different, are hydrogen or 1-10C alkyl, 3-8C cycloalkyl or 4-14C cycloalkylalkyl, each alkyl, cycloalkyl or cycloalkylalkyl optionally carrying one or more F, Cl or Br atoms, provided that one of R.sup.1 and R.sup.2 is halogen substituted, or R.sup.2 is hydrogen and R.sup.1 is R.sup.5 -E-W in which W is 2-6C alkylene optionally substituted by 1 or 2 1-4C alkyls, E is O, S, SO, SO.sub.2 or NR.sup.6 in which R.sup.6 is H or 1-6C alkyl, R.sup.5 is H or 1-6C alkyl optionally substituted by 1 or 2 1-4C alkyls, or R.sup.5 and R.sup.6 are joined to form a pyrrolidine, piperidine, morpholine, piperazine or N-methylpiperazine ring, or R.sup.2 is H and R.sup.1 is H, 1-10C alkyl, 3-8C cycloalkyl, 4-14C cycloalkylalkyl, 3-6C alkenyl, 3-6C alkynyl, 1-6C alkanoyl, 6-10C aryl, 7-11C aralkyl or 7-11C aroyl; ring X is a heterocyclic ring as defined in the specification; A is phenylene or 5-7C cycloalkylene, or a 1-8C alkylene into which is optionally inserted one or two groups; D is O or S; R.sup.4 is H or 1-6C alkyl; R.sup.3 is H or a variety of radicals described in the specification: and the pharmaceutically-acceptable acid-addition salts thereof. Manufacturing processes and pharmaceutical compositions are also described.

  本发明涉及羰基衍生物，其为组胺H-2受体拮抗剂并抑制胃酸分泌。根据本发明，提供了式I的胍衍生物：##STR1## 其中R.sup.1和R.sup.2，相同或不同，是氢或1-10C烷基，3-8C环烷基或4-14C环烷基烷基，每个烷基，环烷基或环烷基烷基可选地携带一个或多个F，Cl或Br原子，前提是R.sup.1和R.sup.2中的一个是卤素取代，或者R.sup.2是氢且R.sup.1是R.sup.5-E-W，其中W是可选地被1或2个1-4C烷基取代的2-6C烷基，E是O，S，SO，SO.sub.2或NR.sup.6，其中R.sup.6是H或1-6C烷基，R.sup.5是H或1-6C烷基，可选地被1或2个1-4C烷基取代，或者R.sup.5和R.sup.6结合形成吡咯烷，哌嗪，吗啉，哌嗪或N-甲基哌嗪环，或者R.sup.2是H且R.sup.1是H，1-10C烷基，3-8C环烷基，4-14C环烷基烷基，3-6C烯基，3-6C炔基，1-6C烷酰基，6-10C芳基，7-11C芳基烷基或7-11C芳酰基；环X是规范中定义的杂环；A是苯基或5-7C环烷基，或者是可选地插入一到两个基团的1-8C烷基；D是O或S；R.sup.4是H或1-6C烷基；R.sup.3是H或规范中描述的各种基团。还描述了制造工艺和制药组合物及其药学上可接受的酸加成盐。
• Haloguanidine intermediates
  申请人：Imperial Chemical Industries, Ltd.

  公开号：US04762932A1

  公开（公告）日：1988-08-09

  Compounds useful for inhibiting gastric acid secretion and for the treatment of peptic ulcers caused or exacerbated by gastric acidity having the following formula (I): ##STR1## in which R.sup.1 and R.sup.2, are H, C.sub.1-10 alkyl, C.sub.3-8 cycloalkyl or cycloalkylalkyl in which the alkyl part is C.sub.1-6 and the cycloalkyl part is C.sub.3-8, each of the alkyl, cycloalkyl and cycloalkylalkyls being optionally substituted by one or more halogens selected from F, Cl and Br, provided that at least one of R.sup.1 and R.sup.2 is a halogen substituted alkyl, cycloalkyl or cycloalkylalkyl and provided that there is no halogen substituent on the carbon directly attached to the nitrogen; and X, m, Y, n and R.sup.3 are as described in the specification; and the pharmaceutically-acceptable acid-addition salts thereof. Processes for producing compounds of formula (I), pharmaceutical compositions containing them, methods of utilizing such compositions and intermediates useful for synthesizing compounds of formula (I) are also described.

  用于抑制胃酸分泌和治疗由胃酸引起或加重的消化性溃疡的化合物具有以下式(I)的结构：##STR1## 其中R.sup.1和R.sup.2是H、C.sub.1-10烷基、C.sub.3-8环烷基或环烷基烷基，其中烷基部分为C.sub.1-6，环烷基部分为C.sub.3-8，每个烷基、环烷基和环烷基烷基可选择地被一种或多种来自F、Cl和Br的卤素取代，前提是R.sup.1和R.sup.2中至少有一个是卤素取代的烷基、环烷基或环烷基烷基，并且直接连接到氮的碳上没有卤素取代基；而X、m、Y、n和R.sup.3如说明书所述；以及其药学上可接受的酸加成盐。还描述了制备式(I)化合物的方法、含有它们的药物组合物、利用这样的组合物的方法和合成式(I)化合物的有用中间体。
• Guanidine derivatives, processes for their manufacture and pharmaceutical compositions containing them
  申请人：IMPERIAL CHEMICAL INDUSTRIES PLC

  公开号：EP0030092A1

  公开（公告）日：1981-06-10

  The invention relates to a guanidine of the formula:- in which R1 and R2 are H, Ci-io alkyl, C3-8 cycloalkyl or cycloalkylalkyl in which the alkyl part is C1-6 and the cycloalkyl part is C3-8, each of the alkyl, cycloalkyl and cycloalkylal- kyls being optionally substituted by one or more halogens selected from F, Cl and Br, provided that at least one of R' and R' is a halogen substituted alkyl, cycloalkyl or cycloalkyl-alkyl and provided that there is no halogen substituent on the carbon directly attached to the nitrogen; ring X is phenyl carrying 1 or 2 optional substitutents or a 5- or 6-membered heterocyclic aromatic ring containing 1, 2 or 3 hetero atoms selected from 0, N and S, which heterocyclic ring may, carry a single optional substituent selected from F, Cl, Br, I, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, trifluoromethyl, hydroxy and amino; Y is 0, S, a direct bond, methylene, vinylene, SO or NR4 in which R4 is H or C1-6 alkyl; m is 0 to 4 and n is 1 to 5, provided that when Y is 0, SO or NR4, n is 2 to 5; R3 has various significances; and the pharmaceutically-acceptable acid-addition salts thereof. Manufacturing processes and pharmaceutical compositions are also described.

  本发明涉及一种胍，其式如下：- 其中 R1 和 R2 为 H、Ci-io 烷基、C3-8 环烷基或环烷基(其中烷基部分为 C1-6，环烷基部分为 C3-8)，每个烷基、环烷基和环烷基可任选被选自 F、Cl 和 Br 的一种或多种卤素取代，条件是 R' 和 R' 中至少有一个是被卤素取代的烷基、环烷基或环烷基烷基，且与氮直接相连的碳上没有卤素取代基； 环 X 是带有 1 或 2 个任选取代基的苯基，或含有 1、2 或 3 个选自 0、N 和 S 的杂原子的 5 或 6 元杂环芳香环，该杂环可带有 1 个选自 F、Cl、Br、I、C1-6 烷基、C1-6 烷氧基、C1-6 烷硫基、三氟甲基、羟基和氨基的任选取代基； Y为0、S、直接键、亚甲基、亚乙烯基、SO或NR4，其中R4为H或C1-6烷基；m为0至4，n为1至5，但当Y为0、SO或NR4时，n为2至5；R3具有各种意义；及其药学上可接受的酸加成盐。 此外，还描述了制造工艺和药物组合物。
• Guanidino-substituted heterocyclic derivatives having histamine H-2 antagonist activity
  申请人：IMPERIAL CHEMICAL INDUSTRIES PLC

  公开号：EP0059597A2

  公开（公告）日：1982-09-08

  The invention relates to carbonyl derivatives which are histamine H-2 antagonists and which inhibit gastric acid secretion. According to the invention where is provided a guanidine derivative of the formula I:- in which R' and R2, same or different, are hydrogen or 1-10C alkyl, 3-8C cycloalkyl or 4-14C cycloalkylalkyl, each alkyl, cycloalkyl or cycloalkylalkyl optionally carrying one or more F, Cl or Br atoms, provided that one of R1 and R2 is halogen substituted, or R2 is hydrogen and R1 is R5-E-W in which W is 2-6C alkylene optionally substituted by 1 or 2 1-4C alkyls, E is O, S, SO. SO2 or NR6 in which R6 is H or 1-6C alkyl, R5 is H or 1-6C alkyl optionally substituted by 1 or 2 1-4C alkyls, or R5 and R6 are joined to form a pyrrolidine, piperidine, morpholine, piperazine or N-methylpiperazine ring, or R2 is H and R1 is H, 1-10C alkyl, 3-8C cycloalkyl, 4-14C cycloalkylalkyl, 3-6C alkenyl, 3-6C alkynyl, 1-6C alkanoyl, 6-10C aryl, 7-11C aralkyl or 7-11C aroyl; ring X is a heterocyclic ring as defined in the specification; A is phenylene or 5-7C cycloalkylene, or a 1-8C alkylene into which is optionally inserted one or two groups: D is O or S; R4 is H or 1-6C alkyl; R3 is H or a variety of radicals described in the specification: and the pharmaceutically-acceptable acid-addition salts thereof. Manufacturing processes and pharmaceutical compositions are also described.

  本发明涉及组胺 H-2 拮抗剂和抑制胃酸分泌的羰基衍生物。根据本发明提供了一种式 I 的胍衍生物 其中R'和R2相同或不同，均为氢或1-10C烷基、3-8C环烷基或4-14C环烷基烷基，每个烷基、环烷基或环烷基烷基可选带一个或多个F、Cl或Br原子，条件是R1和R2之一被卤素取代，或R2为氢，R1为R5-E-W，其中W为可选被1或2个1-4C烷基取代的2-6C亚烷基，E为O、S、SO.SO2 或 NR6，其中 R6 是 H 或 1-6C 烷基，R5 是 H 或可选被 1 或 2 个 1-4C 烷基取代的 1-6C 烷基，或 R5 和 R6 连接形成吡咯烷、哌啶、吗啉、哌嗪或 N-甲基吡咯烷、或 R2 为 H，R1 为 H、1-10C 烷基、3-8C 环烷基、4-14C 环烷基、3-6C 烯基、3-6C 烷炔基、1-6C 烷酰基、6-10C 芳基、7-11C 芳基或 7-11C 芳基；环 X 是如说明书中所定义的杂环； A 是亚苯基或 5-7C 环亚烷基，或 1-8C 亚烷基，其中可选择插入一个或两个基团：D是O或S；R4是H或1-6C烷基；R3是H或说明书中描述的各种基团：及其药学上可接受的酸加成盐。还描述了制造工艺和药物组合物。
• Nitrogen heterocycles
  申请人：IMPERIAL CHEMICAL INDUSTRIES PLC

  公开号：EP0060696B1

  公开（公告）日：1986-01-15