1,1'-(3-氯-1,1-丙烷二基)二(4-氟苯) | 78987-80-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 1,1'-(3-氯-1,1-丙烷二基)二(4-氟苯)
• 英文名称: 1-[3-chloro-1-(4-fluorophenyl)propyl]-4-fluorobenzene
• 英文别名: [1-(2-chloroethyl)]-bis-(4-fluorophenyl)methane；1,1'-(3-Chloropropylidene)bis(4-fluorobenzene)
• CAS: 78987-80-1
• 化学式: C₁₅H₁₃ClF₂
• 分子量: 266.718
• InChiKey: IOVUPKRBIBVGIG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1,1'-(3-氯-1,1-丙烷二基)二(4-氟苯) 在 盐酸 、 氯化亚砜 、 氨 、 potassium iodide 作用下， 以 二甲基亚砜 为溶剂， -30.0~95.0 ℃ 、2.6 MPa 条件下， 反应 197.0h， 生成 2-[2-[3,3-bis(4-fluorophenyl)propyl]-1H-imidazol-5-yl]ethanamine
  参考文献：
  名称：

  Ring-substituted histaprodifen analogues as partial agonists for histamine H1 receptors: synthesis and structure–activity relationships

  摘要：

  Thirteen racemic benzene ring-substituted analogues of histaprodifen (8a; 2-[2-(3,3-diphenylpropyl)-1H-imidazol-4-yl]ethanamine), a novel lead for potent and selective histamine H-1-receptor agonists, have been prepared from substituted 4,4-diphenylbutyronitriles 5 via cyclization of the corresponding methyl butyrimidates 6 with 2-oxo-4-phthalimido-1-butyl acetate in liquid ammonia, followed by deprotection. Nitriles 5 were accessible by alkylation of either substituted diphenylmethanes with 3-bromopropionitrile or diethyl malonate with substituted 1-chloro-diphenylmethanes and subsequent standard reactions. The title compounds 8 displayed partial agonism on contractile H-1 receptors of the guinea-pig ileum (E-max = 2-98% relative to histamine) and, compared with the endogenous agonist, were endowed with agonist potencies of 4-92%. The meta fluorinated (gc) and meta chlorinated (8f) analogues showed the highest relative potency in this series (95% confidence Limits 85-99% and 78-102%), but did not exceed the value of the lead 8a (99-124%). Compound 8c (2-[2-[3-(3-fluorophenyl)-3-phenylpropyl]-1H-imidazol-4-yl]ethanamine) was a partial agonist at contractile H-1 receptors of the guinea-pig aorta (relative potency 154% vs. 100% for histamine) and at relaxation-mediating endothelial H-1 receptors of the rat aorta (relative potency 556% vs. 100% for histamine) and matched with the functional behaviour of 8a. Agonism observed for each compound was sensitive to blockade by the selective H-1-receptor antagonist mepyramine (pA(2) approximate to 9 (guinea-pig) and pA(2) approximate to 8 (rat aorta)). All histaprodifen analogues 8 stimulated neither histaminergic H-2/H-3, nor cholinergic M-3 receptors. They displayed only low to moderate affinity for these sites (H-2: pD'(2), < 5; H-3/M-3: pA(2) < 6). With regard to the substitution pattern on the benzene ring, there was no correlation between the histaprodifen series and the corresponding derivatives of another selective H-1-receptor agonist, viz. 2-phenylhistamine. (C) 2000 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(00)00105-7
• 作为产物：
  描述：

  3,3-bis(4-fluorophenyl)-propanoic acid 在 4-二甲氨基吡啶 、 lithium aluminium tetrahydride 、 氯化亚砜 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 生成 1,1'-(3-氯-1,1-丙烷二基)二(4-氟苯)
  参考文献：
  名称：

  Ring-substituted histaprodifen analogues as partial agonists for histamine H1 receptors: synthesis and structure–activity relationships

  摘要：

  Thirteen racemic benzene ring-substituted analogues of histaprodifen (8a; 2-[2-(3,3-diphenylpropyl)-1H-imidazol-4-yl]ethanamine), a novel lead for potent and selective histamine H-1-receptor agonists, have been prepared from substituted 4,4-diphenylbutyronitriles 5 via cyclization of the corresponding methyl butyrimidates 6 with 2-oxo-4-phthalimido-1-butyl acetate in liquid ammonia, followed by deprotection. Nitriles 5 were accessible by alkylation of either substituted diphenylmethanes with 3-bromopropionitrile or diethyl malonate with substituted 1-chloro-diphenylmethanes and subsequent standard reactions. The title compounds 8 displayed partial agonism on contractile H-1 receptors of the guinea-pig ileum (E-max = 2-98% relative to histamine) and, compared with the endogenous agonist, were endowed with agonist potencies of 4-92%. The meta fluorinated (gc) and meta chlorinated (8f) analogues showed the highest relative potency in this series (95% confidence Limits 85-99% and 78-102%), but did not exceed the value of the lead 8a (99-124%). Compound 8c (2-[2-[3-(3-fluorophenyl)-3-phenylpropyl]-1H-imidazol-4-yl]ethanamine) was a partial agonist at contractile H-1 receptors of the guinea-pig aorta (relative potency 154% vs. 100% for histamine) and at relaxation-mediating endothelial H-1 receptors of the rat aorta (relative potency 556% vs. 100% for histamine) and matched with the functional behaviour of 8a. Agonism observed for each compound was sensitive to blockade by the selective H-1-receptor antagonist mepyramine (pA(2) approximate to 9 (guinea-pig) and pA(2) approximate to 8 (rat aorta)). All histaprodifen analogues 8 stimulated neither histaminergic H-2/H-3, nor cholinergic M-3 receptors. They displayed only low to moderate affinity for these sites (H-2: pD'(2), < 5; H-3/M-3: pA(2) < 6). With regard to the substitution pattern on the benzene ring, there was no correlation between the histaprodifen series and the corresponding derivatives of another selective H-1-receptor agonist, viz. 2-phenylhistamine. (C) 2000 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(00)00105-7

文献信息

• N-(4-piperodinyl)(dihydrobenzofuran or dihydro-2H-benzopyran)
  申请人：Janssen Pharmaceutica N.V.

  公开号：US05185335A1

  公开（公告）日：1993-02-09

  Piperidine derivatives of formula ##STR1## wherein A is a radical of formula ##STR2## wherein one or two hydrogen atoms in said radicals (a-1) to (a-3) may be replaced by a C.sub.1-6 alkyl radical; R.sup.1 is hydrogen or halo; R.sup.2 is hydrogen, amino, mono or di(C.sub.1-6 alkyl)amino or C.sub.1-6 alkylcarbonylamino; R.sup.3 is hydrogen or C.sub.1-6 alkyl; L is C.sub.3-6 cycloalkyl, C.sub.5-6 cycloalkanone, C.sub.3-6 alkenyl optionally substituted with aryl, or L is a radical of formula ##STR3## the N-oxide forms, addition salts and stereochemically isomeric forms thereof, said compounds having gastrointestinal motility stimulating properties. Pharmaceutical compositions containing these compounds as active ingredient, and a method of preparing said compounds and pharmaceutical compositions.

  本发明涉及一种式子为##STR1##的哌啶衍生物，其中A是式子##STR2##的基团，其中在所述基团(a-1)到(a-3)中的一个或两个氢原子可以被C.sub.1-6烷基基团取代；R.sup.1是氢或卤素；R.sup.2是氢，氨基，单或双(C.sub.1-6烷基)氨基或C.sub.1-6烷基羰基氨基；R.sup.3是氢或C.sub.1-6烷基；L是C.sub.3-6环烷基，C.sub.5-6环己酮，C.sub.3-6烯基（可以选择地用芳基取代），或L是式子##STR3##的基团，其N-氧化物形式，加成盐和立体化学异构体形式，这些化合物具有促进胃肠动力的特性。本发明还涉及以这些化合物为活性成分的制药组合物，以及制备这些化合物和制药组合物的方法。
• Isochromane derivatives
  申请人：Akzo N.V.

  公开号：US05137911A1

  公开（公告）日：1992-08-11

  An isochromane derivative having the general formula I ##STR1## in which each of R.sub.1, R.sub.2, and R.sub.3 is one to four substituents independently selected from hydrogen, hydroxy, alkyl (1-4 C), alkoxy (1-4 C), halogen, or CF.sub.3, or represents a methylenedioxy group; R.sub.4 is selected from hydrogen or alkyl (1-4 C); Alk is an alkylene group with 1-4 carbon atoms; Alk' is an alkylene group with 2-4 carbon atoms, when R.sub.5 is selected from hydrogen or alkyl (1-4 C) and X is O or S; or Alk' is an alkylene group with 1-4 carbon atoms or a bond, when R.sub.5 is an alkyl (1-4 C) group and X is CH.sub.2 or a bond; or a pharmaceutically acceptable salt thereof.

  一种具有通式I的异色烷衍生物，其中R.sub.1、R.sub.2和R.sub.3中的每一个都是独立选择的氢、羟基、烷基（1-4 C）、烷氧基（1-4 C）、卤素或CF.sub.3中的1-4个取代基，或表示甲亚氧基基团；R.sub.4从氢或烷基（1-4 C）中选择；Alk是具有1-4个碳原子的烷基；当R.sub.5从氢或烷基（1-4 C）中选择且X为O或S时，Alk'是具有2-4个碳原子的烷基；当R.sub.5为烷基（1-4 C）基团且X为CH.sub.2或键时，Alk'是具有1-4个碳原子的烷基或键；或其药学上可接受的盐。
• N-(4-piperidinyl) (dihydroxybenzofuran or
  申请人：Tanssen Pharmaceutica N.V.

  公开号：US05262418A1

  公开（公告）日：1993-11-16

  Piperidine derivatives of formula ##STR1## wherein A is a radical of formula --CH.sub.2 --CH.sub.2 -- (a-1), --CH.sub.2 --CH.sub.2 --CH.sub.2 -- (a-2), or --CH.sub.2 --CH.sub.2 --CH.sub.2 --CH.sub.2 -- (a-3), wherein one or two hydrogen atoms in said radicals (a-1) to (a-3) may be replaced by a C.sub.1-6 alkyl radical; R.sup.1 is hydrogen or halo; R.sup.2 is hydrogen, amino, mono or di(C.sub.1-6 alkyl)amino or C.sub.1-6 alkylcarbonylamino; R.sup.3 is hydrogen or C.sub.1-6 alkyl; L is C.sub.3-6 cycloalkyl, C.sub.5-6 cycloalkanone, C.sub.3-6 alkenyl optionally substituted with aryl, or L is a radical of formula --Alk--R.sup.4 (b-1), --Alk--X--R.sup.5 (b-2), --Alk--Y--C(.dbd.O)--R.sup.7 (b-3), or --Alk--Y--C(.dbd.O)--NR.sup.9 R.sup.10 (b-4), the N-oxide forms, addition salts and stereochemically isomeric forms thereof, said compounds having gastrointestinal motility stimulating properties. Pharmaceutical compositions containing these compounds as active ingredient, and a method of preparing said compounds and pharmaceutical compositions.

  式为##STR1##的哌啶衍生物，其中A是式--CH.sub.2 --CH.sub.2 -- (a-1)、--CH.sub.2 --CH.sub.2 --CH.sub.2 -- (a-2)或--CH.sub.2 --CH.sub.2 --CH.sub.2 --CH.sub.2 -- (a-3)的基团，其中在所述基团(a-1)到(a-3)中的一个或两个氢原子可以被C.sub.1-6烷基基团取代；R.sup.1是氢或卤素；R.sup.2是氢、氨基、单或双(C.sub.1-6烷基)氨基或C.sub.1-6烷基羰基氨基；R.sup.3是氢或C.sub.1-6烷基；L是C.sub.3-6环烷基、C.sub.5-6环戊酮、C.sub.3-6烯基（可选择用芳基取代）或式--Alk--R.sup.4 (b-1)、--Alk--X--R.sup.5 (b-2)、--Alk--Y--C(.dbd.O)--R.sup.7 (b-3)或--Alk--Y--C(.dbd.O)--NR.sup.9 R.sup.10 (b-4)的基团，其N-氧化物形式、加成盐和立体化学异构体，这些化合物具有胃肠动力促进作用。含有这些化合物作为活性成分的制药组合物以及制备这些化合物和制药组合物的方法。
• N-(4-piperidinyl)(dihydrobenzofuran or dihydro-2H-benzopyran)carboxamide derivatives
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP0445862A2

  公开（公告）日：1991-09-11

  Piperidine derivatives of formula wherein A is a radical of formula         -CH₂-CH₂-   (a-1),         -CH₂-CH₂-CH₂-   (a-2), or         -CH₂-CH₂-CH₂-CH₂-   (a-3), wherein one or two hydrogen atoms in said radicals (a-1) to (a-3) may be replaced by a C₁₋₆alkyl radical;    R¹ is hydrogen or halo; R² is hydrogen, amino, mono or di(C₁₋₆alkyl)amino or C₁₋₆alkylcarbonylamino; R³ is hydrogen or C₁₋₆alkyl; L is C₃₋₆cycloalkyl, C₅₋₆cycloalkanone, C₃₋₆alkenyl optionally substituted with aryl, or L is a radical of formula         -Alk-R⁴   (b-1),         -Alk-X-R⁵   (b-2),         -Alk-Y-C(=O)-R⁷   (b-3), or         -Alk-Y-C(=O)-NR⁹R¹⁰   (b-4), the N-oxide forms, addition salts and stereochemically isomeric forms thereof, said compounds having gastrointestinal motility stimulating properties. Pharmaceutical compositions containing these compounds as active ingredient, and a method of preparing said compounds and pharmaceutical compositions.

  式中的哌啶衍生物 其中 A 是式中的基团 -CH₂-CH₂-(a-1)、 -CH₂-CH₂-CH₂-（a-2），或 -CH₂-CH₂-CH₂-CH₂-（a-3）、 其中，(a-1)至(a-3)中的一个或两个氢原子可被 C₁₋₆ 烷基取代； R¹ 是氢或卤代；R² 是氢、氨基、一或二(C₁₋₆烷基)氨基或 C₁₋₆烷基羰基氨基；R³ 是氢或 C₁₋₆烷基；L是C₃₋₆环烷基、C₅₋₆环烷酮、任选被芳基取代的C₃₋₆烯基，或者L是式中的自由基 -Alk-R⁴ (b-1)、 -Alk-X-R⁵（b-2）、 -Alk-Y-C(=O)-R⁷（b-3），或 -Alk-Y-C(=O)-NR⁹R¹⁰（b-4）、 N-氧化物形式、加成盐及其立体异构形式，所述化合物具有刺激胃肠道蠕动的特性。含有这些化合物作为活性成分的药物组合物，以及制备所述化合物和药物组合物的方法。
• New isochromane derivatives
  申请人：Akzo Nobel N.V.

  公开号：EP0450689A1

  公开（公告）日：1991-10-09

  An isochromane derivative having the general formula I in which each of R₁, R₂, and R₃ is one to four substituents independently selected from hydrogen, hydroxy, alkyl (1-4 C), alkoxy (1-4 C), halogen, or CF₃, or represents a methylenedioxy group; R₄ is selected from hydrogen or alkyl (1-4 C); Alk is an alkylene group with 1-4 carbon atoms; Alk' is an alkylene group with 2-4 carbon atoms, when R₅ is selected from hydrogen or alkyl (1-4 C) and X is O or S; or Alk' is an alkylene group with 1-4 carbon atoms or a bond, when R₅ is an alkyl (1-4 C) group and X is CH₂ or a bond; or a pharmaceutically acceptable salt thereof.

  具有通式 I 的异铬烷衍生物 其中 R₁、R₂ 和 R₃ 各为一至四个取代基，独立选自氢、羟基、烷基（1-4 C）、烷氧基（1-4 C）、卤素或 CF₃，或代表亚甲基二氧基； R₄ 选自氢或烷基（1-4 C）； Alk 是具有 1-4 个碳原子的亚烷基； 当 R₅ 选自氢或烷基（1-4 C）且 X 为 O 或 S 时，"烷基 "是具有 2-4 个碳原子的亚 烷基；或 当 R₅ 是烷基（1-4 C）且 X 是 CH₂ 或键时，'烷基'是具有 1-4 个碳原子的亚烷基或键； 或其药学上可接受的盐。