(6-Methyl-1-oxidopyridin-1-ium-3-yl) 4-methylbenzenesulfonate | 106984-92-3

• 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: (6-Methyl-1-oxidopyridin-1-ium-3-yl) 4-methylbenzenesulfonate
• CAS: 106984-92-3
• 化学式: C₁₃H₁₃NO₄S
• 分子量: 279.317
• InChiKey: BQVSEPFMODSVJD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  77.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (6-Methyl-1-oxidopyridin-1-ium-3-yl) 4-methylbenzenesulfonate 在 盐酸 、 manganese(IV) oxide 、 sodium tetrahydroborate 、 三乙胺 作用下， 以 甲醇 、 氯仿 、 水 为溶剂， 反应 108.0h， 生成 1-<<5-<(p-tolylsulfonyl)oxy>-2-pyridyl>methyl>imidazole-2-thione hydrochloride
  参考文献：
  名称：

  Inhibitors of dopamine .beta.-hydroxylase. 3. Some 1-(pyridylmethyl)imidazole-2-thiones

  摘要：

  The 1-benzylimidazole-2-thione moiety has been previously shown by Kruse et al. to be broadly associated with dopamine beta-hydroxylase (DBH) inhibitory activity both in vitro and in vivo in spontaneously hypertensive rats (SHR). An extension of structure-activity studies to 1-(pyridylmethyl)- and 1-(oxypyridylmethyl)imidazole-2-thiones is reported here in an attempt to exploit the pH differential that exists across the chromaffin vesicle membrane. We hypothesized that the weakly basic pyridyl compounds would diffuse into the acidic vesicles in their neutral forms where protonation and concentration would occur to enhance their in vivo effectiveness as inhibitors. To test this hypothesis, isomeric 2-, 3- and 4-(1-pyridylmethyl)imidazole-2-thiones were synthesized from the appropriate pyridinecarboxaldehydes by reductive alkylation of aminoacetaldehyde dialkyl acetal followed by imidazole-2-thione formation using acidic potassium thiocyanate. Related oxypyridyl compounds were synthesized by first preparing the appropriate aldehyde intermediate followed by conversion to the imidazole-2-thione by the same procedure. The unsubstituted pyridylmethyl compounds showed modest DBH inhibition in vitro but, consistent with a transport-mediated increase in observed potency, showed significant effects in vivo to increase the vascular ratio of dopamine to norepinephrine and to lower blood pressure.

  DOI：

  10.1021/jm00391a008
• 作为产物：
  描述：

  3-羟基-6-甲基吡啶 在 三乙胺 、 间氯过氧苯甲酸 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 (6-Methyl-1-oxidopyridin-1-ium-3-yl) 4-methylbenzenesulfonate
  参考文献：
  名称：

  Inhibitors of dopamine .beta.-hydroxylase. 3. Some 1-(pyridylmethyl)imidazole-2-thiones

  摘要：

  The 1-benzylimidazole-2-thione moiety has been previously shown by Kruse et al. to be broadly associated with dopamine beta-hydroxylase (DBH) inhibitory activity both in vitro and in vivo in spontaneously hypertensive rats (SHR). An extension of structure-activity studies to 1-(pyridylmethyl)- and 1-(oxypyridylmethyl)imidazole-2-thiones is reported here in an attempt to exploit the pH differential that exists across the chromaffin vesicle membrane. We hypothesized that the weakly basic pyridyl compounds would diffuse into the acidic vesicles in their neutral forms where protonation and concentration would occur to enhance their in vivo effectiveness as inhibitors. To test this hypothesis, isomeric 2-, 3- and 4-(1-pyridylmethyl)imidazole-2-thiones were synthesized from the appropriate pyridinecarboxaldehydes by reductive alkylation of aminoacetaldehyde dialkyl acetal followed by imidazole-2-thione formation using acidic potassium thiocyanate. Related oxypyridyl compounds were synthesized by first preparing the appropriate aldehyde intermediate followed by conversion to the imidazole-2-thione by the same procedure. The unsubstituted pyridylmethyl compounds showed modest DBH inhibition in vitro but, consistent with a transport-mediated increase in observed potency, showed significant effects in vivo to increase the vascular ratio of dopamine to norepinephrine and to lower blood pressure.

  DOI：

  10.1021/jm00391a008

文献信息

• [EN] THIAZOLIDINE CARBOXAMIDE DERIVATIVES AS MODULATORS OF THE PROSTAGLANDIN F RECEPTOR<br/>[FR] DERIVES DE THIAZOLIDINE CARBOXAMIDE UTILES EN TANT QUE MODULATEURS DU RECEPTEUR DE PROSTAGLANDINE F
  申请人：APPLIED RESEARCH SYSTEMS

  公开号：WO2003082278A1

  公开（公告）日：2003-10-09

  The present invention is related to thiazolidine carboxamide derivatives of formula (II) for the treatment and/or prophylaxis of preterm labor, premature birth, dysmenorrhea and for stopping labor prior to cesarean delivery. G is selected from the group consisting of C1-C6-alkyl aryl, C1-C6-alkyl heteroaryl, C1-C6 Alkyl cycloalkyl, C1-C6-alkyl heteroaryl, aryl, heteroaryl, C3-C8-cycloalkyl or -heterocyclo­alkyl, said cycloalkyl or aryl or heteroaryl groups may be fused with cycloalkyl or aryl or heteroaryl groups. R1 is selected from the group consisting of aryl, heteroaryl, C3-C8-cycloalkyl or - heterocyclo-alkyl, said (hetero)cycloalkyl or aryl or heteroaryl groups may be fused with (hetero)cycloalkyl or aryl or heteroaryl groups. R2 is selected from the group consisting of H, carboxy, acyl, alkoxycarbonyl, amino­carbonyl, C1-C5-alkyl carboxy, C1-C5-alkyl acyl, C1-C5-alkyl alkoxycarbonyl, C1-C5-alkyl aminocarbonyl, C1-C5-alkyl acyloxy, C1-C5-alkyl acylamino, C1 -C5-alkyl ureido, C1-C5alkyl amino, C1-C5-alkyl alkoxy, C1-C5-alkyl sulfanyl, C1-C5-alkyl sulfinyl, C1-C5-alkyl sulfonyl, C1-C5-alkyl sulfonylamino, C1-C5-alkyl sulfonyloxy, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, aryl, heteroaryl, C3-C8-cycloalkyl, heterocycloalkyl, C1-C6-alkyl aryl, C2-C6-alkyl heteroaryl, C1-C6-alkyl cycloalkyl, C1-C6-alkyl heterocycloalkyl, C2-C6-alkenyl aryl, C2-C6-alkenyl heteroaryl, C2-C6-alkynyl aryl, or C2-C6-alkynyl heteroaryl.

  本发明涉及公式（II）的噻唑烷羧酰胺衍生物，用于治疗和/或预防早产、早产、痛经以及在剖腹产前停止分娩。G选自C1-C6烷基芳基、C1-C6烷基杂芳基、C1-C6烷基环烷基、C1-C6烷基杂芳基、芳基、杂芳基、C3-C8环烷基或-杂环烷基，所述环烷基或芳基或杂芳基基团可能与环烷基或芳基或杂芳基基团融合。R1选自芳基、杂芳基、C3-C8环烷基或-杂环烷基，所述（杂）环烷基或芳基或杂芳基基团可能与（杂）环烷基或芳基或杂芳基基团融合。R2选自H、羧基、酰基、烷氧羰基、氨基羰基、C1-C5烷基羧基、C1-C5烷基酰基、C1-C5烷基烷氧羰基、C1-C5烷基氨基羰基、C1-C5烷基酰氧基、C1-C5烷基酰胺基、C1-C5烷基脲基、C1-C5烷基氨基、C1-C5烷基烷氧基、C1-C5烷基硫醇基、C1-C5烷基亚砜基、C1-C5烷基磺酰基、C1-C5烷基磺酰胺基、C1-C5烷基磺酰氧基、C1-C6烷基、C2-C6烯基、C2-C6炔基、芳基、杂芳基、C3-C8环烷基、杂环烷基、C1-C6烷基芳基、C2-C6烷基杂芳基、C1-C6烷基环烷基、C1-C6烷基杂环烷基、C2-C6烯基芳基、C2-C6烯基杂芳基、C2-C6炔基芳基或C2-C6炔基杂芳基。
• Thiazolidine carboxamide derivatives as modulators of the prostaglandin f receptor
  申请人：Page Naxos Patrick

  公开号：US20050215605A1

  公开（公告）日：2005-09-29

  The present invention is related to thiazolidine carboxamide derivatives of formula (II) for the treatment and/or prophylaxis of preterm labor, premature birth, dysmenorrhea and for stopping labor prior to cesarean delivery. G is selected from the group consisting of C 1 -C 6 -alkyl aryl, C 1 -C 6 -alkyl heteroaryl, C 1 -C 6 Alkyl cycloalkyl, C 1 -C 6 -alkyl heteroaryl, aryl, heteroaryl, C 3 -C 8 -cycloalkyl or -heterocycloalkyl, said cycloalkyl or aryl or hetetoaryl groups may be fused with cycloalkyl or aryl or heteroaryl groups. R 1 is selected from the group consisting of aryl, heteroaryl, C 3 -C 8 -cycloalkyl or -heterocyclo-alkyl, said (hetero)cycloalkyl or aryl or heteroaryl groups may be fused with (hetero)cycloalkyl or aryl or heteroaryl groups. R 2 is selected from the group consisting of H, carboxy, acyl, alkoxycarbonyl, aminocarbonyl, C 1 -C 5 -alkyl carboxy, C 1 -C 5 -alkyl acyl, C 1 -C 5 -alkyl alkoxycarbonyl, C 1 -C 5 -alkyl aminocarbonyl, C 1 -C 5 -alkyl acyloxy, C 1 -C 5 -alkyl acylamino, C 1 -C 5 -alkyl ureido, C 1 -C 5 alkyl amino, C 1 -C 5 -alkyl alkoxy, C 1 -C 5 -alkyl sulfanyl, C 1 -C 5 -alkyl sulfinyl, C 1 -C 5 -alkyl sulfonyl, C 1 -C 5 -alkyl sulfonylamino, C 1 -C 5 -alkyl sulfonyloxy, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, aryl, heteroaryl, C 3 -C 8 -cycloalkyl, heterocycloalkyl, C 1 -C 6 -alkyl aryl, C 2 -C 6 -alkyl heteroaryl, C 1 -C 6 -alkyl cycloalkyl, C 1 -C 6 -alkyl heterocycloalkyl, C 2 -C 6 -alkenyl aryl, C 2 -C 6 -alkenyl heteroaryl, C 2 -C 6 -alkynyl aryl, or C 2 -C 6 -alkynyl heteroaryl.

  本发明涉及式（II）的噻唑烷羧酰胺衍生物，用于治疗和/或预防早产、早产、痛经以及在剖腹产前停止分娩。其中，G选择自C1-C6烷基芳基，C1-C6烷基杂芳基，C1-C6烷基环烷基，C1-C6烷基杂环烷基，芳基，杂芳基，C3-C8环烷基或-杂环烷基，所述环烷基或芳基或杂芳基基团可以与环烷基或芳基或杂芳基基团融合。R1选择自芳基，杂芳基，C3-C8环烷基或-杂环烷基，所述（杂）环烷基或芳基或杂芳基基团可以与（杂）环烷基或芳基或杂芳基基团融合。R2选择自H，羧基，酰基，烷氧羰基，氨基羰基，C1-C5烷基羧基，C1-C5烷基酰基，C1-C5烷基烷氧羰基，C1-C5烷基氨基羰基，C1-C5烷基酰氧基，C1-C5烷基酰胺基，C1-C5烷基脲基，C1-C5烷基氨基，C1-C5烷基烷氧基，C1-C5烷基硫醇基，C1-C5烷基亚砜基，C1-C5烷基磺酰基，C1-C5烷基磺酰胺基，C1-C5烷基磺酰氧基，C1-C6烷基，C2-C6烯基，C2-C6炔基，芳基，杂芳基，C3-C8环烷基，杂环烷基，C1-C6烷基芳基，C2-C6烷基杂芳基，C1-C6烷基环烷基，C1-C6烷基杂环烷基，C2-C6烯基芳基，C2-C6烯基杂芳基，C2-C6炔基芳基或C2-C6炔基杂芳基。
• THIAZOLIDINE CARBOXAMIDE DERIVATIVES AS MODULATORS OF THE PROSTAGLANDIN F RECEPTOR
  申请人：PAGE Patrick Naxos

  公开号：US20080255094A1

  公开（公告）日：2008-10-16

  The present invention is related to thiazolidine carboxamide derivatives of formula (II) for the treatment and/or prophylaxis of preterm labor, premature birth, dysmenorrhea and for stopping labor prior to cesarean delivery.

  本发明涉及式（II）的噻唑烷羧酰胺衍生物，用于治疗和/或预防早产、早产、痛经以及在剖腹产前停止分娩。
• Dopamine-beta-hydroxylase inhibitors
  申请人：SMITHKLINE BECKMAN CORPORATION

  公开号：EP0214740A2

  公开（公告）日：1987-03-18

  Compounds of structure (I) in which Y is H, OH, halogen or C1-4 alkoxy; X is H, halogen, halo C1-4 alkyl, n is 1 to 5 and R is H or C1-4 alkyl and phar- maceu- tically acceptable salts or hydrates thereof, processes fortheir preparation, compositions containing them and their use in therapy.

  结构(I)的化合物 其中 Y 为 H、OH、卤素或 C1-4 烷氧基；X 为 H、卤素、卤代 C1-4 烷基，n 为 1 至 5，R 为 H 或 C1-4 烷基，以及它们的可接受盐或水合物。 及其可接受的盐或水合物、其制备工艺、含有它们的组合物以及它们在治疗中的用途。
• 4-Anilino-7-pyridyl-3-quinolinecarbonitriles as Src kinase inhibitors
  作者：Nan Zhang、Biqi Wu、Diane H. Boschelli、Jennifer M. Golas、Frank Boschelli

  DOI：10.1016/j.bmcl.2009.07.043

  日期：2009.9

  A series of 4-anilino-7-pyridyl-3-quinolinecarbonitriles was prepared as Src kinase inhibitors. A systematic SAR study of substitutions on both the pyridine ring and the 3-quinolinecarbonitrile core established the requirements for optimal activity. The lead compound, 17, showed potent activity in both the Src enzyme assay and cell assays, and demonstrated in vivo anti-tumor activity in a xenograft model. (C) 2009 Elsevier Ltd. All rights reserved.