N-[[5-(4-benzylpiperidin-1-yl)sulfonylthiophen-2-yl]methyl]-4-chlorobenzamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: N-[[5-(4-benzylpiperidin-1-yl)sulfonylthiophen-2-yl]methyl]-4-chlorobenzamide
• 化学式: C₂₄H₂₅ClN₂O₃S₂
• 分子量: 489.059
• InChiKey: XSVQCVPAJGLLBR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-Chloro-N-thiophen-2-ylmethyl-benzamide 在 氯磺酸 、 polymer-bound morpholine 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.5h， 生成 N-[[5-(4-benzylpiperidin-1-yl)sulfonylthiophen-2-yl]methyl]-4-chlorobenzamide
  参考文献：
  名称：

  Design, Synthesis, and Biological Activity of Novel, Potent, and Selective (Benzoylaminomethyl)thiophene Sulfonamide Inhibitors of c-Jun-N-Terminal Kinase

  摘要：

  Several lines of evidence support the hypothesis that c-Jun N-terminal kinases (JNKs) play a critical role in a wide range of disease states including cell death (apoptosis)-related and inflammatory disorders (epilepsy, brain, heart and renal ischemia, neurodegenerative diseases, multiple sclerosis, rheumatoid arthritis, and inflammatory bowel syndrome). The screening of a compound collection led to the identification of a 2-(benzoylaminomethyl)thiophene sulfonamide (AS004509, compound I) as a potent and selective JNK inhibitor. Chemistry and structure-activity relationship (SAR) studies performed around this novel kinase-inhibiting motif indicated that the left and central parts of the molecule were instrumental to maintaining potency at the enzyme. Accordingly, we investigated the JNK-inhibiting properties of a number of variants of the right-hand moiety of the molecule, which led to the identification of 2-(benzoylaminomethyl)thiophene sulfonamide benzotriazole (AS600292, compound 50a), the first potent and selective JNK inhibitor of this class which demonstrates a protective action against neuronal cell death induced by growth factor and serum deprivation.

  DOI：

  10.1021/jm031112e

文献信息

• [EN] PHARMACEUTICALLY ACTIVE SULFONAMIDE DERIVATIVES<br/>[FR] DERIVES SULFONAMIDES ACTIFS SUR LE PLAN PHARMACOLOGIQUE
  申请人：APPLIED RESEARCH SYSTEMS

  公开号：WO2001023378A1

  公开（公告）日：2001-04-05

  The present invention is related to sulfonamide derivatives of formula (I) notably for use as pharmaceutically active compounds, as well as to pharmaceutical formulations containing such sulfonamide derivatives. Said sulfonamide derivatives are efficient modulators of the JNK pathway, they are in particular efficient and selective inhibitors of JNK 2 and 3. The present invention is furthermore related to novel sulfonamide derivatives as well as to methods of their preparation. The compounds of formula (I) according to the present invention being suitable pharmaceutical agents are those wherein Ar?1 and Ar2¿ are independently from each other substituted or unsubstituted aryl or heteroaryl groups, X is O or S, preferably O; R1 is hydrogen or a C¿1?-C6-alkyl group, or R?1¿ forms a substituted or unsubstituted 5-6-membered saturated or unsaturated ring with Ar1; n is an integer from 0 to 5, preferably between 1-3 and most preferred 1; Y within formula (I) is an unsubstituted or a substituted 4-12-membered saturated cyclic or bicyclic alkyl containing at least one nitrogen atom, whereby one nitrogen atom within said ring is forming a bond with the sulfonyl group of formula (I) thus providing a sulfonamide.

  本发明涉及公式（I）的磺酰胺衍生物，特别是作为药物活性化合物的用途，以及包含这种磺酰胺衍生物的制药配方。所述的磺酰胺衍生物是JNK通路的有效调节因子，特别是JNK 2和3的有效且选择性抑制剂。本发明还涉及新的磺酰胺衍生物以及其制备方法。根据本发明的公式（I）化合物适合作为药物代理，其中Ar?1和Ar2¿是独立于彼此的取代或未取代的芳基或杂环芳基基团，X为O或S，优选为O; R1是氢或C¿1?-C6烷基，或R?1¿与Ar1形成取代或未取代的5-6成员饱和或不饱和环；n为0到5的整数，优选为1-3，最优选为1；公式（I）中的Y是未取代或取代的4-12成员饱和环或双环烷基，其中至少有一个氮原子，在该环内与公式（I）的磺酰基形成化学键，从而提供磺酰胺。
• PHARMACEUTICALLY ACTIVE SULFONAMIDE DERIVATIVES
  申请人：Applied Research Systems ARS Holding N.V.

  公开号：EP1218374B1

  公开（公告）日：2005-11-16
• SULFONAMIDE DERIVATIVES FOR THE TREATMENT OF DIABETES
  申请人：Applied Research Systems ARS Holding N.V.

  公开号：EP1663193A1

  公开（公告）日：2006-06-07
• JNK INHIBITORS FOR THE TREATMENT OF ENDOMETREOSIS
  申请人：LABORATOIRES SERONO S.A.

  公开号：EP1904181A2

  公开（公告）日：2008-04-02
• Sulfonamide derivatives for the treatment of diabetes
  申请人：Rueckle Thomas

  公开号：US20070043027A1

  公开（公告）日：2007-02-22

  The present invention is related to the use of sulfonamide derivatives in the treatment of metabolic disorders mediated by insulin resistance or hyperglycemia, comprising diabetes type II, inadequate glucose tolerance, insulin resistance, obesity, polycystic ovary syndrome (PCOS). Formula (I). R 1 is selected from the group comprising or consisting of hydrogen, C 1 -C 6 -alkoxy, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, amino, sulfanyl, sulfinyl, sulfonyl, sulfonyloxy, sulfonamide, acylamino, aminocarbonyl, C 1 -C 6 alkoxycarbonyl, aryl, heteroaryl, carboxy, cyano, halogen, hydroxy, nitro, hydrazides. R 2 is selected from the group comprising or consisting of hydrogen, COOR3, —CONR 3 R 3′ , OH, a C 1 -C 4 alkyl substituted with an OH or amino group, a hydrazido carbonyl group, a sulfate, a sulfonate, an amine or an ammonium salt. Y is an 4-12-membered saturated cyclic or bicyclic alkyl containing at least one nitrogen atom, whereby one nitrogen atom within said ring is forming a bond with the sulfonyl group of formula I thus providing the sulfonamide.