2-(2-甲基-吲哚-3-基)-丙酸 | 50776-24-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 2-(2-甲基-吲哚-3-基)-丙酸
• 英文名称: 2-(2-methyl-1H-indol-3-yl)propanoic acid
• CAS: 50776-24-4；69296-71-5；69296-72-6
• 化学式: C₁₂H₁₃NO₂
• 分子量: 203.241
• InChiKey: LBUZTVHYRCEKKF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  53.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(3,5-dimethyl-1-phenyl-1H-pyrazol-4-yl)-2-hydroxyacetamide 、 2-(2-甲基-吲哚-3-基)-丙酸 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以75%的产率得到2-((3,5-dimethyl-1-phenyl-1H-pyrazol-4-yl)amino)-2-oxoethyl 2-(2-methyl-1H-indol-3-yl)propanoate
  参考文献：
  名称：

  Depsipeptides Featuring a Neutral P1 Are Potent Inhibitors of Kallikrein-Related Peptidase 6 with On-Target Cellular Activity

  摘要：

  Kallikrein-related peptidase 6 (KLK6) is a secreted serine protease that belongs to the family of tissue kallikreins (KLKs). Many KLKs are investigated as potential biomarkers for cancer as well as therapeutic drug targets for a number of pathologies. KLK6, in particular, has been implicated in neurodegenerative diseases and cancer, but target validation has been hampered by a lack of selective inhibitors. This work introduces a class of depsipeptidic KLK6 inhibitors, discovered via high-throughput screening, which were found to function as substrate mimics that transiently acylate the catalytic serine of KLK6. Detailed structure-activity relationship studies, aided by in silico modeling, uncovered strict structural requirements for potency, stability, and acyl-enzyme complex half-life. An optimized scaffold, DKFZ-251, demonstrated good selectivity for KLK6 compared to other KLKs, and on-target activity in a cellular assay. Moreover, DKFZ-633, an inhibitor-derived activity based probe, could be used to pull down active endogenous KLK6.

  DOI：

  10.1021/acs.jmedchem.8b01106
• 作为产物：
  描述：

  2-bromo-1-(2-methyl-1H-indol-3-yl)propan-1-one 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以27%的产率得到2-(2-甲基-吲哚-3-基)-丙酸
  参考文献：
  名称：

  CHEMICAL SUBSTANCES WHICH INHIBIT THE ENZYMATIC ACTIVITY OF HUMAN KALLIKREIN-RELATED PEPTIDASE 6 (KLK6)

  摘要：

  这项发明涉及适用于治疗与kallikrein样肽酶6过度表达相关疾病的化合物，以及含有这些化合物的药物组合物。该发明还涉及包括这些化合物或药物组合物的配套工具包。

  公开号：

  EP3305781A1

文献信息

• CHEMICAL SUBSTANCES WHICH INHIBIT THE ENZYMATIC ACTIVITY OF HUMAN KALLIKREIN-RELATED PEPTIDASE 6 (KLK6)
  申请人：Deutsches Krebsforschungszentrum

  公开号：EP3305781A1

  公开（公告）日：2018-04-11

  The invention relates to compounds which are suitable for the treatment of a disease associated with kallikrein-like peptidase 6 overexpression and to pharmaceutical compositions containing such compounds. The invention further relates to a kit of parts comprising such compounds or pharmaceutical compositions.

  这项发明涉及适用于治疗与kallikrein样肽酶6过度表达相关疾病的化合物，以及含有这些化合物的药物组合物。该发明还涉及包括这些化合物或药物组合物的配套工具包。
• 3-(1-Substituted-4-piperidyl)-1,2-benzisoxazoles, a process for the preparation thereof, a pharmaceutical composition comprising the same, and their use as medicaments
  申请人：HOECHST-ROUSSEL PHARMACEUTICALS INCORPORATED

  公开号：EP0079564A1

  公开（公告）日：1983-05-25

  Novel 3-(1-substituted-4-piperidyl)-1,2-benzisoxazoles, of the formula 1 wherein X is halogen, loweralkyl, loweralkoxy or hydroxy and m is 0, 1 or 2, R is a group of the formula wherein n is 2 or 3; a group of the formula wherein n is 2 or 3; a group of the formula wherein n is 2 or 3; a group of the formula wherein R, and R2 are each independently hydrogen or loweralkyl, R3 is hydrogen, halogen or loweralkyl and n is 2 or 3: a group of the formula wherein R4 is hydrogen or loweralkyl, R5 is hydrogen, halogen or loweralkyl; and n is 2 or 3; and a group of the formula the optical antipodes thereof; or pharmaceutically acceptable acid addition salts thereof. processes for the preparation thereof, their use for treating psychoses and compositions thereof are disclosed.

  式 1 的新型 3-(1-取代-4-哌啶基)-1,2-苯并异噁唑 其中 X 为卤素、低级烷基、低级烷氧基或羟基，m 为 0、1 或 2，R 为式中的基团 式中 n 为 2 或 3 的基团 式中 n 为 2 或 3 的基团 式中 n 为 2 或 3 的基团 其中 R 和 R2 各自独立地为氢或低级烷基，R3 为氢、卤素或低级烷基，且 n 为 2 或 3 的式子的基团 其中 R4 是氢或低级烷基，R5 是氢、卤素或低级烷基，且 n 是 2 或 3；以及式中的基团 其光学反义词；或其药学上可接受的酸加成盐。 公开了其制备工艺、治疗精神病的用途及其组合物。
• BERGMAN J.; BAECKVALL J. E., TETRAHEDRON <TETR-AB>, 1975, 31, NO 17, 2063-2073
  作者：BERGMAN J.、 BAECKVALL J. E.

  DOI：——

  日期：——
• US4352811A
  申请人：——

  公开号：US4352811A

  公开（公告）日：1982-10-05
• [EN] CHEMICAL SUBSTANCES WHICH INHIBIT THE ENZYMATIC ACTIVITY OF HUMAN KALLIKREIN RELATED PEPTIDASE 6 (KLK6)<br/>[FR] SUBSTANCES CHIMIQUES QUI INHIBENT L'ACTIVITÉ ENZYMATIQUE DE LA PEPTIDASE 6 LIÉE À LA KALLIKRÉINE HUMAINE (KLK6)
  申请人：DEUTSCHES KREBSFORSCHUNGSZENTRUM STIFTUNG DES OEFFENTLICHEN RECHTS

  公开号：WO2018065607A1

  公开（公告）日：2018-04-12

  The invention relates to compounds which are suitable for the treatment of a disease associated with kallikrein related peptidase 6 overexpression and to pharmaceutical compositions containing such compounds. The invention further relates to a kit of parts comprising such compounds or pharmaceutical compositions.