2-氯-3-硝基-5,6,7,8-四氢喹啉 | 187243-00-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: 2-氯-3-硝基-5,6,7,8-四氢喹啉
• 英文名称: 2-chloro-5,6,7,8-tetrahydro-3-nitroquinoline
• 英文别名: 2-Chloro-3-nitro-5,6,7,8-tetrahydroquinoline
• CAS: 187243-00-1
• 化学式: C₉H₉ClN₂O₂
• 分子量: 212.636
• InChiKey: ZKCCJTPLBDQLLO-UHFFFAOYSA-N

物化性质

• 沸点：
  331.9±42.0 °C(Predicted)
• 密度：
  1.387±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  58.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-氯-3-硝基-5,6,7,8-四氢喹啉 在 镍 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 5.0~20.0 ℃ 、202.65 kPa 条件下， 反应 10.0h， 生成 N-(2-Methoxy-5,6,7,8-tetrahydro-quinolin-3-yl)-2,2-dimethyl-propionamide
  参考文献：
  名称：

  4-Benzyl and 4-Benzoyl-3-dimethylaminopyridin-2(1H)-ones:  In Vitro Evaluation of New C-3-Amino-Substituted and C-5,6-Alkyl-Substituted Analogues against Clinically Important HIV Mutant Strains

  摘要：

  In a program to optimize the anti-HIV activity of the 4-benzyl and 4-benzoyl-3-dimethylaminopyridinones 9 and 10, lead compounds in a new class of highly potent non-nucleoside type inhibitors of HIV-1 reverse transcriptase, modification of the alkyl substitutents at the C-5 and C-6 positions on the pyridinone ring and of the substitutents on the C-3 amino group has been studied. Of the 17 new 5/6-modified analogues prepared, compounds 31b and 32b substituted at C-5 by an extended nonpolar chain containing an ether function and a C-6 methyl group and compound 35 bearing a C-5 ethyl/C-6 hydroxymethyl substituent pattern were selected on the basis of their in vitro activity against wild-type HIV and the three principle mutant strains, K103N, Y181C, and Y188L. When tested further, it was shown that these molecules, and in particular compound 35, are globally more active than 9, 10, and efavirenz against an additional eight single [L100I, K101E, V106A, E138K, V179E, G190A/S, and F227C] and four double HIV mutant strains [L1001 + K103N, K101E + K103N, K103N + Y181C, and F227L + V106A] which are clinically relevant. Concerning modulation of the N-3 substituent, 36 new analogues were prepared. Of these, the N-methyl-N-(2-methoxyethyl)-substituted compounds 40, 42, and 62, as well as the doubly modified compounds 77a and 77b, were selected from the initial screen and were subsequently shown to be active at sub-micromolar concentrations (IC50'S) against all the other mutant strains except K103N + Y181C and F227L + V106A. Two possible, but distinct, modes of binding of these analogues in RT were suggested from molecular modeling studies. The preferred mode of binding for compound 62, corresponding to the predicted "orientation 1", was revealed in the X-ray crystal structure of the compound 62-RT complex.

  DOI：

  10.1021/jm0408621
• 作为产物：
  描述：

  3-Nitro-1,4,5,6,7,8-hexahydroquinolin-2-amine 在 盐酸 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 1.0h， 以57%的产率得到2-氯-3-硝基-5,6,7,8-四氢喹啉
  参考文献：
  名称：

  多功能合成6取代的8-脱氮庚啶-2,4-二胺。8,10-二氮杂氨基蝶呤的正式全合成

  摘要：

  描述了4-氨基-4-脱氧-8，10-二氮杂氮杂壬酸（11d）和6-取代的和5，6-带烯丙基的8-脱氮杂啶-2，4-二胺10a，10d，25的新合成。从烯酮缩醛1或12和烯胺酮4或β-氨基酮17开始，可以通过2-氨基-3-硝基吡啶5或烟酸酯13a的官能团转化制备标题化合物，得到3-氨基-α-吡啶啉9，其与胍环缩合。 。

  DOI：

  10.1002/jhet.5570330643
• 作为试剂：
  描述：

  5,6,7,8-tetrahydro-3-nitro-2(1H)-quinolinone 、 三氯氧磷 在 苄基三乙基氯化铵 水 、 ammonium hydroxide 、 二氯甲烷 、 2-氯-3-硝基-5,6,7,8-四氢喹啉 作用下， 以 乙腈 为溶剂， 反应 8.0h， 以yielding 15 g of 2-chloro-5,6,7,8-tetrahydro-3-nitroquinoline (intermediate 9)的产率得到2-氯-3-硝基-5,6,7,8-四氢喹啉
  参考文献：
  名称：

  Substituted homopiperidinyl benzimidazole analogues as fundic relaxants

  摘要：

  本发明涉及式（I）化合物及其前药、N-氧化物、加成盐、季铵盐和立体化学异构体，其中双价基团-{circle around (A)}-表示具有一个双键的饱和或不饱和同环异丙基，且所述双价基团-{circle around (A)}-被取代为R2，R2为氢、羟基、C1-4烷基或C1-4烷氧基；-a1=a2-a3=a4-表示可选取代的双价基团；R1为氢、C1-6烷基、芳基1、C1-6烷基取代的芳基1、C1-4烷氧羰基、芳基1羰基、芳基1-C1-6烷基羰基、C1-4烷基羰基、三氟甲基、三氟甲基羰基、C1-6烷基磺酰基、芳基1磺酰基、甲磺酰基、苯磺酰基、三氟甲基磺酰基、二甲基磺酰氨基；X表示O、S或NR3，其中R3为氢、C1-6烷基、甲磺酰基、苯磺酰基、三氟甲基磺酰基、二甲基磺酰氨基、C1-4烷基取代的芳基2，且可选取代的芳基2具有羟基、C1-4烷基羰基C1-4烷基取代的芳基2；芳基1为可选取代的苯基、可选取代的吡啶基、萘基、喹啉基或1,3-苯并二氧杂环基；芳基2为可选取代的苯基；具有胃底松弛活性。本发明还公开了制备所述产品的方法、包含所述产品的制剂以及其作为药物的用途，特别是用于治疗消化不良症状、肠易激综合征和其他与胃底松弛受阻或受损有关的情况。

  公开号：

  US07304052B2

文献信息

• [EN] INHIBITORS OF TRKA KINASE<br/>[FR] INHIBITEURS DE TRKA KINASE
  申请人：GVK BIOSCIENCES PRIVATE LTD

  公开号：WO2016116900A1

  公开（公告）日：2016-07-28

  The present invention is directed to the compounds of Formula I which are inhibitors of tropomyosin-related kinase A (TrkA): Formula (I) or steroisomers, tautomers or a pharmaceutically acceptable salts, metabolites, isotopes, solvates or prodrugs thereof, wherein, Ra, Rb, Rc, Rd, R1, R2, L and Het-Ar are as defined herein. These compounds can be used for the preventive and/or therapeutic treatment of diseases or disorders associated with abnormal activities of nerve growth factor (NGF) receptor TrkA such as Pain, inflammation or an inflammatory diseases, Cancer, atherosclerosis, restenosis, thrombosis, Neurodegenerative diseases, Erectile Dysfunction (ED), Skin disorders, Autoimmune disease like Multiple sclerosis, Sjögren's syndrome, endometriosis, diabetic peripheral neuropathy, prostatitis, Infectious diseases, diseases related to an imbalance of the regulation of bone remodeling, endometriosis, pelvic pain syndrome and diseases resulting from abnormal tissue remodelling and fibrotic disorders; or a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination.

  本发明涉及式I的化合物，该化合物是Tropomyosin-related kinase A（TrkA）的抑制剂：式（I）或其立体异构体、互变异构体或药学上可接受的盐、代谢物、同位素、溶剂合物或前药，其中，Ra、Rb、Rc、Rd、R1、R2、L和Het-Ar如本文所定义。这些化合物可用于预防和/或治疗与神经生长因子（NGF）受体TrkA的异常活动相关的疾病或障碍，如疼痛、炎症或炎症性疾病、癌症、动脉粥样硬化、再狭窄、血栓形成、神经退行性疾病、勃起功能障碍（ED）、皮肤疾病、多发性硬化、干燥综合征、子宫内膜异位症、糖尿病周围神经病变、前列腺炎、传染病、与骨重塑调节失衡相关的疾病、子宫内膜异位症、盆腔疼痛综合征以及由异常组织重塑和纤维化疾病引起的疾病；或与失髓鞘形成或脱髓鞘相关的疾病、障碍、损伤或功能障碍。
• SUBSTITUTED HOMOPIPERIDINYL BENZIMIDAZOLE ANALOGUES AS FUNDIC RELAXANTS
  申请人：Janssen Pharmaceutica NV

  公开号：EP1250337B1

  公开（公告）日：2008-12-03
• US7304052B2
  申请人：——

  公开号：US7304052B2

  公开（公告）日：2007-12-04
• [EN] SUBSTITUTED HOMOPIPERIDINYL BENZIMIDAZOLE ANALOGUES AS FUNDIC RELAXANTS<br/>[FR] ANALOGUES DE BENZIMIDAZOLE HOMOPIPERIDINYLE SUSBTITUE COMME RELAXANTS GASTRIQUES
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2001046189A1

  公开（公告）日：2001-06-28

  The present invention relates to compounds of formula (I), their prodrugs, N-oxides, addition salts, quaternary amines and stereochemically isomeric forms, wherein the bivalent radical -A- represents a saturated or an unsaturated homopiperidinyl having one double bond, and wherein said bivalent radical -A- is substituted with R2 being hydrogen, hydroxy, C¿1-4?alkyl, or C1-4alkyloxy; -a?1=a2-a3=a4¿- represents an optionally substituted bivalent radical; R1 is hydrogen, C¿1-6?alkyl, aryl?1, C¿1-6alkyl substituted with aryl1, C1-4alkyloxycarbonyl, aryl1carbonyl, aryl1C1-6alkylarbonyl C1-4alkylcarbonyl, trifluoromethyl, trifluoromethylcarbonyl, C1-6alkylsulfonyl, aryl1sulfonyl, methanesulfonyl, benzenesulfonyl, trifluoromethanesulfonyl, dimethylsulfamoyl; X represents O, S or NR3, wherein R3 is hydrogen, C¿1-6?alkyl, methanesulfonyl, benzenesulfonyl, trifluoromethanesulfonyl, dimethylsulfamoyl, C1-4alkyl substituted with aryl?2¿ and optionally with hydroxy, C¿1-4?alkylcarbonylC1-4alkyl substituted with aryl?2; aryl1¿ is optionally substituted phenyl, optionally substituted pyridinyl, naphthyl, quinolinyl, or 1,3-benzodioxolyl; aryl2 is optionally substituted phenyl; fundic relaxating activity. Processes for preparing said products, formulations comprising said products and their use as a medicine are disclosed, in particular for treating dyspeptic symptoms, irritable bowel syndrome and other conditions related to a hampered or impaired relaxation of the fundus.
• Substituted homopiperidinyl benzimidazole analogues as fundic relaxants
  申请人：——

  公开号：US20030139393A1

  公开（公告）日：2003-07-24

  The present invention relates to compounds of formula (I) 1 their prodrugs, N-oxides, addition salts, quaternary amines and stereochemically isomeric forms, wherein the bivalent radical —circle over (A)}— represents a saturated or an unsaturated homopiperidinyl having one double bond, and wherein said bivalent radical —circle over (A)}— is substituted with R 2 being hydrogen, hydroxy, C 1-4 alkyl, or C 1-4 alkyloxy; -a 1 =a 2 -a 3 =a 4 - represents an optionally substituted bivalent radical; R 1 is hydrogen, C 1-6 alkyl, aryl 1 , C 1-6 alkyl substituted with aryl 1 , C 1-4 alkyloxycarbonyl, aryl 1 carbonyl, aryl 1 C 1-6 alkylarbonyl C 1-4 alkylcarbonyl, trifluoromethyl, trifluoromethylcarbonyl, C 1-6 alkylsulfonyl, aryl 1 sulfonyl, methanesulfonyl, benzenesulfonyl, trifluoromethanesulfonyl, dimethylsulfamoyl; X represents O, S or NR 3 , wherein R 3 is hydrogen, C 1-6 alkyl, methanesulfonyl, benzenesulfonyl, trifluoromethanesulfonyl, dimethylsulfamoyl, C 1-4 alkyl substituted with aryl 2 and optionally with hydroxy, C 1-4 alkylcarbonylC 1-4 alkyl substituted with aryl 2 ; aryl 1 is optionally substituted phenyl, optionally substituted pyridinyl, naphthyl, quinolinyl, or 1,3-benzodioxolyl; aryl 2 is optionally substituted phenyl; fundic relaxating activity. Processes for preparing said products, formulations comprising said products and their use as a medicine are disclosed, in particular for treating dyspeptic symptoms, irritable bowel syndrome and other conditions related to a hampered or impaired relaxation of the fundus.

  本发明涉及以下式（I）的化合物及其前药、N-氧化物、加成盐、季铵盐和立体化学异构体，其中二价基团—circle over (A)}—代表具有一个双键的饱和或不饱和的同环戊二烯基，并且所述二价基团—circle over (A)}—被取代为R 2 ，R 2 为氢、羟基、C 1-4 烷基或C 1-4 烷氧基；-a 1 =a 2 -a 3 =a 4 -代表一个可选择取代的二价基团；R 1 为氢、C 1-6 烷基、芳基 1 、芳基 1 取代的C 1-6 烷基、C 1-4 烷氧羰基、芳基 1 羰基、芳基 1 C 1-6 烷基羰基C 1-4 烷基羰基、三氟甲基、三氟甲基羰基、C 1-6 烷基磺酰基、芳基 1 磺酰基、甲磺酰基、苯磺酰基、三氟甲磺酰基、二甲基磺酰胺基；X代表O、S或NR 3 ，其中R 3 为氢、C 1-6 烷基、甲磺酰基、苯磺酰基、三氟甲磺酰基、二甲基磺酰胺基、C 1-4 烷基取代的芳基 2 并可选择取代羟基、C 1-4 烷基羰基C 1-4 烷基取代的芳基 2 ；芳基 1 为可选择取代的苯基、可选择取代的吡啶基、萘基、喹啉基或1,3-苯并二氧杂环戊基；芳基 2 为可选择取代的苯基；胃底松弛活性。公开了制备所述产品的方法、包含所述产品的配方以及它们作为药物的用途，特别用于治疗消化不良症状、肠易激综合征和其他与胃底松弛受阻或受损有关的疾病。