N,N-dimethyl-4-(tributylstannyl)-1H-imidazole-1-sulfonamide | 1070217-86-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N,N-dimethyl-4-(tributylstannyl)-1H-imidazole-1-sulfonamide
• 英文别名: N,N-dimethyl-4-tributylstannylimidazole-1-sulfonamide
• CAS: 1070217-86-5
• 化学式: C₁₇H₃₅N₃O₂SSn
• 分子量: 464.26
• InChiKey: YNZFFFUXGMKVNC-UHFFFAOYSA-N

物化性质

• 沸点：
  488.5±55.0 °C(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.59
• 重原子数：
  24
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  63.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N,N-dimethyl-4-(tributylstannyl)-1H-imidazole-1-sulfonamide 、 6-chloro-1-cyclopropyl-3,3-dimethyl-1,3-dihydro-pyrrolo[3,2-c]pyridin-2-one 在 四(三苯基膦)钯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以62%的产率得到4-(1-cyclopropyl-3,3-dimethyl-2-oxo-2,3-dihydro-1H-pyrrolo[3,2-c]pyridin-6-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide
  参考文献：
  名称：

  [EN] INDOLIN-2-ONE AND 1,3-DIHYDRO-PYRROLO[3,2-c]PYRIDIN-2-ONE DERIVATIVES
  [FR] DÉRIVÉS D'INDOLIN-2-ONE ET DE 1,3-DIHYDRO-PYRROLO[3,2-C]PYRIDIN-2-ONE

  摘要：

  本发明涉及一般式(I)的吲哚啉-2-酮和1,3-二氢吡咯并[3,2-c]吡啶-2-酮衍生物，其中Ar1是苯基、吡啶基或嘧啶基；Ar2是含有2个或3个N、O或S杂原子的5或6元杂芳基团；R1是氢、低碳基、卤素或低烷氧基；R2是氢或低碳基；R3是氢、低碳基、低碳基取代的羟基、环烷基、氧杂环丙烯基、吡啶基、咪唑基、吡唑基、嘧啶基，这些环可能被低碳基取代，或者是-(CH2)3-S(O)2-环丙基；X是CH或N；n为1或2；以及其药学上可接受的盐、消旋混合物、对映体和/或光学异构体和/或立体异构体，用于治疗某些中枢神经系统疾病，包括精神病（正性症状和负性症状）、精神分裂症、物质滥用、酒精和药物成瘾、强迫症、认知障碍、双相情感障碍、情绪障碍、重度抑郁症、治疗难治性抑郁症、焦虑症、阿尔茨海默病、自闭症、帕金森病、慢性疼痛、边缘性人格障碍、睡眠障碍、慢性疲劳综合征、僵硬、关节炎中的抗炎作用和平衡问题。

  公开号：

  WO2015177110A1
• 作为产物：
  描述：

  三丁基氯化锡 、 N,N-二甲基-4-碘-1H-咪唑-1-磺酰胺 在 异丙基氯化镁 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 N,N-dimethyl-4-(tributylstannyl)-1H-imidazole-1-sulfonamide
  参考文献：
  名称：

  使用4-（Piperidin-4-yl）-1-hydroxypyrazoles 3-或5-Imidazolyl取代来探索A型γ-氨基丁酸受体的正构结合位点：设计，合成和药理学评估

  摘要：

  已经设计，合成和表征了一系列4-（哌啶-4-基）-1-羟基吡唑（4-PHP）3-或5-咪唑基取代的类似物。所有的类似物表现出结合亲和力的低微以低纳摩尔范围在天然大鼠GABA甲受体和被认为是在人α拮抗剂1 β 2 γ 2S受体。该化合物系列的结构-活性关系表明，在正构结合位点4-PHP支架附近，先前发现的腔在大小和结构上存在明显差异。

  DOI：

  10.1021/jm4006466

文献信息

• INDOLIN-2-ONE OR PYRROLO-PYRIDIN/PYRIMIDIN-2-ONE DERIVATIVES
  申请人：Hoffmann-La Roche Inc.

  公开号：US20160095844A1

  公开（公告）日：2016-04-07

  The present invention is concerned with 2-oxo-2,3-dihydro-indoles of general formula wherein Ar is a 6-membered heteroaryl group, containing one or two N-atoms, which are the groups, pyridinyl, pyrimidinyl, pyridazinyl, or a 5-membered heteroaryl group containing from 1 to 3 heteroatoms, selected from N, S or O, which groups are imidazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadazolyl, isoxazolyl, oxazolyl, 1,3,4-thiadiazolyl or pyrazolyl; R 1 is hydrogen, lower alkyl, halogen, amino, dimethylamino, cyano, lower alkyl substituted by halogen, lower alkyl substituted by hydroxy, CH(OH)CF 3 , (CH 2 ) o -lower alkoxy, cycloalkyl optionally substituted by CF 3 , or heterocycloalkyl optionally substituted by lower alkyl; R 2 is hydrogen, lower alkyl, (CH 2 ) o -cycloalkyl, (CH 2 ) o —O-cycloalkyl, (CH 2 ) o -lower alkoxy, CH 2 ) o -lower alkoxy substituted by halogen, (CH 2 ) o -heterocycloalkyl optionally substituted by lower alkyl, (CH 2 ) o —S(O) 2 -cycloalkyl, lower alkyl substituted by one or two hydroxy, lower alkyl substituted by one or two lower alkoxy, (CH 2 ) o —S(O) 2 -lower alkyl, lower alkyl substituted by halogen or CH 2 CH(OH)CF 3 ; R 3 is halogen or lower alkyl; X is CH or N; X 1 is CH or N; n is 1 or 2; is 0, 1, 2 or 3; m is 0, 1 or 2; and the dotted line indicates a bond may or may not be present; or, a pharmaceutically acceptable salts thereof, with a racemic mixture, or with its corresponding enantiomer and/or optical isomer and/or stereoisomer thereof The compounds may be used for the treatment of certain central nervous system disorders which are positive (psychosis) and negative symptoms of schizophrenia, substance abuse, alcohol and drug addiction, obsessive-compulsive disorders, cognitive impairment, bipolar disorders, mood disorders, major depression, treatment resistant depression, anxiety disorders, Alzheimer's disease, autism, Parkinson's disease, chronic pain, borderline personality disorder, sleep disturbances, chronic fatigue syndrome, stiffness, antiinflammatory effects in arthritis and balance problems.

  本发明涉及一般式为的2-氧代-2,3-二氢吲哚，其中Ar是6元杂环芳基基团，含有一个或两个N原子，该基团为吡啶基，嘧啶基，吡嗪基或含有1至3个杂原子的5元杂环芳基基团，所述杂原子选自N，S或O，该基团为咪唑基，1,2,4-噁二唑基，1,3,4-噁二唑基，异噁唑基，噁唑基，1,3,4-噻二唑基或吡唑基；R1为氢，低碳基，卤素，氨基，二甲氨基，氰基，低碳基取代的卤素，低碳基取代的羟基，CH（OH）CF3，（CH2）o-低碳基氧基，环烷基（可选）取代 或杂环烷基（可选）取代低碳基；R2为氢，低碳基，（ ）o-环烷基，（ ）o—O-环烷基，（ ）o-低碳基氧基，（ ）o-低碳基取代的卤素，（ ）o-杂环烷基（可选）取代低碳基，（ ）o—S（O）2-环烷基，低碳基取代1或2个羟基，低碳基取代1或2个低碳基氧基，（ ）o—S（O）2-低碳基，低碳基取代卤素或 CH（OH） ；R3为卤素或低碳基；X为CH或N；X1为CH或N；n为1或2；为0,1,2或3；m为0,1或2；虚线表示可能存在或不存在键；或其药学上可接受的盐，与外消旋混合物或其对应的对映体和/或光学异构体和/或立体异构体一起使用。这些化合物可用于治疗某些中枢神经系统紊乱，包括精神病（阳性症状）和阴性症状的精神分裂症，物质滥用，酒精和药物成瘾，强迫症，认知障碍，双相障碍，情绪障碍，重度抑郁症，治疗难治性抑郁症，焦虑症，阿尔茨海默病，自闭症，帕金森病，慢性疼痛，边缘人格障碍，睡眠障碍，慢性疲劳综合症，僵硬，关节炎的抗炎作用和平衡问题的治疗。
• Structure−Activity Studies on a Series of a 2-Aminopyrimidine-Containing Histamine H₄ Receptor Ligands
  作者：Robert J. Altenbach、Ronald M. Adair、Brian M. Bettencourt、Lawrence A. Black、Shannon R. Fix-Stenzel、Sujatha M. Gopalakrishnan、Gin C. Hsieh、Huaqing Liu、Kennan C. Marsh、Michael J. McPherson、Ivan Milicic、Thomas R. Miller、Timothy A. Vortherms、Usha Warrior、Jill M. Wetter、Neil Wishart、David G. Witte、Prisca Honore、Timothy A. Esbenshade、Arthur A. Hancock、Jorge D. Brioni、Marlon D. Cowart

  DOI：10.1021/jm8005959

  日期：2008.10.23

  A series of 2-aminopyrimidines was synthesized as ligands of the histamine H-4 receptor (H4R). Working in part from a pyrimidine hit that was identified in an HTS campaign, SAR studies were carried out to optimize the potency, which led to compound 3,4-tert-butyl-6-(4-methylpiperazin-1-yl)pyrimidin-2-ylamine. We further studied this compound by systematically modifying the core pyrimidine moiety, the methylpiperazine at position 4, the NH2 at position 2, and positions 5 and 6 of the pyrimidine ring. The pyrimidine 6 position benefited the most from this optimization, especially in analogs in which the 6-tert-butyl was replaced with aromatic and secondary amine moieties. The highlight of the optimization campaign was compound 4, 4-[2-amino-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]benzonitrile, which was potent in vitro and was active as an anti-inflammatory agent in an animal model and had antinociceptive activity in a pain model, which supports the potential of H4R antagonists in pain.