4-[(S)-(1-丙基-1H-咪唑-5-基)甲亚磺酰基]苯胺 | 497223-38-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-[(S)-(1-丙基-1H-咪唑-5-基)甲亚磺酰基]苯胺
• 英文名称: (S)-4-{[(1-propyl-1H-imidazol-5-yl)methyl]sulfinyl}phenylamine
• 英文别名: 4-(((1-propyl-1H-imidazol-5-yl)methyl)sulfinyl)aniline；4(((1-propyl-1H-imidazol-5-yl)methyl)sulfinyl)aniline；(S)-4-(((1-propyl-1H-imidazol-5-yl)methyl)sulfinyl)aniline；(S)-4-[[(1-propyl-1H-imidazol-5-yl)methyl]sulfinyl]aniline；4-[(S)-(3-propylimidazol-4-yl)methylsulfinyl]aniline
• CAS: 497223-38-8
• 化学式: C₁₃H₁₇N₃OS
• 分子量: 263.363
• InChiKey: QPYRLSBRGMJDHW-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  80.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[(S)-(1-丙基-1H-咪唑-5-基)甲亚磺酰基]苯胺 、 7-[4-(2-Butoxy-ethoxy)-phenyl]-1-isobutyl-2,3-dihydro-1H-benzo[b]azepine-4-carbonyl chloride 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 (S)-(-)-7-{4-[2-(butoxy)ethoxy]phenyl}-1-isobutyl-N-({4-[(1-propyl-1H-imidazol-5-yl)methyl]sulfinyl}phenyl)-2,3-dihydro-1H-1-benzazepine-4-carboxamide
  参考文献：
  名称：

  Unusual asymmetric oxidation of sulfide; the diastereoselective oxidation of prochiral sulfide-chiral acid salt with hydrogen peroxide without metal

  摘要：

  The sulfide 4 was treated with chiral acid in a mixture of toluene and methyl iso-butylketone to precipitate the salt, which reacted with 30% H2O2 for 3 weeks at rt. The resulting crystals were collected followed by recrystallization to give the salt of enantiometrically pure sulfoxide and chiral acid 7 in 72% yield and 98.1% de, which was led to chiral sulfoxide S-3 after neutralization. Sulfoxide S-3 was led to S-1a as the candidate for an orally active HIV-1 therapeutic agent. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2005.03.036
• 作为产物：
  描述：

  (1-propyl-2-sulfanyl-1H-imidazol-5-yl)methanol 在 盐酸 、 氯化亚砜 、 双氧水 、 三乙胺 作用下， 以 二氯甲烷 、 水 、 乙酸乙酯 、 异丙醇 、 甲苯 、 正丁醇 为溶剂， 反应 139.0h， 生成 4-[(S)-(1-丙基-1H-咪唑-5-基)甲亚磺酰基]苯胺
  参考文献：
  名称：

  BIPHENYL COMPOUND AS CCR2/CCR5 RECEPTOR ANTAGONIST

  摘要：

  公开号：

  EP3567028B1

文献信息

• ACRYLAMIDE DERIVATIVE, PROCESS FOR PRODUCING THE SAME, AND USE
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1593673A1

  公开（公告）日：2005-11-09

  A compound represented by the formula: wherein R1 is a 5- or 6-membered ring; R3 is a hydrogen atom, a lower alkyl group or a lower alkoxy group; R7 and R8 are each a hydrogen atom or a lower alkyl group; Z1 is another 5- or 6-membered aromatic ring; Z2 is a group represented by -Z2a-W1-Z2b- [wherein Z2a and Z2b are each O, S(O)m (wherein m is 0, 1 or 2), an imino group or a bond, and W1 is an alkylene chain]; X is CR (wherein R is a hydrogen atom, a lower alkyl group, a lower alkoxy group, an acyl group, or R and adjacent R4 may form a 5- or 6-membered alicyclic heterocyclic group) or N; R4 is NR5R6 (wherein R5 and R6 are each a hydrogen atom, a hydrocarbon group, a heterocyclic group or an acyl group), or R5 and R6 are bonded to each other to form a heterocyclic group of NR5R6; and R2 is (1) an amino group which may be a quaternary ammonium or oxide, (2) a nitrogen-containing heterocyclic group which may contain a sulfur atom or an oxygen atom as the ring-constituting atom, in which the nitrogen atom may be converted to a quaternary ammonium or an oxide, or the like; or a salt thereof. The compound has excellent CCR5 antagonistic activity and thus is useful as a prophylactic and/or therapeutic medicine for HIV infection into human peripheral blood monocyte, especially for AIDS.

  一种化合物，其化学式表示为：其中R1是一个5-或6-成员环；R3是氢原子、较低的烷基或较低的烷氧基；R7和R8分别是氢原子或较低的烷基；Z1是另一个5-或6-成员芳香环；Z2是一个由-Z2a-W1-Z2b-表示的基团[其中Z2a和Z2b分别是O、S(O)m（其中m为0、1或2）、亚胺基或键，W1是一个烷基链]；X是CR（其中R是氢原子、较低的烷基、较低的烷氧基、酰基，或R和相邻的R4可能形成5-或6-成员脂环杂环基）或N；R4是NR5R6（其中R5和R6分别是氢原子、烃基、杂环基或酰基），或R5和R6相互连接形成NR5R6的杂环基；R2是（1）可能是季铵盐或氧化物的氨基团，（2）可能包含硫原子或氧原子作为构成环的原子的含氮杂环基，其中氮原子可以转化为季铵盐或氧化物，或类似物；或其盐。该化合物具有出色的CCR5拮抗活性，因此可用作预防和/或治疗HIV感染进入人类外周血单核细胞，特别是艾滋病的药物。
• Highly Potent and Orally Active CCR5 Antagonists as Anti-HIV-1 Agents:  Synthesis and Biological Activities of 1-Benzazocine Derivatives Containing a Sulfoxide Moiety
  作者：Masaki Seto、Katsuji Aikawa、Naoki Miyamoto、Yoshio Aramaki、Naoyuki Kanzaki、Katsunori Takashima、Yoji Kuze、Yuji Iizawa、Masanori Baba、Mitsuru Shiraishi

  DOI：10.1021/jm0509703

  日期：2006.3.1

  potent CCR5 antagonist, sulfoxide compound 4, mainly focusing on replacement of the [6,7]-fused 1-benzazepine nucleus. We designed, synthesized, and evaluated the biological activities of ring-expanded [6,8]-, [6,9]-, and [6,10]-fused compounds containing S-sulfoxide moieties, which led to the discovery of 1-benzazocine and 1-benzazonine compounds that exhibited potent inhibitory activities (equivalent

  已对口服生物利用型有效CCR5拮抗剂亚砜化合物4进行了化学修饰，主要致力于取代[6,7]融合的1-苯并ze庚因核。我们设计，合成和评估了含有S-亚砜部分的环扩展[6,8]-，[6,9]-和[6,10]稠合化合物的生物活性，从而发现了1在结合测定法中表现出强抑制活性（相当于化合物4）的β-苯并偶氮化合物和1-苯并zon嗪化合物。另外，在融合测定中，具有S-亚砜部分（（S）-（-）-5a，b，d，e）的1-苯并偶氮化合物显示出比化合物4更大的效价。从多轮感染测定法的进一步研究中发现，含有S-[（（1-丙基-1H-咪唑）-5]的1-异丁基-1-苯并偶氮化合物（S）-（-）-5b -基]甲基}亚磺酰基，显示出最有效的抗HIV-1活性（在MOLT4 / CCR5细胞中，IC90 = 0.81 nM）。化合物（S）-（-）-5b（TAK-652）还抑制了外周血单核细胞（PBMC）中六种巨噬细胞嗜性（
• NITROGEN-CONTAINING BENZOHETEROCYCLE COMPOUND COMPRISING CARBOXYLIC ACID GROUP, PREPARATION METHOD AND USE THEREOF
  申请人：Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.

  公开号：US20200361911A1

  公开（公告）日：2020-11-19

  Related is a nitrogen-containing benzoheterocycle compound containing a carboxylic acid group as shown in general formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof. The compound has excellent pharmacokinetic properties and extremely remarkable liver targeting properties, and a pharmaceutical composition comprising the same may be used as a CCR antagonist, in particular a CCR2 and/or CCR5 antagonist and can be used in mediated disease, including, but not limited to, nonalcoholic fatty liver disease (NAFLD) or the like.

  相关的是一种含氮苯杂环化合物，其通式(I)所示，包含一个羧酸基团，或其立体异构体或药学上可接受的盐。该化合物具有优异的药代动力学性质和极其显著的肝靶向性能，包含该化合物的药物组合物可用作CCR拮抗剂，特别是CCR2和/或CCR5拮抗剂，并可用于介导的疾病，包括但不限于非酒精性脂肪肝病（NAFLD）或类似疾病。
• PURIFIED CENICRIVIROC AND PURIFIED INTERMEDIATES FOR MAKING CENICRIVIROC
  申请人：Tobira Therapeutics, Inc.

  公开号：US20170362207A1

  公开（公告）日：2017-12-21

  The disclosure includes high purity compounds having CCR5 and/or CCR2 antagonism, or salts thereof, high purity intermediates thereto and processes for synthesizing the same.

  该文件涉及高纯度化合物，具有CCR5和/或CCR2拮抗作用，或其盐，以及制备这些化合物的高纯度中间体和合成过程。
• Fused-ring pyridine derivative, process for producing the same, and use
  申请人：Shiraishi Mitsuru

  公开号：US20060100197A1

  公开（公告）日：2006-05-11

  The present invention provides a compound represented by the formula: wherein R 1 is a 5- or 6-membered ring which may be substituted; R 3 is a hydrogen atom, a lower alkyl group or a lower alkoxy group; Z 1 is a 5- or 6-membered aromatic ring; Z 2 is a group represented by -Z 2a -W 2 -Z 2b wherein Z 2a and Z 2b are each O, S(O) m (wherein m is 0, 1 or 2), an imino group, or a bond; and W 2 is an alkylene chain which may be substituted; n is an integer of 0 to 4; Y is O, S(O) p (wherein p is 0, 1 or 2), CH 2 or NR 4 (wherein R 4 is a hydrogen atom, a hydrocarbon group, a heterocyclic group, or an acyl group); and R 2 is (1) an amino group, in which the nitrogen atom is converted to quaternary ammonium or oxide, (2) a nitrogen-containing heterocyclic group which may contain a sulfur atom or an oxygen atom as a ring-constituting atom, in which the nitrogen atom may be converted to a quaternary ammonium or an oxide, and the like, or a salt thereof. The compound has excellent CCR5 antagonist activity and is useful as a prophylactic and/or therapeutic medicine for HIV infection in human peripheral mononuclear blood cells, especially AIDS.

  本发明提供了一种化合物，其表示为以下式子：其中，R1是一个可能被取代的5或6元环；R3是氢原子、低碳基或低氧基基团；Z1是一个5或6元芳香环；Z2是一个由-Z2a-W2-Z2b表示的基团，其中Z2a和Z2b分别是O、S（O）m（其中m为0、1或2）、亚胺基或键；W2是一个可能被取代的烷基链；n是0到4的整数；Y是O、S（O）p（其中p为0、1或2）、CH2或NR4（其中R4是氢原子、碳氢基团、杂环基团或酰基）；以及R2是（1）一个氨基基团，其中氮原子被转化成季铵或氧化物，（2）一个含氮杂环基团，其中可能含有硫原子或氧原子作为环构成原子，其中氮原子可以被转化为季铵或氧化物等，或其盐。该化合物具有优异的CCR5拮抗活性，并可用作人体外周单核细胞HIV感染的预防和/或治疗药物，特别是艾滋病。