(S_S)-2-methyl-propane-2-sulfinic acid [(S)-2-methyl-1-(5-methyl-2-piperazin-1-yl-phenyl)-propyl]-amide | 869478-56-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (S_S)-2-methyl-propane-2-sulfinic acid [(S)-2-methyl-1-(5-methyl-2-piperazin-1-yl-phenyl)-propyl]-amide
• 英文别名: (S)-2-methyl-N-[(1S)-2-methyl-1-(5-methyl-2-piperazin-1-ylphenyl)propyl]propane-2-sulfinamide
• CAS: 869478-56-8
• 化学式: C₁₉H₃₃N₃OS
• 分子量: 351.557
• InChiKey: YVTXQFYAFSCLLG-UUOWRZLLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  63.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S_S)-2-methyl-propane-2-sulfinic acid [(S)-2-methyl-1-(5-methyl-2-piperazin-1-yl-phenyl)-propyl]-amide 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 (S)-N-((S)-1-(2-(4-((3S,4R)-4-(4-chlorophenyl)pyrrolidine-3-carbonyl)piperazin-1-yl)-5-methylphenyl)-2-methylpropyl)-2-methylpropane-2-sulfinamide
  参考文献：
  名称：

  Pyrrolidines as potent functional agonists of the human melanocortin-4 receptor

  摘要：

  A series of pyrrolidine derivatives were synthesized and characterized as potent agonists of the human melanocortin-4 receptor. For example, 28c had a K-i of 13 nM in binding affinity and EC50 of 6.9 nM in agonist potency with an intrinsic activity of 100% of the endogenous ligand alpha-MSH. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.06.088
• 作为产物：
  描述：

  4-(2-formyl-4-methyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester 在 titanium(IV) tetraethanolate 、 三甲基铝 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醇 、 正庚烷 、 二氯甲烷 、 正戊烷 为溶剂， 反应 18.0h， 生成 (S_S)-2-methyl-propane-2-sulfinic acid [(S)-2-methyl-1-(5-methyl-2-piperazin-1-yl-phenyl)-propyl]-amide
  参考文献：
  名称：

  Practical Asymmetric Synthesis of α-Branched 2-Piperazinylbenzylamines by 1,2-Additions of Organometallic Reagents to N-tert-Butanesulfinyl Imines

  摘要：

  2-[4-(tert-Butoxycarbonyl)piperazinyl]benzylidene-tert-butanesulfinamides underwent nucleophilic 1,2-addition with different organometallic reagents to give highly diastereomerically enriched adducts. X-ray crystallography of the resulting alpha-branched N-Boc-2-piperazinylbenzyl-tert-butanesulfinamides confirms different mechanisms depending on the organometallic reagent used. Differential deprotection of the N-Boc and the tert-butanesulfinamides was investigated, and the dehydration byproducts have been identified and characterized. To avoid the formation of byproducts in the acidic deprotection step, the N-tert-butanesulfinamide group was converted to the corresponding N-tert-butanesulfonamide (Bus), which allowed for clean orthogonal deprotection. The efficient synthesis and deprotection of the N-Boc-2-piperazinylbenzyl-tert-butanesulfinamides herein described constitutes an attractive method for extensive structure-activity studies in the search for novel ligands of the human melanocortin 4 receptor.

  DOI：

  10.1021/jo051514p

文献信息

• [EN] LIGANDS OF MELANOCORTIN RECEPTORS AND COMPOSITIONS AND METHODS RELATED THERETO<br/>[FR] LIGANDS DU RECEPTEUR DE LA MELANOCORTINE ET COMPOSITIONS ET METHODES ASSOCIEES
  申请人：NEUROCRINE BIOSCIENCES INC

  公开号：WO2005040109A1

  公开（公告）日：2005-05-06

  Compounds which function as melanocortin receptor ligands and having utility in the treatment of melanocortin receptor-based disorders. The compounds have the following structure (I): (R4)s (R 2)n N~ X1-X2 (CR1aCRlb)q 1~ N R1-lm 1 O R3 (I) including stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein m, n, q, s, R1, R1a, R1b, R2, R3, R4, X1 X2 and X3 are as defined herein. Pharmaceutical compositions containing a compound of structure (I), as well as methods relating to the use thereof, are also disclosed.

  化合物作为黑色素皮质激素受体配体，并在治疗基于黑色素皮质激素受体的疾病中具有用途。这些化合物具有以下结构（I）：（R4）s（R 2）n N〜X1-X2（CR1aCRlb）q 1〜N R1-lm 1 O R3（I），包括立体异构体，前药和其药用盐，其中m、n、q、s、R1、R1a、R1b、R2、R3、R4、X1、X2和X3如本文所定义。还公开了含有结构（I）化合物的药物组合物，以及与其使用相关的方法。
• Syntheses of tetrahydrothiophenes and tetrahydrofurans and studies of their derivatives as melanocortin-4 receptor ligands
  作者：Joe A. Tran、Caroline W. Chen、Fabio C. Tucci、Wanlong Jiang、Beth A. Fleck、Chen Chen

  DOI：10.1016/j.bmcl.2007.11.128

  日期：2008.2

  Piperazinebenzylamine derivatives from trans-4-(4-chlorophenyl)tetrahydrothiophene-3-carboxylic acid 6 and its S-oxide 7 and sulfone 8, and the tetrahydrofuran 9 and its two regioisomers 11 and 13 were synthesized and studied for their binding affinities at the human melanocortin-4 receptor. These five-membered ring constrained compounds possessed similar or lower potency compared to the acyclic analogs. (C) 2007 Elsevier Ltd. All rights reserved.
• Identification and characterization of pyrrolidine diastereoisomers as potent functional agonists and antagonists of the human melanocortin-4 receptor
  作者：Chen Chen、Wanlong Jiang、Joe A. Tran、Fabio C. Tucci、Beth A. Fleck、Stacy Markison、Jenny Wen、Ajay Madan、Sam R. Hoare、Alan C. Foster、Dragan Marinkovic、Caroline W. Chen、Melissa Arellano、John Saunders

  DOI：10.1016/j.bmcl.2007.10.115

  日期：2008.1

  A series of trans-4-phenylpyrrolidine-3-carboxamides were synthesized and characterized as potent ligands of the human melanocortin-4 receptor. Interestingly, a pair of diastereoisomers 13b displayed potent functional agonist and antagonist activity, respectively. Thus, the 3S,4R-pyrrolidine 13b-1 possessed a K-i of 1.0 nM and an EC50 of 3.8 nM while its 3R,4S-isomer 13b-2 exhibited a K-i of 4.7 and an IC50 of 64 nM. Both compounds were highly selective over other melanocortin receptor subtypes. The MC4R agonist 13b-1 also demonstrated efficacy in a diet-induced obesity model in rats. (C) 2007 Elsevier Ltd. All rights reserved.
• Synthesis and characterization of pyrrolidine derivatives as potent agonists of the human melanocortin-4 receptor
  作者：Wanlong Jiang、Joe A. Tran、Fabio C. Tucci、Beth A. Fleck、Sam R. Hoare、Stacy Markison、Jenny Wen、Caroline W. Chen、Dragan Marinkovic、Melissa Arellano、Alan C. Foster、Chen Chen

  DOI：10.1016/j.bmcl.2007.09.079

  日期：2007.12

  A series of trans-4-phenylpyrrolidine-3-carboxamides were synthesized and characterized as potent ligands of the human melanocortin-4 receptor. Interestingly, a pair of diastereoisomers 20f-1 and 20f-2 displayed potent functional agonist and antagonist activity, respectively. Thus, the 3S, 4R-compound 20f-1 possessed a K-i of 11 nM and an EC50 of 24 nM, while its 3R, 4S-isomer 20f-2 exhibited a K-i of 8.6 and an IC50 of 65 nM. Both compounds were highly selective over other melanocortin receptor subtypes. The MC4R agonist 20f-1 also demonstrated efficacy in diet-induced obese rats. (c) 2007 Elsevier Ltd. All rights reserved.
• Design and synthesis of 3-arylpyrrolidine-2-carboxamide derivatives as melanocortin-4 receptor ligands
  作者：Joe A. Tran、Fabio C. Tucci、Melissa Arellano、Wanlong Jiang、Caroline W. Chen、Dragan Marinkovic、Beth A. Fleck、Jenny Wen、Alan C. Foster、Chen Chen

  DOI：10.1016/j.bmcl.2008.01.125

  日期：2008.3

  Based on 3-phenylpropionamides, a series of 3-arylpyrrolidine-2-carboxamide derivatives was designed and synthesized to study the effect of cyclizations as melanocortin-4 receptor ligands. It was found that the 2R, 3R-pyrrolidine isomer possessed the most potent affinity among the four stereoisomers. (C) 2008 Elsevier Ltd. All rights reserved.