N-((3-tert-butyl-1-(4-methoxyphenyl)-1H-pyrazol-5-yl)methyl)-2-(3-fluoro-4-(methylsulphonamido)phenyl)propanamide | 1255040-45-9

• 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-((3-tert-butyl-1-(4-methoxyphenyl)-1H-pyrazol-5-yl)methyl)-2-(3-fluoro-4-(methylsulphonamido)phenyl)propanamide
• 英文别名: N-[[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]methyl]-2-[3-fluoro-4-(methanesulfonamido)phenyl]propanamide
• CAS: 1255040-45-9
• 化学式: C₂₅H₃₁FN₄O₄S
• 分子量: 502.61
• InChiKey: XHJSLRDLCDWYCJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  新戊酰基乙腈 在 copper(l) iodide 、 lithium aluminium tetrahydride 、 亚硝酸特丁酯 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 乙醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 13.0h， 生成 N-((3-tert-butyl-1-(4-methoxyphenyl)-1H-pyrazol-5-yl)methyl)-2-(3-fluoro-4-(methylsulphonamido)phenyl)propanamide
  参考文献：
  名称：

  Pyrazole C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists

  摘要：

  A series of 1-substituted 3-(t-butyl/trifluoromethyl)pyrazole C-region analogues of 2-(3-fluoro-4-methyl-sulfonamidophenyl) propanamides were investigated for hTRPV1 antagonism. The structure activity relationship indicated that the 3-chlorophenyl group at the 1-position of pyrazole was the optimized hydrophobic group for antagonistic potency and the activity was stereospecific to the S-configuration, providing exceptionally potent antagonists 13S and 16S with K-i(CAP) = 0.1 nM. Particularly significant, 13S exhibited antagonism selective for capsaicin and NADA and not for low pH or elevated temperature. Both compounds also proved to be very potent antagonists for rTRPV1, blocking in vivo the hypothermic action of capsaicin, consistent with their in vitro mechanism. The docking study of compounds 13S and 16S in our hTRPV1 homology model indicated that the binding modes differed somewhat, with that of 13S more closely resembling that of GRT12360. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.08.020

文献信息

• Substituted Phenylureas and Phenylamides as Vanilloid Receptor Ligands
  申请人：FRANK Robert

  公开号：US20120258946A1

  公开（公告）日：2012-10-11

  Substituted phenylureas and phenylamides, processes for their preparation, pharmaceutical compositions containing these compounds, and the use of these compounds for preparing pharmaceutical compositions.

  取代苯基脲和苯基酰胺，其制备过程，含有这些化合物的制药组合物以及使用这些化合物制备制药组合物的用途。
• METHODS OF USING MONOMETHYLVALINE COMPOSITIONS HAVING PHENYLALANINE CARBOXY MODIFICATIONS AT THE C-TERMINUS
  申请人：Seattle Genetics, Inc.

  公开号：US20150044238A1

  公开（公告）日：2015-02-12

  Auristatin peptide analogs of MeVal-Val-Dil-Dap-Phe (MMAF) having a carboxylic acid equivalent at the C-terminal phenylalanine were prepared and attached to ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand-drug conjugates were active in vitro and in vivo in inhibiting cell proliferation and are represented by the general structure of L v -[(LU) 0-1 -(D) 1-4 ] p wherein L- is Ligand unit; LU is a Linker unit (LU); v is 1; p is an number ranging from about 1 to about 20; and D is a drug moiety having the formula: wherein the moiety —N(R 9 )Z 1 is a phenylalanine bioisostere, wherein Z 1 is —CH(R 10 )Z 2 so that the phenylalanine bioisostere has the structure of Formula A: and wherein the substituents R 2 -R 10 , X 1 and Z 2 are as defined.

  制备了具有C端苯丙氨酸羧酸等效物的MeVal-Val-Dil-Dap-Phe（MMAF）的Auristatin肽类类似物，并通过各种连接剂将其连接到配体上，包括maleimidocaproyl-val-cit-PAB。所得的配体-药物偶联物在体外和体内抑制细胞增殖方面具有活性，并由以下一般结构表示：Lv-[(LU)0-1-(D)1-4]p，其中L-是配体单元；LU是连接单元（LU）；v为1；p为约1至约20的数字；D是具有以下公式的药物基团：其中，—N（R9）Z1基团是苯丙氨酸生物同构体，其中Z1是—CH（R10）Z2，以便苯丙氨酸生物同构体具有A式结构；其中取代基R2-R10、X1和Z2如定义。
• SUBSTITUTED PHENYLUREAS AND PHENYLAMIDES AS VANILLOID RECEPTOR LIGANDS
  申请人：Grünenthal GmbH

  公开号：EP2427435A1

  公开（公告）日：2012-03-14
• US8592471B2
  申请人：——

  公开号：US8592471B2

  公开（公告）日：2013-11-26
• US8946204B2
  申请人：——

  公开号：US8946204B2

  公开（公告）日：2015-02-03