methyl 3-(3-(1-(((1R,5S)-6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)methyl)piperidin-4-yl)ureido)benzoate | 590392-95-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: methyl 3-(3-(1-(((1R,5S)-6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)methyl)piperidin-4-yl)ureido)benzoate
• 英文别名: methyl 3-[[1-[[(1R,5S)-6,6-dimethyl-2-bicyclo[3.1.1]hept-2-enyl]methyl]piperidin-4-yl]carbamoylamino]benzoate
• CAS: 590392-95-3
• 化学式: C₂₄H₃₃N₃O₃
• 分子量: 411.544
• InChiKey: RPCVSKRMGOKULT-RXVVDRJESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  70.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 3-(3-(1-(((1R,5S)-6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)methyl)piperidin-4-yl)ureido)benzoate 生成
  参考文献：
  名称：

  Identification and structure–activity relationships of 1-aryl-3-piperidin-4-yl-urea derivatives as CXCR3 receptor antagonists

  摘要：

  The synthesis and biological evaluation of a series of 1-aryl-3-piperidin-4-yl-urea derivatives as small-molecule CXCR3 antagonists is described. SAR studies resulted in significant improvement of potency and physicochernical properties and established the key pharmacophore of the series, and led to the identification of 9t, which exhibits an IC50 of 16 nM in the GTP gamma S-35 functional assay. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.10.088
• 作为产物：
  描述：

  1-(((1R,5S)-6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)methyl)piperidin-4-amine 、 3-(甲氧基羰基)异氰酸苯酯 生成 methyl 3-(3-(1-(((1R,5S)-6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)methyl)piperidin-4-yl)ureido)benzoate
  参考文献：
  名称：

  Identification and structure–activity relationships of 1-aryl-3-piperidin-4-yl-urea derivatives as CXCR3 receptor antagonists

  摘要：

  The synthesis and biological evaluation of a series of 1-aryl-3-piperidin-4-yl-urea derivatives as small-molecule CXCR3 antagonists is described. SAR studies resulted in significant improvement of potency and physicochernical properties and established the key pharmacophore of the series, and led to the identification of 9t, which exhibits an IC50 of 16 nM in the GTP gamma S-35 functional assay. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.10.088

文献信息

• Piperidin-4-yl urea derivatives and related compounds as chemokine receptor inhibitors for the treatment of inflammatory diseases
  申请人：Watson John Robert

  公开号：US20050113414A1

  公开（公告）日：2005-05-26

  Cyclic amino derivatives of formula (1) are described: (1) wherein: m and n, which may be the same or different, is each zero or the integer 1 or 2; Alk 3 is a covalent bond or a straight or branched C 1-6 alkylene chain; R 1 and R 2 , which may be the same or different, is each a hydrogen atom or a straight or branched C 1-6 alkyl group; D is an optionally substituted aromatic or heteroaromatic group; E is an optionally substituted C 7-10 cycloalkyl, C 7-10 cycloalkenyl or C 7-10 polycycloaliphatic group; and the salts, solvates, hydrates, tautomers or N-oxides thereof. The compounds are potent and selective modulators of the interaction between CXCR3 and its chemokine ligands and are thus of use in medicine, for example in the prevention or treatment of conditions involving inappropriate T-cell trafficking such as certain inflammatory, autoimmune and immunoregulatory disorders as described hereinafter.

  描述了公式（1）的环状氨衍生物：（1）其中：m和n，可以相同或不同，均为零或整数1或2; Alk3是共价键或直链或支链C1-6烷基链; R1和R2，可以相同或不同，均为氢原子或直链或支链C1-6烷基基团; D是可选的取代芳香族或杂环芳香族基团; E是可选的取代C7-10环烷基，C7-10环烯基或C7-10多环脂肪族基团;以及其盐，溶剂化物，水合物，互变异构体或N-氧化物。这些化合物是CXCR3与其趋化因子配体之间相互作用的强效和选择性调节剂，因此在医学上有用，例如在预防或治疗涉及不适当T细胞转移的疾病中，如下所述的某些炎症，自身免疫和免疫调节性疾病。
• Phenyl substituted triazoles and their use as selective inhibitors of akl5 kinase
  申请人：Gaster Mary Laramie

  公开号：US20050014938A1

  公开（公告）日：2005-01-20

  Phenyl substituted triazoles of formula (I) wherein R 1 is naphthyl or phenyl optionally substituted with one or more substituents selected from halo, —O—C 1-6 alkyl, —S—C 1-6 alkyl, C 1-6 alkyl, C 1-6 haloalkyl, —O—(CH 2 ) n -Ph, —S—(CH 2 ) n -Ph, cyano, phenyl, and CO 2 R, wherein R is hydrogen or C 1-6 alkyl, and n is 0, 1, 2 or 3; or R 1 is phenyl or pyridyl fused with an aromatic or non-aromatic cyclic ring of 5-7 members wherein said cyclic ring optionally contains up to three heteroatoms, independently selected from N, O and S, and N may be further optionally substituted by C 1-6 alkyl, and wherein the cyclic ring may be optionally substituted by ═O; R 2 and R 3 are independently selected from H, C 1-6 alkyl, C 1-6 alkoxy, phenyl, NH(CH 2 ) n -Ph, NH—C 1-6 alkyl, halo, alkoxy, CN, NO 2 , CONHR and SO 2 NHR; two of X 1 , X 2 and X 3 are N and the other is NR 4 wherein R 4 is hydrogen, C 1-6 alkyl, C 3-7 cycloalkyl, —(CH 2 ) p —CN, —(CH 2 ) p —CO 2 H, —(CH 2 ) p —CONHR 5 R 6 , —(CH 2 ) p COR 5 , —(CH 2 ) q (CR 7 ) 2 , —(CH 2 ) p OR 5 , (CH 2 ) q CH═CH—CN, —(CH 2 ) q —CH═CH—CO 2 H, —(CH 2 ) p —CH═CH—CONHR 5 R 6 , —(CH 2 ) p NHCOR 8 or —(CH 2 ) p NR 9 R 10 ; R 5 and R 6 are independently hydrogen or C 1-6 alkyl; R 7 is C 1-6 alkyl; R 8 is C 1-7 alkyl, or optionally substituted aryl, heteroaryl, arylC 1-6 alkyl or heteroaryl C 1-6 alkyl; R 9 and R 10 are independently selected from hydrogen, C 1-6 alkyl, aryl and arylC 1-6 alkyl; p is 0-4; and q is 1-4 and salts and solvates thereof, are disclosed, as are methods for their preparation, pharmaceutical compositions containing them and their use in medicine.

  式(I)的苯基取代三唑 其中 R 1 是萘基或苯基，可任选被一个或多个取代基取代，这些取代基选自卤、-O-C 1-6 烷基、-S-C 1-6 烷基、C 1-6 烷基，C 1-6 卤代烷基、-O-(CH 2 ) n -Ph，-S-(CH 2 ) n -Ph、氰基、苯基和 CO 2 R，其中 R 是氢或 C 1-6 烷基，且 n 为 0、1、2 或 3；或 R 1 是苯基或吡啶基，与由 5-7 个成员组成的芳香族或非芳香族环合并，其中所述环可任选包含最多三个杂原子，这些杂原子独立地选自 N、O 和 S，且 N 可进一步任选被 C 1-6 烷基取代。 1-6 烷基取代，其中环环可任选被 ═O 取代； R 2 和 R 3 独立选自 H、C 1-6 烷基、C 1-6 烷氧基、苯基、NH(CH 2 ) n -苯基、NH-C 1-6 烷基、卤代、烷氧基、CN、NO 2 、CONHR 和 SO 2 NHR； X 的两个 1 , X 2 和 X 3 是 N，另一个是 NR 4 其中 R 4 是氢、C 1-6 烷基 3-7 环烷基、-(CH 2 ) p -CN，-(CH 2 ) p -CO 2 H, -(CH 2 ) p -CONHR 5 R 6 ，-(CH 2 ) p COR 5 ，-(CH 2 ) q (CR 7 ) 2 ，-(CH 2 ) p 或 5 , (CH 2 ) q CH═CH-CN, -(CH 2 ) q 2 ) q -CH═CH-CO 2 H, -(CH 2 ) p -CH═CH-CONHR 5 R 6 ，-(CH 2 ) p NHCOR 8 或-(CH 2 ) p NR 9 R 10 ; R 5 和 R 6 独立地为氢或 C 1-6 烷基； R 7 是 C 1-6 烷基； R 8 是 C 1-7 烷基，或任选取代的芳基、杂芳基、芳基C 1-6 烷基或杂芳基 C 1-6 烷基； R 9 和 R 10 独立选自氢、C 1-6 烷基、芳基和芳基C 1-6 烷基；p 为 0-4；q 为 1-4，并公开了它们的盐和溶剂，以及它们的制备方法、含有它们的药物组合物和它们在医学中的用途。
• Identification and structure–activity relationships of 1-aryl-3-piperidin-4-yl-urea derivatives as CXCR3 receptor antagonists
  作者：Daniel R. Allen、Amanda Bolt、Gayle A. Chapman、Roland L. Knight、Johannes W.G. Meissner、David A. Owen、Robert J. Watson

  DOI：10.1016/j.bmcl.2006.10.088

  日期：2007.2

  The synthesis and biological evaluation of a series of 1-aryl-3-piperidin-4-yl-urea derivatives as small-molecule CXCR3 antagonists is described. SAR studies resulted in significant improvement of potency and physicochernical properties and established the key pharmacophore of the series, and led to the identification of 9t, which exhibits an IC50 of 16 nM in the GTP gamma S-35 functional assay. (c) 2006 Elsevier Ltd. All rights reserved.