4-[4-oxo-6-(3-piperidin-1-ylprop-1-ynyl)quinazolin-3-ylmethyl]benzoic acid trifluoroacetic acid salt | 627050-88-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-[4-oxo-6-(3-piperidin-1-ylprop-1-ynyl)quinazolin-3-ylmethyl]benzoic acid trifluoroacetic acid salt
• 英文别名: 4-[4-oxo-6-(3-piperidin-1-yl-prop-1-ynyl)-4H-quinazolin-3-ylmethyl]-benzoic acid trifluoroacetic acid salt；4-[[4-Oxo-6-(3-piperidin-1-ylprop-1-ynyl)quinazolin-3-yl]methyl]benzoic acid;2,2,2-trifluoroacetic acid
• CAS: 627050-88-8
• 化学式: C₂HF₃O₂*C₂₄H₂₃N₃O₃
• 分子量: 515.489
• InChiKey: NFZZANITDHPBQP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.61
• 重原子数：
  37
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  、 三氟乙酸 反应 0.5h， 生成 4-[4-oxo-6-(3-piperidin-1-ylprop-1-ynyl)quinazolin-3-ylmethyl]benzoic acid trifluoroacetic acid salt
  参考文献：
  名称：

  Quinazolinones and Pyrido[3,4-d]pyrimidin-4-ones as Orally Active and Specific Matrix Metalloproteinase-13 Inhibitors for the Treatment of Osteoarthritis

  摘要：

  Quinazolinones 8 and pyrido[3,4-d]pyrimidin-4-ones 9 as orally active and specific matrix metalloproteinase-13 inhibitors were discovered for the treatment of osteoarthritis. Starting from a high-through-put screening (HTS) hit thizolopyrimidin-dione 7, we obtained two chemotypes, 8 and 9, using computer-aided drug design (CADD) and methodical structure-activity relationship (SAR) studies. They occupy the unique S1'-specificity pocket and do not bind to the Zn2+ ion. Some pyrido[3,4-d]pyrimidin-4-ones, such as 10a, possess favorable absorption, distribution, metabolism, and elimination (ADME) and safety profiles. 10a effectively prevents cartilage damage in rabbit animal models of osteoarthritis without inducing musculoskeletal side effects when given at extremely high doses to rats.

  DOI：

  10.1021/jm701274v

文献信息

• Oxo-azabicyclic compounds
  申请人：——

  公开号：US20030220355A1

  公开（公告）日：2003-11-27

  A compound selected from those of formula (I): 1 wherein: X 1 , X 2 , and X 3 , represent N or —CR 3 in which R 3 is as described in the description, G 1 represents a group selected from those of formulae (i/a) and (i/b): 2 in which R 4 , R 5 , and R 6 are as defined in the description, G 2 represents a group selected from carbon-carbon triple bond, —CH═C═CH—, C═O, C═S, S(O) n1 in which n1 represents an integer from 0 to 2 inclusive, or a group of formula (i/c): 3 in which Y 1 represents O, S, —NH or —Nalkyl, and Y 2 represents O, S, —NH or —Nalkyl, n is an integer from 0 to 6 inclusive, and m is an integer from 0 to 7 inclusive, Z 1 represents —CR 9 R 10 wherein R 9 and R 10 are as defined in the description, A represents a ring system, R 1 represents a group selected from H, alkyl, alkenyl, alkynyl, optionally substituted and the group of formula (i/d): 4 in which p, Z 2 , B, q and G 3 are as defined in the description and optionally, its optical isomers, N-oxide, and addition salts thereof with a pharmaceutically-acceptable acid or base, and medicinal products containing the same are useful as specific inhibitors of type-13 matrix mettaloprotease.

  从以下化合物中选择的一种化合物：其中：X1、X2和X3代表N或—CR3，其中R3如说明中所述，G1代表从以下式(i/a)和(i/b)中选择的基团：其中R4、R5和R6如说明中定义，G2代表从碳-碳三键、—CH═C═CH—、C═O、C═S、S(O)n1中选择的基团，其中n1表示从0到2的整数，或者从以下式(i/c)中的基团：其中Y1代表O、S、—NH或—N烷基，Y2代表O、S、—NH或—N烷基，n是从0到6的整数，m是从0到7的整数，Z1代表—CR9R10，其中R9和R10如说明中定义，A代表一个环系统，R1代表从H、烷基、烯基、炔基、可选择地取代的基团和式(i/d)中的基团中选择的一个，其中p、Z2、B、q和G3如说明中定义，以及它的光学异构体、N-氧化物和与药用酸或碱形成的加合盐，以及含有相同的药物制剂作为第13型基质金属蛋白酶的特异性抑制剂。
• US6747147B2
  申请人：——

  公开号：US6747147B2

  公开（公告）日：2004-06-08