4-[4-Oxo-6-(3-phenyl-propa-1,2-dienyl)-4H-quinazolin-3-ylmethyl]-benzoic acid | 602165-98-0

• 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-phenyl-propa-1,2-dienyl)-4H-quinazolin-3-ylmethyl]-benzoic acid
• 英文别名: 4-[[4-oxo-6-(3-phenylpropa-1,2-dienyl)quinazolin-3-yl]methyl]benzoic acid
• CAS: 602165-98-0
• 化学式: C₂₅H₁₈N₂O₃
• 分子量: 394.43
• InChiKey: WGABLHIJVWTAKI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  70
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  methyl 4-[4-oxo-6-(3-phenyl-prop-1-ynyl)-4H-quinazolin-3-ylmethyl]-benzoate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 3.0h， 以30 mg的产率得到4-[4-Oxo-6-(3-phenyl-propa-1,2-dienyl)-4H-quinazolin-3-ylmethyl]-benzoic acid
  参考文献：
  名称：

  Oxo-azabicyclic compounds

  摘要：

  从以下公式（I）中选择的化合物：其中：X1、X2和X3代表N或—CR3，其中R3如描述中所述，G1代表从以下公式（i/a）和（i/b）中选择的基团：其中R4、R5和R6如描述中所定义，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，或者从以下公式（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如描述中所定义，A代表一个环系统，R1代表从H、烷基、烯基、炔基、可选择取代和公式（i/d）中的基团中选择的基团，其中p、Z2、B、q和G3如描述中所定义，以及可选择的其光学异构体、N-氧化物和与药学上可接受的酸或碱形成的加合物，包含相同的药物制剂作为特异性抑制剂类型-13基质金属蛋白酶。

  公开号：

  US06747147B2

文献信息

• Oxo-azabicyclic compounds
  申请人：——

  公开号：US20030216402A1

  公开（公告）日：2003-11-20

  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.

  从公式（I）中选择的一种化合物：其中：X1、X2和X3代表N或—CR3，其中R3如描述中所述，G1代表从下列公式（i/a）和（i/b）中选择的一种基团：其中R4、R5和R6如描述中所定义，G2代表从碳-碳三键、—CH═C═CH—、C═O、C═S、S(O)n1中选择的一种基团，其中n1表示从0到2的整数，或者从下列公式（i/c）中的一个基团：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如描述中所定义，A代表一个环系统，R1代表从H、烷基、烯基、炔基、可选择地取代和公式（i/d）中的一种基团：其中p、Z2、B、q和G3如描述中所定义，以及其光学异构体、N-氧化物和与药用酸或碱形成的加合盐，以及含有它们的药物产品对于作为第13型基质金属蛋白酶的特异抑制剂是有用的。
• US6747147B2
  申请人：——

  公开号：US6747147B2

  公开（公告）日：2004-06-08
• US6894057B2
  申请人：——

  公开号：US6894057B2

  公开（公告）日：2005-05-17
• [EN] OXO AZABICYCLIC COMPOUNDS<br/>[FR] COMPOSES OXO AZABICYCLIQUES
  申请人：WARNER LAMBERT CO

  公开号：WO2003076416A1

  公开（公告）日：2003-09-18

  A compound selected from those of formula (I): formula (I) wherein: - X1, X2, and X3, represent N or CR3 in which R3 is as described in the description, - G1 represents a group selected from those of formulae (i/a) and (i/b): formula (II) in which R4, R5, and R6 are as defined in the description, - G2 represents a group selected from carbon-carbon triple bond, -CH=C=CH-, C=O, C=S, S(O)nt in which n1 represents an integer from 0 to 2 inclusive, or a group of formula (i/c): formula (III) in which Y1 represents O, S, -NH or Nalkyl, and Y2 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, Z1 represents CR9R10, wherein R9 and R10 are as defined in the description, - A represents a ring system, - R1 represents a group selected from H, alkyl, alkenyl, alkynyl, optionally substituted and the group of formula (i/d): formula (IV) in which p, Z2, B, q and G3 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.
• Quinazolinones and Pyrido[3,4-<i>d</i>]pyrimidin-4-ones as Orally Active and Specific Matrix Metalloproteinase-13 Inhibitors for the Treatment of Osteoarthritis
  作者：Jie Jack Li、Joe Nahra、Adam R. Johnson、Amy Bunker、Patrick O’Brien、Wen-Song Yue、Daniel F. Ortwine、Chiu-Fai Man、Vijay Baragi、Kenneth Kilgore、Richard D. Dyer、Hyo-Kyung Han

  DOI：10.1021/jm701274v

  日期：2008.2.1

  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.