4-[6-(3-fluoro-benzylcarbamoyl)-4-oxo-4H-pyrido[3,4-d]pyrimidin-3-ylmethyl]-benzoic acid tert-butyl ester

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-[6-(3-fluoro-benzylcarbamoyl)-4-oxo-4H-pyrido[3,4-d]pyrimidin-3-ylmethyl]-benzoic acid tert-butyl ester
• 英文别名: Tert-butyl 4-[[6-[(3-fluorophenyl)methylcarbamoyl]-4-oxopyrido[3,4-d]pyrimidin-3-yl]methyl]benzoate
• 化学式: C₂₇H₂₅FN₄O₄
• 分子量: 488.518
• InChiKey: YXLBBZQQWXXZAZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-[6-(3-fluoro-benzylcarbamoyl)-4-oxo-4H-pyrido[3,4-d]pyrimidin-3-ylmethyl]-benzoic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 4-[6-(3-fluoro-benzylcarbamoyl)-4-oxo-4H-pyrido[3,4-d]pyrimidin-3-ylmethyl]-benzoic acid
  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
• 作为产物：
  描述：

  3-(4-tert-butoxycarbonylbenzyl)-4-oxo-3,4-dihydropyrido[3,5-d]pyrimidine-6-carboxylic acid methyl ester 、 3-氟苄胺 在 三甲基铝 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 103.0h， 生成 4-[6-(3-fluoro-benzylcarbamoyl)-4-oxo-4H-pyrido[3,4-d]pyrimidin-3-ylmethyl]-benzoic acid tert-butyl ester
  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

• Pyrido[3,4-d]pyrimidine derivatives as matrix metalloproteinase-13 inhibitors
  申请人：Bunker Mae Amy

  公开号：US20050085447A1

  公开（公告）日：2005-04-21

  This invention relates to a pyrido[3,4-d]pyrimidine derivative of Formula I or a pharmaceutically acceptable salt thereof, wherein R 1 , L 1 , L 2 , V, L 3 , and R 2 are as defined in the specification, that inhibits a matrix metalloproteinase-13 enzyme and thus is useful for treating diseases resulting from MMP-13 mediated tissue breakdown such as osteoarthritis, rheumatoid arthritis, cartilage damage, psoriatic arthritis, ankylosing spondylitis, heart failure, atherosclerosis, inflammatory bowel disease, multiple sclerosis, age-related macular degeneration, chronic obstructive pulmonary disease, asthma, periodontal diseases, psoriasis, cancer, and osteoporosis.

  本发明涉及一种式I的吡啶并[3,4-d]嘧啶衍生物或其药学上可接受的盐，其中R1、L1、L2、V、L3和R2如规范中所定义，该衍生物抑制基质金属蛋白酶-13酶，因此可用于治疗由MMP-13介导的组织分解引起的疾病，如骨关节炎、类风湿性关节炎、软骨损伤、银屑病性关节炎、强直性脊柱炎、心力衰竭、动脉粥样硬化、炎性肠病、多发性硬化症、年龄相关性黄斑变性、慢性阻塞性肺疾病、哮喘、牙周疾病、银屑病、癌症和骨质疏松症。
• 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.