(E,3R)-1-(2-methylpyrimidin-5-yl)-7-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)hept-1-en-3-ol | 404869-61-0

• 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: (E,3R)-1-(2-methylpyrimidin-5-yl)-7-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)hept-1-en-3-ol
• CAS: 404869-61-0
• 化学式: C₂₀H₂₆N₄O
• 分子量: 338.453
• InChiKey: DHKLNRIKEMVTRO-UFUQCMIWSA-N

物化性质

• 沸点：
  600.7±55.0 °C(predicted)
• 密度：
  1.19±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  70.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (E,3R)-1-(2-methylpyrimidin-5-yl)-7-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)hept-1-en-3-ol 在 palladium on activated charcoal 1,4-环己二烯 、 丙酸 作用下， 以 溶剂黄146 为溶剂， 反应 3.0h， 生成 Ethyl (I(2)S)-5,6,7,8-tetrahydro-I(2)-(2-methyl-5-pyrimidinyl)-1,8-naphthyridine-2-nonanoate
  参考文献：
  名称：

  Nonpeptide α_vβ₃ Antagonists. Part 11:  Discovery and Preclinical Evaluation of Potent α_vβ₃ Antagonists for the Prevention and Treatment of Osteoporosis

  摘要：

  3-(S)-Pyrimidin-5-yl-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid (5e) and 3-(S)(methylpyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid (5f) were identified as potent and selective antagonists of the alpha(v)beta(3) receptor. These compounds have excellent in vitro profiles (IC50 = 0.07 and 0.08 nM, respectively), significant unbound fractions in human plasma (6 and 4%), and good pharmacokinetics in rat, dog, and rhesus monkey. On the basis of the efficacy shown in an in vivo model of bone turnover following once-daily oral administration, these two compounds were selected for clinical development for the treatment of osteoporosis.

  DOI：

  10.1021/jm049874c
• 作为产物：
  描述：

  6-氧代庚酸甲酯 在 platinum(IV) oxide sodium tetrahydroborate 、 正丁基锂 、 氢气 、 potassium carbonate 、 DL-脯氨酸 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 正己烷 为溶剂， -78.0 ℃ 、101.33 kPa 条件下， 反应 62.58h， 生成 (E,3R)-1-(2-methylpyrimidin-5-yl)-7-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)hept-1-en-3-ol
  参考文献：
  名称：

  Nonpeptide α_vβ₃ Antagonists. Part 11:  Discovery and Preclinical Evaluation of Potent α_vβ₃ Antagonists for the Prevention and Treatment of Osteoporosis

  摘要：

  3-(S)-Pyrimidin-5-yl-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid (5e) and 3-(S)(methylpyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid (5f) were identified as potent and selective antagonists of the alpha(v)beta(3) receptor. These compounds have excellent in vitro profiles (IC50 = 0.07 and 0.08 nM, respectively), significant unbound fractions in human plasma (6 and 4%), and good pharmacokinetics in rat, dog, and rhesus monkey. On the basis of the efficacy shown in an in vivo model of bone turnover following once-daily oral administration, these two compounds were selected for clinical development for the treatment of osteoporosis.

  DOI：

  10.1021/jm049874c

文献信息

• Process for preparation of integrin receptor antagonist intermediates
  申请人：——

  公开号：US20040030134A1

  公开（公告）日：2004-02-12

  A novel process is provided for the preparation of chiral intermediates useful in the asymmetric syntheses of &agr;v&bgr;3 integrin receptor antagonists. Also provided are the enantiomerically enriched intermediates that are obtained from the process.

  提供了一种新的工艺用于制备手性中间体，该中间体在αvβ3整合素受体拮抗剂的不对称合成中有用。还提供了从该工艺中获得的对映富集的中间体。
• Enantioselective bioreduction for the preparation of integrin receptor antagonist intermediates
  申请人：——

  公开号：US20020187988A1

  公开（公告）日：2002-12-12

  The present invention relates to a novel enantioselective bioreduction using a yeast microorganism for the preparation of the chiral allylic alcohols of structural formula I (R is hydrogen or methyl) which are useful in the asymmetric synthesis of integrin &agr;v&bgr;3 receptor antagonists. 1

  本发明涉及一种利用酵母微生物制备结构式 I 手性烯丙基醇（R 为氢或甲基）的新型对映体选择性生物还原方法，该方法可用于不对称合成整合素&agr;v&bgr;3 受体拮抗剂。 1
• US6764842B2
  申请人：——

  公开号：US6764842B2

  公开（公告）日：2004-07-20
• [EN] INTEGRIN TARGETING LIGANDS FOR OCULAR DELIVERY OF RNAI COMPOUNDS<br/>[FR] LIGANDS CIBLANT L'INTÉGRINE POUR L'ADMINISTRATION OCULAIRE DE COMPOSÉS D'ARNI
  申请人：[en]ALNYLAM PHARMACEUTICALS, INC.

  公开号：WO2023283595A2

  公开（公告）日：2023-01-12

  The disclosure relates to RNA agents modified for targeted delivery to the eye. The present invention provides modified double stranded ribonucleic acid (dsRNAi) agents conjugated to an integrin targeting ligand, as well as methods of modulating the expression of a target gene in an ocular cell or tissue and methods of treating subjects having an ocular disease or disorder using such dsRNAi agents.
• Nonpeptide α_vβ₃ Antagonists. Part 11:  Discovery and Preclinical Evaluation of Potent α_vβ₃ Antagonists for the Prevention and Treatment of Osteoporosis
  作者：Paul J. Coleman、Karen M. Brashear、Ben C. Askew、John H. Hutchinson、Carol A. McVean、Le T. Duong、Bradley P. Feuston、Carmen Fernandez-Metzler、Michael A. Gentile、George D. Hartman、Donald B. Kimmel、Chih-Tai Leu、Lorraine Lipfert、Kara Merkle、Brenda Pennypacker、Thomayant Prueksaritanont、Gideon A. Rodan、Gregg A. Wesolowski、Sevgi B. Rodan、Mark E. Duggan

  DOI：10.1021/jm049874c

  日期：2004.9.1

  3-(S)-Pyrimidin-5-yl-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid (5e) and 3-(S)(methylpyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid (5f) were identified as potent and selective antagonists of the alpha(v)beta(3) receptor. These compounds have excellent in vitro profiles (IC50 = 0.07 and 0.08 nM, respectively), significant unbound fractions in human plasma (6 and 4%), and good pharmacokinetics in rat, dog, and rhesus monkey. On the basis of the efficacy shown in an in vivo model of bone turnover following once-daily oral administration, these two compounds were selected for clinical development for the treatment of osteoporosis.