5-(chloromethyl)furo[2,3-b]pyridine | 160729-78-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃吡啶类
• 英文名称: 5-(chloromethyl)furo[2,3-b]pyridine
• CAS: 160729-78-2
• 化学式: C₈H₆ClNO
• mdl: MFCD15144024
• 分子量: 167.595
• InChiKey: IKSOFZFPKKNFLO-UHFFFAOYSA-N

物化性质

• 沸点：
  259.0±25.0 °C(Predicted)
• 密度：
  1.316±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.125
• 拓扑面积：
  26
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-(chloromethyl)furo[2,3-b]pyridine 生成 4-amino-6-chloro-2-(furo[2,3-b]pyridin-5-yl-methylthio)-pyrimidine
  参考文献：
  名称：

  Alpha-substituted pyrimidine-thioalkyl and alkylether compounds as

  摘要：

  该发明涉及式(I)的嘧啶-硫代烷基和烷基醚化合物，以及式(IA)的嘧啶-硫代烷基和烷基醚化合物，即式(I)中R.sub.4选自--H或--NR.sub.15 R.sub.16组，其中R.sub.15为--H且R.sub.16为--H、C.sub.1-C.sub.6烷基、NH.sub.2或R.sub.15和R.sub.16连同--N形成1-吡咯烷基、1-吗啉基或1-哌啶基；以及R.sub.6选自--H或卤素（优选--Cl）的化合物组，总的限制条件是R.sub.4和R.sub.6不能同时为--H。式(IA)的化合物在治疗HIV阳性个体中具有抑制病毒逆转录酶的作用。

  公开号：

  US06043248A1
• 作为产物：
  描述：

  呋喃并[2,3-b]吡啶-5-基甲醇 在 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 以100%的产率得到5-(chloromethyl)furo[2,3-b]pyridine
  参考文献：
  名称：

  实用合成5-（氯甲基）呋喃并[2,3- b ]吡啶，一种HIV蛋白酶抑制剂的关键中间体，L-754,394

  摘要：

  描述了一种实用的合成方法，即5-（氯甲基）呋喃并[2,3- b ]吡啶（10），侧链用于掺入HIV蛋白酶抑制剂的关键药效​​基团L-754,394。所述合成以十个步骤完成，并且由市售的2-糠酸甲酯的总产率为15％。

  DOI：

  10.1002/jhet.5570320431

文献信息

• A practical synthesis of 5-(chloromethyl)furo[2,3-<i>b</i>]pyridine, a key intermediate for the HIV protease inhibitor, L-754,394
  作者：M. Bhupathy、David A. Conlon、Kenneth M. Wells、John R. Nelson、Paul J. Reider、Kai Rossen、Jess W. Sager、R. P. Volante、Bruce D. Dorsey、Jacob M. Hoffman、Sally A. Joseph、Stacey L. Mcdaniel

  DOI：10.1002/jhet.5570320431

  日期：1995.7

  A practical synthesis of 5-(chloromethyl)furo[2,3-b]pyridine (10), the side chain used to incorporate a key pharmacophore of the HIV protease inhibitor, L-754,394, is described. The synthesis was accomplished in ten steps and in 15% overall yield from commercially available methyl 2-furoate.

  描述了一种实用的合成方法，即5-（氯甲基）呋喃并[2,3- b ]吡啶（10），侧链用于掺入HIV蛋白酶抑制剂的关键药效​​基团L-754,394。所述合成以十个步骤完成，并且由市售的2-糠酸甲酯的总产率为15％。
• Alpha-substituted pyrimidine-thioalkyl and alkylether compounds
  申请人：PHARMACIA & UPJOHN COMPANY

  公开号：EP1449835A2

  公开（公告）日：2004-08-25

  The subject invention relates to pyrimidine-thioalkyl and alkylether compounds of Formula I and pyrimidine-thioalkyl and alkylethers of Formula IA, namely the compounds of Formula I where R4 is selected from the group consisting of -H or -NR15R16 where R15 is -H and R16 is -H, C1-C6 alkyl, -NH2 or R15 and R16 taken together with the -N form 1-pyrrolidino, 1-morpholino or 1-piperidino; and R6 is selected from the group consisting of -H, or halo (preferably -CI); with the overall provisio that R4 and R6 are not both -H; The compounds of Formula IA are useful in the treatment of individuals who are HIV positive being inhibitors of viral reverse transcriptase.

  本发明涉及式 I 的嘧啶硫烷基和烷基醚化合物 和式 IA 的嘧啶硫代烷基和烷基醚，即式 I 的化合物，其中 R4 选自由-H 或-NR15R16 组成的组，其中 R15 为-H，R16 为-H、C1-C6 烷基、-NH2 或 R15 和 R16 与-N 共同形成 1-吡咯烷基、1-吗啉基或 1-哌啶基；以及 R6 选自-H 或卤代物（最好是-CI）组成的组；但 R4 和 R6 不能都是-H； 式 IA 的化合物作为病毒逆转录酶的抑制剂，可用于治疗 HIV 阳性患者。
• Identification of MK-944a:  A Second Clinical Candidate from the Hydroxylaminepentanamide Isostere Series of HIV Protease Inhibitors
  作者：Bruce D. Dorsey、Colleen McDonough、Stacey L. McDaniel、Rhonda B. Levin、Christina L. Newton、Jacob M. Hoffman、Paul L. Darke、Joan A. Zugay-Murphy、Emilio A. Emini、William A. Schleif、David B. Olsen、Mark W. Stahlhut、Carrie A. Rutkowski、Lawrence C. Kuo、Jiunn H. Lin、I-W. Chen、Stuart R. Michelson、M. Katharine Holloway、Joel R. Huff、Joseph P. Vacca

  DOI：10.1021/jm9903848

  日期：2000.9.1

  Recent results from human clinical trials have established the critical role of HIV protease inhibitors in the treatment of acquired immune-deficiency syndrome (AIDS). However, the emergence of viral resistance, demanding treatment protocols, and adverse side effects have exposed the urgent need for a second generation of HIV protease inhibitors. The continued exploration of our hydroxylaminepentanamide (HAPA) transition-state isostere series of HIV protease inhibitors, which initially resulted in the identification of Crixivan (indinavir sulfate, MK-639, L-735,524), has now yielded MK-944a (L-756,423). This compound is potent, is selective, and competitively inhibits HIV-1 PR with a Ki value of 0.049 nM. It stops the spread of the HIVIIIb-infected MT4 lymphoid cells at 25.0-50.0 nM, even in the presence of alpha(1) acid glycoprotein, human serum albumin, normal human serum, or fetal bovine serum. MK-944a has a longer half-life in several animal models (rats, dogs, and monkeys) than indinavir sulfate and is currently in advanced human clinical trials.
• A practical synthesis of the 5-chloromethyl-furo[2,3-b]pyridine pharmacophore
  作者：Woo-Baeg Choi、Ioannis N Houpis、Hywyn R.O Churchill、Audrey Molina、Joseph E Lynch、R.P Volante、Paul J Reider、Anthony O King

  DOI：10.1016/0040-4039(95)00850-c

  日期：1995.6

  Synthesis of the furopyridine 2 was accomplished in 52% overall yield from 6-hydroxynicotinic acid (3). The synthesis is highlighted by a Heck coupling of 5 with ethylene followed by an NCS mediated oxidative cyclization and elimination sequence.
• ALPHA-SUBSTITUTED PYRIMIDINE-THIOALKYL AND ALKYLETHER COMPOUNDS AS INHIBITORS OF VIRAL REVERSE TRANSCRIPTASE
  申请人：PHARMACIA & UPJOHN COMPANY

  公开号：EP0824524B1

  公开（公告）日：2004-09-08