tert-butyl 3-(bromomethyl)-4-fluorobenzoate | 193473-82-4

• 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: tert-butyl 3-(bromomethyl)-4-fluorobenzoate
• 英文别名: tert-butyl-4-fluoro-3(alpha-bromomethyl)benzoate
• CAS: 193473-82-4
• 化学式: C₁₂H₁₄BrFO₂
• 分子量: 289.144
• InChiKey: IWACEPIBJFNCDH-UHFFFAOYSA-N

物化性质

• 沸点：
  322.7±32.0 °C(Predicted)
• 密度：
  1.372±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-(bromomethyl)-4-fluorobenzoate 在 palladium on activated charcoal 氢气 、 1-羟基苯并三唑 、 苯甲醚 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 73.0h， 生成 4-(2-amino-ethyl)-2-methoxycarbonylmethyl-3-oxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepine-7-carboxylic acid
  参考文献：
  名称：

  Chemical Adaptor Immunotherapy:  Design, Synthesis, and Evaluation of Novel Integrin-Targeting Devices

  摘要：

  A series of beta-diketone derivatives of RGD peptidornimetics that selectively bind to alphabbeta3 and alphavbeta5 integrins were synthesized and covalently docked to the reactive lysine residues of monoclonal aldolase antibody 38C2. The resulting targeting devices strongly and selectively bound to human cancer cells expressing integrins alphavbeta3 and alphavbeta5 as analyzed by flow cytometry. In vitro and in vivo studies revealed that these novel integrin-targeting devices efficiently inhibit tumor growth. Thus, the combination of beta-diketone derivatives of RGD peptidomimetics that target cell surface integrins alphavbeta3 and alphavbeta5 with monoclonal aldolase antibodies through formation of a covalent bond of defined stoichiometry holds promise as a new approach to cancer therapy.

  DOI：

  10.1021/jm049666k
• 作为产物：
  描述：

  4-fluoro-3-methylbenzoic acid tert-butyl ester 在 N-溴代丁二酰亚胺(NBS) 、 过氧化苯甲酰 作用下， 以 四氯化碳 为溶剂， 生成 tert-butyl 3-(bromomethyl)-4-fluorobenzoate
  参考文献：
  名称：

  对映体合成SB 214857（一种有效的口服活性非肽纤维蛋白原受体拮抗剂）

  摘要：

  据报道，SB 214857的对映体特异性合成是一种有效的非重复性纤维蛋白原受体拮抗剂。合成途径采用分子内芳基氟化物置换形成1，4-苯并二氮杂system系统的七元环作为关键步骤。

  DOI：

  10.1016/0040-4039(95)02054-3

文献信息

• Vitronectin receptor antagonists
  申请人：SmithKline Beecham Corporation

  公开号：US06159964A1

  公开（公告）日：2000-12-12

  Compounds of formula (I) are disclosed, wherein: A is a fibrinogen antagonist template; W is a linking moiety of the form --(CHR.sup.g).sub.a --U--(CHR.sup.g).sub.b --V--; Q.sup.1, Q.sup.2, Q.sup.3 and Q.sup.4 are independently N or C--R.sup.y, provided that no more than one Q.sup.1, Q.sup.2, Q.sup.3 and Q.sup.4 is N; R' is H or C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl-C.sub.0-6 -alkyl or Ar--C.sub.0-6 alkyl; R.sup.g is H or C.sub.1-6 alkyl, Het-C.sub.0-6 alkyl, C.sub.3-7 cycloalkyl-C.sub.0-6 alkyl or Ar--C.sub.0-6 alkyl; R.sup.k is R.sup.g, --C(O)R.sup.g or --C(O)OR.sup.g R.sup.i is H, C.sub.1-6 alkyl, Het-C.sub.0-6 alkyl, C.sub.3-7 cycloalkyl-C.sub.0-6 alkyl, Ar--C.sub.0-6 alkyl, Het-C.sub.0-6 alkyl--U'--C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl-C.sub.0-6 alkyl--U'--C.sub.1-6 alkyl or Ar--C.sub.0-6 alkyl--U'--C.sub.1-6 alkyl; R.sup.y is H, halo, --OR.sup.g, --SR.sup.g, --CN, --NR.sup.g R.sup.k, --NO.sub.2, --CF.sub.3, CF.sub.3 S(O).sub.r, --CO.sub.2 R.sup.g, --COR.sup.g or --CONR.sup.g.sub.2, or C.sub.1-6 alkyl optionally substituted by halo, --OR.sup.g, --SR.sup.g, --CN, --NR.sup.8 R", --NO.sub.2, --CF.sub.3, R'S(O).sub.3 --, --CO.sub.2 R.sup.g, --COR.sup.g or --CONR.sup.g.sub.2 ; U and V are absent or CO, CR.sup.g.sub.2, C(.dbd.CR.sup.g.sub.2), S(O).sub.c, O, NR.sup.g, CR.sup.g OR.sup.g, CR.sup.g (OR.sup.k)CR.sup.g.sub.2, CR.sup.g.sub.7 CR.sup.g (OR.sup.k), C(O)CR.sup.g.sub.2, CR.sup.g.sub.2 C(O), CONR.sup.i, NR.sup.i CO, OC(O), C(O)O, OC(S), C(S)NR.sup.g, NR.sup.8 C(S), S(O.sub..sub.2 NR.sup.g, NR.sup.g S(O).sub.2 N.dbd.N, NR.sup.g NR.sup.g, NR.sup.g CR.sup.g.sub.2, NR.sup.g CR.sup.g.sub.2, CR.sup.g.sub.2 O, OCR.sup.g.sub.2, CR.sup.g .dbd.CR.sup.g, C.ident.C, Ar or Het; a is 0, 1 or 2; c is 0, 1 or 2; r is 0, 1 or 2; and u is 0 or 1; or pharmaceutically acceptable salts thereof, which are vitronectin receptor antagonists useful in the treatment of osteoporosis. ##STR1##

  公式（I）的化合物被披露，其中：A是一种纤维蛋白原拮抗剂模板；W是形式为--(CHR.sup.g).sub.a--U--(CHR.sup.g).sub.b--V--的连接基团；Q.sup.1、Q.sup.2、Q.sup.3和Q.sup.4独立地是N或C--R.sup.y，前提是Q.sup.1、Q.sup.2、Q.sup.3和Q.sup.4中不超过一个是N；R'是H或C.sub.1-6烷基，C.sub.3-7环烷基-C.sub.0-6-烷基或Ar--C.sub.0-6烷基；R.sup.g是H或C.sub.1-6烷基，Het-C.sub.0-6烷基，C.sub.3-7环烷基-C.sub.0-6烷基或Ar--C.sub.0-6烷基；R.sup.k是R.sup.g，--C(O)R.sup.g或--C(O)OR.sup.g；R.sup.i是H，C.sub.1-6烷基，Het-C.sub.0-6烷基，C.sub.3-7环烷基-C.sub.0-6烷基，Ar--C.sub.0-6烷基，Het-C.sub.0-6烷基--U'--C.sub.1-6烷基，C.sub.3-7环烷基-C.sub.0-6烷基--U'--C.sub.1-6烷基或Ar--C.sub.0-6烷基--U'--C.sub.1-6烷基；R.sup.y是H，卤素，--OR.sup.g，--SR.sup.g，--CN，--NR.sup.g R.sup.k，--NO.sub.2，--CF.sub.3，CF.sub.3 S(O).sub.r，--CO.sub.2 R.sup.g，--COR.sup.g或--CONR.sup.g.sub.2，或者C.sub.1-6烷基，可选择地被卤素，--OR.sup.g，--SR.sup.g，--CN，--NR.sup.8 R"，--NO.sub.2，--CF.sub.3，R'S(O).sub.3--，--CO.sub.2 R.sup.g，--COR.sup.g或--CONR.sup.g.sub.2取代；U和V不存在或为CO，CR.sup.g.sub.2，C(.dbd.CR.sup.g.sub.2)，S(O).sub.c，O，NR.sup.g，CR.sup.g OR.sup.g，CR.sup.g(OR.sup.k)CR.sup.g.sub.2，CR.sup.g.sub.7 CR.sup.g(OR.sup.k)，C(O)CR.sup.g.sub.2，CR.sup.g.sub.2 C(O)，CONR.sup.i，NR.sup.i CO，OC(O)，C(O)O，OC(S)，C(S)NR.sup.g，NR.sup.8 C(S)，S(O.sub..sub.2 NR.sup.g，NR.sup.g S(O).sub.2 N.dbd.N，NR.sup.g NR.sup.g，NR.sup.g CR.sup.g.sub.2，NR.sup.g CR.sup.g.sub.2，CR.sup.g.sub.2 O，OCR.sup.g.sub.2，CR.sup.g.dbd.CR.sup.g，C.ident.C，Ar或Het；a为0、1或2；c为0、1或2；r为0、1或2；u为0或1；或其药学上可接受的盐，用于治疗骨质疏松症的维龙蛋白受体拮抗剂。
• Discovery of Aminopyridine-Based Inhibitors of Bacterial Enoyl-ACP Reductase (FabI)
  作者：William H. Miller、Mark A. Seefeld、Kenneth A. Newlander、Irene N. Uzinskas、Walter J. Burgess、Dirk A. Heerding、Catherine C. K. Yuan、Martha S. Head、David J. Payne、Stephen F. Rittenhouse、Terrance D. Moore、Stewart C. Pearson、Valerie Berry、Walter E. DeWolf、Paul M. Keller、Brian J. Polizzi、Xiayang Qiu、Cheryl A. Janson、William F. Huffman

  DOI：10.1021/jm020050+

  日期：2002.7.1

  inhibitor of FabI from S. aureus (IC(50) = 2.4 microM) and Haemophilus influenzae (IC(50) = 4.2 microM). Compound 9 has good in vitro antibacterial activity against several organisms, including S. aureus (MIC = 0.5 microg/mL), and is effective in vivo in a S. aureus groin abscess infection model in rats. Through FabI overexpressor and macromolecular synthesis studies, the mode of action of 9 has been confirmed

  细菌烯酰-ACP还原酶（FabI）催化细菌脂肪酸生物合成的每个循环中的最后一步，是开发新型抗菌剂的有吸引力的目标。我们鉴定有效的选择性FabI抑制剂的努力始于对GlaxoSmithKline专有化合物的筛选，该鉴定了几种金黄色葡萄球菌FabI的小分子抑制剂。通过结合迭代化学化学和基于X射线晶体结构的设计，将这些引线之一开发为新型氨基吡啶衍生物9，一种来自金黄色葡萄球菌（IC（50）= 2.4 microM）和嗜血杆菌的低微摩尔FabI抑制剂。流感（IC（50）= 4.2 microM）。化合物9对包括金黄色葡萄球菌（MIC = 0.5 microg / mL）在内的几种生物具有良好的体外抗菌活性，并且在S. 大鼠金黄色腹股沟脓肿感染模型。通过FabI过表达子和大分子合成研究，已证实9的作用方式是通过抑制FabI来抑制脂肪酸生物合成。综上所述，这些结果支持FabI作为有效的抗菌靶标，并证明了
• Vitronectin receptor antagonist pharmaceuticals
  申请人：Bristol-Myers Squibb Pharma Company

  公开号：US06569402B1

  公开（公告）日：2003-05-27

  The present invention describes novel compounds of the formula: (Q)d—Ln—Ch, useful for the diagnosis and treatment of cancer, methods of imaging tumors in a patient, and methods of treating cancer in a patient. The present invention also provides novel compounds useful for monitoring therapeutic angiogenesis treatment and destruction of new angiogenic vasculature. The present invention further provides novel compounds useful for imaging atherosclerosis, restenosis, cardiac ischemia and myocardial reperfusion injury. The present invention still further provides novel compounds useful for the treatment of rheumatoid arthritis. The pharmaceuticals are comprised of a targeting moiety that binds to a receptor that is upregulated during angiogenesis, an optional linking group, and a therapeutically effective radioisotope or diagnostically effective imageable moiety. The imageable moiety is a gamma ray or positron emitting radioisotope, a magnetic resonance imaging contrast agent, an X-ray contrast agent, or an ultrasound contrast agent.

  本发明描述了新型化合物的结构式：(Q)d—Ln—Ch，用于癌症的诊断和治疗，在患者中成像肿瘤的方法，以及治疗患者癌症的方法。本发明还提供了新型化合物，用于监测治疗血管生成和破坏新的血管生成血管。本发明还提供了新型化合物，用于成像动脉粥样硬化、再狭窄、心肌缺血和心肌再灌注损伤。本发明还提供了用于类风湿关节炎治疗的新型化合物。这些药物由一个靶向基团、该基团结合到在血管生成过程中上调的受体、一个可选的连接基团和一个治疗有效的放射性同位素或诊断有效的成像基团组成。成像基团可以是γ射线或正电子发射放射性同位素、核磁共振成像对比剂、X射线对比剂或超声造影剂。
• Benzodiazepine vitronectin receptor antagonist pharmaceuticals
  申请人：——

  公开号：US20030149262A1

  公开（公告）日：2003-08-07

  The present invention describes novel compounds of the formula: (Q) d —L n —C h , useful for the diagnosis and treatment of cancer, methods of imaging tumors in a patient, and methods of treating cancer in a patient. The present invention also provides novel compounds useful for monitoring therapeutic angiogenesis treatment and destruction of new angiogenic vasculature. The pharmaceuticals are comprised of a targeting moiety that binds to a receptor that is upregulated during angiogenesis, an optional linking group, and a therapeutically effective radioisotope or diagnostically effective imageable moiety. The imageable moiety is a gamma ray or positron emitting radioisotope, a magnetic resonance imaging contrast agent, an X-ray contrast agent, or an ultrasound contrast agent.

  本发明描述了新型化合物的公式：（Q）d-Ln-Ch，用于癌症的诊断和治疗，用于患者肿瘤成像的方法，以及用于患者癌症治疗的方法。本发明还提供了新型化合物，用于监测治疗性血管生成和新生血管的破坏。药物由结合到在血管生成过程中上调的受体的靶向基团、可选的连接基团和治疗有效的放射性同位素或诊断有效的可成像基团组成。可成像基团是γ射线或正电子发射放射性同位素、磁共振成像对比剂、X射线对比剂或超声对比剂。
• 一种新型含噻唑类化合物、中间体及其应用
  申请人：苏州美诺医药科技有限公司

  公开号：CN114605404A

  公开（公告）日：2022-06-10

  本发明公开了一种具有式(I)所示的含噻唑类化合物或者其药学上可接受的盐，所述化合物适合用作酪氨酸激酶特别是ITK抑制剂，适于治疗ITK介导的炎性疾病或癌症或自身免疫疾病。