2'-methyl-5-nitro-biphenyl-2-carboxylic acid methyl ester | 191103-87-4

• 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: 2'-methyl-5-nitro-biphenyl-2-carboxylic acid methyl ester
• 英文别名: 4-nitro-2-(2-methylphenyl)benzoic acid methyl ester；Methyl 4-Nitro-2-(2-methylphenyl)benzoate；methyl 2-(2-methylphenyl)-4-nitrobenzoate
• CAS: 191103-87-4
• 化学式: C₁₅H₁₃NO₄
• 分子量: 271.273
• InChiKey: ROJRZXSLTKPDNJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2'-methyl-5-nitro-biphenyl-2-carboxylic acid methyl ester 在 盐酸 、 溶剂黄146 、 tin(ll) chloride 、 sodium nitrite 作用下， 以 甲醇 、 水 、 乙酸乙酯 为溶剂， 反应 4.25h， 生成 5-iodo-2'-methyl-biphenyl-2-carboxylic acid methyl ester
  参考文献：
  名称：

  拟肽蛋白法尼基转移酶抑制剂的体外和体内抗疟活性具有改善的膜通透性。

  摘要：

  合成了一系列FTI-2148蛋白法呢基转移酶抑制剂酯前药，以评估酯结构修饰对抗疟活性的影响，并进一步开发具有体内活性的法呢基转移酶抑制剂。对红细胞中恶性疟原虫的评估表明，所有研究的酯均表现出显着的抗疟活性，苄基酯16表现出最佳的抑制作用（ED50 = 150 nM）。此外，化合物16在小鼠体内表现出体内活性，并在50 mg kg（-1）day（-1）剂量下对伯氏疟原虫的寄生虫血症抑制了46.1％。与游离酸相比，酯的增强的抑制能力与改善的细胞膜通透性相一致。

  DOI：

  10.1016/j.bmc.2004.09.020
• 作为产物：
  描述：

  2-溴-4-硝基苯甲酸 在 tris(triphenylphosphano)palladium 氯化亚砜 、 potassium carbonate 作用下， 生成 2'-methyl-5-nitro-biphenyl-2-carboxylic acid methyl ester
  参考文献：
  名称：

  Structure-based design of imidazole-containing peptidomimetic inhibitors of protein farnesyltransferase

  摘要：

  报道了一系列含有咪唑基的肽模拟物PFTase抑制剂及其与PFTase和FPP结合的共晶结构。这些结构揭示了肽模拟物采取类似于延伸的CVIM四肽的构象，其中的咪唑基团与催化锌离子配位。含有单咪唑和双咪唑的衍生物13和16，在体外分别表现出对PFTase极高的酶抑制活性，IC50值分别为0.86和1.7 nM。这些肽模拟物对PFTase的选择性优于PGGTase-I，无论是在体外还是在完整的细胞中。此外，肽模拟物13和16在裸鼠异种移植模型中能抑制肿瘤生长，以每天25 mg kg−1的剂量给药时没有明显的毒性。

  DOI：

  10.1039/b508184j

文献信息

• Inhibitors of protein isoprenyl transferases
  申请人：University of Pittsburgh

  公开号：US20020193596A1

  公开（公告）日：2002-12-19

  Compounds having the formula 1 or a pharmaceutically acceptable salt thereof wherein R 1 is (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkoxy, (e) thioalkoxy, (f) halo, (g) haloalkyl, (h) aryl-L 2 —, and (i) heterocyclic-L 2 —; R 2 is selected from (a) 2 (b) —C(O)NH—CH(R 14 )—C(O)OR 15 , (c) 3 (d) —C(O)NH—CH(R 14 )—C(O)NHSO 2 R 16 (e) —C(O)NH—CH(R 14 )-tetrazolyl, (f) —C(O)NH-heterocyclic, and (g) —C(O)NH—CH(R 14 )—C(O)NR 17 R 18 ; R 3 is heterocyclic, aryl, substituted or unsubstituted cycloalkyl; R 4 is hydrogen, lower alkyl, haloalkyl, halogen, aryl, arylakyl, heterocyclic, or (heterocyclic)alkyl; L 1 is absent or is selected from (a) —L 4 —N(R 5 )—L 5 —, (b) —L 4 —O—L 5 —, (c) —L 4 —S(O) n —L 5 — (d) —L 4 -L 6 —C(W)—N(R 5 )—L 5 —, (e) —L 4 -L 6 —S(O) m —N(R 5 )—L 5 —, (f) —L 4 —N(R 5 )—C(W)—L 7 -L 5 —, (g) —L 4 —N(R 5 )—S(O) p —L 7 —L 5 —, (h) optionally substituted alkylene, (i) optionally substituted alkenylene, and (j) optionally substituted alkynylene are inhibitors of protein isoprenyl transferases. Also disclosed are protein isoprenyl transferase inhibiting compositions and a method of inhibiting protein isoprenyl transferases.

  具有以下公式的化合物或其药学上可接受的盐，其中R1为(a)氢，(b)较低的烷基，(c)烯基，(d)烷氧基，(e)硫代烷氧基，(f)卤素，(g)卤代烷基，(h)芳基-L2—，以及(i)杂环-L2—；R2从(a)中选择，(b) -C(O)NH-CH(R14)-C(O)OR15，(c)中选择，(d) -C(O)NH-CH(R14)-C(O)NHSO2R16，(e) -C(O)NH-CH(R14)-四唑基，(f) -C(O)NH-杂环，以及(g) -C(O)NH-CH(R14)-C(O)NR17R18；R3为杂环，芳基，取代或未取代的环烷基；R4为氢，较低烷基，卤代烷基，卤素，芳基，芳基烷基，杂环基，或(杂环)烷基；L1为空缺或从(a) -L4-N(R5)-L5-，(b) -L4-O-L5-，(c) -L4-S(O)n-L5-，(d) -L4-L6-C(W)-N(R5)-L5-，(e) -L4-L6-S(O)m-N(R5)-L5-，(f) -L4-N(R5)-C(W)-L7-L5-，(g) -L4-N(R5)-S(O)p-L7-L5-，(h)可选择取代的烷基，(i)可选择取代的烯基，以及(j)可选择取代的炔基是蛋白异戊二烯转移酶的抑制剂。还公开了蛋白异戊二烯转移酶抑制组合物和抑制蛋白异戊二烯转移酶的方法。
• In vitro and in vivo antimalarial activity of peptidomimetic protein farnesyltransferase inhibitors with improved membrane permeability
  作者：Dora Carrico、Junko Ohkanda、Howard Kendrick、Kohei Yokoyama、Michelle A. Blaskovich、Cynthia J. Bucher、Frederick S. Buckner、Wesley C. Van Voorhis、Debopam Chakrabarti、Simon L. Croft、Michael H. Gelb、Saïd M. Sebti、Andrew D. Hamilton

  DOI：10.1016/j.bmc.2004.09.020

  日期：2004.12

  inhibitor ester prodrugs of FTI-2148 (17) were synthesized in order to evaluate the effects of ester structure modification on antimalarial activity and for further development of a farnesyltransferase inhibitor with in vivo activity. Evaluation against P. falciparum in red blood cells showed that all the investigated esters exhibited significant antimalarial activity, with the benzyl ester 16 showing

  合成了一系列FTI-2148蛋白法呢基转移酶抑制剂酯前药，以评估酯结构修饰对抗疟活性的影响，并进一步开发具有体内活性的法呢基转移酶抑制剂。对红细胞中恶性疟原虫的评估表明，所有研究的酯均表现出显着的抗疟活性，苄基酯16表现出最佳的抑制作用（ED50 = 150 nM）。此外，化合物16在小鼠体内表现出体内活性，并在50 mg kg（-1）day（-1）剂量下对伯氏疟原虫的寄生虫血症抑制了46.1％。与游离酸相比，酯的增强的抑制能力与改善的细胞膜通透性相一致。
• Palladium catalyzed coupling of aryl chlorides with arylboronic acids
  作者：Wang Shen

  DOI：10.1016/s0040-4039(97)01261-6

  日期：1997.8

  Aryl chlorides bearing electron withdrawing groups were successfully coupled with arylboronic acids (Suzuki reaction). Two palladium catalyst ligands, tricyclohexylphosphine (PCy3) and 1,3-bis(diphenylphosphino)propane (dppp), were found to be superior in catalyzing the reaction.

  带有吸电子基团的芳基氯化物成功地与芳基硼酸偶联（Suzuki反应）。发现两种钯催化剂配体三环己基膦（PCy 3）和1，3-双（二苯基膦基）丙烷（dppp）在催化反应方面具有优势。
• Potent inhibitors of protein farnesyltransferase: Heteroarenes as cysteine replacements
  作者：Wang Shen、Stephen Fakhoury、Greg Donner、Kenneth Henry、Jang Lee、Haichao Zhang、Jerry Cohen、Robert Warner、Badr Saeed、Sajeev Cherian、Stephen Tahir、Peter Kovar、Joy Bauch、Shi-Chung Ng、Kennan Marsh、Hing Sham、Saul Rosenberg

  DOI：10.1016/s0960-894x(99)00080-3

  日期：1999.3

  Synthesis and biological evaluation of heteroarenes as reduced cysteine replacements are described. Of the heteroaryl groups examined with respect to FT inhibitor FTI-276 (1), pyridyl was the replacement found to be most effective. Substitutions at C4 of the pyridyl moiety did not affect the in vitro activity. Compound 9a was found to have moderate in vivo bioavailability.
• New Ras CAAX mimetics: Design, synthesis, antiproliferative activity, and RAS prenylation inhibition
  作者：Cristiano Bolchi、Marco Pallavicini、Laura Fumagalli、Nicola Ferri、Alberto Corsini、Chiara Rusconi、Ermanno Valoti

  DOI：10.1016/j.bmcl.2009.07.065

  日期：2009.9

  Mimetics of the C-terminal CAAX tetrapeptide of Ras protein were designed replacing cysteine (C) by 2-hydroxymethylbenzodioxane or 2-aminomethylbenzodioxane, respectively etherified and amidified with 2'-methyl or 2'-methoxy substituted 2-carboxy-4-hydroxybiphenyl and 2,4-dicarboxybiphenyl. These pluri-substituted biphenyl systems, used as internal spacer and AA dipeptide bioisoster, were linked to the methyl ester Of L-methionine, glycine or L-leucine by an amide bond. The resultant twelve pairs of stereoisomers at the dioxane C-2 were tested for anti proliferative effect finding the maximum activity for derivatives with methyleneoxy linker between benzodioxane and 2'-methylbiphenyl. Of these compounds, the one with terminal methionine and S configuration proved a good Ras prenylation inhibitor in a cell-based assay. (C) 2009 Elsevier Ltd. All rights reserved.