bis(3,4-dimethoxycarbonyldihydrocinnamoyl)-L-tartaric acid | 222320-67-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚酯
• 英文名称: bis(3,4-dimethoxycarbonyldihydrocinnamoyl)-L-tartaric acid
• CAS: 222320-67-4
• 化学式: C₃₀H₃₀O₂₀
• 分子量: 710.556
• InChiKey: LQGHRCQETMWEEH-DNQXCXABSA-N

物化性质

• 沸点：
  852.1±65.0 °C(Predicted)
• 密度：
  1.456±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.83
• 重原子数：
  50.0
• 可旋转键数：
  15.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  269.32
• 氢给体数：
  2.0
• 氢受体数：
  18.0

反应信息

• 作为反应物：
  描述：

  bis(3,4-dimethoxycarbonyldihydrocinnamoyl)-L-tartaric acid 在 sodium carbonate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 bis(3,4-dihydroxydihydrocinnamoyl)-L-tartaric acid
  参考文献：
  名称：

  Structure−Activity Relationships:  Analogues of the Dicaffeoylquinic and Dicaffeoyltartaric Acids as Potent Inhibitors of Human Immunodeficiency Virus Type 1 Integrase and Replication

  摘要：

  The dicaffeoylquinic acids (DCQAs) and dicaffeoyltartaric acids (DCTAs) are potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) integrase. They also inhibit HIV-1 replication at nontoxic concentrations; Since integrase is an excellent target for anti-HIV therapy, structure-activity relationships were employed to synthesize compounds with: (1) improved potency against HIV-1 integrase, (2) improved anti-HIV effect in tissue culture, and (3) increased selectivity as indicated by low cellular toxicity. Thirty-four analogues of the DCTAs and DCQAs were synthesized and tested for cell toxicity, anti-HIV activity, and inhibition of HIV-1 integrase. Seventeen of the 34 analogues had potent activity against HIV-1 integrase ranging from 0.07 to >10 mu M. Seventeen analogues that were synthesized or purchased had no inhibitory activity against integrase at concentrations of 25 mu M. Of the biologically active analogues, 7 of the 17 inhibited HIV replication at nontoxic concentrations. The most potent compounds were D-chicoric acid, meso-chicoric acid, bis(3,4-dihydroxydihydrocinnamoyl)-L-tartaric acid, digalloyl-L-tartaric acid, bis(3,4-dihydroxybenzoyl)-L-tartaric acid, dicaffeoylglyceric acid, and bis(3,4-dihydroxyphenylacetyl)-L-tartaric acid. Anti-HIV activity of the active compounds in tissue culture ranged from 35 to 0.66 mu M. Structure-activity relationships demonstrated that biscatechol moieties were absolutely required for inhibition of integrase, while at least one free carboxyl group was required for anti-HIV activity. These data demonstrate that analogues of the DCTAs and the DCQAs can be synthesized which have improved activity against HIV integrase.

  DOI：

  10.1021/jm9804735
• 作为产物：
  描述：

  3,4-dimethoxycarbonyldihydrocinnamic acid 在 氯化亚砜 、 溶剂黄146 作用下， 反应 0.5h， 生成 bis(3,4-dimethoxycarbonyldihydrocinnamoyl)-L-tartaric acid
  参考文献：
  名称：

  Structure−Activity Relationships:  Analogues of the Dicaffeoylquinic and Dicaffeoyltartaric Acids as Potent Inhibitors of Human Immunodeficiency Virus Type 1 Integrase and Replication

  摘要：

  The dicaffeoylquinic acids (DCQAs) and dicaffeoyltartaric acids (DCTAs) are potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) integrase. They also inhibit HIV-1 replication at nontoxic concentrations; Since integrase is an excellent target for anti-HIV therapy, structure-activity relationships were employed to synthesize compounds with: (1) improved potency against HIV-1 integrase, (2) improved anti-HIV effect in tissue culture, and (3) increased selectivity as indicated by low cellular toxicity. Thirty-four analogues of the DCTAs and DCQAs were synthesized and tested for cell toxicity, anti-HIV activity, and inhibition of HIV-1 integrase. Seventeen of the 34 analogues had potent activity against HIV-1 integrase ranging from 0.07 to >10 mu M. Seventeen analogues that were synthesized or purchased had no inhibitory activity against integrase at concentrations of 25 mu M. Of the biologically active analogues, 7 of the 17 inhibited HIV replication at nontoxic concentrations. The most potent compounds were D-chicoric acid, meso-chicoric acid, bis(3,4-dihydroxydihydrocinnamoyl)-L-tartaric acid, digalloyl-L-tartaric acid, bis(3,4-dihydroxybenzoyl)-L-tartaric acid, dicaffeoylglyceric acid, and bis(3,4-dihydroxyphenylacetyl)-L-tartaric acid. Anti-HIV activity of the active compounds in tissue culture ranged from 35 to 0.66 mu M. Structure-activity relationships demonstrated that biscatechol moieties were absolutely required for inhibition of integrase, while at least one free carboxyl group was required for anti-HIV activity. These data demonstrate that analogues of the DCTAs and the DCQAs can be synthesized which have improved activity against HIV integrase.

  DOI：

  10.1021/jm9804735

文献信息

• Novel HIV integrase inhibitors and HIV therapy based on drug combinations including integrase inhibitors
  申请人：Robinson W. Edward

  公开号：US20050049242A1

  公开（公告）日：2005-03-03

  The present invention includes a group of novel compounds that are demonstrated to potently and selectively inhibit HIV integrase (IN) activity in vitro and to potently inhibit HIV replication in live, cultured cells at non-toxic concentrations. The novel compounds disclosed include 2,3-di(3,4-dihydroxy-dihydroxydihydrocinnamoyl)-L-tartaric acid, 2,3-di-(3,4-dihydroxybenzoyl)-L-tartaric acid, 2,3-di-(3,4-dihydroxyphenylacetyl)-L-tartaric acid, 2,3-di-(3,4,5-trihydroxybenzoyl-L-tartaric acid, 2,3-dicaffeoyldiamidopropionic acid, 1,2,-dicaffeoyl-L-glyceric acid, bis,-3,4-dicaffeoyldiamidobenzoic acid, di-3,4-dihydroxybenzylidene succinic acid, di-3,4-dihydrodihydroxybenzylidine succinic acid, 2,3-dicaffeoyl-L-serine, bis-dicaffeoyl-L-isoserine and 1,4-dicaffeoyl-L-lysine. Tests of integrase inhibitors with 2′,3′-dideoxycytidine, zidovudine and nelfinavir (protease inhibitor) indicated a potent synergy against reverse transcriptase inhibitor resistant virus. The potential benefit from the addition of integrase inhibitors to combination drug therapies is significant.

  本发明包括一组新颖的化合物，已被证明能够在体外强力且选择性地抑制HIV整合酶（IN）活性，并在非毒性浓度下有效抑制活体培养细胞中的HIV复制。所披露的新颖化合物包括2,3-二（3,4-二羟基-二羟基二羟基肉桂酰）-L-酒石酸，2,3-二（3,4-二羟基苯甲酰）-L-酒石酸，2,3-二（3,4-二羟基苯乙酰）-L-酒石酸，2,3-二（3,4,5-三羟基苯甲酰）-L-酒石酸，2,3-二咖啡酰二氨基丙酸，1,2-二咖啡酰-L-甘油酸，双-3,4-二咖啡酰二氨基苯甲酸，二-3,4-二羟基苯乙烯琥珀酸，二-3,4-二羟基二羟基苯乙烯琥珀酸，2,3-二咖啡酰-L-丝氨酸，双咖啡酰-L-异丝氨酸和1,4-二咖啡酰-L-赖氨酸。对整合酶抑制剂与2′,3′-二脱氧胞苷、阿司匹林和奈非那韦（蛋白酶抑制剂）的测试表明，对逆转录酶抑制剂耐药病毒具有强大的协同作用。将整合酶抑制剂添加到联合药物疗法中的潜在益处是显著的。