1-Chloro-6-phenylpyrrolo[2,1-d][1,5]benzothiazepin-7-one | 177578-93-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并硫氮卓类
• 英文名称: 1-Chloro-6-phenylpyrrolo[2,1-d][1,5]benzothiazepin-7-one
• CAS: 177578-93-7
• 化学式: C₁₈H₁₂ClNOS
• 分子量: 325.818
• InChiKey: ACNAYDGUDCJGBY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  47.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-Chloro-6-phenylpyrrolo[2,1-d][1,5]benzothiazepin-7-one 、 二甲氨基甲酰氯 在 potassium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 10.0h， 以66%的产率得到1-chloro-7-[(dimethylcarbamoyl)oxy]-6-phenylpyrrolo[2,1-d][1,5]benzothiazepine
  参考文献：
  名称：

  New pyrrolobenzothiazepine derivatives as molecular probes of the ‘peripheral-type’ benzodiazepine receptor (PBR) binding site

  摘要：

  A number of new pyrrolobenzothiazepine derivatives and a pyrrolobenzothiazocine derivative have been synthesized and evaluated for their affinity towards the 'peripheral-type' benzodiazepine receptor (PER). The new compounds were tested in rat cortex, a tissue expressing a high density of mitochondrial PER. Some of the pyrrolobenzothiazepines exhibited IC50 values in the low nanomolar range as measured by the displacement of [H-3]PK 11195 binding. Compound 4i was found to be the most potent ligand for this receptor in the pyrrolobenzothiazepine subgroup with an IC50 practically identical to that determined for PK 11195. Structure-affinity relationships (SARs) have been developed to elucidate the topology of the PER binding site.

  DOI：

  10.1016/s0223-5234(97)83975-x
• 作为产物：
  描述：

  2-[((2-氨基-3-氯苯基)二硫]-6-氯苯胺 在 sodium tetrahydroborate 、 五氯化磷 作用下， 以 溶剂黄146 、 1,2-二氯乙烷 为溶剂， 反应 18.0h， 生成 1-Chloro-6-phenylpyrrolo[2,1-d][1,5]benzothiazepin-7-one
  参考文献：
  名称：

  New pyrrolobenzothiazepine derivatives as molecular probes of the ‘peripheral-type’ benzodiazepine receptor (PBR) binding site

  摘要：

  A number of new pyrrolobenzothiazepine derivatives and a pyrrolobenzothiazocine derivative have been synthesized and evaluated for their affinity towards the 'peripheral-type' benzodiazepine receptor (PER). The new compounds were tested in rat cortex, a tissue expressing a high density of mitochondrial PER. Some of the pyrrolobenzothiazepines exhibited IC50 values in the low nanomolar range as measured by the displacement of [H-3]PK 11195 binding. Compound 4i was found to be the most potent ligand for this receptor in the pyrrolobenzothiazepine subgroup with an IC50 practically identical to that determined for PK 11195. Structure-affinity relationships (SARs) have been developed to elucidate the topology of the PER binding site.

  DOI：

  10.1016/s0223-5234(97)83975-x

文献信息

• Pyrrolobenzothiazepinones and Pyrrolobenzoxazepinones:  Novel and Specific Non-Nucleoside HIV-1 Reverse Transcriptase Inhibitors with Antiviral Activity
  作者：Giuseppe Campiani、Vito Nacci、Isabella Fiorini、Maria P. De Filippis、Antonio Garofalo、Giovanni Greco、Ettore Novellino、Sergio Altamura、Laura Di Renzo

  DOI：10.1021/jm950702c

  日期：1996.1.1

  Two novel classes of pyrrolobenzothiazepinones and pyrrolobenzoxazepinones were investigated as potential anti-AIDS drugs. These compounds were found to inhibit HIV-1 reverse transcriptase (RT) enzyme in vitro and to prevent HIV-1 cytopathogenicity in T4 lymphocytes, without appreciable activity on HIV-2 cytopathic effects, and against HBV as well as calf-thymus DNA alpha-polymerase. Their potency is influenced by substituents at position 6 and on the fused aromatic ring. Specifically, small lipophilic substituents at C-6 were preferred, whereas substitutions on the benzo-fused ring were found to be detrimental to activity, with respect to the unsubstituted compounds. Modification of the pi-system at C-6 is well tolerated, although the replacement of the benzo-fused with a [2,3]naphtho-fused ring leads to a less active compound. Maximum potency and specificity is achieved with a phenyl and an ethyl group at position 6 of the pyrrolobenzoxazepinone system. In the enzymatic assay the oxazepinone derivative (+/-)-6-ethyl-6-phenylpyrrolo[2,1-d][1,5] 16e (IC50 = 0.25 mu M) was found to be more potent than nevirapine (IC50 = 0.5 mu M), tested in the same experimental conditions using rC . dG as a template-primer. In cell culture assay benzoxazepine 16e was active against HIV-1, both wild type and AZT-sensitive, and HIV-1 (IIIB) strains, but not against HIV-2. In enzyme assay although 16e inhibited HIV-1 RT, it was inactive against the nevirapine-resistant recombinant RT Y181C at 50 mu M. Molecular modeling studies suggest that these derivatives present a 3D pharmacophoric arrangement similar to that of other nonnucleoside inhibitors such as nevirapine.