1,2,5-Benzothiadiazepine and pyrrolo[2,1-d][1,2,5]benzothiadiazepine derivatives with specific anti-human immunodeficiency virus type 1 activity
1,2,5-Benzothiadiazepine and pyrrolo[2,1-d][1,2,5]benzothiadiazepine derivatives with specific anti-human immunodeficiency virus type 1 activity
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DOI：
10.1177/095632029800900204
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发表时间：
1998-03-01
影响因子：
--
通讯作者：
La Colla, P
中科院分区：
文献类型：
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作者：
Di Santo, R;Costi, R;La Colla, P
我们合成并测试了 7-氯-2-乙基-2H-1,2,4-苯并噻二嗪-3-(4H)-酮 1,l-二氧化物的双环和三环噻二嗪环同系物作为人类免疫缺陷病毒 1 型 (HIV-1) 的新型抑制剂，该化合物是一种在低微摩尔浓度下具有抗 HIV-1 活性的化合物。苯并噻二氮卓衍生物是由2-(2-氨基-5-氯-苯磺酰氨基)丙酸分子内环化得到的8-氯-2,3-二氢-3-甲基-1,2,5-苯并噻二氮卓-4(5H)-酮1,1-二氧化物经烷基化得到。以N-取代的5-氯-2-(1H-吡咯-1-基)苯磺酰胺为原料，通过三光气处理合成吡咯并苯并噻二氮杂卓。 N-6-取代的吡咯并[2,1-d][1,2,5]苯并噻二氮杂卓-7(6H)-酮5,5-二氧化物具有活性，但不是非常有效。发现氯原子和不饱和烷基链都是抗HIV-1活性的决定因素。具有 TIBO 相关 3,3-二甲基烯丙基链的衍生物显示出最高的效力。 2,3-二氢-1,2,5-苯并噻二氮卓-4(5H)-酮1,l-二氧化物在HIV-1感染的MT-4细胞测定中几乎没有活性；然而，将二甲基烯丙基链引入7-氯-1,2,5-苯并硫杂氮杂卓部分产生双环衍生物，其比含三环吡咯的对应物更有效且细胞毒性更小。
We synthesized and tested as novel inhibitors of human immunodeficiency virus type 1 (HIV-1) bi-and tricyclic thiadiazine ring homologues of 7-chloro-2-ethyl-2H-1,2,4-benzothiadiazin-3-(4H)-one 1,l-dioxide, which is a compound endowed with anti-HIV-l activity at low micromolar concentrations. Benzothiadiazepine derivatives were obtained by alkylation of 8-chloro-2,3-dihydro-3-methyl-1,2,5-benzothiadiazepin-4(5H)-one 1,l-dioxide, which was obtained by intramolecular cyclization of 2-(2-amino-5-chloro-benzenesulphonamido) propanoic acid. Pyrrolobenzothiadiazepines were synthesized from N-substituted 5-chloro-2-(1H-pyrrol-1-yl)benzenesulphonamides by treating with triphosgene. N-6- substituted pyrrolo[2,1-d][1,2,5]benzothiadiazepin-7(6H)-one 5,5-dioxides were active, though not very potent. Both a chlorine atom and an unsaturated alkyl chain were found to be determinants of anti-HIV-l activity. The highest potency was shown by a derivative with a TIBO-related 3,3-dimethylallyl chain. 2,3-Dihydro-1,2,5-benzothiadiazepin-4(5H)-one 1,l-dioxides were scarcely active in HIV-l-infected MT-4 cell assays; however, the introduction of the dimethylallyl chain into 7-chloro-1,2,5-benzothiadiazepine moiety led to a bicyclic derivative which was more potent and less cytotoxic than the tricyclic pyrrole-containing counterpart.