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一种在C-6位缺乏手性中心的二脱氧氮杂四氢叶酸类似物，N-[4-[2-(2-氨基-3,4-二氢-4-氧代-7H-吡咯并[2,3-d]嘧啶-5-基)乙基]苯甲酰基]-L-谷氨酸，是胸苷酸合成酶的抑制剂。

A dideazatetrahydrofolate analogue lacking a chiral center at C-6, N-[4-[2-(2-amino-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5- yl)ethyl]benzoyl]-L-glutamic acid, is an inhibitor of thymidylate synthase.

作者信息

Taylor E C, Kuhnt D, Shih C, Rinzel S M, Grindey G B, Barredo J, Jannatipour M, Moran R G

机构信息

Department of Chemistry, Princeton University, New Jersey 08544.

出版信息

J Med Chem. 1992 Nov 13;35(23):4450-4. doi: 10.1021/jm00101a023.

DOI:10.1021/jm00101a023
PMID:1447744
Abstract

N-[4-[2-(2-Amino-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5- yl)ethyl]benzoyl]-L-glutamic acid (15), prepared in five steps from 2-pivaloyl-7-deazaguanine, has been found to be an antitumor agent with its primary site of action at thymidylate synthase rather than purine synthesis. This compound appears to be a promising candidate for clinical evaluation.

摘要

N-[4-[2-(2-氨基-3,4-二氢-4-氧代-7H-吡咯并[2,3-d]嘧啶-5-基)乙基]苯甲酰基]-L-谷氨酸(15)由2-新戊酰基-7-脱氮鸟嘌呤经五步反应制得，已被发现是一种抗肿瘤剂，其主要作用位点是胸苷酸合成酶而非嘌呤合成。该化合物似乎是临床评估的一个有前景的候选药物。

相似文献

1
A dideazatetrahydrofolate analogue lacking a chiral center at C-6, N-[4-[2-(2-amino-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5- yl)ethyl]benzoyl]-L-glutamic acid, is an inhibitor of thymidylate synthase.一种在C-6位缺乏手性中心的二脱氧氮杂四氢叶酸类似物，N-[4-[2-(2-氨基-3,4-二氢-4-氧代-7H-吡咯并[2,3-d]嘧啶-5-基)乙基]苯甲酰基]-L-谷氨酸，是胸苷酸合成酶的抑制剂。
J Med Chem. 1992 Nov 13;35(23):4450-4. doi: 10.1021/jm00101a023.
2
Synthesis of N-{4-[(2,4-diamino-5-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)thio]benzoyl}-L-glutamic acid and N-{4-[(2-amino-4-oxo-5-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)thio]benzoyl}-L-glutamic acid as dual inhibitors of dihydrofolate reductase and thymidylate synthase and as potential antitumor agents.N-{4-[(2,4-二氨基-5-甲基-4,7-二氢-3H-吡咯并[2,3-d]嘧啶-6-基)硫代]苯甲酰基}-L-谷氨酸和N-{4-[(2-氨基-4-氧代-5-甲基-4,7-二氢-3H-吡咯并[2,3-d]嘧啶-6-基)硫代]苯甲酰基}-L-谷氨酸的合成，作为二氢叶酸还原酶和胸苷酸合成酶的双重抑制剂以及潜在的抗肿瘤药物。
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Design, synthesis, and biological activities of classical N-[4-[2-(2-amino-4-ethylpyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-l-glutamic acid and its 6-methyl derivative as potential dual inhibitors of thymidylate synthase and dihydrofolate reductase and as potential antitumor agents.经典N-[4-[2-(2-氨基-4-乙基吡咯并[2,3-d]嘧啶-5-基)乙基]苯甲酰基]-L-谷氨酸及其6-甲基衍生物作为胸苷酸合成酶和二氢叶酸还原酶的潜在双重抑制剂以及潜在抗肿瘤剂的设计、合成与生物活性
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Benzoyl ring halogenated classical 2-amino-6-methyl-3,4-dihydro-4-oxo-5-substituted thiobenzoyl-7H-pyrrolo[2,3-d]pyrimidine antifolates as inhibitors of thymidylate synthase and as antitumor agents.苯甲酰环卤代的经典2-氨基-6-甲基-3,4-二氢-4-氧代-5-取代硫代苯甲酰基-7H-吡咯并[2,3-d]嘧啶抗叶酸剂，作为胸苷酸合成酶的抑制剂和抗肿瘤剂。
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J Org Chem. 2001 Jun 1;66(11):3726-38. doi: 10.1021/jo001580l.
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5-Arylthio-substituted 2-amino-4-oxo-6-methylpyrrolo[2,3-d]pyrimidine antifolates as thymidylate synthase inhibitors and antitumor agents.5-芳硫基取代的2-氨基-4-氧代-6-甲基吡咯并[2,3-d]嘧啶抗叶酸药作为胸苷酸合成酶抑制剂和抗肿瘤剂。
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