3680-71-5Relevant articles and documents
Preparation method of prodrug intermediate of thymidine phosphorylase inhibitor
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Paragraph 0093-0094, (2021/04/14)
The invention relates to the field of preparation of prodrug intermediates of thymidine phosphorylase inhibitors, and discloses a preparation method of a prodrug intermediate of a thymidine phosphorylase inhibitor. The method comprises the following steps: (1) adding ethyl cyanoacetate into a mixed alcoholic-alkaline solution of thiourea, carrying out reflux reaction for 5-6 hours, performing cooling, crystallizing, filtering, and washing with an ethanol/dioxane mixed solution; (2) mixing pyridine with ammonia water, adding Raney nickel, ZnSO4 and the product obtained in the step (1), heating and reacting at 65-75 DEG C for 7-8 hours, performing filtering while the product is hot, and performing cooling and crystallizing, filtering and washing; and (3) adding the product obtained in the step (2) into a mixed alkali solution, slowly adding 2-bromoacetaldehyde at 45-55 DEG C, reacting for 4-5 hours, and performing cooling, crystallizing, filtering, washing and drying. According to the preparation method disclosed by the invention, the total yield of the prodrug intermediate 4-hydroxypyrrolo[2, 3-d] pyrimidine of the thymidine phosphorylase inhibitor is improved.
Synthetic method of medical intermediate 4-chloropyrrolopyrimidine
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Paragraph 0020; 0024-0025, (2020/02/14)
The invention discloses a synthetic method of a medical intermediate, i.e., 4-chloropyrrolopyrimidine. The synthetic method comprises the following steps: with 4-hydroxypyrrolo[2, 3-d]pyrimidine as areaction substrate and a mixed solution of NMP/methylbenzene as a solvent; adding 2.0 to 4.0 equivalents of 1,2,3-trichloropropane into a reaction kettle, carrying out a refluxing and stirring reaction for 4-5 h at 100-120 DEG C in a chlorine environment, carrying out vucummizing at 160-180 DEG C to evaporate excessive solvent so as to obtain an oily substance, starting stirring, adding a sodium hydroxide solution with a concentration of 0.5-1mol/L into the oily substance, and performing filtering and drying to obtain the 4-chloropyrrolopyrimidine product. POCl3 is replaced by using the novelmethod, so the problems of quenching danger and low working efficiency of conventional synthesis methods are solved.
Synthesis and biological evaluation of some new tricyclic pyrrolo[3,2-e]tetrazolo[1,5-c]pyrimidine derivatives as potential antitubercular agents
Patil, Yogesh,Shingare, Ramesh,Choudhari, Amit,Borkute, Rachana,Sarkar, Dhiman,Madje, Balaji R.
, (2018/08/07)
A series of new tricyclic pyrrolo[3,2-e]tetrazolo[1,5-c]pyrimidines 8a–l were synthesized and characterized by IR, NMR (1H and 13C), and mass spectral analysis. The newly synthesized compounds 8a–l were inspected for their in vitro antitubercular activity against Mycobacterium tuberculosis (MTB) H37Ra using an established XTT reduction menadione assay (XRMA). The title compounds exhibited minimum inhibitory concentrations (MIC90) ranging from 0.09 to >30 μg/mL. Five compounds (8c, 8i–l) were further confirmed for their dose-dependent effect against MTB. These compounds were evaluated in the THP-1 infection model, where 8i (MIC90 = 0.35 μg/mL), 8j (MIC90 = 1.17 μg/mL), 8k (MIC90 = 2.38 μg/mL), and 8l (MIC90 = 1.17 μg/mL) demonstrated significant antitubercular activity. All the ex vivo active compounds showed insignificant cytotoxicity against the human cancer cell lines, HeLa, MCF-7, and THP-1. Inactivity of all these compounds against Gram positive and Gram negative bacteria indicates their specificity. Molecular docking studies in the active site of the sterol 14alpha-demethylase (CYP51) enzyme revealed a similar binding mode to the native ligand in the crystal structure, thereby helping to understand the ligand–protein interactions and to establish a structural basis for inhibition of MTB. The results suggest novel pharmacophores as selective and specific inhibitors against MTB that can be explored further to synthesize lead compounds against tuberculosis. In summary, the results clearly indicate the identification of some novel, selective, and specific inhibitors against MTB that can be explored further for potential antitubercular drugs.
