1979-96-0Relevant articles and documents
Discovery of 5-Nitro-6-thiocyanatopyrimidines as Inhibitors of Cryptococcus neoformans and Cryptococcus gattii
Donlin, Maureen J.,Lane, Thomas R.,Riabova, Olga,Lepioshkin, Alexander,Xu, Evan,Lin, Jeffrey,Makarov, Vadim,Ekins, Sean
, p. 774 - 781 (2021/05/04)
Opportunistic infections from pathogenic fungi present a major challenge to healthcare because of a very limited arsenal of antifungal drugs, an increasing population of immunosuppressed patients, and increased prevalence of resistant clinical strains due to overuse of the few available antifungals. Cryptococcal meningitis is a life-threatening opportunistic fungal infection caused by one of two species in the Cryptococcus genus, Cryptococcus neoformans and Cryptococcus gattii. Eighty percent of cryptococcosis diseases are caused by C. neoformans that is endemic in the environment. The standard of care is limited to old antifungals, and under a high standard of care, mortality remains between 10 and 30%. We have identified a series of 5-nitro-6-thiocyanatopyrimidine antifungal drug candidates using in vitro and computational machine learning approaches. These compounds can inhibit C. neoformans growth at submicromolar levels, are effective against fluconazole-resistant C. neoformans and a clinical strain of C. gattii, and are not antagonistic with currently approved antifungals.
NEW PYRIMIDINE DERIVATIVES FOR PREVENTION AND TREATMENT OF GRAM-NEGATIVE BACTERIAL INFECTION, CONTAMINATION AND FOULING
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Page/Page column 87, (2020/10/28)
New pyrimidine derivatives together with a membrane penetrating agent, optionally with a detectable isotope and pharmaceutical composition for use in treatment or prevention of Gram-negative bacterial infection in a host mammal in need of such treatment or prevention and use as inhibitors of Gram-negative biofilm formation on a surface of biomaterial or medical device, particularly of cardiovascular device such as prosthetic heart valve or pacemakers. New pyrimidine derivatives together with a membrane penetrating agent; for use as radiotracer in diagnosing or prognosing Gram-negative bacterial infection in a host mammal.
Synthetic method of 2-methylmercapto-4,6-dichloro-5-nitropyrimidine
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Paragraph 0014-0016, (2019/11/12)
The invention provides a synthetic method of 2-methylmercapto-4,6-dichloro-5-nitropyrimidine. The synthetic method comprises the following steps that 2-methylmercapto-4,6-dihydroxypyrimidine are addedinto nitrosonitric acid in batches, stirring is conducted at the room temperature for 1 h, reaction is conducted by heating; after reaction is completed, the temperature is lowered to the room temperature, the mixture is slowly poured into ice water and stirred for 1 h, filtering is conduced, a filter cake is washed till neutral and dug out to be dried, and a compound B is obtained; the compoundB, phosphorus oxychloride and the organic alkali are mixed for chlorination; after completion, the mixture is cooled, the extra phosphorus oxychloride are removed through vacuum concentration, after water is added for quenching, an organic solvent is used for extraction, drying and concentration are conducted, and a pure product is obtained. According to the synthetic method of the 2-methylmercapto-4,6-dichloro-5-nitropyrimidine, nitrification and chlorination are conducted on raw materials which are available in the market to generate the pure product; the raw materials are supplied by largecommercial supply, and are cheap and easy to obtain, auxiliary materials can be recycled and reused, the cost is obviously lowered, meanwhile, pollution on the environment of toxic substance in the production process is avoided, and safety in the operation process is improved; and the yield is greatly improved, the time is effectively shortened, operation is easy, and the post treatment process issimplified.
