- NEW PYRIMIDINE DERIVATIVES FOR PREVENTION AND TREATMENT OF GRAM-NEGATIVE BACTERIAL INFECTION, CONTAMINATION AND FOULING
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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.
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Page/Page column 86
(2020/10/28)
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- Synthesis of ticagrelor analogues belonging to 1,2,3-triazolo[4,5-d]pyrimidines and study of their antiplatelet and antibacterial activity
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Based on the recent observation that the antiplatelet agent ticagrelor and one of its metabolite exert bactericidal activity against gram-positive bacteria, a series of 1,2,3-triazolo[4,5-d]pyrimidines structurally related to ticagrelor were synthesized and examined as putative antiplatelet and antibacterial agents. The aim was to assess the possibility of dissociating the two biological properties and to find novel 1,2,3-triazolo[4,5-d]pyrimidines expressing antiplatelet activity and devoid of in vitro antibacterial activity. The new compounds synthesized were known metabolites of ticagrelor as well as structurally simplified analogues. Some of them were found to express antiplatelet activity and to lose the antibacterial activity, supporting the view that the two activities were not necessarily linked.
- Goffin, Eric,Jacques, Nicolas,Lancellotti, Patrizio,Musumeci, Lucia,Nchimi, Alain,Pirotte, Bernard,Oury, Cécile
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- Soluble guanylate cyclase stimulators for the treatment of hypertension: Discovery of MK-2947
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The NO-sGC-cGMP signaling pathway plays an important role in the cardiovascular system. Loss of nitric oxide tone or impaired signaling has been associated with cardiovascular diseases, such as hypertension, pulmonary hypertension and heart failure. Direct activation of sGC enzyme independent of NO represents a novel approach for modulating NO signaling with tremendous therapeutic potential. Herein, we describe the design of a structurally novel class of heme-dependent sGC stimulators containing the 3,3-dimethylpyrrolidin-2-one moiety which resulted in the identification of the potent, selective stimulator 30 (MK-2947) for the treatment of hypertension.
- Brockunier, Linda,Stelmach, John,Guo, Jian,Spencer, Tracy,Rosauer, Keith,Bansal, Alka,Cai, Sheng-Jian,Chen, Nancy,Cummings, John,Huang, Li,Johnson, Timothy,Levesque, Sonia,Luo, Lin,Maloney, Kevin,Metzger, Joseph,Mortko, Christopher,Ortega, Karen,Pai, Lee-Yuh,Pereira, Antonio,Salituro, Gino,Shang, Jackie,Shepherd, Cherrie,Sherrie Xu, Shiyao,Yang, Qifeng,Cui, Jisong,Roy, Sophie,Parmee, Emma,Raghavan, Subharekha
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supporting information
(2020/10/12)
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- Synthetic method of 2-methylmercapto-4,6-dichloro-5-nitropyrimidine
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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.
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Paragraph 0014-0016
(2019/11/12)
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- PYRIMIDINE DERIVATIVES FOR PREVENTION AND TREATMENT OF BACTERIAL INFECTIONS
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New pyrimidine derivatives of formula (I), optionally with a detectable isotope, pharmaceutical composition and method of preparation thereof. New pyrimidine derivatives for use in treatment or prevention of bacterial infection in a host mammal in need of such treatment or prevention and use as inhibitors of biofilm formation on a surface of biomaterial or medical device, particularly of cardiovascular device such as prosthetic heart valve or pacemakers. New pyrimidine derivatives for use as radiotracer in diagnosing or prognosing bacterial infection in a host mammal.
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Page/Page column 74; 75
(2019/09/04)
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- Convenient synthesis of 2-(methylsulfonyl)pyrimidine derivatives
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An efficient and convenient approach for the preparation of functionalized 2-(methylsulfonyl)pyrimidine derivatives has been developed through cyclic condensation of malonate derivatives with S-methylisothiouronium sulfate followed by derivation and oxidation in water–acetone mixture using oxone as the oxidant. This synthetic strategy provides an efficient and environmentally friendly approach for easy access to 2-(methylsulfonyl)pyrimidine derivatives with considerable yields.
- Huang, Tong-Hui,Zhou, Shan-Shan,Wu, Xin,An, Lin,Yin, Xiao-Xing
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supporting information
p. 714 - 720
(2018/02/16)
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- MACROCYCLIC PURINES FOR THE TREATMENT OF VIRAL INFECTIONS
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This invention relates macrocyclic purine derivatives having formula (I), processes for their preparation, pharmaceutical compositions, and their use in treating viral infections.
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Page/Page column 26; 28
(2014/02/15)
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- PURINE DERIVATIVES FOR THE TREATMENT OF VIRAL INFECTIONS
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The present invention relates to purine derivatives of formula (I), processes for their preparation, pharmaceutical compositions, and their use in treating viral infections.
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Page/Page column 29
(2013/05/23)
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- SOLUBLE GUANYLATE CYCLASE ACTIVATORS
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The invention relates to compounds having the structure of Formula (I) and pharmaceutically acceptable salts thereof, which are soluble guanylate cyclase activators. The compounds are capable of modulating the body's production of cyclic guanosine monophosphate ("cGMP") and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The compounds are useful for treatment or prevention of cardiovascular diseases, endothelial dysfunction, diastolic dysfunction, atherosclerosis, hypertension, pulmonary hypertension, angina pectoris, thromboses, restenosis, myocardial infarction, strokes, cardiac insufficiency, pulmonary hypertonia, erectile dysfunction, asthma bronchiale, chronic kidney insufficiency, diabetes, or cirrhosis of the liver.
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Page/Page column 39; 80-81
(2011/10/13)
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- MODULATORS OF TOLL-LIKE RECEPTORS
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Provided are modulators of TLRs of Formula II: pharmaceutically acceptable salts thereof, compositions containing such compounds, and therapeutic methods that include the administration of such compounds.
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Page/Page column 45
(2010/06/19)
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- 5-Aminopyrimidin-2-ylnitriles as Cathepsin K inhibitors
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A series of pyrimidine nitrile inhibitors of Cathepsin K with reduced glutathione reactivity has been identified and Molecular Core Matching (MoCoM) has been used to quantify the effect of an amino substituent at C5.
- Morley, Andrew D.,Kenny, Peter W.,Burton, Brenda,Heald, Robert A.,MacFaul, Philip A.,Mullett, Julia,Page, Ken,Porres, Soraya S.,Ribeiro, Lyn Rosenbrier,Smith, Phil,Ward, Stuart,Wilkinson, Tina J.
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scheme or table
p. 1658 - 1661
(2009/12/03)
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- Imidazolo-, oxazolo-, and thiazolopyrimidine modulators of TRPV1
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Certain TRPV1-modulating imidazolo-, oxazolo-, and thiazolopyrimdine compounds are described. The compounds may be used in pharmaceutical compositions and methods for treating disease states, disorders, and conditions mediated by TRPV1 activity, such as pain, arthritis, itch, cough, asthma, or inflammatory bowel disease.
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Page/Page column 12
(2009/07/03)
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- 9- (PYRAZOL- 3 -YL) - 9H- PURINE-2 -AMINE AND 3- (PYRAZ0L-3-YL) -3H-IMIDAZ0 [4, 5-B] PYRIDIN-5-AMINE DERIVATIVES AND THEIR USE FOR THE TREATMENT OF CANCER
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The present invention relates to compounds of Formula (I): and to their pharmaceutical compositions, and to their methods of use. These compounds provide a treatment for myeloproliferative disorders and cancer.
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Page/Page column 69
(2009/01/20)
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- Thiazolopyrimidine modulators of TRPV1
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Certain TRPV1-modulating thiazolopyrimidine compounds are described. The compounds may be used in pharmaceutical compositions and methods for treating disease states, disorders, and conditions mediated by TRPV1 activity, such as pain, arthritis, itch, cough, asthma, or inflammatory bowel disease.
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Page/Page column 13
(2008/06/13)
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- Thiazolo-pyrimidine/pyridine urea derivatives
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There are presented compounds of the formula or a pharmaceutically acceptable salt thereof, which are active adenosine A2B receptor antagonists and useful in the treatment of diabetes, diabetic retinopathy, asthma and diarrhea.
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Page/Page column 51
(2008/06/13)
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- Triazolo[4,5-D]pyrimidinyl derivatives and their use as medicaments
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The invention relates to triazolo[4,5-d]pyrimidin-3-yl derivatives which are useful in the treatment of platelet aggregation disorders.
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- Pyrimidine derivatives
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The present invention relates to novel 5-(ω-substituted amino-alkanoyl amino)pyrimidine derivatives, processes for producing the derivatives, and pharmaceutical compositions containing said derivatives. The compounds in the present invention have potent effects of inhibiting ACAT activity and lowering serum cholesterol. The compounds of the present invention are extremely useful for the treatment and/or prevention of arteriosclerosis or hyperlipidemia.
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- The Chemistry of Pyrimidinethiols. III The Synthesis of Some Substituted Pyrimidinethiols and Some Thiazolopyrimidines
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The preparation of a number of pyrimidinethiols and (substituted)thiopyrimidines has been carried out.The reaction of 5-acetylamino-2-aminopyrimidine-4,6-diol with phosphorus pentasulfide in pyridine gave 5-amino-2-methylthiazolopyrimidine-7-thiol which was used to prepare several additional novel pyrimidine derivatives.Hydrolysis of the 4-carboxymethylthio derivative by using 5 M hydrochloric acid gave 2,5-diamino-6-mercaptopyrimidin-4-ol hydrochloride whilst hydrolysis of 2-methyl-7-methylthiothiazolopyrimidin-5-amine gave the corresponding 4-hydroxy derivative.Several 4-arenecarbonylmethylthio derivatives were recovered unchanged from such hydrolysis reactions.
- Harnden, Michael R.,Hurst, Derek T.
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