- Synthesis method of 2-aminothiazole pyrimidine serving as CDK2 inhibitor
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The invention relates to the technical field of organic synthesis and medicines, and particularly discloses a synthesis method of 2-aminothiazole pyrimidine serving as a CDK/2 inhibitor. The synthesismethod comprises the following steps: converting amino into isothiocyanate, reacting the isothiocyanate with primary amine to generate thiourea, and carrying out Hantzsch thiazole synthesis reaction,fluorination reaction and condensation of enaminone and guanidine hydrochloride to form a pyrimidine ring. According to the method, through five steps of reactions, the total yield reaches 35%-48%. The method has the advantages that a traditional fluorination method is replaced by photocatalysis; the yield of the whole process is greatly increased, the yield is increased to 85% from 35% through the fluorination reaction, and compared with a traditional fluorination method in a low-temperature ice salt bath, the method is milder in condition, only needs to be carried out at the room temperature, and is a good process for synthesizing the CDK/2 inhibitor 2-aminothiazole pyrimidine.
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- Highly Potent, Selective, and Orally Bioavailable 4-Thiazol-N-(pyridin-2-yl)pyrimidin-2-amine Cyclin-Dependent Kinases 4 and 6 Inhibitors as Anticancer Drug Candidates: Design, Synthesis, and Evaluation
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Cyclin D dependent kinases (CDK4 and CDK6) regulate entry into S phase of the cell cycle and are validated targets for anticancer drug discovery. Herein we detail the discovery of a novel series of 4-thiazol-N-(pyridin-2-yl)pyrimidin-2-amine derivatives as highly potent and selective inhibitors of CDK4 and CDK6. Medicinal chemistry optimization resulted in 83, an orally bioavailable inhibitor molecule with remarkable selectivity. Repeated oral administration of 83 caused marked inhibition of tumor growth in MV4-11 acute myeloid leukemia mouse xenografts without having a negative effect on body weight and showing any sign of clinical toxicity. The data merit 83 as a clinical development candidate.
- Tadesse, Solomon,Yu, Mingfeng,Mekonnen, Laychiluh B.,Lam, Frankie,Islam, Saiful,Tomusange, Khamis,Rahaman, Muhammed H.,Noll, Benjamin,Basnet, Sunita K. C.,Teo, Theodosia,Albrecht, Hugo,Milne, Robert,Wang, Shudong
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p. 1892 - 1915
(2017/03/17)
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- COMPOSITIONS AND METHODS FOR THE TREATMENT OF MALARIA
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The present invention provides aminohydantoin anti-malarial agents. In some embodiments, these agents have the property of functions of targeting malarial aspartic proteases while at the same time having low activity against human BACE. Methods of employing such agents are also provided.
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Page/Page column 73; 74
(2014/10/15)
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- SUBSTITUTED THIAZOLE AND PYRIMIDINE DERIVATIVES AS MELANOCORTIN RECEPTOR MODULATORS
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The present invention provides substituted thiazole and pyrimidine derivatives of Formula (I), methods of their preparation, pharmaceutical compositions comprising the compounds of Formula (I), and methods of use in treating human or animal disorders. The compounds of the invention can be useful as inhibitors of action of AgRP on a melanocortin receptor and thus can be useful for the management, treatment, control, or the adjunct treatment of diseases which may be responsive to the modulation of melanocortin receptors including obesity-related disorders.
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Page/Page column 112-113
(2010/02/14)
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- THIAZOLE DERIVATIVES AND USE THEREOF
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The present invention is related to thiazole derivatives of Formula (I) in particular for the treatment and/or prophylaxis of autoimmune disorders and/or inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, bacterial or viral infections, kidney diseases, platelet aggregation, cancer, transplantation, graft rejection or lung injuries.
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Page/Page column 157
(2008/06/13)
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- CYSTEINE PROTEASE INHIBITORS
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A compound of the formula (II) wherein one of R1 and R2 is halo and the other is H or halo; R3 is C1-C4 straight or branched chain, optionally fluorinated, alkyl; R4 is H; or R3 together with R4 and the adjoining backbone carbon defines: a spiro-C5-C7 cycloalkyl, optionally substituted with 1 to 3 substituents selected from halo, hydroxyl, C1-C4 alkyl or C1-C4 haloalkyl; or optionally bridged with a methylene group; or a C4-C6 saturated heterocycle having a hetero atom selected from O, NRa, S, S(=O)2 ; where Ra is H, C1-C4 alkyl or CH3C(=O); R5 is independently selected from H or methyl; E is -C(=O)-, -S(=O)m-, -NR5S(=O)m-, -NR5C(=O)-, -OC(=O)-, R6 is a stable, optionally substituted, monocyclic or bicyclic, carbocycle or hetorocycle; m is independently 0,1 or 2; are inhibitors of cathepsin K and useful in the treatment or prophylaxis of osteoporosis.
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Page/Page column 96
(2010/02/12)
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- HEPATITIS C INHIBITOR COMPOUNDS
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Compounds of formula (I): wherein B, X, R3, L0, L1, L2, R2, R1 and RC are defined herein. The compounds are useful as inhibitors of HCV NS3 protease for the treatment of hepatitis C viral infection.
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- Macrocyclic peptides active against the hepatitis C virus
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Compounds of formula I: wherein R1 is hydroxy or NHSO2R1A wherein R1A is (C1-8)alkyl, (C3-7)cycloalkyl or {(C1-6)alkyl-(C3-7)cycloalkyl}, which are all optionally substituted from 1 to 3 times with halo, cyano, nitro, O(C1-6)alkyl, amido, amino or phenyl, or R1A is C6 or C10 aryl which is optionally substituted from 1 to 3 times with halo, cyano, nitro, (C1-6)alkyl, O(C1-6)alkyl, amido, amino or phenyl; R2 is (C5-6)cycloalkyl and R3 is cyclopentyl; or a pharmaceutically acceptable salt thereof, useful as inhibitors of the HCV NS3 protease.
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- Macrocyclic peptides active against the hepatitis C virus
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The present invention covers macrocyclic compounds of formula I active in-vitro and in cellular assays against the NS3 protease of the hepatitis C virus. wherein W, R21, R22, R3, R4, D and A are as defined herein, or a pharmaceutically acceptable salts or ester thereof.
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