302964-08-5Relevant academic research and scientific papers
Design and synthesis of novel dasatinib analogues
Buchappa,Durgaprasad,Suneelkumar,Rani, P. Baby,Babu, K. Ravi,Rao, A. K. S. Bhujanga,Aparna
, p. 1275 - 1280 (2016)
Design, synthesis, characterization and in vitro biological assay of a series of novel carboxylic acid and amino acid analogs of dasatinib (1) as anticancer agents are reported. Some of the synthesized analogs were identified as potent Src/Abl kinase inhibitors with greater antiproliferative activity against K652 and T315I cancer cell lines. The synthetic process involves condensation of N-(2-chloro-6-methylphenyl)-2-[[6-[4(-1-pipearazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazolecarboxamide with carboxylic acids in the presence of dicyclohexylcarbodiimide and oxyma in organic solvent medium. Compounds were characterized and tested for anticancer activity on leukemia cancer cell lines K562 and Baf3/T315. Analogues of lactic acid, mandalic acid, leucine and proline have shown promising antiproliferative activity compared to dasatinib.
HALOGENATED-HETEROARYL AND OTHER HETEROCYCLIC KINASE INHIBITORS, AND USES THEREOF
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, (2021/11/04)
The invention relates to kinase inhibitors, in particular inhibitors of protein kinases including the SIK-family CSF1R, ABL/BCR-ABL, SRC, HCK, PDGFR, KIT and/or their mutants. Although structurally similar to dasatinib, the kinase inhibitors of the invention are distinctive; possessing a particular class of halogenated heteroaryls. Such kinase inhibitors can display one or more certain properties distinct to dasatinib and other structurally similar kinase inhibitors. The kinase inhibitors of the invention or pharmaceutical compositions comprising them may be used in the treatment of a disorder or condition, such as a proliferative disorder, for example, a leukaemia or solid tumour. In particular, these and other structurally similar kinase inhibitors may be used in the treatment of a proliferative disorder - such as a mixed phenotype acute leukaemia (MPAL) - characterised by (inter-alia) the presence of MEF2C protein, a human chromosomal translocation at 11q23, and/or a KMT2A fusion oncoprotein. The kinase inhibitors or pharmaceutical compositions disclosed herein may be used topically to modulate skin pigmentation in a subject, for example to impart UV protection and reduce skin cancer risk.
HETEROCYCLIC KINASE INHIBITORS AND USES THEREOF
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, (2020/05/30)
The invention relates to kinase inhibitors, in particular inhibitors of protein kinases including the protein-tyrosine kinases LCK, ABL, SRC, KIT, SIK-family and/or their mutants. Although structurally similar to dasatinib, the kinase inhibitors of the invention can display one or more certain properties distinct to dasatinib. Also, the invention relates to pharmaceutical compositions that comprise one or more of the kinase inhibitors. The kinase inhibitors or pharmaceutical compositions of the invention may be used in the treatment of a disorder or condition, such as a proliferative disorder, for example, a leukaemia or solid tumour. The kinase inhibitors or pharmaceutical compositions may be used in a treatment regimen that corresponds to, is similar to or is distinct from that used with dasatinib for a corresponding disorder, and in particular may be used in a combination treatment regimen together with one or more additional therapeutic agents, such as immune-checkpoint inhibitors.
Synthesis method of dasatinib key intermediate
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, (2019/04/26)
The invention discloses a synthesis method of a dasatinib key intermediate. The synthesis method comprises the step of carrying out dehydration condensation reaction on a compound 2 and a compound 3 to generate a compound 4, i.e., the dasatinib key intermediate. By adopting the synthesis method of the dasatinib key intermediate, disclosed by the invention, the occurrence of side reaction is greatly reduced, the selectivity of the reaction is improved, and the final yield of dasatinib is improved; the synthesis method is suitable for industrial production. A formula is shown in the description.
Scalable and impurity-free process for dasatinib: Src and BCR-Abl inhibitor
Buchappa,Sagar Vijay Kumar,Durga Prasad,Aparna
, p. 1621 - 1628 (2018/06/12)
An efficient, telescopic, impurity-free and scalable process for Bcr-Abl and Src family tyrosine kinase inhibitor for synthesis of Dasatinib with high yield and purity is described.
AN IMPROVED PROCESS FOR THE PREPARATION OF DASATINIB POLYMORPH
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Page/Page column 10-11, (2018/06/22)
The present invention is related to an improved process for the preparation of dasatinib anhydrous crystalline Neat form N-6 with high purity and high yield. The present invention also relates to purification of dasatinib crystalline Neat form N-6.
CRYSTALLINE FORMS OF N-(2-CHLORO-6-METHY]PHENVN-2-[F6-[4-(2-HVDROXVETHVL)-L- PIPERAZINVIL-2-METHVL-4-PVRIMIDINVLLAMINOL-5-THIAZOLECARBOXAMIDE AND THEIR PROCESS THEREOF
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, (2017/01/26)
The present invention relates to crystalline 1,2-Propanediol solvate of N-(2-chloro-6- methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-l-piperazinyl]-2-methyl-4-pyrimidinyl]ainino]-5- thiazolecarboxamide compound of formula- lb, its process for the preparation and its use in the preparation of anhydrous crystalline form (N-6) and monohydrate of N-(2-chloro-6- methy lphenyl)-2- [ [6- [4-(2 -hydroxy ethyl)- 1 -piperazinyl] -2-methyl-4-pyrimidinyl]amino] -5 - thiazolecarboxamide. [formula] 1,2-Propanediol solvate Formula- lb
New method for preparing dasatinib and dasatinib intermediates
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, (2017/09/01)
The invention discloses a new method for preparing dasatinib and dasatinib intermediates. The method is characterized in that dasatinib (1) is prepared from 2-aminothiazole (2) through substitution, hydroxymethylation, oxidation amidation, fixed site chlorination and amination reactions. The method has the advantages of short synthesis route, high reaction yield, cheap and easily available raw materials, great reduction of the production cost, mild reaction conditions, suitableness for industrial large-scale production, avoiding of use of acyl chloride, and reduction of environmental pollution.
A reach sha Tini synthesis of intermediates method (by machine translation)
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Paragraph 0016; 0026; 0027; 0029; 0031; 0033; 0035; 0037, (2017/08/26)
The invention belongs to the field of medical technology, in particular to a reach sha Tini intermediate N - (2 - chloro - 6 - methylphenyl) - 2 - [(6 - chloro - 2 - methyl - 4 - pyrimidinyl) amino] - 5 - thiazole carboxamide synthetic method, the specific method is, first under the low temperature condition, to the non-proton solvent, sequentially adding organic base, 2 - amino - N - (2 - chloro - 6 - methyl phenyl) thiazole - 5 - carboxamide and 2 - methyl - 4, 6 - two chlorine pyrimidine, then raise the temperature of the reaction process for preparing N - (2 - chloro - 6 - methylphenyl) - 2 - [(6 - chloro - 2 - methyl - 4 - pyrimidinyl) amino] - 5 - thiazole carboxamide, compared with the prior art, the present invention has higher yield and more low maximum shan Za content, is suitable for industrial production. (by machine translation)
A convenient new and efficient commercial synthetic route for dasatinib (Sprycel)
Suresh, Garbapu,Nadh, Ratnakaram Venkata,Srinivasu, Navuluri,Yennity, Durgaprasad
supporting information, p. 1610 - 1621 (2017/09/08)
A new and efficient synthetic route for dual-Src/Abl kinase inhibitor dasatinib (Sprycel), an anticancer drug, is described. This commercially viable process yields dasatinib monohydrate free of potential impurities with consistent yield of 68% in route A and 61% in route B with HPLC purity >99.80% over four stages.
