- FUSED PYRIMIDINE COMPOUNDS, COMPOSITIONS AND MEDICINAL APPLICATIONS THEREOF
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The present disclosure relates to a class of fused pyrimidine compounds of Formula I, their stereoisomers, tautomers, pharmaceutically acceptable salts, polymorphs, solvates, and hydrates thereof. The present disclosure also relates to a process of preparation of these fused pyrimidine compounds, and to pharmaceutical compositions containing them.
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- BICYCLIC NITROGEN CONTAINING HETEROCYCLES AS INHIBITORS OF SALT-INUCED KINASE SIK2
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Provided are compounds of the Formula (I), and salts and solvates thereof: (Formula (I)) wherein R2, R3, X1, L, A, R6, R7 and Z are defined in the specification. The compounds are inhibitors of salt-inducible kinase (SIK), particular SIK2, and are useful in therapy, particularly in the treatment of a proliferative disorder, a benign neoplasm, pathological angiogenesis, an inflammatory disease or condition, a musculoskeletal disease or condition, an autoimmune disease, a haematological disease or condition, a neurological disease or condition, a psychiatric disorder, or a metabolic disorder.
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- FGFR4 Inhibitor. Compositions and their use in pharmaceutical preparations
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The invention provides 3 inhibitor which takes 4 - 4 dihydropyrimidine [5 - d,2] pyrimidine - (1H) FGFR4 ketone as a mother nucleus and has a covalent structure. The examples give 9 specific compounds and kinase inhibitory activity testing of these 9 compounds, wherein LX08 for FGFR4 kinase inhibitory activity is only 7 nm, lower than FIIN - 2 of the active control, and potential application prospects. In addition, by subjecting the synthesized compound to MALDI-TOF mass spectrometry, we found that compounds of LX01, LX05, LX06, LX07, LX08 are covalently bound to FGFR4 of Cys552, cannot covalently bind FGFR4 of Cys477, and LX09 are FGFR4 inhibitors which can be covalently bound to the two cysteines Cys552 and Cys477 in FGFR4.
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- BICYCLIC KINASE INHIBITORS AND USES THEREOF
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The invention relates to kinase inhibitors, in particular inhibitors of protein kinases including the SIK-family, CSF1R, HCK, TEK-family, BRK, ABL, KIT and/or their mutants. Although structurally similar to other bicyclic kinase inhibitors, the kinase inhibitors of the invention are distinctive; possessing a particular class of heterocyclic moiety. Such kinase inhibitors can display one or more certain properties distinct to their 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 related 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 of the invention may be used topically to modulate skin pigmentation in a subject, for example to impart UV protection and reduce skin cancer risk.
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- AMINOPYRIMIDINE COMPOUNDS, PREPARATION METHODS AND USES THEREOF
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Provided herein are novel compounds, for example, compounds having a Formula (I) or Formula (II), or a pharmaceutically acceptable salt thereof. Also provided herein are methods of preparing the compounds and methods of using the compounds, for example, for treating various cancer described herein, such as lung cancer (e.g., non-small cell lung cancer).
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Paragraph 248
(2021/12/12)
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- PYRIMIDINE DERIVATIVES AND THEIR USE IN TREATING OR PREVENTING A RESPIRATORY SYNCYTIAL VIRUS INFECTION
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Pyrimidine derivatives of formula (I) wherein: Z is a direct bond or -(CH2)n- wherein n is 1 or 2; one of X and Y is N, CH or CF, and the other of X and Y is CH; one of R1 and R2 is selected from -NHR, -NR2, -OR, -SR, -S(O)R, -S(O)2R and a group of the following formula (A) and the other of R1 and R2 is selected from -NHR', -OH, -OR' and a group of the above formula (A); R is unsubstituted C1-C6 alkyl; R' is a group selected from C1-C6 alkyl, 5- to 12-membered aryl and C3-C6 cycloalkyl, which group is unsubstituted or substituted; W is -(CH2)m-, -CH2-O-CH2-, -CH2-S-CH2- or -CH2-S(O)2-CH2-; p is 1, q is an integer of 1 - 6 and V is N; or p is 1, q is 0 and V is CH; or p is 0, q is 0 and V is N; r is 0 or 1; and R3 is -(CH2)s-NH2 or -(CH2)s-OH wherein s is 0 or an integer of 1 to 4; and the pharmaceutically acceptable salts thereof are inhibitors of RSV and can therefore be used to treat or prevent an RSV infection.
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- BICYCLIC UREA KINASE INHIBITORS AND USES THEREOF
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The present disclosure provides compounds of Formula (I), (II), and (III). The provided compounds are able to bind protein kinases (e.g., SIK) and may be useful in modulating (e.g., inhibiting) the activity of a protein kinase (e.g., SIK, (e.g., SIK1, SIK2, or SIK3)) in a subject or cell. The provided compounds may be useful in treating or preventing a disease (e.g., proliferative disease, musculoskeletal disease, genetic disease, hematological disease, neurological disease, painful condition, psychiatric disorder, or metabolic disorder) in a subject in need thereof. Also provided are pharmaceutical compositions, kits, methods, and uses that include or involve a compound described herein.
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- USES OF SATL-INDUCIBLE KINASE (SIK) INHIBITORS FOR TREATING OSTEOPOROSIS
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The present disclosure provides methods of treating and/or preventing osteoporosis using salt-inducible kinase (SIK) inhibitors. Also provided are methods of using SIK inhibitors for increasing the function of osteocytes, increasing the number of osteoblasts, increasing the activity of osteoblasts, inhibiting the resorption of a bone, decreasing the number of osteoclasts, inhibiting the activity of osteoclasts, increasing the mass of a bone, down-regulating the expression of the gene SOST, and/or inhibiting the activity of sclerostin. The SIK inhibitors may be combined with Src inhibitors or CSF I R inhibitors. Exemplary SIK inhibitors include the compounds of the formula: (I), (II), (III), (IV), (V) or (VI).
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Paragraph 00485; 00486
(2018/04/13)
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- USES OF PYRIMIDOPYRIMIDINONES AS SIK INHIBITORS
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The present disclosure provides methods of increasing skin pigmentation in a subject in need thereof using salt-inducible kinase (SIK) inhibitors, such as macrocyclic compounds of Formula (I), bicyclic urea compounds of Formula (II), (III), and (IV), and compounds of Formula (V), (VI), (VI-A), or (VII). Also provided are pharmaceutical compositions, methods, and uses that include or involve a compound described herein.
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Paragraph 00377; 00378
(2018/09/21)
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- MK2 INHIBITORS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same.
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- BICYCLIC HETEROCYCLES AS FGFR4 INHIBITORS
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The present invention relates to bicyclic heterocycles, and pharmaceutical compositions of the same, that are inhibitors of the FGFR4 enzyme and are useful in the treatment of FGFR4-associated diseases such as cancer.
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- BICYCLIC HETEROCYCLES AS FGFR4 INHIBITORS
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The present disclosure relates to bicyclic heterocycles of formula (I), and pharmaceutical compositions of the same, that are inhibitors of the FGFR4 enzyme and are useful in the treatment of FGFR4-associated diseases such as cancer.
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- BICYCLIC HETEROCYCLES AS FGFR4 INHIBITORS
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The present invention relates to bicyclic heterocycles, and pharmaceutical compositions of the same, that are inhibitors of the FGFR4 enzyme and are useful in the treatment of FGFR4-associated diseases such as cancer.
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- HETEROARYL COMPOUNDS AND USES THEREOF
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The present invention relates to compounds useful as inhibitors of protein kinases, containing a cysteine residue in the ATP binding site. The invention further provides for pharmaceutically acceptable compositions comprising therapeutically effective amounts of one or more of the protein kinase inhibitor compounds and methods of using said compositions in the treatment of cancers and carcinomas.
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- COMPOSITIONS AND METHODS FOR FGF RECEPTOR KINASES INHIBITORS
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Described are compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat or prevent disease or disordered associated with abnormal or deregulated kinase activity, particularly diseases or disorders that
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- Novel dihydropyridinone compounds
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Disclosed are novel dihydropridinone compounds that are selective inhibitors of both KDR and FGFR kinases. These compounds and their pharmaceutically acceptable salts are anti-proliferative agents useful in the treatment or control of solid tumors, in particular breast, colon lung and prostate tumors. Also, disclosed are pharmaceutical compositions containing these compounds and methods of treating cancer.
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Page/Page column 11
(2010/02/07)
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- Pyrimido compounds having antiproliferative activity
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Disclosed are novel pyrimido compounds that are selective inhibitors of both KDR and FGFR kinases. These compounds and their pharmaceutically acceptable salts are anti-proliferative agents useful in the treatment or control of solid tumors, in particular breast, colon, lung and prostate tumors. Also disclosed are pharmaceutical compositions containing these compounds and methods of treating cancer.
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Page/Page column 6; 10
(2010/02/08)
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