- HALOGENATED-HETEROARYL AND OTHER HETEROCYCLIC 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, 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.
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Paragraph 0598; 0636-0639
(2021/11/04)
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- The novel method to synthesis of cantharidin intermediate
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Sulfur-containing dehydrocantharidin(SD) was yielded (76% to 96%) by Diels-Alder reaction in an ionic-liquid system under ordinary pressure and temperature. We explored the influences of different ionic-liquid types, reaction temperatures, and reaction times in this reaction. We found that the optimal reaction temperature was about 35°C, the reaction time was 20 h, and the most suitable ionic liquid was 1-butyl-3-methylimidazolium tetrafluoroborate. Furthermore, in the recycling process of ionic liquid, we found that CH3CN was the most suitable extraction solvent. We explored four steps in the synthetic route to SD and achieved a good yield of 38% in total. We envisage that this process could be further developed at an industrial scale for the synthesis of Cantharidin and is destined to be an environmentally friendly way to solve the lack of cantharis as a natural resource.
- Tan, Chunbin,Liu, Xiaoling,Du, Hongfei
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p. 271 - 276
(2019/07/31)
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- SYNTHESIS OF CANTHARIDIN
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The invention provides synthetic methods for the preparation of cantharidin and analogs thereof. In one aspect, the invention provides an improved Diels-Alder cycloaddition to generate a key intermediate en route to cantharidin and analogs thereof. In certain embodiments, the new Diels-Alder reaction involves reacting Compound (2) in the presence of furan, and in the absence of acid or increased pressure, in an aprotic polar solvent with slight warming, to yield Compound (1) in favorable yield and exo-endo ratio. In another aspect, the invention also provides a new Diels-Alder reaction between compounds of Formula (III) and furan to yield compounds of Formula (IV), which can then be transformed into cantharidin or analogs thereof. In yet another aspect, the invention describes a new palladium-mediated carbonylation providing another key intermediate en route to cantharidin and analogs thereof. In addition to synthetic methods, present invention also provides compounds {i.e., intermediates) useful in the synthesis of cantharidin and analogs thereof. Compounds provided herein may have biological activity, and therefore may be used in the treatment of diseases or conditions {e.g., infectious diseases and skin conditions).
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Paragraph 00266
(2019/04/27)
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- SEMICONDUCTING POLYMERS AND TERNARY BLENDS THEREOF
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Semiconducting photovoltaic polymers and compositions are disclosed. The polymers and compositions exhibit increased power conversion efficiency in solar cells and other applications.
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Paragraph 0084; 0088
(2016/08/17)
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- Development of a Practical Process for the Synthesis of PDE4 Inhibitors
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A practical, safe, and efficient process for the synthesis of PDE4 (phosphodiesterase type 4) inhibitors represented by 1 and 2 was developed and demonstrated on a multi-kilogram scale. Key aspects of the process include the regioselective synthesis of dihydrothieno[3,2-d]pyrimidine-2,4-diol 9 and the asymmetric sulfur oxidation of intermediate 11.
- Frutos, Rogelio P.,Tampone, Thomas G.,Mulder, Jason A.,Rodriguez, Sonia,Yee, Nathan K.,Yang, Bing-Shiou,Senanayake, Chris H.
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p. 982 - 988
(2016/06/09)
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- NOVEL PIPERIDINO-DIHYDROTHIENOPYRIMIDINE SULFOXIDES AND THEIR USE FOR TREATING COPD AND ASTHMA
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Piperidino-dihydrothienopyrimidine sulfoxides of formula I wherein: Ring A is a 6-membered aromatic ring optionally comprising one or two nitrogen atoms andR is Cl and is located in the para-, meta-, or ortho-position of Ring A,S* is a sulphur atom that represents a chiral center, and all pharmaceutically acceptable salts, enantiomers and racemates, hydrates and solvates thereof and the use of these compounds for the treatment of inflammatory or allergic diseases of the respiratory tract such as COPD or asthma.
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Paragraph 0071-0072
(2015/02/25)
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- SPECIFIC PDE4B-INHIBITORS FOR THE TREATMENT OF DIABETES MELLITUS
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A method of treating diabetes mellitus or a microvascular or macrovascular complication of diabetes mellitus in a patient in need thereof, the method comprising administering to the patient a compound of formula 1 wherein R1, R2, R3, and R4 are as defined in claim 1.
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Paragraph 0238-0239
(2014/08/19)
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- SPECIFIC PDE4B-INHIBITORS FOR THE TREATMENT OF DIABETES MELLITUS
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The invention relates to compounds of formula 1 for their use for the treatment of diabetes mellitus or for the treatment of a microvascular or macrovascular complication of diabetes mellitus wherein R1, R2, R3 and R4 are defined as summarized in claim 1. Further the invention relates to the use of compounds of the above formula 1 for the manufacture of a medicament for the treatment of diabetes mellitus or for the treatment of a microvascular or macrovascular complication of diabetes mellitus.
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Page/Page column 41
(2014/09/03)
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- MORPHOLINO SUBSTITUTED BICYCLIC PYRIMIDINE UREA OR CARBAMATE DERIVATIVES AS MTOR INHIBITORS
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The invention relates to compounds of formula (I) wherein m, o, Ra, Rb, R1 and T1 have the meaning as cited in the description and the claims. Said compounds are useful as inhibitors of mTOR for the treatment or prophylaxis of mTOR related diseases and disorders. The invention also relates to pharmaceutical compositions including said compounds, the preparation of such compounds as well as the use as medicaments
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Page/Page column 42; 44; 54
(2013/04/24)
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- NOVEL PIPERIDINO-DIHYDROTHIENOPYRIMIDINE SULFOXIDES AND THEIR USE FOR TREATING COPD AND ASTHMA
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The invention relates to novel piperidino-dihydrothienopyrimidine sulfoxides of formula I, wherein Ring A is a 6-membered aromatic ring which may optionally comprise one or two nitrogen atoms and wherein R is CI and wherein R may be located either in the para-, meta- or ortho-position of Ring A, wherein S* is a sulphur atom that represents a chiral center, and all pharmaceutically acceptable salts, enantiomers and racemates, hydrates and solvates thereof and the use of these compounds for the treatment of inflammatory or allergic diseases of the respiratory tract such as COPD or asthma.
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Page/Page column 22
(2013/03/26)
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- ANTI-CANCER DRUGS AND USES RELATING THERETO FOR METASTATIC MALIGNANT MELANOMA AND OTHER CANCERS
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The present invention discloses triazene analogs of the general formula (I) and formula (II), their tautomeric forms, stereoisomers, polymorphs, hydrates, solvates, and pharmaceutically acceptable salts thereof for the metastatic malignant melanoma and other cancers including but not limited to lymphomas, sarcomas, carcinomas, and gliomas. The invention further discloses a process for the preparation of the above said triazene analogs of formula (I) and formula (II), and their pharmaceutically acceptable compositions.
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Page/Page column 41
(2010/04/06)
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- ANTI-CANCER DRUGS AND USES RELATING THERETO FOR METASTATIC MALIGNANT MELANOMA AND OTHER CANCERS
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The present invention discloses triazene analogs of the general formula (I) and formula (II), their tautomeric forms, stereoisomers, polymorphs, hydrates, solvates, and pharmaceutically acceptable salts thereof for the metastatic malignant melanoma and other cancers including but not limited to lymphomas, sarcomas, carcinomas, and gliomas. The invention further discloses a process for the preparation of the above said triazene analogs of formula (I) and formula (II), and their pharmaceutically acceptable compositions.
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Page/Page column 17
(2010/04/23)
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- THIENOPYRIDINONE DERIVATIVES AS MACROPHAGE MIGRATION INHIBITORY FACTOR INHIBITORS
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Inhibitors of macrophage migration inhibitory factor having a thienopyridinone backbone are provided which have utility in the treatment of a variety of disorders, including the treatment of pathological conditions associated with macrophage migration inhibitory factor activity. The inhibitors of macrophage migration inhibitory factor have the following structures formula (I), (II), (III) including forms such as stereoisomers, free forms, pharmaceutically acceptable salts or esters thereof, solvates, or combinations of such forms, wherein n, R1, R2, R3, X, and Y are as defined herein. Compositions comprising an inhibitor of macrophage migration inhibitory factor in combination with a pharmaceutically acceptable carrier are also provided, as well as methods for use of the same.
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Page/Page column 56; 87-88
(2010/11/24)
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- 2-Phenyl-5,6-dihydro-2H-thieno[3,2-c]pyrazol-3-ol derivatives as new inhibitors of bacterial cell wall biosynthesis
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Twenty-five 2-phenyl-5,6-dihydro-2H-thieno[3,2-c]pyrazol-3-ol derivatives were synthesized for evaluation as new inhibitors of bacterial cell wall biosynthesis. Many of them demonstrated good inhibitory activity against Staphylococcus aureus MurB, MurC and MurD enzymes in vitro and antimicrobial activity against gram-positive bacteria including MRSA, VRE and PRSP. However, when they were tested in the presence of 4% bovine serum albumin, the MIC values increased to greater than 128 μg/mL against PRSP. None of the compounds demonstrated activity against gram-negative bacteria at MIC 32 μg/mL.
- Li, Zhong,Francisco, Gerardo D.,Hu, William,Labthavikul, Pornpen,Petersen, Peter J.,Severin, Anatoly,Singh, Guy,Yang, Youjun,Rasmussen, Beth A.,Lin, Yang-I,Skotnicki, Jerauld S.,Mansour, Tarek S.
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p. 2591 - 2594
(2007/10/03)
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- POLY(ADP-RIBOSE) POLYMERASE INHIBITORS CONSISTING OF PYRIMIDINE DERIVATIVES
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A medicament for therapeutic and/or preventive treatment of a brain disease, which comprises a compound represented by the following general formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient: wherein R represents hydrogen atom, a C1-C8 alkyl group, a substituted C1-C8 alkyl group, an aryl group, a substituted aryl group, an aryl(C1-C8)alkyl group and the like; Y represents hydrogen atom or -C(R2)R3 (R2 and R3 represent hydrogen atom, a C1-C8 alkyl group, a C1-C8 alkoxy(C1-C8)alkyl group, a hydroxy(C1-C8)alkyl group and the like); symbol "a" represents single bond when Y represents hydrogen atom, or "a" represents double bound when Y represents -C(R2)R3; -A-B- represents -CH2-CH2-, -S-CH2-, -O-CH2-, -CH2-S-, -CH2-O-, -SO-CH2-, -CH2-SO-, -SO2-CH2-, or -CH2-SO2-; and Z represents -CH2- or single bond.
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- Zeolite mediated Michael addition of 1,3-dicarbonyl compounds and thiols
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Zeolites, an environmentally attractive solid catalyst, proves to be an efficient catalyst for Michael addition of several 1,3-dicarbonyl compounds and thiols as donors with methyl vinyl ketone, acrolein and methyl acrylate as acceptors without any solvent are described.
- Sreekumar,Rugmini,Padmakumar, Raghavakaimal
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p. 6557 - 6560
(2007/10/03)
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- Surface-Mediated Phase Reaction: Dramatic Improvement of Michael Reaction on the Surface of Alumina
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The Michael reaction of several 1,3-dicarbonyl compounds, nitroalkanes, and thiols as donors with methl vinyl ketone, acrolein, methyl acrylate, methyl methacrylate, and mesityl oxide as acceptors on the surface of alumina without any solvent proceed very efficiently and furnish high yield of adducts. Key Words: Michael reaction; Al2O3; dramatic improvement
- Ranu, Brindaban C.,Bhar, Sanjay
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p. 1327 - 1332
(2007/10/02)
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- Free Radical Ring-Expansion Leading to Novel Six- and Seven-Membered Heterocycles
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Free radical promoted ring-expansion of nitrogen-, oxygen- and sulfur-containing heterocyclic β-keto esters is described.Treatment of the derived phenylselenomethyl derivatives with tri-n-butyltin hydride leads to smooth one-carbon ring expansion.
- Dowd, Paul,Choi, Soo-Chang
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p. 4847 - 4860
(2007/10/02)
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- Thiophene compounds and their manufacture
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New thiophene compounds and a new process for the manufacture of thiophene compounds by dehydrogenating dihydrothiophene with certain halogen compounds. The products are starting materials for the manufacture of pharmaceuticals, dyes and plant protection agents and, in particular, for the manufacture of additives to foodstuffs, feeds, beverages and pharmaceuticals.
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