- Thiazole derivative and synthesis method thereof
-
The invention belongs to the technical field of organic synthesis, particularly relates to a thiazole derivative and a synthetic method thereof, and particularly relates to a thiazole derivative (Z)-4-((2-(2-(2-(2,5-dimethoxyphenyl)-thiazole-5-yl)-ethylimino)(phenyl)methyl)-1,3-benzenediol and a synthetic method thereof. The synthesis method provided by the invention comprises the following steps:by taking 2,5-dimethoxybenzamide and ethyl 2-chloroacetate as raw materials, carrying out six reaction steps of carbonyl sulfide reaction, substitution, cyclization, substitution, chlorination, cyanidation, amidation, hydrolysis and substitution reaction to prepare the (Z)-4-((2-(2-(2-(2,5-dimethoxyphenyl)-thiazole-5-yl)-ethylimino)(phenyl)methyl)-1,3-benzenediol. According to the invention, an efficient synthesis method is provided for the synthesis of the thiazole derivative.
- -
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Paragraph 0025; 0028-0029; 0044; 0047-0048; 0063; 0066-0067
(2020/11/22)
-
- Benzo [d] [1, 3] oxathiol, benzo [d] [1, 3] benzo [d] [1, 3] oxathiol 3 - oxide or 3, 3 - dioxide compounds and G protein-coupled receptor 119 oxathiol action of number as method/use
-
There are provided compounds containing benzo[d][1,3]oxathiole, benzo[d][1,3]oxathiole 3-oxide, and benzo[d][1,3]oxathiole 3,3-dioxide, as well as uses/methods related thereto, including treatment of diseases and condition associated with GPR119 dysregulation, Type 2 diabetes mellitus, and related metabolic disorders.
- -
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Paragraph 0768-0770
(2019/04/02)
-
- COMPOUNDS CONTAINING POLYSUBSTITUTED BENZO[D][1,3]OXATHIOLE, BENZO[D][1,3]OXATHIOLE 3-OXIDE OR BENZO[D][1,3]OXATHIOLE 3,3-DIOXIDE AND METHODS/USES THEREOF AS AGONISTS OF G PROTEIN-COUPLED RECEPTOR 119
-
There are provided compounds having formula (I), in which: X1 and X2 are selected from certain combinations of O, S, SO and SO2; X3 is selected from CH, CF and N; X4 is selected from CH and N; X6, X6' and X6'' are selected from H, halogen, and certain alkyl, haloalkyl, alkoxy, hydroxyalkyl, and amide groups; X7 and X7' are selected from H, halogen, and certain alkyl, haloalkyl, alkoxy, hydroxyalkyl, aminoalkyl and amide groups, or both X7 and X7' together form a cycloalkyl or heterocycle; and A is selected from certain optionally substituted, alkoxy, piperazinyl and pyrrolidinyl groups. Also provided are compositions comprising these compounds, as well as uses/methods related thereto, including treatment of diseases and conditions associated with GPR119 dysregulation, Type 2 diabetes mellitus, and related metabolic disorders. (I)
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Paragraph 0506-0507
(2019/07/04)
-
- CYCLIC SULFAMIDE COMPOUNDS AND METHODS OF USING SAME
-
The present disclosure provides, in part, cyclic sulfamide compounds, and pharmaceutical compositions thereof, useful as modulators of Hepatitis B (HBV) core protein, and methods of treating Hepatitis B (HBV) infection.
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Page/Page column 278
(2018/09/21)
-
- FIVE-MEMBERED HETEROCYCLIC AMIDES WNT PATHWAY INHIBITOR
-
The present invention discloses a five-membered heterocyclic amide WNT pathway inhibitor, which belongs to a compound that regulates the activity of a Wnt signaling pathway, and provides a method for preparing such a compound, and the use of such a compound in preparing a medicament that antagonizes the Wnt signaling pathway. The five-membered heterocyclic amide WNT pathway inhibitor provided by the invention has a remarkable anti-tumor activity based on a target-based rational drug design of, and can be used for the development of a new generation of Wnt pathway inhibitors, and has a great clinical application value and considerable market potential.
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Paragraph 0121-0123
(2018/10/19)
-
- Heteroatom-Interchanged Isomers of Lissoclinamide 5: Copper(II) Complexation, Halide Binding, and Biological Activity
-
Cyclic peptides, especially those produced by marine cyanobacteria symbionts, are considered to play an important ecological role in host defence. Chemists have long compared the cyclic peptide cavitand architecture with that of macrocyclic ligands, and proposed that they mediate metal-ion transport. The study presented herein investigated the metal chelation of non-natural heteroatom-interchanged (HI) isomers of lissoclinamide 5, by using MS, EPR, and DFT calculations. The latter identified three possible structures for the CuII complex with natural lissoclinamide 5, with the most likely determined to be that with the metal ion bound through the nitrogen donors of the thiazoles and one deprotonated amide. For HI-lissoclinamide 5 the calculations suggest that the CuII ion is bound in a bidentate manner by the oxazoline nitrogen atom and one deprotonated amide nitrogen atom, with the S donor of the thiazole not involved in coordination. Along with evidence of copper binding these systems also bound halide ions. Evaluation of the anti-cancer properties demonstrated that the biological activity of HI-lissoclinamide 5 against T24 bladder cells was eleven-fold lower as compared to natural lissoclinamide 5. Addition of a CuII salt had no effect on the activity of lissoclinamide 5. Overall, this comprehensive study of the HI concept has demonstrated that small changes propagate dramatic effects in complexation, halide binding, and biological activity.
- Xie, Sida,Savchenko, Andrei I.,Kerscher, Marion,Grange, Rebecca L.,Krenske, Elizabeth H.,Harmer, Jeffrey R.,Bauer, Michelle J.,Broit, Natasa,Watters, Dianne J.,Boyle, Glen M.,Bernhardt, Paul V.,Parsons, Peter G.,Comba, Peter,Gahan, Lawrence R.,Williams, Craig M.
-
supporting information
p. 1465 - 1476
(2018/04/06)
-
- ANTIBIOTIC COMPOUNDS
-
The present invention relates to antibiotic compounds of formula (I), to compositions containing these compounds and to methods of treating bacterial diseases and infections using the compounds. The compounds find application in the treatment of infection with, and diseases caused by, Gram-positive and/or Gram-negative bacteria, and in particular in the treatment of infection with, and diseases caused by, Neisseria gonorrhoeae.
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Page/Page column 219; 220
(2018/03/25)
-
- HEPATITIS B CORE PROTEIN MODULATORS
-
The present disclosure provides, in part, compounds having allosteric effector properties against Hepatitis B virus Cp. Also provided herein are methods of treating viral infections, such as hepatitis B, comprising administering to a patient in need thereof a disclosed compound of formula:
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-
Page/Page column 108; 109
(2018/04/13)
-
- PROCESS FOR MAKING HEPATITIS B CORE PROTEIN MODULATORS
-
The present disclosure provides, in part, a process for preparing compounds (I) having allosteric effector properties against Hepatitis B virus Cp.
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Page/Page column 19
(2018/10/19)
-
- CK2 INHIBITORS, COMPOSITIONS AND METHODS THEREOF
-
The present invention provides synthesis, pharmaceutically acceptable formulations and uses of compounds in accordance with Formula (I), or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof. For Formula (I) compounds R1, R2, R3, Ar and Z are as defined in the specification. The inventive Formula (I) compounds are inhibitors of CK2 and find utility in any number of therapeutic applications, including but not limited to treatment of proliferative disorders such as cancer, inflammation and immunological disorders.
- -
-
Paragraph 0454; 0457
(2018/02/01)
-
- Synthesis, Antiviral Potency, in Vitro ADMET, and X-ray Structure of Potent CD4 Mimics as Entry Inhibitors That Target the Phe43 Cavity of HIV-1 gp120
-
In our attempt to optimize the lead HIV-1 entry antagonist, NBD-11021, we present in this study the rational design and synthesis of 60 new analogues and determination of their antiviral activity in a single-cycle and a multicycle infection assay to derive a comprehensive structure-activity relationship (SAR). Two of these compounds, NBD-14088 and NBD-14107, showed significant improvement in antiviral activity compared to the lead entry antagonist in a single-cycle assay against a large panel of Env-pseudotyped viruses. The X-ray structure of a similar compound, NBD-14010, confirmed the binding mode of the newly designed compounds. The in vitro ADMET profiles of these compounds are comparable to that of the most potent attachment inhibitor BMS-626529, a prodrug of which is currently undergoing phase III clinical trials. The systematic study presented here is expected to pave the way for improving the potency, toxicity, and ADMET profile of this series of compounds with the potential to be moved to the early preclinical development.
- Curreli, Francesca,Kwon, Young Do,Belov, Dmitry S.,Ramesh, Ranjith R.,Kurkin, Alexander V.,Altieri, Andrea,Kwong, Peter D.,Debnath, Asim K.
-
p. 3124 - 3153
(2017/04/21)
-
- SUBSTITUTED IMIDAZO[1,2-A]PYRIDINECARBOXAMIDES AND THEIR USE
-
The present application relates to novel substituted imidazo[1,2-a]pyridine-3-carboxamides, to processes for preparation thereof, to the use thereof, alone or in combinations, for treatment and/or prophylaxis of diseases, and to the use thereof for production of medicaments for treatment and/or prophylaxis of diseases, especially for treatment and/or prophylaxis of cardiovascular disorders.
- -
-
Paragraph 0652; 0653
(2017/03/21)
-
- CYANO-SUBSTITUTED IMIDAZO[1,2-A]PYRIDINECARBOXAMIDES AND THEIR USE
-
The present application relates to novel substituted imidazo[1,2-a]pyridine-3-carboxamides, to processes for preparation thereof, to the use thereof, alone or in combinations, for the treatment and/or prophylaxis of diseases, and to the use thereof for production of medicaments for the treatment and/or prophylaxis of diseases, especially for the treatment and/or prophylaxis of cardiovascular disorders.
- -
-
-
- IMIDAZOPYRIDAZINE KINASE INHIBITORS USEFUL TO TREATING A DISEASE OR DISORDER MEDIATED BY AAK1, SUCH AS ALZHEIMER'S DISEASE, BIPOLAR DISORDER, PAIN, SCHIZOPHRENIA
-
The present disclosure is generally directed to compounds which can inhibit AAK1 (adaptor associated kinase 1), compositions comprising such compounds, and methods for inhibiting AAK1.
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-
Page/Page column 44-45
(2015/03/13)
-
- COMBINATION OF KINASE INHIBITORS AND USES THEREOF
-
The present invention provides for a method for treating a disease condition associated with PI3-kinase a and/or a receptor tyrosine kinase (RTK) in a subject. In another aspect, the invention provides for a method for treating a disease condition associated with PI3-kinase α and/or an RTK in a subject. In yet another aspect, a method of inhibiting phosphorylation of Akt (S473) in a cell is set forth.
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-
Page/Page column 67
(2015/02/19)
-
- PROTEIN KINASE INHIBITORS
-
The present invention relates to a novel family of inhibitors of protein kinases. In particular, the present invention relates to inhibitors of the members of the Tec and Src protein kinase families.
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-
Paragraph 0170
(2015/07/15)
-
- HEPATITIS B CORE PROTEIN ALLOSTERIC MODULATORS
-
ABSTRACT The present disclosure provides, in part, compounds having allosteric effector properties against Hepatitis B virus Cp. Also provided herein are methods of treating viral infections, such as hepatitis B, comprising administering to a patient in need thereof a disclosed compound.
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-
Paragraph 000234
(2015/10/05)
-
- (1aR,12bS)-8-cyclohexyl-11-fluoro-N-((1-methylcyclopropyl)sulfonyl)-1a-((3-methyl-3,8-diazabicyclo[3.2.1]oct-8-yl)carbonyl)-1,1a,2,2b-tetrahydrocyclopropa[d]indolo[2,1-a][2]benzazepine-5-carboxamide for use in treating HCV
-
The invention relates to an administration unit comprising a compound of formula and/or pharmaceutically acceptable salts thereof, and to a packaging comprising the administration unit according to the invention.
- -
-
Paragraph 0221-0222
(2014/10/29)
-
- PROTEIN KINASE INHIBITORS
-
The present invention relates to a novel family of inhibitors o f protein kinase of formula 1 and process for their production and pharmaceutical compositions thereof. In particular, the present invention relates to inhibitors of the members of the Tec, Src and Btk protein kinase families
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-
Page/Page column 23
(2014/01/18)
-
- PROTEIN KINASE INHIBITORS
-
The present invention relates to a novel family of inhibitors of protein kinases. In particular, the present invention relates to inhibitors of the members of the Tec and Src protein kinase families, more particularly Btk, having the general formula (1): A-Y-E-W-Z (1.)
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-
Page/Page column 22; 23
(2014/03/25)
-
- Hydroxy-substituted imidazo[1,2-a]pyridinecarboxamides and their use
-
The present application relates to novel substituted imidazo[1,2-a]pyridine-3-carboxamides, to processes for their preparation, to their use alone or in combinations for the treatment and/or prophylaxis of diseases and to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, in particular for the treatment and/or prophylaxis of cardiovascular disorders.
- -
-
Paragraph 1114; 1115
(2014/05/20)
-
- Amino-substituted imidazo[1,2-a]pyridinecarboxamides and their use
-
The present application relates to novel substituted imidazo[1,2-a]pyridine-3-carboxamides, to processes for their preparation, to their use alone or in combinations for the treatment and/or prophylaxis of diseases and to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, in particular for the treatment and/or prophylaxis of cardiovascular disorders.
- -
-
Paragraph 0477; 0478
(2014/05/20)
-
- COMBINATION OF KINASE INHIBITORS AND USES THEREOF
-
The present invention provides for a method for treating a disease condition associated with PI3-kinase a and/or mTOR in a subject. In another aspect, the invention provides for a method for treating a disease condition associated with PI3-kinase a and/or mTOR in a subject. In yet another aspect, a method of inhibiting phosphorylation of both Akt (S473) and Akt (T308) in a cell is set forth. The present invention also provides a pharmaceutical kit effective for treating a disease condition associated with PI3 -kinase α and/or mTOR in a subject.
- -
-
Paragraph 00641
(2014/10/04)
-
- KINASE INHIBITOR POLYMORPHS
-
Polymorphs of chemical compounds that modulate kinase activity, including PI3K activity, and chemical compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3K activity, are described herein.
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-
Paragraph 00276-00297
(2013/05/23)
-
- PROTEIN KINASE INHIBITORS
-
The present invention relates to a novel family of inhibitors of protein kinases. In particular, the present invention relates to inhibitors of the members of the Tec and Src protein kinase families.
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Page/Page column 55
(2014/01/07)
-
- COMPOSITIONS AND METHODS FOR MODULATING FXR
-
The present invention relates to compounds of Formula (I), a stereoisomer, enantiomer, a pharmaceutically acceptable salt or an amino acid conjugate thereof; wherein variables are as defined herein; and their pharmaceutical compositions, which are useful as modulators of the activity of Farnesiod X receptors (FXR).
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Page/Page column 113
(2012/07/13)
-
- SUBSTITUTED N-(1H-INDAZOL-4-YL)IMIDAZO[1,2-a]PYRIDINE-3-CARBOXAMIDE COMPOUNDS AS TYPE III RECEPTOR TYROSINE KINASE INHIBITORS
-
Compounds of Formula I: and pharmaceutically acceptable salts thereof in which R1, R2, R3, R4, R5 and R6 have the meanings given in the specification, are inhibitors of cFMS and are useful in the treatment of fibrosis, bone-related diseases, cancer, autoimmune disorders, inflammatory diseases, cardiovascular diseases, pain and burns in a mammal
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Page/Page column 54
(2012/06/30)
-
- SUBSTITUTED N-(1H-INDAZOL-4-YL)IMIDAZO[1, 2-A]PYRIDINE-3- CARBOXAMIDE COMPOUNDS AS CFMS INHIBITORS
-
Compounds of Formula (I): and pharmaceutically acceptable salts thereof in which R1, R2, R3, R4 and R5 have the meanings given in the specification, are inhibitors of cFMS and are useful in the treatment of bone-related diseases, cancer, autoimmune disorders, inflammatory diseases, cardiovascular diseases and pain.
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Page/Page column 68; 69
(2011/07/09)
-
- IMIDAZOPYRIDAZINECARBONITRILES USEFUL AS KINASE INHIBITORS
-
The invention provides compounds of Formula (I) and pharmaceutically acceptable salts thereof. The Formula (I) imidazopyridazines inhibit protein kinase activity thereby making them useful as anticancer agents.
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Page/Page column 115
(2010/04/28)
-
- HETEROARYL COMPOUNDS USEFUL AS RAF KINASE INHIBITORS
-
The present invention provides compounds of formula (I) useful as inhibitors of Raf protein kinase. The present invention also provides compositions thereof, and methods of treating Raf -mediated diseases.
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Page/Page column 86; 87
(2010/08/04)
-
- Heterocyclic Compounds Useful as RAF Kinase Inhibitors
-
The present invention provides compounds useful as inhibitors of Raf protein kinase. The present invention also provides compositions thereof, and methods of treating Raf-mediated diseases.
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-
Page/Page column 32
(2009/01/24)
-
- COMPOUNDS USEFUL AS RAF KINASE INHIBITORS
-
The present invention provides compounds useful as inhibitors of Raf protein kinase. The present invention also provides compositions thereof, and methods of treating Raf-mediated diseases.
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Page/Page column 77
(2009/03/07)
-
- SUBSTITUTED IMIDAZOPYRIDAZINES USEFUL AS KINASE INHIBITORS
-
The invention provides compounds of formula I and pharmaceutically acceptable salts thereof. The formula I imidazopyridazines inhibit protein kinase activity thereby making them useful as anticancer agents.
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Page/Page column 45
(2009/10/09)
-
- PYRIDO PYRIMIDINONES, DIHYDRO PYRIMIDO PYRIMIDINONES AND PTERIDINONES USEFUL AS RAF KINASE INHIBITORS
-
The present invention provides compounds having the formula: (I) wherein A-B together represents one of the following structures; (II), (III), (IV) and n, R1, R2, R3, R4, L1, L2, Y and Z are as defined in classes and subclasses herein, and pharmaceutical compositions thereof, as described generally and in subclasses herein, which compounds are useful as inhibitors of protein kinase (e.g., RAF), and thus are useful, for example, for the treatment of RAF mediated diseases.
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Page/Page column 114-115
(2010/11/08)
-
- Methods of treatment of amyloidosis using bi-aryl aspartyl protease inhibitors
-
The invention relates to novel compounds and methods of treating diseases, disorders, and conditions associated with amyloidosis. Amyloidosis refers to a collection of diseases, disorders, and conditions associated with abnormal deposition of A-beta protein.
- -
-
Page/Page column 40
(2010/02/15)
-
- Vanilloid receptor ligands and their use in treatments
-
Compounds having the general structure and compositions containing them, for the treatment of acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritus, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders.
- -
-
-
- Retroviral protease inhibiting compounds
-
A compound comprising a substituent of the formula (II) is disclosed as an HIV protease inhibitor. Intermediates for making such compounds and processes for making such intermediates are also disclosed.
- -
-
-
- RETROVIRAL PROTEASE INHIBITING COMPOUNDS
-
A compound of the formula: STR1 is disclosed as an HIV protease inhibitor. Methods and compositions for inhibiting an HIV infection are also disclosed.
- -
-
-
- Pharmaceutical composition
-
A solid pharmaceutical composition is disclosed which comprises a pharmaceutically acceptable adsorbent or a mixture of pharmaceutically acceptable adsorbents to which is adsorbed a mixture of (1) a pharmaceutically acceptable organic solvent or a mixture of pharmaceutically acceptable organic solvents, (2) an HIV protease inhibiting compound and (3) one or more pharmaceutically acceptable acids. The solid composition can optionally be encapsulated in a hard gelatin capsule.
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-
-
- Pharmaceutical composition for inhibiting HIV protease
-
A pharmaceutical composition is disclosed which comprises a solution of an HIV protease inhibiting compound in a pharmaceutically acceptable organic solvent comprising a mixture of (1) (a) a solvent selected from propylene glycol and polyethylene glycol or (b) a solvent selected from polyoxyethyleneglycerol triricinoleate, polyethylene glycol 40 hydrogenated castor oil, fractionated coconut oil, polyoxyethylene (20) sorbitan monooleate and 2-(2-ethoxyethoxy)ethanol or (c) a mixture thereof and (2) ethanol or propylene glycol.
- -
-
-
- RETROVIRAL PROTEASE INHIBITING PIPERAZINE COMPOUNDS
-
Retroviral protease inhibiting compounds of the formula: STR1 are disclosed.
- -
-
-
- RETROVIRAL PROTEASE INHIBITING COMPOUNDS
-
A retroviral protease inhibiting compound of the formula: STR1 is disclosed wherein R 1, R 2, R 5, R 6, Y m and Y' n are herein defined.
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-
-
- SYNTHESIS OF TWO NEW THIAZOLE-CONTAINING OLIGOPEPTIDES AS POTENTIAL DNA MINOR GROOVE BINDING ANALOGS OF NETROPSIN
-
On the basis of previous studies on synthetic models related to the antibiotic agents Netropsin and Distamycin-A, the design and synthesis of two potential DNA minor groove ligands are described.Methia-Nt and Isothia-Nt were prepared by liquid-phase peptidic synthesis from the key compounds ethyl 2-amino-5-methylthiazole-4-carboxaldehyde (1) and ethyl 2-aminothiazole-5-carboxylate (8) respectively.
- Plouvier, Bertrand,Bailly, Christian,Houssin, Raymond,Henichart, Jean-Pierre
-
p. 693 - 701
(2007/10/02)
-