- THYROID HORMONE RECEPTOR BETA AGONIST COMPOUNDS
-
Provided herein are compounds, preferably thyroid hormone receptor beta (THR beta) agonist compounds, compositions thereof, and methods of their preparation, and methods of agonizing THR beta and methods for treating disorders mediated by THR beta.
- -
-
Paragraph 0202; 0248
(2021/03/05)
-
- PROTEIN TYROSINE PHOSPHATASE DEGRADERS AND METHODS OF USE THEREOF
-
Provided herein are compounds, compositions, and methods useful for degrading protein tyrosine phosphatase, e.g., protein tyrosine phosphatase non-receptor type 2 (PTPN2) and/or protein tyrosine phosphatase non-receptor type 1 (PTPN1), and for treating related diseases favorably responsive to PTPN1 or PTPN2 inhibitor treatment, e.g., a cancer 5 or a metabolic disease.
- -
-
Page/Page column 180
(2021/06/26)
-
- BIFUNCTIONAL DEGRADERS OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASES AND THERAPEUTIC USE THEREOF
-
The present disclosure provides bifunctional compounds as IRAK4 degraders via ubiquitin proteasome pathway, and method for treating diseases modulated by IRAK4.
- -
-
Page/Page column 92-93
(2021/08/27)
-
- STAT DEGRADERS AND USES THEREOF
-
The present invention provides compounds, compositions thereof, and methods of using the same.
- -
-
Paragraph 00770; 00771
(2021/09/26)
-
- Cu-Catalyzed C-H Allylation of Benzimidazoles with Allenes
-
CuH-catalyzed intramolecular cyclization and intermolecular allylation of benzimidazoles with allenes have been described. The reaction proceeded smoothly with the catalytic system of Cu(OAc)2/Xantphos and catalytic amount of (MeO)2MeSiH. This protocol features mild reaction conditions and a good tolerance of substrates bearing electron-withdrawing, electron-donating, or electron-neutral groups. A new catalytic mechanism was proposed for this copper hydride catalytic system.
- Dong, Yaxi,Breit, Bernhard
-
p. 6765 - 6769
(2021/09/11)
-
- COMPOUNDS AND THEIR METHODS OF USE
-
The present invention is directed to, in part, fused heteroaryl compounds and compositions useful for preventing and/or treating a disease or condition relating to aberrant function of a voltage-gated, sodium ion channel, for example, abnormal late/persistent sodium current. Methods of treating a disease or condition relating to aberrant function of a sodium ion channel including Dravet syndrome or epilepsy are also provided herein.
- -
-
Paragraph 0303; 0304-0305
(2021/11/20)
-
- Benzopyrazine compound, and preparation method and application thereof
-
A preparation method of a benzopyrazine compound comprises the following steps: dissolving 5-bromo-2-nitroaniline in an organic solvent, then adding an alkali and a methylation reagent, and reacting for a period of time at room temperature to obtain an intermediate III; dissolving the intermediate III in an organic solvent, adding a reducing reagent, and reacting at room temperature for a period of time to obtain an intermediate IV; dissolving the intermediate IV in an organic solvent, adding the alkali and 1,2-dibromoethane, and carrying out a heating reaction for a period of time to obtain an intermediate V; dissolving the intermediate V in an organic solvent, adding the alkali and isopropyl bromide, and heating to react for a period of time to obtain an intermediate VI; dissolving the intermediate VI in an organic solvent, adding bis(pinacolato)diboron, a palladium catalyst and the alkali, and heating to react for a period of time to obtain an intermediate VII; and dissolving the intermediate VII in an organic solvent, adding a 5-bromopyridine derivative, a palladium catalyst and the alkali, and heating to react for a period of time to obtain the benzopyrazine compound. The benzopyrazine compound provided by the invention can be used as a PI3K inhibitor for anticancer treatment.
- -
-
Paragraph 0048-0051
(2020/07/02)
-
- MERTK DEGRADERS AND USES THEREOF
-
The present invention provides compounds, compositions thereof, and methods of using the same.
- -
-
Paragraph 00693
(2020/01/31)
-
- 1,3,4-OXADIAZOLE DERIVATIVE COMPOUNDS AS HISTONE DEACETYLASE 6 INHIBITOR, AND THE PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
-
The present invention relates to 1,3,4-oxadiazole derivative compounds having a histone deacetylase 6 (HDAC6) inhibitory activity, stereoisomers thereof or pharmaceutically acceptable salts thereof, a use thereof in preparation of a medicament, a pharmaceutical composition comprising the same, a therapeutic method using the composition, and a method for preparing the same, and the 1,3,4-oxadiazole derivative compounds are represented by a following chemical formula (I).
- -
-
Page/Page column 631-632
(2020/12/11)
-
- IRAK DEGRADERS AND USES THEREOF
-
The present invention provides compounds, compositions thereof, and methods of using the same.
- -
-
Paragraph 00962; 001247-001249
(2020/06/19)
-
- IRAK DEGRADERS AND USES THEREOF
-
The present invention provides compounds, compositions thereof, and methods of using the same. The compounds include an IRAK binding moiety and a degradation inducing moiety (DIM). The DIM could be DTM a ligase binding moiety (LBM) or lysine mimetic. The compounds could be useful as IRAK protein kinase inhibitors and applied to IRAK mediated disorders.
- -
-
Paragraph 00794; 00921-00923
(2021/01/23)
-
- SYK INHIBITOR AND USE METHOD THEREFOR
-
Provided are a Syk inhibitor and a use method therefor, and in particular, disclosed are quinolinone represented by formula (I) or quinazoline derivatives or pharmaceutically acceptable salts thereof, a preparation method, a pharmaceutical composition, and uses in preparing a medicament for treatment of Syk receptor related diseases.
- -
-
Paragraph 0216-0217; 0266-0267
(2020/05/07)
-
- SHP2 PHOSPHATASE INHIBITORS AND METHODS OF USE THEREOF
-
The present disclosure relates to novel compounds including formula (X) and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with SHP2 deregulation with the compounds and compositions of the disclosure.
- -
-
Paragraph 0210
(2019/10/15)
-
- CRBN LIGANDS AND USES THEREOF
-
The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of CRBN, and the treatment of CRBN-mediated disorders.
- -
-
Paragraph 00420-00421
(2019/04/16)
-
- IRAK DEGRADERS AND USES THEREOF
-
The present invention provides compounds, compositions thereof, and methods of using the same.
- -
-
Paragraph 4087; 4088
(2019/07/10)
-
- PROTEIN DEGRADERS AND USES THEREOF
-
The present invention provides compounds, compositions thereof, and methods of using the same for the targeted degradation of proteins, and the treatment of target protein-mediated disorders.
- -
-
Paragraph 00374-00376
(2019/04/16)
-
- BIS-BENZIMIDAZOLE COMPOUNDS AND METHODS OF USING SAME
-
Provided herein are compounds and methods for modulating abnormal repeat expansions of gene sequences. More particularly, provided are inhibitors of RNA and the uses of such inhibitors in regulating nucleotide repeat expansions, e.g., to treat Myotonic Dystrophy Type 1 (DM1 ), Myotonic Dystrophy Type 2 (DM2), Fuchs dystrophy, Huntington Disease, Amyotrophic Lateral Sclerosis, or Frontotemporal Dementia.
- -
-
Paragraph 00507-00510
(2019/06/05)
-
- Nitrogen-containing bicyclic compounds and preparation method and use thereof
-
The present invention relates to nitrogen-containing bicyclic compounds and a preparation method and use thereof. The compounds or pharmaceutical compositions can be used as an inhibitor of retinoic acid-related orphan receptor gamma t (ROR gamma t). The invention also relates to the preparation method of the compounds and pharmaceutical compositions, and use of the in the compounds and pharmaceutical compositions in treatment or prevention of RORyt-mediated inflammatation or autoimmune diseases in mammals, particularly humans.
- -
-
Paragraph 0463; 0465-0466
(2018/11/04)
-
- AMINOISOXAZOLINE COMPOUNDS AS AGONISTS OF ALPHA7-NICOTINIC ACETYLCHOLINE RECEPTORS
-
The present invention relates to novel aminoisoxazoline compounds, and pharmaceutical compositions of the same, that are suitable as agonists or partial agonists of α7-nAChR, and methods of preparing these compounds and compositions, and the use of these compounds and compositions in methods of maintaining, treating and/or improving cognitive function. In particular, methods of administering the compound or composition to a patient in need thereof, for example a patient with a cognitive deficiency and/or a desire to enhance cognitive function, that may derive a benefit therefrom.
- -
-
Paragraph 00416; 00417
(2017/05/19)
-
- PYRAZOLO[1,5-A]PYRIMIDINYL CARBOXAMIDE COMPOUNDS AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS
-
The invention provides substituted pyrazolo[1,5-a]pyrimidinyl carboxamide and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted pyrazolo[1,5-a]pyrimidinyl carboxamide compounds described herein include 2-heterocyclyl-4-alkyl-pyrazolo[1,5-a]pyrirnidine-3-carboxarnide compounds and variants thereof.
- -
-
Paragraph 00747
(2017/11/06)
-
- SUBSTITUTED QUINOXALINE DERIVATIVES
-
The present invention relates to substituted quinoxaline derivatives. These compounds are useful for the prevention and/or treatment of several medical conditions including hyperproliferative disorders and diseases.
- -
-
Page/Page column 326
(2016/12/01)
-
- Amine-free melanin-concentrating hormone receptor 1 antagonists: Novel 1-(1H-benzimidazol-6-yl)pyridin-2(1H)-one derivatives and design to avoid CYP3A4 time-dependent inhibition
-
Melanin-concentrating hormone (MCH) is an attractive target for antiobesity agents, and numerous drug discovery programs are dedicated to finding small-molecule MCH receptor 1 (MCHR1) antagonists. We recently reported novel pyridine-2(1H)-ones as aliphatic amine-free MCHR1 antagonists that structurally featured an imidazo[1,2-a]pyridine-based bicyclic motif. To investigate imidazopyridine variants with lower basicity and less potential to inhibit cytochrome P450 3A4 (CYP3A4), we designed pyridine-2(1H)-ones bearing various less basic bicyclic motifs. Among these, a lead compound 6a bearing a 1H-benzimidazole motif showed comparable binding affinity to MCHR1 to the corresponding imidazopyridine derivative 1. Optimization of 6a afforded a series of potent thiophene derivatives (6q-u); however, most of these were found to cause time-dependent inhibition (TDI) of CYP3A4. As bioactivation of thiophenes to form sulfoxide or epoxide species was considered to be a major cause of CYP3A4 TDI, we introduced electron withdrawing groups on the thiophene and found that a CF3 group on the ring or a Cl adjacent to the sulfur atom helped prevent CYP3A4 TDI. Consequently, 4-[(5-chlorothiophen-2-yl)methoxy]-1-(2-cyclopropyl-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one (6s) was identified as a potent MCHR1 antagonist without the risk of CYP3A4 TDI, which exhibited a promising safety profile including low CYP3A4 inhibition and exerted significant antiobesity effects in diet-induced obese F344 rats.
- Igawa, Hideyuki,Takahashi, Masashi,Shirasaki, Mikio,Kakegawa, Keiko,Kina, Asato,Ikoma, Minoru,Aida, Jumpei,Yasuma, Tsuneo,Okuda, Shoki,Kawata, Yayoi,Noguchi, Toshihiro,Yamamoto, Syunsuke,Fujioka, Yasushi,Kundu, Mrinalkanti,Khamrai, Uttam,Nakayama, Masaharu,Nagisa, Yasutaka,Kasai, Shizuo,Maekawa, Tsuyoshi
-
p. 2486 - 2503
(2016/05/09)
-
- HEPARAN SULFATE BIOSYNTHESIS INHIBITORS FOR THE TREATMENT OF DISEASES
-
Described herein are compounds of Formula I, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or conditions in need of inhibition of heparan sulfate biosynthesis.
- -
-
Paragraph 000799
(2016/05/02)
-
- PRMT5 INHIBITORS AND USES THEREOF
-
Described herein are compounds of Formula (A), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof:wherein Y1 is of formula (?) or formula (y):Ring Y is a 5- to 6-membered heteroaryl ring; and V4, V5, Rx, x, y, and n are as defined herein. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.
- -
-
Paragraph 00455; 00456
(2016/04/20)
-
- BENZIMIDAZOLE DERIVATIVES AND USES THEREOF
-
Benzimidazole derivatives of Formula I, that modulate the activity of ACSS2 are disclosed for therapeutic use. The fused imidazole ring of the compounds disclosed has a diarylmethyl or diarylmethanol moiety attached at the 2-position and the compounds have at least one other substituent at the 5 or 6 position of the benzimidazole. Also disclosed are methods of using the benzimidazole compounds for the treatment of diseases or disorders, such as cancer.
- -
-
Paragraph 0443
(2015/12/31)
-
- AROMATIC RING COMPOUND
-
The present invention provides an aromatic ring compound having a melanin-concentrating hormone receptor antagonistic action and useful as an agent for the prophylaxis or treatment of obesity and the like. The present invention relates to a compound represented by the formula wherein each symbol as defined in the specification, or a salt thereof.
- -
-
Paragraph 0294
(2015/03/28)
-
- PYRIDINE CDK9 KINASE INHIBITORS
-
Disclosed are compound of Formula (Ia), wherein R2, R12, R16, J, Q, X, Y and Z are as defined in the specification, and pharmaceutically acceptable salts thereof.The compounds may be used as agents in the treatment of diseases, including cancer. Also provided are pharmaceutical compositions comprising one or more compounds of Formula (Ia).
- -
-
Paragraph 1536; 1870
(2014/09/29)
-
- PRMT5 INHIBITORS AND USES THEREOF
-
Described herein are compounds of formula (A), pharmaceutically acceptable salts thereof, and pharmaceutical com-positions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.
- -
-
Paragraph 00318
(2014/07/08)
-
- BIARYL-CONTAINING COMPOUNDS AS INVERSE AGONISTS OF ROR-GAMMA RECEPTORS
-
The present invention relates to biaryl-containing inverse agonists of ROR-gamma receptors. The invention also provides pharmaceutical compositions comprising these biaryl- containing inverse agonists, and methods of modulating ROR-gamma receptors using these inverse agonists. Also provided are methods of using biaryl-containing inverse agonists to treat ROR-gamma mediated diseases.
- -
-
Paragraph 00327-00328
(2014/01/18)
-
- BENZIMIDAZOLE DERIVATIVES AS MCH RECEPTOR ANTAGONISTS
-
The present invention provides an aromatic ring compound having a melanin-concentrating hormone receptor antagonistic action and useful as an agent for the prophylaxis or treatment of obesity and the like. The present invention relates to a compound represented by the formula (I) wherein each symbol as defined in the specification, or a salt thereof.
- -
-
Page/Page column 106; 107
(2013/07/25)
-
- BENZIMIDAZOLE DERIVATIVES AS ANTIVIRAL AGENTS
-
Provided are compounds of Formulas I, II, III, IV, V, and pharmaceutically acceptable salts thereof, their pharmaceutical compositions, their methods of preparation, and their use for treating viral infections mediated by a member of the Flaviviridae family of viruses such as hepatitis C virus (HCV).
- -
-
Page/Page column 216
(2013/02/28)
-
- POSITIVE ALLOSTERIC MODULATORS OF MGLUR2
-
The present invention is directed to benzimidazolone derivatives which are positive allosteric modulators of the mGluR2 receptor, useful in the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 receptor is involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which metabotropic glutamate receptors are involved, such as schizophrenia.
- -
-
Page/Page column 29
(2012/03/09)
-
- INHIBITORS OF 11beta-HYDROXYSTEROID DEHYDROGENASE 1
-
This invention relates to novel compounds of the Formula (I), (Ia1-10), (Ib1-10), (Ic1-10), (Id1-7), (Ie1-5) pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful for the therapeutic treatment of diseases associated with the modulation or inhibition of 11β-HSD1 in mammals. The invention further relates to pharmaceutical compositions of the novel compounds and methods for their use in the reduction or control of the production of cortisol in a cell or the inhibition of the conversion of cortisone to cortisol in a cell.
- -
-
Page/Page column 26
(2012/05/07)
-
- BENZOXAZINONE DERIVATIVES FOR THE TREATMENT OF GLYTL MEDIATED DISORDERS
-
The present invention relates to benzoxazinone derivatives, processes for their preparation, pharmaceutical compositions and medicaments containing them and to their use in treating disorders mediated by GlyT1, including neurological and neuropsychiatric disorders, in particular psychoses, dementia or attention deficit disorder.
- -
-
Page/Page column 67; 68
(2011/02/24)
-
- POSITIVE ALLOSTERIC MODULATORS OF MGLUR2
-
The present invention is directed to 5-substituted 1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide and 1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2,-dioxide derivatives which are potentiators of metabotropic glutamate receptors, particularly the mGluR2 receptor, and which are useful in the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which metabotropic glutamate receptors are involved
- -
-
Page/Page column 30
(2011/10/03)
-
- BENZODIAZEPINONE COMPOUNDS AND METHODS OF TREATMENT USING SAME
-
The invention provides 1,4-benzodiazepinone compounds, pharmaceutical compositions, and methods of treating autoimmune disorders, chronic inflammatory disorders, and hyperproliferative disorders. For example, the 1,4-benzodiazepinone compounds and pharmaceutical compositions are contemplated to be useful for treating rheumatoid arthritis, graft-versus-host disease, inflammatory bowel disease, and the like.
- -
-
Page/Page column 75
(2011/04/19)
-
- SUBSTITUTED HETEROCYCLIC COMPOUNDS
-
The present invention relates to compounds that are late sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes. In particular embodiments, the structure of the compounds is given by Formula (I): wherein R1, R2, R3, and R4 are as described herein, to methods for the preparation and use of the compounds and to pharmaceutical compositions containing the same.
- -
-
Page/Page column 16
(2010/05/13)
-
- The development of benzimidazoles as selective rho kinase inhibitors
-
Rho Kinase (ROCK) is a serine/threonine kinase whose inhibition could prove beneficial in numerous therapeutic areas. We have developed a promising class of ATP-competitive inhibitors based upon a benzimidazole scaffold, which show excellent potency toward ROCK (IC50 10 nM). This report details the optimization of selectivity for ROCK over other related kinases such as Protein kinase A (PKA).
- Sessions, E. Hampton,Smolinski, Michael,Wang, Bo,Frackowiak, Bozena,Chowdhury, Sarwat,Yin, Yan,Chen, Yen Ting,Ruiz, Claudia,Lin, Li,Pocas, Jennifer,Schr?ter, Thomas,Cameron, Michael D.,LoGrasso, Philip,Feng, Yangbo,Bannister, Thomas D.
-
scheme or table
p. 1939 - 1943
(2010/09/03)
-
- BICYCLIC TRIAZOLES AS PROTEIN KINASE MODULATORS
-
The present disclosure provides bicyclic triazole protein kinase modulators and methods of using these compounds to treat diseases mediated by kinase activity.
- -
-
Page/Page column 82
(2008/12/05)
-
- NOVEL JNK INHIBITORS
-
Disclosed are compounds of the formula (I) wherein X is N or CH, and Y is N or CR5. Also disclosed are methods of treating JNK and ERK mediated diseases using the compounds of formula 1.0.
- -
-
Page/Page column 111
(2008/12/07)
-
- BENZIMIDAZOLYL COMPOUNDS AS POTENTIATORS OF MGLUR2 SUBTYPE OF GLUTAMATE RECEPTOR
-
Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula (I) as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.
- -
-
Page/Page column 60
(2010/11/30)
-
- BENZIMIDAZOLYL COMPOUNDS
-
Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of formula (I) or pharmaceutically acceptable salts thereof, wherein Y1, R17, R2, R4, R5, R6, R7, R8, X2 and n are as defined in the detailed description of the invention. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.
- -
-
Page/Page column 65-66
(2010/11/29)
-
- VIRAL POLYMERASE INHIBITORS
-
An enantiomer, diastereoisomer or tautomer of a compound, represented by formula (I): wherein either A or B is nitrogen and the other B or A is C, and the radicals R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are as defined herein, or a salt or ester thereof as viral polymerase inhibitors. The compound is used as an inhibitor of RNA dependent RNA polymerases, particularly those viral polymerases within the Flaviviridae family, more particularly to HCV polymerase.
- -
-
Page/Page column 94
(2008/06/13)
-
- 4- (HETEROCYCLYL- FUSED PHENYL)- 3- (PHENYL OR PYRID -2- YL) PYRAZOLES AS INHIBITORS OF THE ALK-5- RECEPTOR
-
The invention relates to novel pyrazole derivatives which are inhibitors of the transforming growth factor, ("TGF")-β signalling pathway, in particular, the phosphorylation of smad2 or smad3 by the TGF-β type I or activin-like kinase ("ALK")-5 receptor, m
- -
-
-
- COMPOUNDS
-
The invention relates to novel aminothiazole derivatives which are inhibitors of the transforming growth factor, ("TGF")-? signaling pathway, in particular, the phosphorylation of smad2 or smad3 by the TGF-? type I or activin-like kinase ("ALK")-5 recepto
- -
-
Page/Page column 17-18
(2010/02/10)
-
- Subtype-selective N-methyl-D-aspartate receptor antagonists: Synthesis and biological evaluation of 1-(heteroarylalkynyl)-4-benzylpiperidines
-
4-[4-(4-Benzylpiperidin-1-yl)but-1-ynyl]phenol (8) and 4-[3-(4-benzylpiperidin-1-yl)prop-1-ynyl]-phenol (9) are potent NR1A/2B receptor antagonists (IC50 values 0.17 and 0.10 μM, respectively). Administered intraperitoneally, they both potentia
- Wright,Gregory,Kesten,Boxer,Serpa,Meltzer,Wise,Espitia,Konkoy,Whittemore,Woodward
-
p. 3408 - 3419
(2007/10/03)
-