- BAX INHIBITORS AND USES THEREOF
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A compound having formula (I) or (II) for use inhibiting Bax mediated cell death and/or apoptosis.
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Paragraph 00469; 00470
(2021/01/23)
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- METHODS AND COMPOUNDS FOR RESTORING MUTANT p53 FUNCTION
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Mutations in oncogenes and tumor suppressors contribute to the development and progression of cancer. The present disclosure describes compounds and methods to recover wild-type function to p53 mutants. The compounds of the present disclosure can bind to mutant p53 and restore the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers that contain a p53 mutation.
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Paragraph 0657
(2021/11/20)
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- PIKFYVE KINASE INHIBITORS
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The present invention relates to compounds useful as inhibitors of phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) as well as their use for treating diseases and disorders associated with PIKfyve.
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Page/Page column 249
(2021/08/20)
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- Design and Synthesis of Pyrrolo[2,3-d]pyrimidine-Derived Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitors Using a Checkpoint Kinase 1 (CHK1)-Derived Crystallographic Surrogate
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Inhibitors of leucine-rich repeat kinase 2 (LRRK2) and mutants, such as G2019S, have potential utility in Parkinson’s disease treatment. Fragment hit-derived pyrrolo[2,3-d]pyrimidines underwent optimization using X-ray structures of LRRK2 kinase domain surrogates, based on checkpoint kinase 1 (CHK1) and a CHK1 10-point mutant. (2R)-2-Methylpyrrolidin-1-yl derivative 18 (LRRK2 G2019S cKi0.7 nM, LE 0.66) was identified, with increased potency consistent with an X-ray structure of 18 /CHK1 10-pt. mutant showing the 2-methyl substituent proximal to Ala147 (Ala2016 in LRRK2). Further structure-guided elaboration of 18 gave the 2-[(1,3-dimethyl-1H-pyrazol-4-yl)amino] derivative 32 . Optimization of 32 afforded diastereomeric oxolan-3-yl derivatives 44 and 45 , which demonstrated a favorablein vitroPK profile, although they displayed species disconnects in thein vivoPK profile, and a propensity for P-gp- and/or BCRP-mediated efflux in a mouse model. Compounds 44 and 45 demonstrated high potency and exquisite selectivity for LRRK2 and utility as chemical probes for the study of LRRK2 inhibition.
- Williamson, Douglas S.,Smith, Garrick P.,Mikkelsen, Gitte K.,Jensen, Thomas,Acheson-Dossang, Pamela,Badolo, Lassina,Bedford, Simon T.,Chell, Victoria,Chen, I-Jen,Dokurno, Pawel,Hentzer, Morten,Newland, Samantha,Ray, Stuart C.,Shaw, Terry,Surgenor, Allan E.,Terry, Lindsey,Wang, Yikang,Christensen, Kenneth V.
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supporting information
p. 10312 - 10332
(2021/07/26)
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- PYRROLO [2, 3-B] PYRIDINES OR PYRROLO [2, 3-B] PYRAZINES AS HPK1 INHIBITOR AND THE USE THEREOF
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Disclosed herein is a compound of Formula (AIII) or (III), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and pharmaceutical compositions comprising thereof. Also disclosed is a method of treating HPK1 related disorders or diseases by using the compound disclosed herein.
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Paragraph 0401; 1600-1602
(2020/01/08)
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- Aromatic polycyclic carboxylic acid derivatives
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The invention specifically relates to aromatic polycyclic carboxylic acid derivative GPR40 receptor agonists as shown in a general formula (I) which is described in the specification, and pharmaceutically acceptable salts, esters or stereoisomers thereof,
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Paragraph 0181; 0182; 0183
(2017/08/19)
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- QUINAZOLINE HETEROCYCLIC COMPOUND AS EGFR KINASE INHIBITOR AND PREPARATION AND APPLICATION THEREOF
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The present invention relates to an N-substituted-phenyl-5-substituted-alkoxy-2,3-dihydro-[1,4]dioxane[2,3-f]quinazolin-10-amine (I) or 4-substituted-arylamino-6-substituted-alkyl-6H-[1,4]oxazino[3,2-g]quinazoline-7(8H)-one (II) type compounds, a preparation method thereof and an application thereof as an inhibitor for epidermal growth factor receptor (EGFR) (comprising some mutant forms of EGFR) to treat cancer. These compounds and salts thereof can be used to treat or prevent various cancer diseases.
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Paragraph 0197; 0198
(2018/01/19)
-
- Discovery of CNS Penetrant CXCR2 Antagonists for the Potential Treatment of CNS Demyelinating Disorders
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Structure-activity relationship exploration of the historical biarylurea series led to the identification of novel CNS penetrant CXCR2 antagonists with nanomolar potency, favorable PK profile, and good developability potentials. More importantly, the key
- Xu, Heng,Lu, Hongfu,Xu, Zhongmiao,Luan, Linbo,Li, Chengyong,Xu, Yan,Dong, Kelly,Zhang, Jinqiang,Li, Xiong,Li, Yvonne,Liu, Gentao,Gong, Sophie,Zhao, Yong-Gang,Liu, Ailian,Zhang, Yueting,Zhang, Wei,Cai, Xin,Xiang, Jia-Ning,Elliott, John D.,Lin, Xichen
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supporting information
p. 397 - 402
(2016/05/19)
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- TETRAHYDROPYRIDOPYRIMIDINES AND TETRAHYDROPYRIDOPYRIDINES AS INHIBITORS OF HBSAG (HBV SURFACE ANTIGEN) AND HBV DNA PRODUCTION FOR THE TREATMENT OF HEPATITIS B VIRUS INFECTIONS
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The present invention provides tetrahydropyridopyrimidines and tetrahydropyridopyridines having the general formula (I) wherein R1, R2, U, W, X, Y and Z are as described herein, as inhibitors of HBsAg (HBV surface antigen) and HBV DNA production for the treatment and prophylaxis of hepatitis B virus infections.
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Page/Page column 172
(2016/11/21)
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- SUBSTITUTED PYRIMIDINE COMPOUNDS, COMPOSITIONS AND MEDICINAL APPLICATIONS THEREOF
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The present disclosure relates to pyrimidine compounds of formula (I), their stereoisomers, tautomers, pharmaceutically acceptable salts, polymorphs, solvates, and hydrates thereof. The present disclosure also relates to process of preparation of these pyrimidine compounds, and to pharmaceutical compositions containing them. The compounds of the present disclosure are useful in the treatment, prevention or suppression of diseases and disorders mediated by epidermal growth factor receptor (EGFR) family kinases.
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Paragraph 000116
(2015/03/13)
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- HIGHLY SELECTIVE C-MET INHIBITORS AS ANTICANCER AGENTS
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Disclosed are novel nitrogen-containing, heterocyclic, c-Met inhibitor compounds, processes for their preparation and formulations thereof. The compounds are useful as therapeutical agents for the inhibition, regulation, and control of c-Met kinase signal pathway, and useful for treating in a subject a cell proliferative disorder or disorders mediated by c-Met.
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Page/Page column 12
(2014/03/25)
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- DERIVATIVES OF 1-PHENYL-2-PYRIDINYL ALKYL ALCOHOLS AS PHOSPHODIESTERASE INHIBITORS
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Compounds, pyridine N-oxides, and pharmaceutically acceptable salts of formula (I) are useful as inhibitors of the phosphodiesterase 4 (PDE4) enzyme and for preventing and/ or treating diseases of the respiratory tract characterized by airway obstruction, such as asthma or COPD.
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Paragraph 0627
(2013/05/08)
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- DERIVATIVES OF 1-PHENYL-2-PYRIDINYL ALKYL ALCOHOLS AS PHOSPHODIESTERASE INHIBITORS
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The invention relates to inhibitors of the phosphodiesterase 4 (PDE4) enzyme. More particularly, the invention relates to compounds that are derivatives of 1-phenyl-2-pyridinyl alkyl alcohols, methods of preparing such compounds, compositions containing them and therapeutic use thereof.
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Page/Page column 202; 203
(2013/05/09)
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- PYRAZOLOTHIAZOLE COMPOUND
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A compound represented by the formula (I) or pharmacologically acceptable salt thereof exhibits an excellent CRF receptor antagonism wherein X is a nitrogen atom or CH; R1 is -A11-A12; A11 is a single bond or a C1-6 alkylene group; A12 is a hydrogen atom, a C1-6 alkyl group or a C3-6 cycloalkyl group, etc.; R2 is -A21-A22; A21 is a single bond or a C1-6 alkylene group; A22 is a hydrogen atom, a C1-6 alkyl group, a C3-6 cycloalkyl group, a non-aromatic heterocyclic group, or a heteroaryl group, etc.; R3 is a C 1-6 alkyl group, a C3-6 cycloalkyl group, a C1-6 alkoxy group, a C3-6 cycloalkoxy C1-6 alkyl group, di-C1-6 alkyl amino group, a halogen atom, a cyano group, a formyl group, or a carboxyl group, etc; R4 is a hydrogen atom or a C1-6 alkoxy group; R5 is a halogen atom, a C1-6 alkyl group, or a C1-6 alkoxy group; R6 is a hydrogen atom, a C1-6 alkyl group, a C1-6 alkoxy group, a C1-6 alkylthio group, or a C1-6 alkyl sulfinyl group etc.; and R7 is a C1-6 alkyl group, a C1-6 alkoxy group, or a C1-6 alkylthio group
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Page/Page column 22
(2011/04/25)
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- DIOXA-BICYCLO[3.2.1.]OCTANE-2,3,4-TRIOL DERIVATIVES
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Compounds of Formula (I) are described herein and the uses thereof for the treatment of diseases, conditions and/or disorders mediated by sodium-glucose transporter inhibitors (in particular, SGLT2 inhibitors).The compounds disclosed herein are useful for the prevention and treatment of obesity and its associated co-morbidities, inn particular type Il (type 2) diabetes.
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Page/Page column 33-34
(2010/04/06)
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- METHOD FOR PRODUCING 3-AMINOMETHYLTETRAHYDROFURAN DERIVATIVE
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Disclosed is a method for highly efficiently producing a 3-aminomethyltetrahydrofuran derivative from a low-cost industrial raw material. Specifically, a 3-cyanotetrahydrofuran derivative is produced at high yield from a low-cost, industrially easily-available malic acid derivative, and then a 3-aminomethyltetrahydrofuran derivative is produced by reducing the cyano group of the 3-cyanotetrahydrofuran derivative.
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Page/Page column 34-35
(2008/06/13)
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- Pyrrolopyrimidines as therapeutic agents
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Chemical compounds having structural formula I and physiologically acceptable salts and metabolites thereof, are inhibitors of serine/threonine and tyrosine kinase activity. Several of the kinases, whose activity is inhibited by these chemical compounds, are involved in immunologic, hyperproliferative, or angiogenic processes. Thus, these chemical compounds can ameliorate disease states where angiogenesis or endothelial cell hyperproliferation is a factor. These compounds can be used to treat cancer and hyper proliferative disorders, rheumatiod arthritis, disorders of the immune system, trasplant refections and imflammatory disorders.
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- Halocyclization of Unsaturated Alcohols and Carboxylic Acids Using Bis(sym-collidine)iodine(I) Perchlorate
-
Reaction of I(collidine)2(1+) ClO4(1-) with unsaturated alcohols and carboxylic acids in dichloromethane at ambient temperature has afforded three- to seven-membered-ring iodoethers and four- to seven-membered-ring iodolactones, respectively, in moderate
- Evans, Robert D.,Magee, Joseph W.,Schauble, J. Herman
-
p. 862 - 868
(2007/10/02)
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- Herbicidal 1-aryl-delta2-1,2,4-triazolin-5-ones
-
Aryltriazolinones of the formula STR1 in which W is oxygen or sulfur; X1 and X2 are independently selected from halogen, haloalkyl, and alkyl; R is a three- to eight-membered ring heterocyclic group of one or two, same or different, ring heteroatoms selected from oxygen, sulfur, and nitrogen, or an alkyl radical substituted with said heterocyclic group; R1 is alkyl, haloalkyl, cyanoalkyl, alkenyl, alkynyl, or a group of the formula -alkyl-Y--R3 ; R2 is halogen, alkyl, cyanoalkyl, haloalkyl, arylalkyl, or a group of the formula -alkyl-Y--R3 ; R3 is alkyl, alkenyl, or alkynyl; and Y is oxygen or S(O)r in which r is 0 to 2 are disclosed and exemplified.
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