- BIFUNCTIONAL COMPOUNDS FOR DEGRADING BTK VIA UBIQUITIN PROTEOSOME PATHWAY
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The present invention relates to compounds of formula (I) useful for degrading BTK via a ubiquitin proteolytic pathway. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.
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Paragraph 0426-0427
(2021/05/15)
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- NOVEL TRIAZINE DERIVATIVE
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The purpose of the present invention is to provide a novel triazine derivative of the formula (I): wherein R1 represents a substituted or unsubstituted lower alkyl group,R2 represents a hydrogen atom or a substituted or unsubstituted lower alkyl group,A represents a nitrogen atom or C—R3,R3 represents a hydrogen atom, a cyano group, a substituted or unsubstituted acyl group, a substituted or unsubstituted sulfonyl group, or a substituted or unsubstituted carbamoyl group, andR4 represents a substituted or unsubstituted lower alkyl group,or a substituted or unsubstituted cycloalkyl group,or a pharmaceutically acceptable salt thereof.
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Paragraph 0079; 0080; 0081
(2016/07/05)
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- NOVEL TRIAZINE DERIVATIVE
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The purpose of the present invention is to provide a novel triazine derivative of the formula (I): wherein R 1 represents a substituted or unsubstituted lower alkyl group, R 2 represents a hydrogen atom or a substituted or unsubstituted lower alkyl group, A represents a nitrogen atom or C-R 3 , R 3 represents a hydrogen atom, a cyano group, a substituted or unsubstituted acyl group, a substituted or unsubstituted sulfonyl group, or a substituted or unsubstituted carbamoyl group, and R 4 represents a substituted or unsubstituted lower alkyl group, or a substituted or unsubstituted cycloalkyl group, or a pharmaceutically acceptable salt thereof.
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Paragraph 0127; 0128
(2016/10/08)
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- NOVEL 2,6-DIAMINOPYRIMIDINE DERIVATIVE
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To provide a novel 2,6-diaminopyrimidine derivative by the following formula (I): A 2,6-diaminopyrimidine derivative is represented by the formula (I): wherein R1 represents a substituted or unsubstituted lower alkyl group, or a substituted or unsubstituted alkoxy group, Ar represents a substituted or unsubstituted aryl group, or a substituted or unsubstituted heteroaryl group, Z1 and Z2 represent carbon atoms, or either 1 or 2 of the Z1 and Z2 represent nitrogen atoms, Q is selected from a structure (a) or (b) described below: R2 represents a substituted or unsubstituted lower alkyl group, or a substituted or unsubstituted cycloalkyl group, R3 represents a hydrogen atom or a halogen atom, Y represents a nitrogen atom or a carbon atom, and the bond drawn with a dotted line parallel to a solid line on structure (a) represents either double bond or single bond.
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Page/Page column 8; 9
(2016/08/17)
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- Structure-based drug design of RN486, a potent and selective Bruton's tyrosine kinase (BTK) inhibitor, for the treatment of rheumatoid arthritis
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Structure-based drug design was used to guide the optimization of a series of selective BTK inhibitors as potential treatments for Rheumatoid arthritis. Highlights include the introduction of a benzyl alcohol group and a fluorine substitution, each of which resulted in over 10-fold increase in activity. Concurrent optimization of drug-like properties led to compound 1 (RN486) (J. Pharmacol. Exp. Ther. 2012, 341, 90), which was selected for advanced preclinical characterization based on its favorable properties.
- Lou, Yan,Han, Xiaochun,Kuglstatter, Andreas,Kondru, Rama K.,Sweeney, Zachary K.,Soth, Michael,McIntosh, Joel,Litman, Renee,Suh, Judy,Kocer, Buelent,Davis, Dana,Park, Jaehyeon,Frauchiger, Sandra,Dewdney, Nolan,Zecic, Hasim,Taygerly, Joshua P.,Sarma, Keshab,Hong, Junbae,Hill, Ronald J.,Gabriel, Tobias,Goldstein, David M.,Owens, Timothy D.
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p. 512 - 516
(2015/03/03)
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- Inhibitors of Bruton's Tyrosine Kinase
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This application discloses 5-phenyl-1H-pyridin-2-one, 6-phenyl-2H-pyridazin-3-one, and 5-Phenyl-1H-pyrazin-2-one derivatives according to generic Formulae I-III: wherein, variables Q, R, X, X′, Y1, Y2, Y2′, Y3, Y4, Y5, m, and n are defined as described herein, which inhibit Btk. The compounds disclosed herein are useful to modulate the activity of Btk and treat diseases associated with excessive Btk activity. The compounds are further useful to treat inflammatory and auto immune diseases associated with aberrant B-cell proliferation such as rheumatoid arthritis. Also disclosed are compositions containing compounds of Formulae I-III and at least one carrier, diluent or excipient.
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Page/Page column 58
(2010/09/07)
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