- Design of selective PI3Kα inhibitors starting from a promiscuous pan kinase scaffold
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Starting from compound 1, a potent PI3Kα inhibitor having poor general kinase selectivity, we used structural data and modelling to identify key exploitable differences between PI3Kα and the other kinases. This approach led us to design chemical modifications of the central pyrazole, which solved the poor kinase selectivity seen as a strong liability for the initial compound 1. Amongst the modifications explored, a 1,3,4-triazole ring (as in compound 4) as a replacement of the initial pyrazole provided good potency against PI3Kα, with excellent kinase selectivity.
- Barlaam, Bernard,Cosulich, Sabina,Fitzek, Martina,Green, Stephen,Harris, Craig S.,Hudson, Kevin,Lambert-Van Der Brempt, Christine,Ouvry, Gilles,Page, Ken,Ruston, Linette,Ward, Lara,Delouvrié, Bénédicte
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Read Online
- TRPML MODULATORS
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The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.
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Paragraph 0367
(2021/06/26)
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- SSAO INHIBITOR
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The present invention provides an SSAO inhibitor and an application thereof in preparing a drug for treating a disease related to SSAO. In particular, the present invention provides a compound shown in formula (IV) and a pharmaceutically acceptable salt thereof.
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Paragraph 0420; 0421; 0422; 0566-0568
(2020/04/02)
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- HETEROCYCLYLAMINO-SUBSTITUTED TRIAZOLES AS MODULATORS OF RHO-ASSOCIATED PROTEIN KINASE
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This invention relates to novel compounds and pharmaceutical compositions comprising. Compounds of the invention useful as modulators of Rho-associated protein kinase (ROCK), for example ROCK1 and/or ROCK2 inhibitors. Methods of treatment employing the compounds are also contemplated by the present invention. The compounds of the invention are useful in treating ROCK mediated diseases.
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Page/Page column 84
(2019/08/12)
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- Synthesis of 1-Alkyl-5-amino-1,2,4-triazoles Based on Nucleophilic Substitution and Reduction Reactions
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A series of 1-alkyl-5-amino-1H-1,2,4-triazoles were synthesized starting from 3,5-dibromo-1H- 1,2,4-triazole by alkylation and subsequent nucleophilic substitution of the 5-bromine atom by azido group, reduction of the latter to amino group, and hydrodebromination.
- Tolstyakov
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p. 1537 - 1547
(2019/01/04)
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- PHENOXYTRIAZOLES
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The present invention relates to a compound of formula I, HetAr is a five or six membered heteroaryl group, selected from wherein R1 is hydrogen, halogen, lower alkyl, lower alkoxy or lower alkyl substituted by halogen, and may be the same or d
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Page/Page column 55
(2018/05/27)
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- TRIAZOLE COMPOUNDS AND THEIR USE AS GAMMA SECRETASE MODULATORS
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The present invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof. The invention also relates to pharmaceutical compositions comprising these compounds, to processes for making these compounds, and to their use as medicaments for treatment and/or prevention of Aβ-related diseases.
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Page/Page column 16; 17
(2015/01/06)
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- TRIAZOLE COMPOUNDS AND THEIR USE AS GAMMA SECRETASE MODULATORS
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The present invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof. The invention also relates to pharmaceutical compositions comprising these compounds, to processes for making these compounds, and to their use as medicaments for treatment and/or prevention of Αβ-related diseases.
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Page/Page column 16
(2015/01/06)
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- Anilinotriazoles as potent gamma secretase modulators
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The design and synthesis of a novel series of potent gamma secretase modulators is described. Exploration of various spacer groups between the triazole ring and the aromatic appendix in 2 has led to anilinotriazole 28, which combined high in vitro and in
- Velter, Adriana I.,Bischoff, Franois P.,Berthelot, Didier,De Cleyn, Michel,Oehlrich, Daniel,Jaroskova, Libuse,Macdonald, Gregor,Minne, Garrett,Pieters, Serge,Rombouts, Frederik,Van Brandt, Sven,Van Roosbroeck, Yves,Surkyn, Michel,Trabanco, Andrs A.,Tresadern, Gary,Wu, Tongfei,Borghys, Herman,Mercken, Marc,Masungi, Chantal,Gijsen, Harrie
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p. 5805 - 5813
(2015/01/08)
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- NOVEL SUBSTITUTED TRIAZOLE DERIVATIVES AS GAMMA SECRETASE MODULATORS
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The present invention is concerned with novel substituted triazole derivatives of Formula (I) wherein Het1, R1, R2, A1, A2, A3, A4, L1, and L2 have the mean
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Page/Page column 27
(2012/12/13)
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- NOVEL SUBSTITUTED TRIAZOLE DERIVATIVES AS GAMMA SECRETASE MODULATORS
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The present invention is concerned with novel substituted triazole derivatives of Formula (I) wherein Het1, R1, R2, A1, A2, A3, A4, L1, and L2 have the meaning defined in the claims. The compounds according to the present invention are useful as gamma sec
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Page/Page column 58
(2011/08/04)
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