- NOVEL PYRAZOLO PYRIMIDINE DERIVATIVES AND THEIR USE AS MALT1 INHIBITORS
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The present invention describes new pyrazolo-pyrimidine derivatives of formula (I) or a pharmaceutically acceptable salt thereof; (I) wherein, R1 is halogen, cyano, or C1-C3alkyl optionally substituted by halogen; R2 is C1-C6alkyl optionally substituted one or more times by C1-C6alkyl, C2-C6alkenyl, hydroxyl, N,N-di-C1-C6alkyl amino, N-mono-C1-C6alkyl amino, O-Rg, Rg, phenyl, or by C1-C6alkoxy wherein said alkoxy again may optionally be substituted by C1-C6alkoxy, N,N-di-C1-C6alkyl amino, Rg or phenyl; C3-C6cycloalkyl optionally substituted by C1-C6alkyl, N,N-di-C1-C6alkyl amino or C1-C6alkoxy-C1-C6alkyl, and/or two of said optional substituents together with the atoms to which they are bound may form an annulated or spirocyclic 4 - 6 membered saturated heterocyclic ring comprising 1 - 2 O atoms; phenyl optionally substituted by C1-C6alkoxy; a 5 - 6 membered heteroaryl ring having 1 to 3 heteroatoms selected from N and O said ring being optionally substituted by C1-C6alkyl which may be optionally substituted by amino or hydroxy; Rg; or N,N-di-C1-C6alkyl amino carbonyl; and R is phenyl independently substituted two or more times by Ra, 2-pyridyl independently substituted one or more times by Rb, 3-pyridyl independently substituted one or more times by Rc, or 4-pyridyl independently substituted one or more times by Rd; which are generally interacting with MALT1 proteolytic and/or autoproteolytic activity, and in particular which may inhibit said activity. The present invention further describes the synthesis of said new pyrazolo-pyrimidine derivatives, their use as a medicament, especially by interacting with MALT1 proteolytic and/or autoproteolytic activity.
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Page/Page column 38; 39
(2015/12/31)
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- THIAZOLOPYRIMIDINONES AS MODULATORS OF NMDA RECEPTOR ACTIVITY
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The present invention relates to certain thiazolopyrimidinone compounds for use in modulating NMDA receptor activity, pharmaceutical compositions comprising such compounds and methods of treating neurological and psychiatric conditions.
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Paragraph 0500
(2015/04/28)
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- Discovery of ((S)-5-(methoxymethyl)-7-(1-methyl-1 H -indol-2-yl)-2- (trifluoromethyl)-4,7-dihydropyrazolo[1,5- a ]pyrimidin-6-yl)((S)-2-(3- methylisoxazol-5-yl)pyrrolidin-1-yl)methanone as a potent and selective I Kur inhibitor
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Previously disclosed dihydropyrazolopyrimidines are potent and selective blockers of IKur current. A potential liability with this chemotype is the formation of a reactive metabolite which demonstrated covalent binding to protein in vitro. When substituted at the 2 or 3 position, this template yielded potent IKur inhibitors, with selectivity over hERG which did not form reactive metabolites. Subsequent optimization for potency and PK properties lead to the discovery of ((S)-5-(methoxymethyl)-7-(1-methyl-1H-indol- 2-yl)-2-(trifluoromethyl)-4,7-dihydropyrazolo[1,5-a]pyrimidin-6-yl)((S) -2-(3-methylisoxazol-5-yl)pyrrolidin-1-yl)methanone (13j), with an acceptable PK profile in preclinical species and potent efficacy in the preclinical rabbit atrial effective refractory period (AERP) model.
- Finlay, Heather J.,Lloyd, John,Vaccaro, Wayne,Kover, Alexander,Yan, Lin,Bhave, Gauri,Prol, Joseph,Huynh, Tram,Bhandaru, Rao,Caringal, Yolanda,Dimarco, John,Gan, Jinping,Harper, Tim,Huang, Christine,Conder, Mary Lee,Sun, Huabin,Levesque, Paul,Blanar, Michael,Atwal, Karnail,Wexler, Ruth
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experimental part
p. 3036 - 3048
(2012/06/01)
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- METHYL SULFANYL PYRMIDMES USEFUL AS ANTIINFLAMMATORIES, ANALGESICS, AND ANTIEPILEPTICS
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The present invention relates to pyrimidine derivatives of Formula (Ia) and (Ib) (including tautomers, isomers, prodrugs, and pharmaceutically acceptable salts thereof). Said compounds are useful in the treatment of pain (such as neuropathic pain), inflammation, and epilepsy (by acting as anticonvulsants). Methods of medical treatment making use of said compounds, as well as additional compounds of Formula (IIa) and (IIb), are also disclosed.
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Page/Page column 184
(2010/12/18)
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- PYRAZOLES USEFUL IN THE TREATMENT OF INFLAMMATION
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There is provided compounds of formula (I), wherein R1, R2, X1, X2 and n have meanings given in the description, and pharmaceutically-acceptable salts thereof, which compounds are useful in the treatment of diseases in which inhibition of the activity of a lipoxygenase (e.g. 15-lipoxygenase) is desired and/or required, and particularly in the treatment of inflammation.
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Page/Page column 44
(2008/06/13)
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