553672-03-0Relevant articles and documents
Isothiazole and isoxazole fused pyrimidones as PDE7 inhibitors: SAR and pharmacokinetic evaluation
Banerjee, Abhisek,Yadav, Pravin S.,Bajpai, Malini,Sangana, Ramachandra Rao,Gullapalli, Srinivas,Gudi, Girish S.,Gharat, Laxmikant A.
supporting information; experimental part, p. 3223 - 3228 (2012/06/18)
The synthesis and structure-activity relationship studies of isothiazole and isoxazole fused pyrimidones as PDE7 inhibitors are discussed. The pharmacokinetic profile of 10 and 21 with adequate CNS penetration, required for in vivo Parkinson's disease mod
A small molecule inhibitor selective for a variant ATP-binding site of the chaperonin GroEL
Chapman, Eli,Farr, George W.,Furtak, Krystyna,Horwich, Arthur L.
scheme or table, p. 811 - 813 (2009/09/25)
The chaperonin GroEL is a megadalton-sized molecular machine that plays an essential role in the bacterial cell assisting protein folding to the native state through actions requiring ATP binding and hydrolysis. A combination of medicinal chemistry and genetics has been employed to generate an orthogonal pair, a small molecule that selectively inhibits ATPase activity of a GroEL ATP-binding pocket variant. An initial screen of kinase-directed inhibitors identified an active pyrazolo-pyrimidine scaffold that was iteratively modified and screened against a collective of GroEL nucleotide pocket variants to identify a cyclopentyl carboxamide derivative, EC3016, that specifically inhibits ATPase activity and protein folding by the GroEL mutant, I493C, involving a side chain positioned near the base of ATP. This orthogonal pair will enable in vitro studies of the action of ATP in triggering activation of GroEL-mediated protein folding and might enable further studies of GroEL action in vivo. The approach originated for studying kinases by Shokat and his colleagues may thus also be used to study large macromolecular machines.
PYRAZOLOPYRIMIDINONE DERIVATIVES HAVING PDE7?INHIBITORY ACTIVITY
-
Page 23, (2010/02/08)
Pyrazolopyrimidinone derivatives expressed by the following general formula (IA) or (IB): and the following general formula (IA') or (IB'): where the symbols are as disclosed in the specification, are provided as desired compounds. These compounds have the action of selectively inhibiting PDE7, thereby increasing the intracellular cAMP level and inhibiting the activation of T cells. Thus, they are useful for prevention and treatment of various allergic diseases and inflammatory or immunological diseases.
PYRIDINYLPYRAZOLOPYRIMIDINONE DERIVATIVES AS PDE 7 INHIBITORS
-
Page 28, (2008/06/13)
To provide the compounds inhibiting PDE 7 selectively, and therefore, enhance cellular cAMP level. Consequently, the compound is useful for treating various kinds of disease such as allergic disease, inflammatory disease or immunologic disease. The compound is pyridinylpyrazolopyrimidinone compound represented by the following formula (IA) or (IB): especially, R1 is cyclohexyl or cycloheptyl group, R2 is methyl; R3 is a group: -NR5R6 or -S(O)0-2R8; hydrogen atom; nitro group; cyano group; a halogen atom; heteroaryl group; and R4 is methoxy or ethoxy group.
