663194-38-5Relevant academic research and scientific papers
Discovery and mechanism of action studies of 4,6-diphenylpyrimidine-2-carbohydrazides as utrophin modulators for the treatment of Duchenne muscular dystrophy
Vuorinen, Aini,Wilkinson, Isabel V.L.,Chatzopoulou, Maria,Edwards, Ben,Squire, Sarah E.,Fairclough, Rebecca J.,Bazan, Noelia Araujo,Milner, Josh A.,Conole, Daniel,Donald, James R.,Shah, Nandini,Willis, Nicky J.,Martínez, R. Fernando,Wilson, Francis X.,Wynne, Graham M.,Davies, Stephen G.,Davies, Kay E.,Russell, Angela J.
supporting information, (2021/05/03)
Duchenne muscular dystrophy is a fatal disease with no cure, caused by lack of the cytoskeletal protein dystrophin. Upregulation of utrophin, a dystrophin paralogue, offers a potential therapy independent of mutation type. The failure of first-in-class utrophin modulator ezutromid/SMT C1100 in Phase II clinical trials necessitates development of compounds with better efficacy, physicochemical and ADME properties and/or complementary mechanisms. We have discovered and performed a preliminary optimisation of a novel class of utrophin modulators using an improved phenotypic screen, where reporter expression is derived from the full genomic context of the utrophin promoter. We further demonstrate through target deconvolution studies, including expression analysis and chemical proteomics, that this compound series operates via a novel mechanism of action, distinct from that of ezutromid.
AMIDE COMPOUND
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, (2008/06/13)
The present invention relate to a compound represented by the formula (I) or (II) wherein ring A is an optionally substituted ring (the ring should not be pyrrolidine, piperidine and piperazine), ring B is an optionally substituted aromatic ring, ring D is an optionally substituted ring, R1 and R2 are each independently a hydrogen atom or a substituent, R3 is a hydrogen atom or a C1-6 alkyl group, or R3 is bonded to ring A to form a non-aromatic ring, ring Aa is an optionally substituted aromatic hydrocarbon, Y is CH or N, Ra1 is an optionally substituted hydrocarbon group, and Ra2 and Ra3 are each independently a hydrogen atom or a substituent, or a salt thereof. The present invention provides a compound having a DGAT inhibitory activity, which is useful for the treatment or amelioration of diseases or pathologies caused by high expression or high activation of DGAT.
AMIDE COMPOUND
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Page/Page column 97-98, (2008/06/13)
Disclosed is a compound represented by the formula (I) or (II) below, or a salt thereof. [In the formulae, ring A represents an optionally substituted ring (which is not a pyrrolidine, piperidine or piperazine); ring B represents an optionally substituted aromatic ring; ring D represents an optionally substituted ring; R1 and R2 independently represent a hydrogen atom or a substituent; R3 represents a hydrogen atom or a C1-6 alkyl group, or alternatively it combines with the ring A to form a non-aromatic ring; ring Aa represents an optionally substituted aromatic hydrocarbon; Y represents CH or N; Ra1 represents an optionally substituted hydrocarbon group; and Ra2 and Ra3 independently represent a hydrogen atom or a substituent.] The compound has a DGAT inhibitory effect and is useful for treatment or improvement of diseases or conditions caused by high expression or high activation of DGAT.
