133010-41-0Relevant academic research and scientific papers
Mediators of hedgehog signaling pathways, compositions and uses related thereto
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Page/Page column 67; 68; 69, (2015/11/27)
The present invention makes available methods and reagents for inhibiting aberrant growth states resulting from hedgehog gain-of-function by contacting the cell with a hedgehog antagonist, such as a small molecule, in a sufficient amount to aberrant growth state, e.g., to agonize a normal ptc pathway or antagonize hedgehog activity.
Potent inhibitors of the Hedgehog signaling pathway
Brunton, Shirley A.,Stibbard, John H. A.,Rubin, Lee L.,Kruse, Lawrence I.,Guicherit, Oivin M.,Boyd, Edward A.,Price, Steven
, p. 1108 - 1110 (2008/09/19)
A small family of phenyl quinazolinone ureas is reported as potent modulators of Hedgehog protein function. Preliminary SAR studies of the urea substituent led to a nanomolar Hedgehog antagonist.
Mediators of hedgehog signaling pathways, compositions and uses related thereto
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, (2008/06/13)
The present invention makes available methods and reagents for inhibiting aberrant growth states resulting from hedgehog gain-of-function by contacting the cell with a hedgehog antagonist, such as a small molecule, in a sufficient amount to aberrant growt
Novel nonpeptide CCK-B antagonists: Design and development of quinazolinone derivatives as potent, selective, and orally active CCK-B antagonists
Padia, Janak K.,Field, Mark,Hinton, Joanna,Meecham, Ken,Pablo, Julius,Pinnock, Rob,Roth, Bruce D.,Singh, Lakhbir,Suman-Chauhan, Nirmala,Trivedi, Bharat K.,Webdale, Louise
, p. 1042 - 1049 (2007/10/03)
We have designed a novel series of CCK-B receptor antagonists by combining key pharmacophores, an arylurea moiety of 1 and a quinazolinone ring of 3, from two known series. Our earlier studies showed that compounds with methylene linkers in our 'target' produced moderate binding affinity and selectivity for CCK-B receptors, whereas its higher and lower homologues resulted in loss of affinity. Introduction of -NH- as a linker dramatically enhanced binding affinity and selectivity for CCK-B receptors, thus providing several compounds with single-digit nanomolar binding affinity and excellent selectivity. Analogous to the earlier studies of the series of quinazolinone derivatives 3, we also found 3-isopropoxyphenyl as a preferred substitution on the N-3 quinazolinone. Electron-withdrawing substitutions on the urea terminal phenyl ring enhanced the CCK-B potency. Representative compounds of this series were tested in the functional assay and showed pure antagonist profiles. Compounds 51 and 61 were orally active in the elevated rat X-maze test. These compounds were also evaluated for their pharmacokinetic profile. The absolute oral bioavailability of compound 61 was 22% in rats.
Design and synthesis of novel nonpeptide CCK-B receptor antagonists
Padia,Chilvers,Daum,Pinnock,Suman-Chauhan,Webdale,Trivedi
, p. 805 - 810 (2007/10/03)
A novel hybrid series of nonpeptide CCK-B receptor antagonists has been designed from two known series derived from asperlicin. An efficient synthesis of 2-aminoquinazolinone, an intermediate for the synthesis of a targeted analog, has been developed.
