Discovery of new benzhydrol biscarbonate esters as potent and selective apoptosis inducers of human melanomas bearing the activated ERK pathway: SAR studies on an ERK MAPK signaling modulator, ACA-28
摘要:
The recent discovery that an ERK signaling modulator [ACA-28 (2a)] preferentially kills human melanoma cell lines by inducing ERK-dependent apoptosis has generated significant interest in the field of anti-cancer therapy. In the first SAR study on 2a, here, we successfully developed candidates (2b, 2c) both of which induce more potent and selective apoptosis towards ERK-active melanoma cells than 2a, thus revealing the structural basis for inducing the ERK-dependent apoptosis and proposing the therapeutic prospect of these candidates against ERK-dependent cancers represented by melanoma.
(Phenylethenyl) phenylpropionic acid and its ester, and method for producing (benzoylphenyl) propionic acid or its ester
申请人:NIPPON PETROCHEMICALS COMPANY, LIMITED
公开号:EP0282065A2
公开(公告)日:1988-09-14
New compounds, i.e.α-(3-(1-phenylethenyl)phenyl)propionic acid and its esters and a method for producing α-(3-benzoylphenyl)propionic acid which is prepared by oxidizing the former compound as an intermediate. The method is characterized by the easiness in operation, the low cost and the high purity of the product.
(Phenylethenyl) phenylpropionaldehyde and method for producing (benzoylphenyl) propionic acid using the same
申请人:NIPPON PETROCHEMICALS COMPANY, LIMITED
公开号:EP0282066A2
公开(公告)日:1988-09-14
A novel compound of α-(3-(1-phenylethenyl)phenyl)propionaldehyde and a method for producing α-(3-benzoylphenyl)propionic acid which is prepared by oxidizing the former compound as an intermediate. The method is characterized in the easiness in operation, the low cost and the high purity of the product.
(Acyloxy)benzophenones and (acyloxy)-4-pyrones. A new class of inhibitors of human neutrophil elastase
作者:Masateru Miyano、James R. Deason、Akira Nakao、Michael A. Stealey、Clara I. Villamil、Daniel D. Sohn、Richard A. Mueller
DOI:10.1021/jm00400a030
日期:1988.5
A series of 4-(acyloxy)- and 4,4'-bis(acyloxy)benzophenones were synthesized. Some of them, pivalates (trimethylacetates) and isobutyrates in particular, were found to be potent and selective inhibitors of human neutrophil (leukocyte) elastase. A series of 2-[(acyloxy)methyl]-5-(acyloxy)-4-pyrones were synthesized regioselectively from kojic acid. The 4-pyrones bearing a long chain acyl group at the 2-position and either pivaloyloxy or isobutyryloxy at the 5-position were potent and selective inhibitors of the human elastase. A number of analogues and derivatives in both series were synthesized in order to study the structure-activity relationship as summarized in Tables I-VI and in Tables IX and X. The inhibition was selective to human neutrophil elastase. No inhibition of porcine pancreatic elastase or bovine pancreatic chymotrypsin (Tables VII and XI) was observed. The most likely mechanism of inhibition is discussed. The implication of these findings for the treatment of rheumatoid arthritis and emphysema is outlined.
MIYANO, MASATERU;DEASON, JAMES R.
作者:MIYANO, MASATERU、DEASON, JAMES R.
DOI:——
日期:——
MIYANO, MASATERU;DEASON, JAMES R.;NAKAO, AKIRA;STEALEY, MICHAEL A.;VILLAM+, J. MED. CHEM., 31,(1988) N 5, 1052-1061
作者:MIYANO, MASATERU、DEASON, JAMES R.、NAKAO, AKIRA、STEALEY, MICHAEL A.、VILLAM+