219311-20-3Relevant academic research and scientific papers
N-Substituted homopiperazine barbiturates as gelatinase inhibitors
Wang, Jun,Medina, Carlos,Radomski, Marek W.,Gilmer, John F.
experimental part, p. 4985 - 4999 (2011/10/04)
Matrix metalloproteinases are implicated in a wide range of pathophysiological processes and potent selective inhibitors for these enzymes continue to be eagerly sought. 5,5-Disubstituted barbiturates hold promise as inhibitor types being stable in vivo and relatively selective for the gelatinases (MMP-2 and MMP-9). In this paper we describe the synthesis of 5-piperazine and -homopiperazine substituted barbiturates. The activity of these compounds as gelatinase inhibitors was evaluated using supernatants from 12-O-tetradecanoylphorbol-13-acetate (PMA)-stimulated HT-1080 cells as well as using recombinant human MMPs. N-Acyl homopiperazine compounds were found to be potent inhibitors of the gelatinases (range in nM) and generally more potent than the corresponding piperazine analogues. The panel of N-acyl homopiperazines was enlarged in order to exploit differences between the gelatinases at the S2′ site in order to design MMP-2- or MMP-9-selective inhibitors. Compounds in this group exhibited single digit nano-molar potency and some selectivity between the two enzymes. Representative potent compounds were effective inhibitors of cancer cell migration.
Palladium-catalyzed arylation of diisopropyl malonate applied to the efficient synthesis of the selective MMP inhibitor 5-(4-phenoxyphenyl)-5-[4-(2-pyrimidinyl)-1-piperazinyl]barbituric acid
Hutchings, Stanley,Liu, Wen,Radinov, Roumen
, p. 763 - 768 (2007/10/03)
An efficient synthesis of the highly selective MMP inhibitor 5-(4-phenoxyphenyl)-5-[4-(2-pyrimidinyl)-1-piperazinyl]barbituric acid is reported. The title compound was prepared in three steps and 72% overall yield from 4-bromophenyl phenyl ether via an im
Barbituric acid derivatives with antimetastatic and antitumor activity
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Page column 14, (2010/01/21)
The invention is directed to barbituric acid derivatives having inhibitory activity for matrix maetalloproteases comprised of formula (I): pharmaceutical compositions thereof, processes for preparing the derivatives, and methods for treating diseases associated with elevated or uncontrolled levels of matrix metalloprotease activity, e.g., cancer, specifically tumor progression and tumor metastasis, inflammation, or as a method of contraception.
Novel 5,5-disubstitutedpyrimidine-2,4,6-triones as selective MMP inhibitors
Foley, Louise H,Palermo, Robert,Dunten, Pete,Wang, Ping
, p. 969 - 972 (2007/10/03)
The 5,5-disubstitutedpyrimidine-2,4,6-triones represent a new class of MMP inhibitors showing selectivity for the gelatinases A and B, collagenase-3, and human neutrophil collagenase. The SAR presented here is in good agreement with an X-ray structure of compound 5 bound to the catalytic domain of stromelysin-1. While of the barbiturate structural class, compound 5 did not show any toxic or sedative effects.
Pyrimidine-2,4,6-triones
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, (2008/06/13)
A compound of formula I wherein R1is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkoxy, aryloxy or alkylalkoxy, and R2is aryloxy, or a pharmaceutically acceptab
Barbituric acid derivatives, processes for their production and pharmaceutical agents containing these compounds
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, (2008/06/13)
PCT No. PCT/EP96/05766 Sec. 371 Date Aug. 26, 1998 Sec. 102(e) Date Aug. 26, 1998 PCT Filed Dec. 20, 1996 PCT Pub. No. WO97/23465 PCT Pub. Date Jul. 3, 1997Compounds of formula I, useful as matrix metalloprotease inhibitors, wherein X, Y and Z are each oxygen; R1 is selected from the group consisting of (a) n-octyl, (b) n-decyl, (c) biphenyl and (d) (4-phenoxy)phenyl, wherein the terminal monocycle for moieties (c)-(d) is unsubstituted or substituted by a substituent selected from the group consisting of -NH2, -NO2, -SO2NH2, -SO2CH3, acetyl, hydroxy, methoxy, ethoxy, cyano and halogen; R2 and R3 are each hydrogen; and R4 and R5, together with the nitrogen atom to which they are bound, form a piperazinyl or piperidyl ring, wherein the piperazinyl ring is substituted in the 4-position with a substituent selected from the group consisting of (a) a 6-membered aromatic monocycle having 0, 1 or 2 nitrogen atoms and the remainder of the atoms in the monocycle being carbon and (b) hydroxy-C1-C6 alkyl, wherein the monocycle is unsubstituted or substituted by a substituent selected from the group consisting of halogen, -NH2, -NO2, -SO2NH2, -SO2CH3, acetyl and cyano.
