130723-09-0Relevant articles and documents
Design, synthesis and biological evaluation of benzo[1.3.2]dithiazolium ylide 1,1-dioxide derivatives as potential dual cyclooxygenase-2/5-lipoxygenase inhibitors
Tan, Chen-Ming,Chen, Grace Shiahuy,Chen, Chien-Shu,Chang, Pei-Teh,Chern, Ji-Wang
experimental part, p. 6316 - 6328 (2011/12/02)
3-(4-Bromophenyl)-6-nitrobenzo[1.3.2]dithiazolium ylide 1,1-dioxide (5) was discovered as a new prototype for dual inhibitors of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX). Thus, the structure-activity relationships of benzo[1.3.2]dithiazolium ylide 1,1-dioxide skeleton were carried out. The 6-NO2 group played an essential role in the inhibitory activity. In addition, moderate-sized lipophilic substituents at the para-position of the 3-aryl moiety were required for dual COX-2/5-LOX inhibitory activity. Among the identified potent dual inhibitors, 3-(4-tbutylphenyl) derivative 30c (IC50 values of 0.27 μM and 0.30 μM against COX-2 and 5-LOX, respectively) and 3-(4-biphenyl) derivative 30f (IC50 values of 0.50 μMand 0.15 μMagainst COX-2 and 5-LOX, respectively) were the most potent dual COX-2/ 5-LOX inhibitors. Intraperitoneal administration of 30c at 100 mg/kg demonstrated potent acute antiinflammatory activity. As a result, benzo[1.3.2]dithiazolium ylide 1,1-dioxide represented a novel scaffold for the exploitation in developing dual COX-2/5-LOX inhibitors.
TRICYCLIC INHIBITORS OF 5-LIPOXYGENASE
-
Page/Page column 85, (2010/11/28)
Described herein are compounds and pharmaceutical compositions containing such compounds, which inhibit the activity of 5-lipoxygenase (5-LO). Also described herein are methods of using such 5-LO inhibitors, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other leukotriene-dependent or leukotriene mediated conditions, diseases, or disorders.
New COX-2/5-LOX inhibitors: Apoptosis-inducing agents potentially useful in prostate cancer chemotherapy
Pommery, Nicole,Taverne, Thierry,Telliez, Aurélie,Goossens, Laurence,Charlier, Caroline,Pommery, Jean,Goossens, Jean-Fran?ois,Houssin, Raymond,Durant, Fran?ois,Hénichart, Jean-Pierre
, p. 6195 - 6206 (2007/10/03)
The arachidonic acid metabolizing enzymes cyclooxygenase-2 (COX-2) and lipoxygenases (LOXs) have been found to be implicated in a variety of cancers, including prostate cancer. To develop new therapeutic treatments, it therefore seemed interesting to design dual COX-2/5-LOX inhibitors. We report here the synthesis and in vitro pharmacological properties of diarylpyrazole derivatives that have in their structure key pharmacophoric elements to obtain optimal interaction with subsites of active pockets in both enzyme systems. Using a molecular modeling approach, a set of SAR data is proposed, highlighting the importance of the sulfonyl group of one of the aryl moieties in terms of proliferation inhibition and/or apoptosis induction.
Synthesis and activity of a new methoxytetrahydropyran derivative as dual cyclooxygenase-2/5-lipoxygenase inhibitor
Barbey, Sabine,Goossens, Laurence,Taverne, Thierry,Cornet, Josephine,Choesmel, Valerie,Rouaud, Celine,Gimeno, Gilles,Yannic-Arnoult, Sylvie,Michaux, Catherine,Charlier, Caroline,Houssin, Raymond,Henichart, Jean-Pierre
, p. 779 - 782 (2007/10/03)
Dual COX-2/5-LO inhibitors are described as potential new therapeutic agents for inflammatory diseases. A surprisingly potent effect of a 5-LO pharmacophoric group on the COX-2 inhibition is presented as well as pharmacological in vitro and in vivo results.
Imidazole lipoxygenase inhibitors
-
, (2008/06/13)
Certain novel imidazole derivatives having the ability to inhibit the lipoxygenase enzyme and having formula (I), wherein Y is hydrogen, C1 -C8 alkyl, halosubstituted C1 -C4 alkyl, phenyl, substituted phenyl, C7 -C14 phenylalkyl, C7 -C14 (substituted phenyl)alkyl, pyridyl, substituted pyridyl, C6 -C13 pyridylalkyl or C6 -C13 (substituted pyridyl)alkyl, wherein each substituent is independently halo, nitro, cyano, C1 -C4 alkyl, C1 -C4 alkoxy, halosubstituted C1 -C4 alkyl, halosubstituted C1 -C4 alkoxy, NR4 R5, CO2 R4 or CONR4 R5, wherein R4 and R5 are each, independently, hydrogen or C1 -C6 alkyl; Ar1 and Ar2 are each, independently, phenylene, mono-substituted phenylene or di-substituted phenylene, wherein the substituents are, independently, halo, C1 -C4 alkyl, C1 -C4 alkoxy, halo-substituted C1 -C4 alkyl or halo-substituted C1 -C4 alkoxy; X and X1 are each, independently, O, S, SO or SO2 ; R' is hydrogen or C1 -C4 alkyl; and R2 and R3 are each, independently, methylene, ethylene or propylene. These compounds are useful for the treatment of disease states such as bronchial asthma, skin disorders and arthritis in mammals, and as the active ingredient in pharmaceutical compositions for treating such conditions.
BICYCLIC HETEROCYCLIC DERIVATIVES AS 5-LIPOXYGENASE INHIBITORS
-
, (2008/06/13)
The invention concerns a bicyclic heterocyclic derivative of the formula I wherein Q is an optionally substituted 9-membered bicyclic heterocyclic moiety containing 1 or 2 N's and optionally a further N, O or S heteroatom; A1 is a direct link to X1 or (1-3C)alkylene; X1 is oxy, thio, sulphinyl, sulphonyl or imino; Ar is optionally substituted phenylene or pyridylene; R1 is (1-4C)alkyl, (3-4C)alkenyl or (3-4C)alkynyl; and R2 and R3 together form a group of the formula ?A2?X2?A3? which, together with the carbon atom to which A2 and A3 are attached, defines a ring having 5 to 7 ring atoms, wherein each of A2 and A3 is (1-3C)alkylene and X2 is oxy, thio, sulphinyl or sulphonyl; or a pharmaceutically-acceptable salt thereof. The compounds of the invention are inhibitors of the enzyme 5-lipoxygenase
BENZOXAZINE DERIVATIVES AS INHIBITORS OF LEUKOTRIENES
-
, (2008/06/13)
The invention concerns a bicyclic heterocyclic compound of the formula I wherein Q is an optionally substituted 10-membered bicyclic heterocyclic moiety containing 1 or 2 N's and a further O or S heteroatom; A1 is a direct link to X1 or (1-3C)alkylene; X1 is oxy, thio, sulphinyl, sulphonyl or imino; Ar is optionally substituted phenylene or pyridylene; R1 is (1-4C)alkyl, (3-4C)alkenyl or (3-4C)alkynyl; and R2 and R3 together form a group of the formula -A2-X2-A3- which, together with the carbon atom to which A2 and A3 are attached, defines a ring having 5 to 7 ring atoms, wherein each of A2 and A3 is (1-3C)alkylene and X2 is oxy, thio, sulphinyl or sulphonyl; or a pharmaceutically-acceptable salt thereof. The compounds of the invention are inhibitors of the enzyme 5-lipoxygenase
Thioxo quinoline compounds, composition and method of use
-
, (2008/06/13)
The invention concerns a thioxo heterocycle of the formula I STR1 wherein Q is a 10-membered bicyclic heterocyclic moiety containing 1 or 2 N's which bears 1 or 2 thioxo substituents and which is optionally further substituted; A1 is a direct l
SULPHONAMIDE DERIVATIVES
-
, (2008/06/13)
The invention concerns sulphonamide derivatives of the formula I wherein R1 includes (1-4C)alkyl; R2 and R3 together form ?A2 ?X2 ?A3? which defines a ring having 5 to 7 ring atoms, wherein A2 and A3 each is (1-3 C)alkylene and X2 is oxy, thio, sulphinyl or sulphonyl; A1 is a direct link to X1 or is (1-3 C)alkylene; X1 is oxy, thio, sulphinyl, sulphonyl or imino; Ar is optionally substituted phenylene or Ar is pyridylene; Q is nitrogen or of the formula CR7, wherein R7 includes hydrogen, halogeno, (1-4 C)alkyl and (1-4 C)alkoxy; each of R4 and R5 is (1-4 C)alkyl, (3-4 C)alkenyl, (3-4 C)alkynyl or optionally substituted phenyl, benzyl or pyridyl, or R5 may be hydrogen; and R6 has any of the meanings defined for R7; or a pharmaceutically-acceptable salt thereof; processes for their manufacture; pharmaceutical compositions containing them and their use as 5-lipoxygenase inhibitors
PYRAN DERIVATIVES AND THEIR USE AS INHIBITORS OF 5-LIPOXYGENASE
-
, (2008/06/13)
The invention concerns a cyclic ether derivative of the formula I, wherein Ar1 is optionally substituted phenyl, naphthyl or a 9-or 10-membered bicyclic heterocyclic moiety; A1 is a direct link to X1 or (l-3C)alkylene; X1 is oxy, thio, sulphinyl, sulphony
