- New quaternary ammonium oxicam derivatives: synthesis and in vitro antiosteoarthritis evaluation
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A series of new oxicam derivatives bearing a quaternary ammonium (QA) moiety was synthesized and evaluated in vitro for antiosteoarthritis properties. Propyltrimethyl ammonium 3 and propyldiethylmethyl ammonium 11 stimulated aggrecan expression and mitigated the inhibitory action of IL-1. QA derivative 3 also increased TGF-β2 and type II receptor expression. These results suggest that such derivatives may not only inhibit the osteoarthritis degradation process but also stimulate its regeneration. QA derivatives 3 and 11 offer potential for developing new therapeutic approaches to osteoarthritis treatment.
- Vidal, Aurelien,Chezal, Jean-Michel,Mounetou, Emmanuelle
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- BENZYL SUBSTITUTED INDAZOLES
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Compounds of formula (I) and their use as pharmaceuticals.
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Page/Page column 256; 257
(2016/04/10)
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- 1,1-dioxo-2h-1,2-benzothiazine-3-carboxamide derivatives,method for preparing same and pharmaceutical compositions comprising same
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1wherein: represents a single or double bond, R1 represents a hydrogen atom or a hydroxy, alkoxy, acyloxy, alkylsulphonyloxy, arylsulphonyloxy or arylalkoxy group, R2 represents a hydrogen atom or an alkyl group, R3 and R4, which may be identical or different, each represent a hydrogen atom, a halogen atom or an alkyl, hydroxy or alkoxy group, Ak represents an alkylene chain, R5, R6 and R7, which may be identical or different, each represent an alkyl group, or R5, R6 and R7, taken together with the nitrogen atom carrying them, form a saturated or unsaturated nitrogen-containing heterocycle, X represents a halogen atom, and its optical isomers when they exist. Medicaments.
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Page/Page column 4
(2008/06/13)
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- Regioselective covalent modification of hemoglobin in search of antisickling agents
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Although the molecular defect in sickle hemoglobin that produces sickle cell disease has been known for decades, there is still no effective drug treatment that acts on hemoglobin itself. In this work, a series of diversely substituted isothiocyanates (R-NCS) were examined for their regioselective reaction with hemoglobin in an attempt to alter the solubility properties of sickle hemoglobin. Electrospray mass spectrometry, molecular modeling, X-ray crystallography, and conventional protein chemistry were used to study this regioselectivity and the resulting increase in solubility of the modified hemoglobin. Depending on the attached R-group, the isothiocyanates were found to react either with the Cysβ93 or the N-terminal amine of the α-chain. One of the most effective compounds in the series, 2-(N,N-dimethylamino)ethyl isothiocyanate, selectively reacts with the thiol of Cysβ93 which, in conjunction with the cationic group, was seen to perturb the local hemoglobin structure. This modified HbS shows an approximately 30% increase in solubility for the fully deoxygenated state, along with a significant increase in oxygen affinity. This compound and a related analogue appear to readily traverse the erythrocyte membrane. A discussion of the relation of these structural changes to inhibition of gelation is presented. The dual activities of increasing HbS oxygen affinity and directly inhibiting deoxy HbS polymerization, in conjunction with facile membrane traversal, suggest that these cationic isothiocyanates show substantial promise as lead compounds for development of therapeutic agents for sickle cell disease.
- Park, Soobong,Hayes, Brittany L.,Marankan, Fatima,Mulhearn, Debbie C.,Wanna, Linda,Mesecar, Andrew D.,Santarsiero, Bernard D.,Johnson, Michael E.,Venton, Duane L.
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p. 936 - 953
(2007/10/03)
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- Method for inhibiting angiogenesis using squalamine and squalamine steroid derivatives
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A method of inhibiting angiogenesis in a patient includes administering to the patient an effective amount of squalamine or a pharmaceutically acceptable salt of squalamine. Alternatively, a compound according to the following Formula (III) (or a pharmaceutically acceptable salt thereof) can be administered: STR1 wherein Z5 is α-H or β-H; each of the substituents Z7 is selected from the group of --H, --OH, --SH, --NH2, --F, --(C1 -C3)-alkyl, and --(C1 -C3)-alkoxy; and one of the substituents Z12 is --H and the other is --H or --OH. X' is a polyamine side chain of the formula --X1 --(CH2)p --X2 --(CH2)q --N(RII)(RIII), wherein one of X1 and X2 is --N(RIV) and the other is selected from the group of --N(RV), --O, --S, and --CH2. RIV and RV are each --H or --(C1 -C3)-alkyl, p and q are each an integer of from 0 to 5 (but both are not 0). RII and RIII in the formula for X' are each --H, --(C1 -C3)-alkyl, or --(CH2)r --N(R10)(R11) wherein r is an integer from 2 to 5 and R10 and R11 are each --H or --(C1 -C3)-alkyl. R' in Formula (III) is --H or --(C1 -C3)-alkyl, and Y' is --(C1 -C10)-alkyl, unsubstituted or substituted with --CO2 H, --OH, --NH--SO2 CF3, --SO3 H, --PO3 H2, --OSO3 H, --CF3, --F, STR2
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- Steroid derivatives, pharmaceutical compositions containing them, and their use as antibiotics or disinfectants
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Compounds having a broad range of antimicrobial activity generally have a structure including asteroid nucleus with a cationic, preferably polyamine, side chain (X) and an anionic side chain (Y). The invention is also directed to compounds of the Formula III: STR1 preferably where the steroid ring nucleus is saturated; the steroid ring substituent Z5 is α-H; one Z7 is β-H and the other is α-H or α-OH; both substituents Z12 are hydrogen; X' is a polyamine side chain of the formula --NH--(CH2)p --NH--(CH2)q --N(RII)(RIII) where p and q are each independently 3 or 4, and RII and RIII are each independently hydrogen or methyl; R' is methyl; and Y' is (C1 -C10)-alkyl substituted with a group such as --CO2 H or --SO3 H.
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- 4-fluorobenzoic compounds with 5-HT2 - and α1 -antagonistic activities
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The invention relates to the compounds of general formula I: STR1 in which: m represents an integer from 2 to 4, n and p, which may be identical or different, each represent an integer from 1 to 3, q represents 0 or 1, and R represents: either a group of formula (A): STR2 or a radical of formula (B): STR3 or a 2,4-dioxo-1,2,3,4-tetrahydroquinazolinyl radical, on condition, however, that, in this case, n and p do not simultaneously represent the number 2, or a benzhydryloxy group, or a 1-oxophthalazinyl radical, or a 5-oxothiazolo[3,2-A]pyrimidinyl radical, or a group of formula C: STR4 their possible stereoisomers and their addition salts with a pharmaceutically acceptable inorganic or organic acid. The compounds of formula I are medicinal products with useful 5-HT2 - and α1 -antagonistic activities.
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- Bleaching composition
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Bleaching (detergent) compositions are disclosed comprising a peroxide bleaching agent and a novel cationic peroxyacid bleach precursor having at least one of the following groups (A) and (B) : wherein R1 and R2 are each individually H, or a substituent group containing at least one carbon atom, provided that R1 and R2 are not both H. The novel bleach precursor of the cationic nitrile type shows no tendency to deliquesce under normal atmospheric conditions.
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