- INTEGRIN EXPRESSION INHIBITORS
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The present invention provides an integrin expression inhibitor, and an agent for treating arterial sclerosis, psoriasis, cancer, retinal angiogenesis, diabetic retinopathy or inflammatory diseases, an anticoagulant, or a cancer metastasis suppressor on the basis of an integrin inhibitory action. Namely, it provides an integrin expression inhibitor comprising, as an active ingredient, a sulfonamide compound represented by the following formula (I), a pharmacologically acceptable salt thereof or a hydrate of them. In the formula, B means a C6-C10 aryl ring or 6- to 10-membered heteroaryl ring which may have a substituent and in which a part of the ring may be saturated; K means a single bond, -CH=CH- or - (CR4bR5b)mb- (wherein R4b and R5b are the same as or different from each other and each means hydrogen atom or a C1-C4 alkyl group; and mb means an integer of 1 or 2); R1 means hydrogen atom or a C1-C6 alkyl group; Z means a single bond or -CO-NH-; and R means a C6-C10 aryl ring or 6- to 10-membered heteroaryl ring which may have a substituent and in which a part of the ring may be saturated, respectively.
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- Structure-activity relationships in platelet-activating factor (PAF). 11-From PAF-antagonism to phospholipase A2 inhibition: Syntheses and structure-activity relationships in 1-arylsulfamido-2-alkylpiperazines
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1-Benzoyl-2-alkyl piperazines are strong inhibitors of Group I and II secreted PLA2s. An improvement of their activity was obtained by replacing the amide function by a sulfamide and by introduction of electrodonor substituents on the para position of the benzenesulfonyl moiety. Neither the position on one of the carbon of the piperazine ring nor the absolute configuration of this carbon have an effect on the affinity for one or the other group of PLA2, but the lipophilicity remains for these series an essential parameter. In addition structure-activity relationships allow new hypothesis on interaction of these piperazine derivatives with the catalytic site of PLA2s.
- Binisti, Carine,Assogba, Leon,Touboul, Estera,Mounier, Carine,Huet, Jack,Ombetta, Jean-Edouard,Dong, Chang Zhi,Redeuilh, Catherine,Heymans, Francoise,Godfroid, Jean-Jacques
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p. 809 - 828
(2007/10/03)
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- Bispiperidines as antithrombotic agents
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Novel compounds which are inhibitors of the binding of fibrinogen to the Gp IIb/IIIa platelet receptors, and which can be used therepeutically as antithrombotic agents
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- Heterobicyclic sulfonamide and sulfonic ester derivatives
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Novel heterobicyclic sulfonamide and sulfonic ester derivatives represented by the following general formula(I), which exhibit an antitumor activity and are lowly toxic, and processes for the preparation thereof. A sulfonamide derivative and a sulfonic ester derivative represented by the general formula (I) or a pharmacologically acceptable salt thereof: STR1 wherein A represents a monocyclic or bicyclic aromatic ring which may be substituted; B represents a six-membered unsaturated hydrocarbon ring or a six-membered unsaturated heterocycle containing one nitrogen atom, each of which may be substituted; C represents a five-membered heterocycle containing one or two nitrogen atoms which may be substituted; W represents a single bond or a group represented by formula --CH=CH--; X represents a group represented by formula --N(R1)-- or oxygen; Y represents carbon or nitrogen; Z represents a group represented by formula --N(R2)-- or nitrogen; and R1 and R2 may be the same or different from each other and each represent hydrogen or lower alkyl.
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- Sulfonyl esters 7. The second and third sequences in the Trithioorthoformate Reaction
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A previous report has established the intermediacy of a sulfide-sulfonate ester in the one-pot conversion of an aryl mercaptan and a sulfonate ester into the corresponding trithioorthoformate. This report describes evidence for the sequential intermediacy of a bissulfide-sulfonate ester and a dithiosulfene in the conversion of the sulfide-sulfonate ester into the trithioorthoformate. A new sulfonate ester is shown to give the highest yield of trithioorthoformate.
- Ginige, Kashyapa Ananda,Goehl, John Edward,Langler, Richard Francis
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p. 1638 - 1648
(2007/10/03)
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- STUDIEN ZUM VORGANG DER WASSERSTOFFUEBERTRAGUNG.61. Chemische Reaktivitaet und Halbstufenpotential Vergleichende Versuche am Beispiel einiger Arylsulfonsaeurederivate
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In arylsulfonyl halides, the half-wave potentials of the corresponding chlorides and fluorides differ by more than 1000 mV, the fluoride being more negative; the influence of para-substituents is small for the chlorides, large for the fluorides.In agreement with the half-wave potentials, arylsulfonyl chlorides are considerably more reactive chemically than the corresponding fluorides.The O-selectivity found for P(O)F compounds is not observed in arylsulfonyl fluorides.Studies of competitive ester formation using primary and secondary alcohols and various arylsulfonyl chlorides yielded no clear analogy to the half-wave potentials.The primary alcohol is always sulfonated in preference to the secondary alcohol, whether the hydroxy functions are present in different molecules or the same molecule.In the latter case, the secondary hydroxyl function is then attacked in a further step by a second, different, arylsulfonyl chloride, giving the compounds 4-8.The further electroreduction of these diesters may be carried out in high yields, giving selective fission of one ester linkage only (that with the more positive potential) provided the difference in the half-wave potentials of the different ester linkages is sufficiently large.In the electroreductive fission the monosulfinic acid and the corresponding alcohol are liberated (see table II).In the competition reaction between phenol and 1:1 mixtures of tosyl chloride (A) and p-carboxyethyl-benzenesulfonyl chloride (B), the chloride with the more positive potential (B), E1/2=72 mV reacts quicker by a factor of 2.5.In competitive Finkelstein reactions, the selectivity was 1:11 at a difference in half-wave potentials of 760 mV (table IV).Arylsulfonates with free secondary alcohol functions may be oxidized smoothly and in high yield to the corresponding ketone using Na2Cr2O7 (3), without effecting the sulfonate linkage.The alkali hydrolysis of n-hexyl para-substituted arylsulfonates follows the Hammett relation but shows a lesser selectivity than was observed in the electroreductive fission of the same esters at the required potentials.Tables VI, VII and VIII concentrate on the preparative importance of the potential-controlled electroreductive fission of aliphatic and aromatic arylsulfonates.The corresponding hydroxy compounds are liberated in yields of up to over 90percent: N-alkyl- and N-aryl arylsulfonamides give analogous results. (table IX)
- Horner, Leopold,Schmitt, Rolf-Erhard
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p. 189 - 212
(2007/10/02)
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