Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1997-08-15
1999-12-21
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
544 82, 544238, 544296, A01N 4354, C07D41300, C07D40100, C07D40300
Patent
active
060049650
DESCRIPTION:
BRIEF SUMMARY
The present invention is concerned with novel sulphonamides and their use as medicaments. In particular, the invention is concerned with novel compounds of the formula ##STR2## wherein R.sup.1 signifies phenyl or phenyl substituted by halogen, C.sub.1-7 -alkyl, C.sub.1-7 -alkoxy, C.sub.1-7 -alkylenedioxy, carboxyl or trifluoromethyl; or heterocyclyl selected from mono- or bicyclic, 5- and 6-membered heterocycles having oxygen, nitrogen or sulphur as the hetero atom; cyano, carboxy, C.sub.1-7 -alkoxycarbonyl, hydroxymethyl, formyl, carbamoyl, thiocarbamoyl, amidino or hydroxyamidino; by halogen, C.sub.1-7 -alkyl, C.sub.1-7 -alkoxy, C.sub.1-7 -alkylenedioxy, carboxyl or trifluoromethyl; or a residue --C(O)NHR.sup.10 ; C.sub.1-7 -alkyl, C.sub.1-7 -alkoxy, C.sub.1-7 -alkylenedioxy, carboxyl or trifluoromethyl; or pyridyl or pyridyl substituted by 1 or 2 C.sub.1-7 -alkyl groups; other signifies CH; or (N.fwdarw.O) and the other signifies CH,
Examples of residues of mono- or bicyclic, 5- and 6-membered heterocycles having oxygen, nitrogen or sulphur as the hetero atom, such as 2- and 3-furyl, 2-, 4- and 5-pyrimidinyl, 2-, 3- and 4-pyridyl, 1,2- and 1,4-diazinyl, 2- and 3-thienyl, oxazolyl, thiazolyl, imidazolyl, benzofuranyl, benzothienyl, purinyl, quinolyl, isoquinolyl and quinazolyl, which residues can be substituted, e.g. by 1 or 2 C.sub.1-7 -alkyl groups. Preferred are pyridyl or pyridyl substituted by 1 or 2 C.sub.1-7 -alkyl groups.
The term "C.sub.1-7 " used here denotes groups with 1-7 C atoms, preferably 1-4 C atoms. Alkyl and alkoxy groups can be straight-chain or branched. Methyl, ethyl, propyl, isopropyl, butyl, sec. and tert.butyl are examples of such alkyl groups. Halogen denotes fluorine, chlorine, bromine and iodine, with chlorine being preferred.
A preferred group of compounds of formula I comprises those in which A and B are CH or one of the symbols A and B is nitrogen. R.sup.1 is preferably a phenyl residue, which is mono- or di-substituted, or a pyridyl residue, which is mono-substituted by C.sub.1-7 -alkyl, especially an C.sub.1-7 -alkyl substituted 2-pyridyl residue. R.sup.2 is preferably a tetrazolyl residue. R.sup.3 is preferably --O(CH.sub.2).sub.n OH, --O(CH.sub.2).sub.n O-benzyl or --O(CH.sub.2).sub.n OC(O)NHR.sup.10, in which R.sup.10 is pyridyl, especially 2-pyridyl. n is preferably 2. Of particular interest among these compounds are those in which R.sup.4 is C.sub.1-7 -alkoxy and R.sup.5 -R.sup.8 are hydrogen; or R.sup.4 is halogen, R.sup.7 is C.sub.1-7 -alkoxy and R.sup.5, R.sup.6 and R.sup.8 are hydrogen; A is nitrogen and B is CH.
The documents, EP-A-0 510 526 and EP-A-0 526 708 disclose sulfonamides having endothelin-inhibiting activity.
The compounds of formula I can be manufactured by ##STR3##
wherein R.sup.12 is 3- or 4-cyanophenyl or 2- or 4-pyridyl N-oxide and Hal is halogen and the remaining symbols have the significance set forth above, wherein M is an alkali metal and R.sup.91 is hydrogen, benzyl or benzyl substituted in the phenyl ring by halogen, C.sub.1-7 -alkyl, C.sub.1-7 -alkoxy, C.sub.1-7 -alkylenedioxy, carboxyl or trifluoromethyl; and R.sup.a, R.sup.b and n have the significance set forth above; or ##STR4##
wherein R.sup.11 is 2- or 4-pyridyl N-oxide and the remaining symbols have the significance set forth above, remaining symbols have the significance set forth above with an azide in the presence of an aprotic Lewis acid; or remaining symbols have the significance set forth above with an alkali metal alcoholate and thereafter with hydrazine into the corresponding amidrazone and treating this with a nitrite and an acid; or isocyanate of the formula R.sup.10 NCO; or is cyano and the remaining symbols have the significance set forth above into an amidino, carbamoyl, thiocarbamoyl, C.sub.1-7 -alkoxycarbonyl, carboxy, hydroxymethyl, formyl or hydroxyamidino group; or R.sup.2 is tetrazolyl and R.sup.9 is benzyl, benzyl substituted in the phenyl ring by halogen, C.sub.1-7 -alkyl, C.sub.1-7 -alkoxy, C.sub.1-7 -alkylenedioxy, carboxyl or trifluoromethyl; and cleaving off
REFERENCES:
patent: 5270313 (1993-12-01), Burri et al.
patent: 5292740 (1994-03-01), Burri et al.
patent: 5420129 (1995-05-01), Breu et al.
Breu Volker
Burri Kaspar
Cassal Jean-Marie
Clozel Martine
Hirth Georges
Epstein William H.
Hoffmann-La Roche Inc.
Johnston George W.
Parise John P.
Shah Mukund J.
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