| 摘要 |
<p>EP--61425 A 2-Thio-substd. 4,5-diaryl-thiazole derivs. (I) and their salts are new (where R1 and R2 are aryl or opt. N-oxidised heteroaryl residues opt. substd. by aliphatic hydrocarbon residues; by free, esterified or etherified OH; by etherified, opt. S-oxidised mercapto; by aliphatically substd. amino; and/or by CF3; n is 0, 1 or 2; and R3 is an (a) an aliphatic residue (opt. substd. by etherified or esterified OH; by etherified opt. S-oxidised mercapto, and/or (except in the alpha-position) by oxo and/or OH, and/or by a terminal OH gp. or sulpho gp. (in salt form)), (b) an araliphatic gp. (opt. substd. in the aryl residue as for R1 and R2, (c) a cycloaliphatic or cycloaliphatic-aliphatic residue (opt. substd., other than in the alpha-position) by free, etherified or esterified OH), or (d) a residue of formula (Ia) (where m is 0, 1 or 2; R4 is a gp. as defined for R3, except the gp. (Ia), or (when m and n are both 0) may additionally be a direct bond; and R1' and R2' are gps. as defined for R1 and R2; with the proviso that (a) when n is 0 or 1 and R3 is alkyl, then at least one of R1 and R2 is other than phenyl or phenyl substd. by alkyl, alkoxy, halogen and/or CF3, (b) when n is 0 and R3 is omega-hydroxy- or omega-oxo (lower alkyl) with more than 3 C-atoms, then at least one R1 and R2 is opt. substd. heteroaryl, and (c) at least one of R1 and R2 is opt. substd. heteroaryl, or R1 and R2 are both p-hydroxyphenyl when R3 is omega-hydroxy or omega-oxo (2-3C alkyl)). - The new cpds. display marked antinociceptive activity, inhibit prostaglandin synthesis, and display marked anti-inflammatory activity. They are partic. suitable for the treatment of chronic rheumatic diseases. (119pp) GBAB- GB2098203 B A 2,4,5-trisubstituted thiazole of the formula (I) in which each of R1 and R2, independently of the other, represents an aryl or optionally N-oxidised heteroaryl radical which is unsubstituted or substituted by aliphatic hydrocarbon radicals, free, etherified or esterified hydroxy, etherified optionally S-oxidised mercapto, aliphatically substituted amino, nitro and/or trifluoromethyl, X represents thio, n represents 0, 1 or 2, and R3 represents an aliphatci hydrocarbon radical that is unsubstituted or substituted by etherified or esterified hydroxy, etherified optionally S-oxidised mercapto and/or, in a position higher than the alpha-position, by oxo and/or hydroxy and optionally contains, in addition to terminally bonded hydroxy, sulpho that is present in salt form, or represents an araliphatic hydrocarbon radical that is unsubstituted or substituted in the aryl moiety as indicated for R1 and R2, or represents a cycloaliphatic or cycloaliphatic-aliphatic hydrocarbon radical that is unsubstituted or substituted in a position higher than the alpha-position by free, etherified or esterified hydroxy, or represents a group of the formula (Ia) in which m represents 0, 1 or 2, R4 represents an aliphatci hydrocarbon radical that is unsubstituted or substituted by etherified or esterified hydroxy, optionally S-oxidised etherified mercapto or, in a position higher than the alpha-position and lower than the omega-position, by oxo and/or hydroxy and that is optionally interrupted by oxa or thia, which may also be S-oxidised, or, if and m represent 0, represent 0, represents a direct bond, and R1 and R2 have one of the meanings given for R1 and R2, with the proviso that in compounds in which n represents 1 or 2, if R3 denotes alkyl, at least one of the radicals R1 and R2 denotes heteroaryl which is unsubstituted or substituted as indicated hereinbefore, and with the further provsi proviso that in compounds in which n represents 0, if R3 represents isopropyl or an omega-hydroxy - GB2098203 B A 2,4,5-trisubstituted thiazole of the formula (I) in which each of R1 and R2, independently of the other, represents an aryl or optionally N-oxidised heteroaryl radical which is unsubstituted or substituted by aliphatic hydrocarbon radicals, free, etherified or esterified hydroxy, etherified optionally S-oxidised mercapto, aliphatically substituted amino, nitro and/or trifluoromethyl, X represents thio, n represents 0, 1 or 2, and R3 represents an aliphatci hydrocarbon radical that is unsubstituted or substituted by etherified or esterified hydroxy, etherified optionally S-oxidised mercapto and/or, in a position higher than the alpha-position, by oxo and/or hydroxy and optionally contains, in addition to terminally bonded hydroxy, sulpho that is present in salt form, or represents an araliphatic hydrocarbon radical that is unsubstituted or substituted in the aryl moiety as indicated for R1 and R2, or represents a cycloaliphatic or cycloaliphatic-aliphatic hydrocarbon radical that is unsubstituted or substituted in a position higher than the alpha-position by free, etherified or esterified hydroxy, or represents a group of the formula (Ia) in which m represents 0, 1 or 2, R4 represents an aliphatci hydrocarbon radical that is unsubstituted or substituted by etherified or esterified hydroxy, optionally S-oxidised etherified mercapto or, in a position higher than the alpha-position and lower than the omega-position, by oxo and/or hydroxy and that is optionally interrupted by oxa or thia, which may also be S-oxidised, or, if and m represent 0, represent 0, represents a direct bond, and R1 and R2 have one of the meanings given for R1 and R2, with the proviso that in compounds in which n represents 1 or 2, if R3 denotes alkyl, at least one of the radicals R1 and R2 denotes heteroaryl which is unsubstituted or substituted as indicated hereinbefore, and with the further provsi proviso that in compounds in which n represents 0, if R3 represents isopropyl or an omega-hydroxy USAB- US4451471 A 2,4,5-Tri-substd. thiazoles of formula (I) and their salts are new. In the formula, R1 and/or R2 is opt. N-oxidised pyridyl and the other is pH opt. substd. by lower alkyl, -alkoxy, alkanoyloxy, -alkylthio, -alkanesulphinyl or -alkanesulphonyl, or OH, halogen, NH2, mono- or di-lower alkylamino, NO2, and/or CF3; X is thio; n is 0-2; R3 is lower alkyl, -alkenyl, -alkynyl, -alkylenedioxy-lower alkyl, -alkanoyloxy-lower alkyl (carrying the alkanoyloxy gp. in position higher than alpha), or mono- or di-lower alkoxy-lower alkyl, polyhalo-lower alkyl, hydroxy-lower alkyl (carrying OH in positions higher than alpha), oxo-lower alkyl (carrying oxo in position higher than alpha) or phenyl-lower alkyl opt. substd. by an R1 and R2 gp. - (I) esp. comprises e.g. 2-methylthio-5-phenyl -4-(3-pyridyl)-thiazole and is used with a carrier in an antiinflammatory compsn. (129pp)o</p> |
