Patent DE-19962532-A1 (DE)
Title: New 2-acylamino-5-aminosulfonyl-1,3-thiazole derivatives, useful as antiviral agents, especially for treatment or prophylaxis of herpes simplex virus infections
Inventor: FISCHER RUEDIGER
IPC: C07D417/12
Filed: 1999-12-23
Abstract: 2-Acylamino-5-aminosulfonyl-1,3-thiazole derivatives (I) are new. Thiazole derivatives of formula (I) and their salts are new.  R1  = H, halo, alkyl, alkoxy, aminoalkyl or haloalkyl;  R2, R3  = H, alkoxy, cycloalkyl or biphenylaminocarbonyl; alkyl (optionally substituted (os) by 1-3 of 3-6C cycloalkyl, alkoxy, halo, OH, NH2, trialkylsilyloxy, 3,4-methylenedioxyphenyl, tetrahydrofuran-2-yl, -N(R'2)-COOCMe3, Het1, Het2 or aryl (itself os by OH or alkoxy); -COCH(R10)-NH2; or -CH(R11)-OCOR12; or  NR2R3  = 5- or 6-membered saturated heterocycle optionally containing O;  R'2, R8, R9  = H or 1-4C alkyl;  Het1  = optionally N-bonded 5- or 6-membered aromatic heterocycle containing 1-3 of S, N and O as heteroatom(s);  Het2  = optionally N-bonded 3-8 membered saturated or unsaturated non-aromatic heterocycle containing 1-3 of S, N and O as heteroatom(s);  R10  = side-chain of a naturally occurring  alpha -amino acid;  R11  = 1-4C alkyl;  R12  = H, 1-4C alkyl or -CHR10-NH2; R4  = H, 1-6C acyl, 2-6C alkenyl or cycloalkyl; or alkyl os by (i) 1-3 of halo, OH, cycloalkyl, 1-6C acyl, alkoxy, COOH, -NHCOOCMe3, -(OCH2CH2)nOEt, OPh, aryl or NR13R14 or (ii) Het1 (optionally fused with benzo), 1-(R16)-2-pyrrolidinyl, tetrahydrofuran-2-yl, benzo-1,4-dioxan-2-yl, 2-oxo-1-pyrrolidinyl or -OCONR17R18;  n  = 0 or 1;  R13, R14  = H, 1-6C acyl, alkyl, CONH2, mono- or dialkylaminoalkyl, mono- or dialkylaminocarbonyl, aryl or alkoxycarbonyl; or  NR13R14  = 5- or 6-membered saturated heterocycle optionally containing O, S or NR15 as additionally heteroatom and os by oxo;  R15  = H or 1-4C alkyl;  R17, R18  = H; or alkyl or aryl (both os by 1-3 of OH, alkoxy and halo);  R5, R7  = H, alkyl, halo, NH2, mono- or dialkylamino or (1-6C) alkanoylamino; R6  = phenyl, os by 1-3 Q;  Q  = halo, aryl (os by 1-3 Q'), alkoxy (os by 1-6 F), alkoxycarbonyl, alkylthio, OH, COOH, alkyl (os by tetrahydrofuran-2-yl), Het1 (os by 1-3 Q'), mono- or bicyclic Het2 (os by 1-3 of oxo, halo, OH, alkoxycarbonyl, alkoxycarbonylamino, alkyl, haloalkyl and hydroxyalkyl), 2-6C alkenyl, OR19, NR20R21, CONR22R23, carbazole, dibenzofuran, dibenzothiepin, xanthene or 9,10-dihydroacridine;  Q'  = (1-6C) alkanoyl, alkoxy, alkyl, halo, alkoxycarbonyl, NO2, haloalkyl, haloalkoxy, NH2, alkylthio, OH, COOH, CONH2, mono- or dialkylaminocarbonyl, mono- or di-(1-6C alkanoyl)-amino, alkoxycarbonylamino, alkylsulfoxy, alkylsulfonyl, trialkylsilyloxy, CN or mono- or bicyclic Het2;  R19  = phenyl (os by NR24R25) or alkyl (os by 1-3 of OH or halo); R24, R25  = H, alkyl or 1-6C acyl;  R20, R21  = H, CONH2, mono- or dialkylaminocarbonyl, phenyl, 1-6C acyl or alkyl (where alkyl is os by alkoxy, 1-6C acyl, phenyl or Het1; and phenyl and Het1 are os by one or more of halo and/or OH);  R22, R23  = H or alkyl; and D'  = halogen. alkyl moieties have 1-6C, cycloalkyl moieties 3-8C and aryl moieties 6-10C unless specified otherwise.  Independent claims are included for: (i) the preparation of (I); (ii) new sulfonyl halide intermediates of formula (IV); and  (iii) the use of N-(5-(aminosulfonyl)-1,3-thiazol-2-yl)-acetamide, N-(5-(aminosulfonyl)-1,3-thiazol-2-yl)-2-phenylacetamide or N-(5-(aminosulfonyl)-1,3-thiazol-2-yl)-2-(1,1'-biphenyl)-4-ylacetamide derivatives for the preparation of medicaments.