Patent DE-10129717-A1 (DE)
Title: Combination preparation containing nucleoside compound and 5-sulfonyl-2-phenylacetamido-thiazole derivative, useful as antiviral agent effective againts herpes viruses, especially herpes simplex
Inventor: KLEYMANN GERALD
IPC: A61K31/426
Filed: 2001-06-22
Abstract: New combination preparations (A) contain (a) nucleoside compounds (specifically acyclovir or penciclovir) and (b) 5-aminosulfonyl-2-phenylacetamido-thiazole derivatives (I) or 5-halosulfonyl-2-phenylacetamido-thiazole derivatives (IV).  New combination preparations (A) contain nucleoside compounds (specifically acyclovir, penciclovir or their prodrugs) and (b) thiazole derivatives of formula (I) (or their salts) or (IV).  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)COOtBu, Het1, Het2 or aryl (os by OH or alkoxy)); -P(O)(OR8)(OR9), -COCH(NH2)-R10, -CHR11-OCOR12 or -CH(NH2)-R10;  or NR2R3  = 5- or 6-membered saturated heterocycle, optionally containing a further O heteroatom;  R'2, R8, R9  = H or 1-4C alkyl; Het1  = C- or N-bonded 5- or 6-membered aromatic heterocycle containing 1-3 of S, N and/or O as heteroatom(s));  Het2  = C- or N-bonded 3-8 membered, saturated or unsaturated, non-aromatic heterocycle containing 1-3 of S, N and/or O as heteroatom(s));  R10 = side-chain of a naturally occurring aminoacid;  R11  = 1-4C alkyl; R12  = H, 1-4C alkyl or -CH(NH2)-R10;  R4  = H, acyl, 2-6C alkenyl or cycloalkyl; or alkyl (os by 1-3 of halo, OH, cycloalkyl, acyl, alkoxy, COOH, NHCOOtBu, OEt, -CH2CH2OEt, phenoxy, aryl or NR13R14); or alkyl substituted by optionally benzo-fused Het1, 2-(R16)-pyrrolidino, tetrahydrofuran-2-yl, benzo-1,4-dioxan-2-yl, 2-oxo-pyrrolidino or -OCOR17R18;  R13, R14  = H, acyl, alkyl, CONH2, mono- or dialkylaminoalkyl, mono- or dialkylaminocarbonyl, aryl or alkoxycarbonyl;  or NR13R14  = 5- or 6-membered saturated heterocyclyl, optionally containing a further O, S or NR15 heteroatom and os by =O;  R15  = H or 1-4C alkyl;  R16  = H or alkyl;  R17, R18 = H; or alkyl or aryl (both os by 1-3 of OH, alkoxy or halo);  R5, R7 = H, alkyl, halo, NH2, mono- or dialkylamino or alkanoylamino;  R6  = phenyl (os by 1-3 groups R'6);  R'6  = halo, aryl (os by 1-3 of alkanoyl, alkoxy, alkyl, halo, alkoxycarbonyl, NO2, haloalkyl, haloalkoxy, NH2, alkylthio, OH, COOH, CONH2, mono- or dialkylaminocarbonyl, mono- or dialkanoylamino, alkoxycarbonylamino, alkylsulfoxy, alkylsulfonyl, trialkylsilyloxy, Het2 or CN), alkoxy (os by 1-6 F, but not perfluorinated), alkoxycarbonyl, alkylthio, OH, COOH, alkyl (os by tetrahydrofuran-2-yl), Het1 (os by 1-3 of alkanoyl, alkoxy, alkyl, halo, alkoxycarbonyl, NO2, haloalkyl, haloalkoxy, NH2, alkylthio, OH, COOH, CONH2, mono- or dialkylaminocarbonyl, mono- or dialkanoylamino, alkoxycarbonylamino, alkylsulfoxy, alkylsulfonyl, Het2 (mono- or bicyclic) or CN), Het2 (mono- or bicyclic; and os by 1-3 of =O, halo, OH, alkoxycarbonyl, alkoxycarbonylamino, alkyl, haloalkyl or hydroxyalkyl), 2-6C alkenyl, OR19, NR20R21, CONR22R23, carbazole, dibenzofuran, dibenzothiophene, xanthene or 9,10-dihydroacridine;  R19  = phenyl (os by NR24R25) or alkyl (os by 1-3 of OH or halo);  R24, R25  = H, alkyl or acyl;  R20, R21  = H, CONH2, mono- or dialkylaminocarbonyl, phenyl, acyl or alkyl (os by alkoxy or acyl; or by phenyl or Het1 (both os by 1-3 of halo or OH));  R22, R23  = H or alkyl;  D  = halogen;  alkyl moieties or acyl groups have 1-6C, cycloalkyl moieties 3-8C and aryl moieties 6-10C unless specified otherwise.