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US 5,602,277 AGranted
Substituted benzene derivatives useful as neuraminidase inhibitors
AssigneeBioCryst Pharmaceuticals, Inc.
InventorsYarlagadda S. Babu, Pooran Chand, David A. Walsh
Life of this patent
Estimating the term…
Abstract
A compound of the Formula (I): ##STR1## or pharmaceutically-suitable salts or prodrug forms thereof, wherein: n is 0-1; m is 0; p is 0-1; R.sup.1 is --CO.sub.2 H; R.sup.2 is selected from the group consisting of H, --OH, and --NH.sub.2 ; R.sup.3 is H; R.sup.4 is --C(O)NHR.sup.8 ; R.sup.5 is --NHC(R.sup.6)NH.sub.2 R.sup.6 is selected from the group consisting of .dbd.NH, .dbd.NOH, .dbd.NCN, .dbd.O, and .dbd.S; and R.sup.8 is selected from the group consisting of C.sub.1 -C.sub.4 linear or branched alkyl substituted with 0-3 halogens on each carbon.
Claims25
A method for the treatment of infections caused by viral influenza, said method comprising the step of:
- administering to a host in need of such treatment a pharmaceutically-effective amount of a compound of the Formula (I):
- ##STR58## or pharmaceutically-suitable salts or prodrug forms thereof, wherein:
- n is 0-1;
- m is 0-3;
- p is 0-1;
- R.sup.1 is selected from the group consisting of --CO.sub.2 H, --SO.sub.2 H, --SO.sub.3 H, --PO.sub.3 H.sub.2, and tetrazolyl;
- provided that n is 1 when R.sup.1 is other than SO.sub.2 H;
- R.sup.2 is selected from the group consisting of H, --OH, and --NH.sub.2 ;
- R.sup.3 is selected independently at each occurrence from the group consisting of --OR, --N(R).sub.2, --N.sub.3, --NHC(R.sup.6)NH.sub.2, --CN, --C(R.sup.6)NH.sub.2, H, --C(R)(.dbd.N)NHC(.dbd.NH)NH.sub.2, --C(.dbd.N)RC(.dbd.NH)NH.sub.2, NHCN, and CH.dbd.NOH;
- R.sup.4 is selected from the group consisting of H, --OR, --(CH.sub.2).sub.p NHR.sup.7, and --C(O)NHR.sup.8 ;
- R.sup.5 is selected from the group consisting of H, --(CH(R.sup.3).sub.n).sub.m CH.sub.2 R.sup.3, --NHC(R.sup.6)NH.sub.2, --CH.dbd.CHCH.sub.2 R.sup.3, and CH.dbd.NOH;
- R.sup.6 is selected from the group consisting of .dbd.NH, .dbd.NOH, .dbd.NCN, .dbd.O, and .dbd.S;
- R.sup.7 is selected from the group consisting of --C(.dbd.Y)R.sup.8, --S(O.sub.2)R, --C(O)OR.sup.8, --C(.dbd.Y) NHR.sup.8, and --CH.sub.2 C(.dbd.Y)R.sup.8 ;
- R.sup.8 is selected from the group consisting of C.sub.1 -C.sub.4 linear or branched alkyl substituted with 0-3 halogens on each carbon;
- R is selected from the group consisting of H, C.sub.1 -C.sub.4 linear or branched alkyl, C.sub.1 -C.sub.4 linear or branched alkyl-OH, C.sub.1 -C.sub.4 linear or branched alkyl-NH.sub.2 ;
- and
- Y is O or S.
14 more elements
A method for the treatment of infections caused by viral influenza, said method comprising the step of:
- administering to a host in need of such treatment a pharmaceutically-effective amount of a compound of the Formula (I):
- ##STR59## or pharmaceutically-suitable salts or prodrug forms thereof, wherein:
- n is 0-1;
- m is 0-3;
- p is 0-1;
- R.sup.1 is selected from the group consisting of --CO.sub.2 H, --SO.sub.2 H, --SO.sub.3 H, --PO.sub.3 H.sub.2, and tetrazolyl;
- R.sup.2 is selected from the group consisting of H, --OH, and --NH.sub.2 ;
- R.sup.3 is selected independently at each occurrence from the group consisting of --OR, --N(R).sub.2, --N.sub.3, --NHC(R.sup.6)NH.sub.2, --CN, --C(R.sup.6)NH.sub.2, --C(R)(.dbd.N)NHC(.dbd.NH)NH.sub.2, --C(.dbd.N)RC(.dbd.NH)NH.sub.2, NHCN, and CH.dbd.NOH;
- provided that when R.sup.3 is --OR, R is selected from the group consisting of C.sub.1 -C.sub.4 branched alkyl;
- R.sup.4 is selected from the group consisting of H, --OR, --(CH.sub.2).sub.p NHR.sup.7, and --C(O)NHR.sup.8 ;
- R.sup.5 is selected from the group consisting of H, --(CH(R.sup.3).sub.n).sub.m CH.sub.2 R.sup.3, --NHC(R.sup.6)NH.sub.2, --CH.dbd.CHCH.sub.2 R.sup.3, and CH.dbd.NOH;
- R.sup.6 is selected from the group consisting of .dbd.NH, .dbd.NOH, .dbd.NCN, .dbd.O, and .dbd.S;
- R.sup.7 is selected from the group consisting of --C(.dbd.Y)R.sup.8, --S(O.sub.2)R, --C(O)OR.sup.8, --C(.dbd.Y)NHR.sup.8, and --CH.sub.2 C(.dbd.Y)R.sup.8 ;
- R.sup.8 is selected from the group consisting of C.sub.1 -C.sub.4 linear or branched alkyl substituted with 0-3 halogens on each carbon;
- R is selected from the group consisting of H, C.sub.1 -C.sub.4 linear or branched alkyl, C.sub.1 -C.sub.4 linear or branched alkyl-OH, C.sub.1 -C.sub.4 linear or branched alkyl-NH.sub.2 ;
- and
- Y is O or S.
14 more elements
A method for the treatment of infections caused by viral influenza, said method comprising the step of:
- administering to a host in need of such treatment a pharmaceutically-effective amount of a compound of the Formula (I):
- ##STR60## or pharmaceutically-suitable salts or prodrug forms thereof, wherein:
- n is 0-1;
- m is 0-3;
- p is 0-1;
- R.sup.1 is selected from the group consisting of --CO.sub.2 H, --SO.sub.2 H, --SO.sub.3 H, --PO.sub.3 H.sub.2, and tetrazolyl;
- R.sup.2 is selected from the group consisting of H, --OH, and --NH.sub.2 ;
- R.sup.3 is selected independently at each occurrence from the group consisting of --OR, --N(R).sub.2, --N.sub.3, --NHC(R.sup.6)NH.sub.2, --CN, --C(R.sup.6)NH.sub.2, H, --C(R)(.dbd.N)NHC(.dbd.NH)NH.sub.2, --C(.dbd.N)RC(.dbd.NH)NH.sub.2, NHCN, and CH.dbd.NOH;
- R.sup.4 is selected from the group consisting of H, --(CH.sub.2).sub.p NHR.sup.7, --C(O)NHR.sup.8, --OH, --OCH.sub.3, and --CONHCH.sub.3 ;
- provided that when p=0 and R.sup.7 =C(.dbd.O)R.sup.8, R.sup.8 is a C.sub.4 linear or branched alkyl substituted with 0-3 halogens on each carbon;
- R.sup.5 is selected from the group consisting of H, --(CH(R.sup.3).sub.n).sub.m CH.sub.2 R.sup.3, --NHC(R.sup.6)NH.sub.2, --CH.dbd.CHCH.sub.2 R.sup.3, and CH.dbd.NOH;
- R.sup.6 is selected from the group consisting of .dbd.NH, .dbd.NOH, .dbd.NCN, .dbd.O, and .dbd.S;
- R.sup.7 is selected from the group consisting of --C(.dbd.Y)R.sup.8, --S(O.sub.2)R, --C(O)OR.sup.8, --C(.dbd.Y)NHR.sup.8, and --CH.sub.2 C(.dbd.Y)R.sup.8 ;
- R.sup.8 is selected from the group consisting of C.sub.1 -C.sub.4 linear or branched alkyl substituted with 0-3 halogens on each carbon;
- R is selected from the group consisting of H, C.sub.1 -C.sub.4 linear or branched alkyl, C.sub.1 -C.sub.4 linear or branched alkyl-OH, C.sub.1 -C.sub.4 linear or branched alkyl-NH.sub.2 ;
- and
- Y is O or S.
14 more elements
A method for the treatment of infections caused by viral influenza, said method comprising the step of:
- administering to a host in need of such treatment a pharmaceutically-effective amount of a compound of the Formula (I):
- ##STR61## or pharmaceutically-suitable salts or prodrug forms thereof, wherein:
- n is 0-1;
- m is 0-3;
- p is 0-1;
- R.sup.1 is selected from the group consisting of --CO.sub.2 H, --SO.sub.2 H, --SO.sub.3 H, --PO.sub.3 H.sub.2, and tetrazolyl, provided that n is 1 when R.sup.1 is other than SO.sub.2 H;
- R.sup.2 is selected from the group consisting of H, --OH, and --NH.sub.2 ;
- R.sup.3 is selected independently at each occurrence from the group consisting of --OR, --N(R).sub.2, --N.sub.3, --NHC(R.sup.6)NH.sub.2, --CN, --C(R.sup.6)NH.sub.2, H, --C(R)(.dbd.N)NHC(.dbd.NH)NH.sub.2, --C(.dbd.N)RC(.dbd.NH)NH.sub.2, NHCN, and CH.dbd.NOH;
- R.sup.4 is selected from the group consisting of H, --OR, --(CH.sub.2).sub.p NHR.sup.7, and --C(O)NHR.sup.8 ;
- R.sup.5 is selected from the group consisting of --(CH(R.sup.3).sub.n).sub.m CH.sub.2 R.sup.3, --NHC(R.sup.6)NH.sub.2, --CH.dbd.CHCH.sub.2 R.sup.3, CH.dbd.NOH, CH.sub.2 OR, NHCN;
- provided that when R.sup.5 is CH.sub.2 OR, R is not H;
- that R.sup.3 in not H;
- that when R.sup.3 is OR, R is not H;
- and that when R.sup.3 is N(R).sub.2, R is not H;
- R.sup.6 is selected from the group consisting of .dbd.NH, .dbd.NOH, .dbd.NCN, .dbd.O, and .dbd.S;
- R.sup.7 is selected from the group consisting of --C(.dbd.Y)R.sup.8, --S(O.sub.2)R, --C(O)OR.sup.8, --C(.dbd.Y)NHR.sup.8, and --CH.sub.2 C(.dbd.Y)R.sup.8 ;
- R.sup.8 is selected from the group consisting of C.sub.1 -C.sub.4 linear or branched alkyl substituted with 0-3 halogens on each carbon;
- R is selected from the group consisting of H, C.sub.1 -C.sub.4 linear or branched alkyl, C.sub.1 -C.sub.4 linear or branched alkyl-OH, C.sub.1 -C.sub.4 linear or branched alkyl-NH.sub.2 ;
- and
- Y is O or S.
17 more elements
A method for the treatment of infections caused by viral influenza, said method comprising the step of:
- administering to a host in need of such treatment a pharmaceutically-effective amount of a compound of the Formula (I):
- ##STR62## or pharmaceutically-suitable salts or prodrug forms thereof, wherein:
- n is 0-1;
- m is 0-3;
- p is 0-1;
- R.sup.1 is tetrazolyl;
- R.sup.2 is selected from the group consisting of H, --OH, and --NH.sub.2 ;
- R.sup.3 is selected from the group consisting of --N.sub.3, amidine, substituted amidines, hydroxyamidine, substituted hydroxyamidines, cyanoamidine, substituted cyanoamidines, urea, substituted ureas, thiourea, substituted thioureas, --C(R)(.dbd.N)NHC(.dbd.NH)NH.sub.2, --C(.dbd.N)RC(.dbd.NH)NH.sub.2, --NHCN, and --CH.dbd.NOH;
- R.sup.4 is selected from the group consisting of --NHC(.dbd.S)R.sup.8, and --C(O)NHR.sub.8 ;
- R.sup.5 is the same as R.sup.3 ;
- R.sup.8 is selected from the group consisting of C.sub.1 -C.sub.4 linear or branched alkyl substituted with 0-3 halogens on each carbon;
- R is selected from the group consisting of H, C.sub.1 -C.sub.4 linear or branched alkyl, C.sub.1 -C.sub.4 linear or branched alkyl-OH, C.sub.1 -C.sub.4 linear or branched alkyl-NH.sub.2.
9 more elements
A method for the treatment of infections caused by viral influenza, said method comprising the step of:
- administering to a host in need of such treatment a pharmaceutically-effective amount of a compound selected from the group consisting of:
- Phenylguanidine;
- 1-Phenylbiguanide;
- 4-Acetylaminobenzoic acid;
- 2-Acetylaminobenzenesulfonic acid;
- 4-Acetylaminophenylphosphoric acid;
- 4-(Trifluoroacetamido)benzoic acid;
- 4-Thioacetamidobenzoic acid;
- 4-[(Methylsulfonyl)amino]benzoic acid;
- 3-Guanidinobenzoic acid;
- 3-[Amino(cyanoimino)methyl]aminobenzoic acid;
- 3-Cyanoaminobenzoic acid;
- 3-(2-Amino-2-imino)ethylbenzoic acid;
- 4-(Acetamino)phenylacetic acid;
- 4-(Methylaminocarbonyl)benzoic acid;
- 4-Acetylamino-3-hydroxymethylbenzoic acid;
- .beta.-(2-N-Acetylamino-5-carboxyphenyl)ethanol;
- 4-Acetylamino-3-(2',3'-dihydroxypropyl)benzoic acid;
- 4-Acetylamino-3-aminobenzoic acid;
- 4-Acetylamino-3-[(aminoiminomethyl)amino]benzoic acid;
- 3-[(Aminoiminomethyl)amino]-4-(2-methylpropionylamino)benzoic acid;
- 4-Acetylamino-3-[(hydroxylimino)methyl]benzoic acid;
- 3-[(Aminoiminomethyl)amino]-4-[(methylsulfonyl)amino]benzoic acid;
- 3-[(N-Hydroxyimino)methyl]-4-[(methylsulfonyl)amino]benzoic acid;
- 3-[((Aminoimino)methyl)amino]-4-methoxybenzoic acid;
- 3-[(Aminoiminomethyl)amino]-4-hydroxybenzoic acid;
- 3,5-Bis-[(aminoiminomethyl)amino]benzoic acid;
- 3-Amino-5-{[(aminoimino)methyl]amino}benzoic acid;
- 3-[(Aminoiminomethyl)amino]-5-[(N-hydroxylimino)methyl]benzoic acid;
- and
- 3-[(Aminoiminomethyl)amino-5-hydroxymethyl)-4-(methylsulfonyl)aminobenzoic acid.
28 more elements
A pharmaceutical composition comprising a pharmaceutically-suitable carrier and a therapeutically-effective antiviral amount of a compound according to the Formula (I):
- ##STR63## or pharmaceutically-suitable salts or prodrug forms thereof, wherein:
- n is 0-1;
- m is 0-3;
- p is 0-1;
- R.sup.1 is tetrazolyl;
- R.sup.2 is selected from the group consisting of H, --OH, and --NH.sub.2 ;
- R.sup.3 is selected from the group consisting of --N.sub.3, --N(R).sub.2, --CN, --C(R.sup.6)NH.sub.2, --NHC(R.sub.6)NH.sub.2, --C(R)(.dbd.N)NHC(.dbd.NH)NH.sub.2, --C(.dbd.N)RC(.dbd.NH)NH.sub.2, --NHCN, and --CH.dbd.NOH;
- R.sup.4 is selected from the group consisting of --NHC(.dbd.S)R.sup.8, and --C(O)NHR.sup.8 ;
- R.sup.5 is the same as R.sup.3 ;
- R.sup.6 is selected from the group consisting of .dbd.NH, .dbd.NOH, .dbd.NCN, .dbd.O, and .dbd.S;
- R.sup.8 is selected from the group consisting of C.sub.1 -C.sub.4 linear or branched alkyl substituted with 0-3 halogens on each carbon;
- R is selected from the group consisting of H, C.sub.1 -C.sub.4 linear or branched alkyl, C.sub.1 -C.sub.4 linear or branched alkyl-OH, C.sub.1 -C.sub.4 linear or branched alkyl-NH.sub.2.
9 more elements
A compound of the Formula (I):
- ##STR64## or pharmaceutically-suitable salts or prodrug forms thereof, wherein:
- n is 0-1;
- m is 0;
- R.sup.1 is --CO.sub.2 H;
- R.sup.2 is selected from the group consisting of H, --OH, and --NH.sub.2 ;
- R.sup.3 is H;
- R.sup.4 is --C(O)NHR.sup.8 ;
- R.sup.5 is --NHC(R.sup.6)NH.sub.2
- R.sup.6 is selected from the group consisting of .dbd.NH, .dbd.NOH, .dbd.NCN, .dbd.O, and .dbd.S;
- and
- R.sup.8 is selected from the group consisting of C.sub.1 -C.sub.4 linear or branched alkyl substituted with 0-3 halogens on each carbon.
8 more elements
Dependencies are inferred from the claim text.