Claims for Patent: 8,980,878

Summary for Patent: 8,980,878

Title:	Compounds and methods for antiviral treatment
Abstract:	Compounds and pharmaceutically acceptable salts and esters and compositions thereof, for treating viral infections are provided. The compounds and compositions are useful for treating Pneumovirinae virus infections. The compounds, compositions, and methods provided are particularly useful for the treatment of Human respiratory syncytial virus infections.
Inventor(s):	Siegel; Dustin (Foster City, CA), Sperandio; David (Palo Alto, CA), Yang; Hai (San Mateo, CA), Sangi; Michael (Oakland, CA), Parrish; Jay P. (Redwood City, CA), Hui; Hon Chung (San Mateo, CA)
Assignee:	Gilead Sciences, Inc. (Foster City, CA)
Application Number:	13/865,069
Patent Claims:	1. A compound of Formula I: ##STR00304## or a pharmaceutically acceptable salt thereof; wherein: a) Y.sup.1 is N, NH or CH, Y.sup.2 is C, Y.sup.3 is N or CR.sup.8', Y.sup.4 is N or C and Y.sup.5 is N, NR.sup.2' or CR.sup.2, wherein at least two of Y.sup.1, Y.sup.2, Y.sup.3, Y.sup.4 and Y.sup.5 are independently N, NH or NR.sup.2'; or b) Y.sup.1 is N, NH or CH, Y.sup.2 is N or C, Y.sup.3 is N or CR.sup.8', Y.sup.4 is N or C, and Y.sup.5 is N or NR.sup.2', wherein at least two of Y.sup.1, Y.sup.2, Y.sup.3, Y.sup.4 and Y.sup.5 are independently N, NH or NR.sup.2'; or c) Y.sup.1 is N, NH or CH, Y.sup.2 is N or C, Y.sup.3 is CR.sup.8', Y.sup.4 is N or C, and Y.sup.5 is N, NR.sup.2' or CR.sup.2, wherein at least two of Y.sup.1, Y.sup.2, Y.sup.3, Y.sup.4 and Y.sup.5 are independently N, NH or NR.sup.2'; the dashed bonds - - - are selected from single bonds and double bonds so as to provide an aromatic ring system; A is --(CR.sup.4R.sup.4').sub.n--; n is 3, 4, 5 or 6; each p is 1 or 2; Ar is a C.sub.2-C.sub.20 heterocyclyl group or a C.sub.6-C.sub.20 aryl group, wherein the C.sub.2-C.sub.20 heterocyclyl group or the C.sub.6-C.sub.20 aryl group is optionally substituted with 1 to 5 R.sup.6; X is --C(R.sup.13)(R.sup.14)--, --N(CH.sub.2R.sup.14)-- or --NH--, or X is absent; R.sup.1 is H, --OR.sup.11, --NR.sup.11R.sup.12, --NR.sup.11C(O)R.sup.11, --NR.sup.11C(O)OR.sup.11, --NR.sup.11C(O)NR.sup.11R.sup.12, N.sub.3, CN, NO.sub.2, --SR.sup.11, --S(O).sub.pR.sup.a, NR.sup.11S(O).sub.pR.sup.a, --C(.dbd.O)R.sup.11, --C(.dbd.O)OR.sup.11, --C(.dbd.O)NR.sup.11R.sup.12, --C(.dbd.O)SR.sup.11, --S(O).sub.p(OR.sup.11), --SO.sub.2NR.sup.11R.sup.12, --NR.sup.11S(O).sub.p(OR.sup.11), --NR.sup.11SO.sub.pNR.sup.11R.sup.12, --NR.sup.11C(.dbd.NR.sup.11)NR.sup.11R.sup.12, halogen, (C.sub.1-C.sub.8)alkyl, (C.sub.2-C.sub.8)alkenyl, (C.sub.2-C.sub.8)alkynyl, aryl(C.sub.1-C.sub.8)alkyl, C.sub.6-C.sub.20 aryl, C.sub.2-C.sub.20 heterocyclyl, C.sub.2-C.sub.20 heterocyclyl(C.sub.1-C.sub.8)alkyl, (C.sub.3-C.sub.7)cycloalkyl or (C.sub.3-C.sub.7)cycloalkyl(C.sub.1-C.sub.8)alkyl; R.sup.2 is H, CN, NO.sub.2, halogen or (C.sub.1-C.sub.8)alkyl; R.sup.2' is H or (C.sub.1-C.sub.8)alkyl; R.sup.3 is H, --OR.sup.11, --NR.sup.11R.sup.12, --NR.sup.11C(O)R.sup.11, --NR.sup.11C(O)OR.sup.11, --NR.sup.11C(O)NR.sup.11R.sup.12, N.sub.3, CN, NO.sub.2, --SR.sup.11, --S(O).sub.pR.sup.a, --NR.sup.11S(O).sub.pR.sup.a, --C(.dbd.O)R.sup.11, --C(.dbd.O)OR.sup.11, --C(.dbd.O)NR.sup.11R.sup.12, --C(.dbd.O)SR.sup.11, --S(O).sub.p(OR.sup.11), --SO.sub.2NR.sup.11R.sup.12, --NR.sup.11S(O).sub.p(OR.sup.11), --NR.sup.11SO.sub.pNR.sup.11R.sup.12, --NR.sup.11C(.dbd.NR.sup.11)NR.sup.11R.sup.12, halogen, (C.sub.1-C.sub.8)alkyl, (C.sub.2-C.sub.8)alkenyl, (C.sub.2-C.sub.8)alkynyl, aryl(C.sub.1-C.sub.8)alkyl, C.sub.6-C.sub.20 aryl, C.sub.2-C.sub.20 heterocyclyl, C.sub.2-C.sub.20 heterocyclyl(C.sub.1-C.sub.8)alkyl, (C.sub.3-C.sub.7)cycloalkyl or (C.sub.3-C.sub.7)cycloalkyl(C.sub.1-C.sub.8)alkyl; R.sup.3' is H, --OR.sup.11, (C.sub.1-C.sub.8)alkyl, (C.sub.2-C.sub.8)alkenyl, (C.sub.2-C.sub.8)alkynyl, aryl(C.sub.1-C.sub.8)alkyl, C.sub.6-C.sub.20 aryl, C.sub.2-C.sub.20 heterocyclyl, C.sub.2-C.sub.20 heterocyclyl(C.sub.1-C.sub.8)alkyl, (C.sub.3-C.sub.7)cycloalkyl or (C.sub.3-C.sub.7)cycloalkyl(C.sub.1-C.sub.8)alkyl; each R.sup.4 is independently H, --OR.sup.11, --NR.sup.11R.sup.12, --NR.sup.11C(O)R.sup.11, --NR.sup.11C(O)OR.sup.11, --NR.sup.11C(O)NR.sup.11R.sup.12, N.sub.3, CN, NO.sub.2, SR.sup.11, --S(O).sub.pR.sup.a, --NR.sup.11S(O).sub.pR.sup.a, --C(.dbd.O)R.sup.11, --C(.dbd.O)OR.sup.11, --C(.dbd.O)NR.sup.11R.sup.12, --C(.dbd.O)SR.sup.11, --S(O).sub.p(OR.sup.11), --SO.sub.2NR.sup.11R.sup.12, --NR.sup.11S(O).sub.p(OR.sup.11), --NR.sup.11SO.sub.pNR.sup.11R.sup.12, NR.sup.11C(.dbd.NR.sup.11)NR.sup.11R.sup.12, halogen, (C.sub.1-C.sub.8)alkyl, (C.sub.2-C.sub.8)alkenyl, (C.sub.2-C.sub.8)alkynyl, aryl(C.sub.1-C.sub.8)alkyl, C.sub.6-C.sub.20 aryl, C.sub.2-C.sub.20 heterocyclyl, C.sub.2-C.sub.20 heterocyclyl(C.sub.1-C.sub.8)alkyl, (C.sub.3-C.sub.7)cycloalkyl or (C.sub.3-C.sub.7)cycloalkyl(C.sub.1-C.sub.8)alkyl; and each R.sup.4' is independently H, OR.sup.11, (C.sub.1-C.sub.8)alkyl, (C.sub.2-C.sub.8)alkenyl, (C.sub.2-C.sub.8)alkynyl, aryl(C.sub.1-C.sub.8)alkyl, C.sub.6-C.sub.20 aryl, C.sub.2-C.sub.20 heterocyclyl, C.sub.2-C.sub.20 heterocyclyl(C.sub.1-C.sub.8)alkyl, (C.sub.3-C.sub.7)cycloalkyl or (C.sub.3-C.sub.7)cycloalkyl(C.sub.1-C.sub.8)alkyl; or two R.sup.4 on adjacent carbon atoms, when taken together, may form a double bond between the two carbons to which they are attached or may form a (C.sub.3-C.sub.7)cycloalkyl ring wherein one carbon atom of said (C.sub.3-C.sub.7)cycloalkyl ring may be optionally replaced by --O--, --S--, --S(O).sub.P--, --NH-- or --NR.sup.a--; or two R.sup.4 on non-adjacent carbon atoms, when taken together, may form a (C.sub.3-C.sub.7)cycloalkyl ring wherein one carbon atom of said (C.sub.3-C.sub.7)cycloalkyl ring may be optionally replaced by --O--, --S--, --S(O).sub.P--, --NH-- or --NR.sup.a--; or two R.sup.4 and two R.sup.4' on adjacent carbon atoms, when taken together, may form an optionally substituted C.sub.6 aryl ring; or one R.sup.4 and one R.sup.4' on the same carbon atom, when taken together, may form a (C.sub.3-C.sub.7)cycloalkyl ring wherein one carbon atom of said (C.sub.3-C.sub.7)cycloalkyl ring may be optionally replaced by --O--, --S--, --S(O).sub.P--, --NH-- or --NR.sup.a--; each R.sup.5 is independently H, --OR.sup.11, --NR.sup.11R.sup.12, --NR.sup.11C(O)R.sup.11, --NR.sup.11C(O)OR.sup.11, --NR.sup.11C(O)NR.sup.11R.sup.12, N.sub.3, CN, NO.sub.2, --SR.sup.11, --S(O).sub.pR.sup.a, --NR.sup.11S(O).sub.pR.sup.a, --C(.dbd.O)R.sup.11, --C(.dbd.O)OR.sup.11, --C(.dbd.O)NR.sup.11R.sup.12, --C(.dbd.O)SR.sup.11, --S(O).sub.p(OR.sup.11), --SO.sub.2NR.sup.11R.sup.12, --NR.sup.11S(O).sub.p(OR.sup.11), --NR.sup.11SO.sub.pNR.sup.11R.sup.12, --NR.sup.11C(.dbd.NR.sup.11)NR.sup.11R.sup.12, halogen, (C.sub.1-C.sub.8)alkyl, (C.sub.2-C.sub.8)alkenyl, (C.sub.2-C.sub.8)alkynyl, aryl(C.sub.1-C.sub.8)alkyl, C.sub.6-C.sub.20 aryl, C.sub.2-C.sub.20 heterocyclyl, C.sub.2-C.sub.20 heterocyclyl(C.sub.1-C.sub.8)alkyl, (C.sub.3-C.sub.7)cycloalkyl or (C.sub.3-C.sub.7)cycloalkyl(C.sub.1-C.sub.8)alkyl; each R.sup.5' is independently H, --OR.sup.11, (C.sub.1-C.sub.8)alkyl, (C.sub.2-C.sub.8)alkenyl, (C.sub.2-C.sub.8)alkynyl, aryl(C.sub.1-C.sub.8)alkyl, C.sub.6-C.sub.20 aryl, C.sub.2-C.sub.20 heterocyclyl, C.sub.2-C.sub.20 heterocyclyl(C.sub.1-C.sub.8)alkyl, (C.sub.3-C.sub.7)cycloalkyl or (C.sub.3-C.sub.7)cycloalkyl(C.sub.1-C.sub.8)alkyl; each R.sup.6 is independently H, oxo, --OR.sup.11, --NR.sup.11R.sup.12, --NR.sup.11C(O)R.sup.11, --NR.sup.11C(O)OR.sup.11, --NR.sup.11C(O)NR.sup.11R.sup.12, N.sub.3, CN, NO.sub.2, --SR.sup.11, --S(O).sub.pR.sup.a, --NR.sup.11S(O).sub.pR.sup.a, --C(.dbd.O)R.sup.11, --C(.dbd.O)OR.sup.11, --C(.dbd.O)NR.sup.11R.sup.12, --C(.dbd.O)SR.sup.11, --S(O).sub.p(OR.sup.11), --SO.sub.2NR.sup.11R.sup.12, --NR.sup.11S(O).sub.p(OR.sup.11), --NR.sup.11SO.sub.pNR.sup.11R.sup.12, --NR.sup.11C(.dbd.NR.sup.11)NR.sup.11R.sup.12, halogen, (C.sub.1-C.sub.8)alkyl, (C.sub.2-C.sub.8)alkenyl, (C.sub.2-C.sub.8)alkynyl, aryl(C.sub.1-C.sub.8)alkyl, C.sub.6-C.sub.20 aryl, C.sub.2-C.sub.20 heterocyclyl, C.sub.2-C.sub.20 heterocyclyl(C.sub.1-C.sub.8)alkyl, (C.sub.3-C.sub.7)cycloalkyl or (C.sub.3-C.sub.7)cycloalkyl(C.sub.1-C.sub.8)alkyl; or two R.sup.6 on adjacent carbon atoms, when taken together, may form a (C.sub.3-C.sub.7)cycloalkyl ring wherein one carbon atom of said (C.sub.3-C.sub.7)cycloalkyl ring may be optionally replaced by --O--, --S--, --S(O).sub.P--, --NH-- or --NR.sup.a--; or any R.sup.6 adjacent to the obligate carbonyl group of said Ar, when taken together with R.sup.3, may form a bond or a --(CR.sup.5R.sup.5').sub.m-- group wherein m is 1 or 2; or any R.sup.6 adjacent to the obligate carbonyl group of said Ar, when taken together with R.sup.2 or R.sup.2' may form a bond; R.sup.7 is H, --OR.sup.11, --NR.sup.11R.sup.12, --NR.sup.11C(O)R.sup.11, --NR.sup.11C(O)OR.sup.11, --NR.sup.11C(O)NR.sup.11R.sup.12, N.sub.3, CN, NO.sub.2, --SR.sup.11, --S(O).sub.pR.sup.a, --NR.sup.11S(O).sub.pR.sup.a, --C(.dbd.O)R.sup.11, --C(.dbd.O)OR.sup.11, --C(.dbd.O)NR.sup.11R.sup.12, --C(.dbd.O)SR.sup.11, --S(O).sub.p(OR.sup.11), --SO.sub.2NR.sup.11R.sup.12, --NR.sup.11S(O).sub.p(OR.sup.11), --NR.sup.11SO.sub.pNR.sup.11R.sup.12, --NR.sup.11C(.dbd.NR.sup.11)NR.sup.11R.sup.12, halogen, (C.sub.1-C.sub.8)alkyl, (C.sub.2-C.sub.8)alkenyl, (C.sub.2-C.sub.8)alkynyl, aryl(C.sub.1-C.sub.8)alkyl, C.sub.6-C.sub.20 aryl, C.sub.2-C.sub.20 heterocyclyl, C.sub.2-C.sub.20 heterocyclyl(C.sub.1-C.sub.8)alkyl, (C.sub.3-C.sub.7)cycloalkyl or (C.sub.3-C.sub.7)cycloalkyl(C.sub.1-C.sub.8)alkyl; R.sup.8 is H, --OR.sup.11, --NR.sup.11R.sup.12, --NR.sup.11C(O)R.sup.11, --NR.sup.11C(O)OR.sup.11, --NR.sup.11C(O)NR.sup.11R.sup.12, N.sub.3, CN, NO.sub.2, --SR.sup.11, --S(O).sub.pR.sup.a, --NR.sup.11S(O).sub.pR.sup.a, --C(.dbd.O)R.sup.11, --C(.dbd.O)OR.sup.11, --C(.dbd.O)NR.sup.11R.sup.12, --C(.dbd.O)SR.sup.11, --S(O).sub.p(OR.sup.11), --SO.sub.2NR.sup.11R.sup.12, --NR.sup.11S(O).sub.p(OR.sup.11), --NR.sup.11SO.sub.pNR.sup.11R.sup.12, NR.sup.11C(.dbd.NR.sup.11)NR.sup.11R.sup.12, halogen, (C.sub.1-C.sub.8)alkyl, (C.sub.2-C.sub.8)alkenyl, (C.sub.2-C.sub.8)alkynyl, aryl(C.sub.1-C.sub.8)alkyl, C.sub.6-C.sub.20 aryl, C.sub.2-C.sub.20 heterocyclyl, C.sub.2-C.sub.20 heterocyclyl(C.sub.1-C.sub.8)alkyl, (C.sub.3-C.sub.7)cycloalkyl or (C.sub.3-C.sub.7)cycloalkyl(C.sub.1-C.sub.8)alkyl; R.sup.8' is H, --OR.sup.11, --NR.sup.11R.sup.12, --NR.sup.11C(O)R.sup.11, --NR.sup.11C(O)OR.sup.11, --NR.sup.11C(O)NR.sup.11R.sup.12, N.sub.3, CN, NO.sub.2, --SR.sup.11, --S(O).sub.pR.sup.a, --NR.sup.11S(O).sub.pR.sup.a, --C(.dbd.O)R.sup.11, --C(.dbd.O)OR.sup.11, --C(.dbd.O)NR.sup.11R.sup.12, --C(.dbd.O)SR.sup.11, --S(O).sub.p(OR.sup.11), --SO.sub.2NR.sup.11R.sup.12, --NR.sup.11S(O).sub.p(OR.sup.11), --NR.sup.11SO.sub.pNR.sup.11R.sup.12, --NR.sup.11C(.dbd.NR.sup.11)NR.sup.11R.sup.12, halogen, (C.sub.1-C.sub.8)alkyl, (C.sub.2-C.sub.8)alkenyl, (C.sub.2-C.sub.8)alkynyl, aryl(C.sub.1-C.sub.8)alkyl, C.sub.6-C.sub.20 aryl, C.sub.2-C.sub.20 heterocyclyl, C.sub.2-C.sub.20 heterocyclyl(C.sub.1-C.sub.8)alkyl, (C.sub.3-C.sub.7)cycloalkyl or (C.sub.3-C.sub.7)cycloalkyl(C.sub.1-C.sub.8)alkyl; each R.sup.a is independently (C.sub.1-C.sub.8)alkyl, (C.sub.1-C.sub.8)haloalkyl, (C.sub.2-C.sub.8)alkenyl, (C.sub.2-C.sub.8)alkynyl, aryl(C.sub.1-C.sub.8)alkyl, C.sub.6-C.sub.20 aryl, C.sub.2-C.sub.20 heterocyclyl, C.sub.2-C.sub.20 heterocyclyl(C.sub.1-C.sub.8)alkyl, (C.sub.3-C.sub.7)cycloalkyl or (C.sub.3-C.sub.7)cycloalkyl(C.sub.1-C.sub.8)alkyl wherein any (C.sub.1-C.sub.8)alkyl, (C.sub.1-C.sub.8)haloalkyl, (C.sub.2-C.sub.8)alkenyl or (C.sub.2-C.sub.8)alkynyl of R.sup.a is optionally substituted with one or more OH, NH.sub.2, CO.sub.2H, C.sub.2-C.sub.20 heterocyclyl, and wherein any aryl(C.sub.1-C.sub.8)alkyl, C.sub.6-C.sub.20 aryl, C.sub.2-C.sub.20 heterocyclyl, (C.sub.3-C.sub.7)cycloalkyl or (C.sub.3-C.sub.7)cycloalkyl(C.sub.1-C.sub.8)alkyl of R.sup.a is optionally substituted with one or more --OH, --NH.sub.2, CO.sub.2H, C.sub.2-C.sub.20 heterocyclyl or (C.sub.1-C.sub.8)alkyl; each R.sup.11 or R.sup.12 is independently H, (C.sub.1-C.sub.8)alkyl, (C.sub.2-C.sub.8)alkenyl, (C.sub.2-C.sub.8)alkynyl, aryl(C.sub.1-C.sub.8)alkyl, C.sub.6-C.sub.20 aryl, C.sub.2-C.sub.20 heterocyclyl, (C.sub.3-C.sub.7)cycloalkyl, (C.sub.3-C.sub.7)cycloalkyl(C.sub.1-C.sub.8)alkyl, --C(.dbd.O)R.sup.a or --S(O).sub.pR.sup.a; or when R.sup.11 and R.sup.12 are attached to a nitrogen they may optionally be taken together with the nitrogen to which they are both attached to form a 3 to 7 membered heterocyclic ring wherein any one carbon atom of said heterocyclic ring can optionally be replaced with --O--, --S--, --S(O).sub.p--, --NH--, --NR.sup.a-- or --C(O)--; R.sup.13 is H or (C.sub.1-C.sub.8)alkyl; R.sup.14 is H, (C.sub.1-C.sub.8)alkyl, NR.sup.11R.sup.12, NR.sup.11C(O)R.sup.11, NR.sup.11C(O)OR.sup.11, NR.sup.11C(O)NR.sup.11R.sup.12, NR.sup.11S(O).sub.pR.sup.a, --NR.sup.11S(O).sub.p(OR.sup.11) or NR.sup.11SO.sub.pNR.sup.11R.sup.12; and wherein each (C.sub.1-C.sub.8)alkyl, (C.sub.2-C.sub.8)alkenyl, (C.sub.2-C.sub.8)alkynyl, aryl(C.sub.1-C.sub.8)alkyl, C.sub.6-C.sub.20 aryl, C.sub.2-C.sub.20 heterocyclyl, C.sub.2-C.sub.20 heterocyclyl(C.sub.1-C.sub.8)alkyl, (C.sub.3-C.sub.7)cycloalkyl or (C.sub.3-C.sub.7)cycloalkyl(C.sub.1-C.sub.8)alkyl of each R.sup.1, R.sup.2, R.sup.2', R.sup.3, R.sup.3', R.sup.4, R.sup.4', R.sup.5, R.sup.5', R.sup.6, R.sup.7, R.sup.8, R.sup.8' or R.sup.12 is independently, optionally substituted with one or more oxo, halogen, hydroxy, --NH.sub.2, CN, N.sub.3, --N(R.sup.a).sub.2, --NHR.sup.a, --SH, --SR.sup.a, --S(O).sub.pR.sup.a, --OR.sup.a, (C.sub.1-C.sub.8)alkyl, (C.sub.1-C.sub.8)haloalkyl, --C(O)R.sup.a, --C(O)H, --C(.dbd.O)OR.sup.a, --C(.dbd.O)OH, --C(.dbd.O)N(R.sup.a).sub.2, --C(.dbd.O)NHR.sup.a, --C(.dbd.O)NH.sub.2, --NHS(O).sub.pR.sup.a, --NR.sup.aS(O).sub.pR.sup.a, --NHC(O)R.sup.a, --NR.sup.aC(O)R.sup.a, --NHC(O)OR.sup.a, --NR.sup.aC(O)OR.sup.a, --NR.sup.aC(O)NHR.sup.a, --NR.sup.aC(O)N(R.sup.a).sub.2, --NR.sup.aC(O)NH.sub.2, --NHC(O)NHR.sup.a, --NHC(O)N(R.sup.a).sub.2, --NHC(O)NH.sub.2, .dbd.NH, .dbd.NOH, .dbd.NOR.sup.a, --NR.sup.aS(O).sub.pNHR.sup.a, --NR.sup.aS(O).sub.pN(R.sup.a).sub.2, --NR.sup.aS(O).sub.pNH.sub.2, --NHS(O).sub.pNHR.sup.a,--NHS(O).sub.pN(R.sup.a).sub.2, --NHS(O).sub.pNH.sub.2, --OC(.dbd.O)R.sup.a, --OP(O)(OH).sub.2 or R.sup.a. 2. The compound of claim 1 wherein: a) Y.sup.1 is N, NH or CH, Y.sup.2 is C, Y.sup.3 is N or CR.sup.8', Y.sup.4 is N or C and Y.sup.5 is N, NR.sup.2' or CR.sup.2, wherein at least two of Y.sup.1, Y.sup.2, Y.sup.3, Y.sup.4 and Y.sup.5 are independently N, NH or NR.sup.2'; or b) Y.sup.1 is N, NH or CH, Y.sup.2 is N or C, Y.sup.3 is N or CR.sup.8', Y.sup.4 is N or C, and Y.sup.5 is N or NR.sup.2', wherein at least two of Y.sup.1, Y.sup.2, Y.sup.3, Y.sup.4 and Y.sup.5 are independently N, NH or NR.sup.2'; or c) Y.sup.1 is N, NH or CH, Y.sup.2 is N or C, Y.sup.3 is CR.sup.8', Y.sup.4 is N or C, and Y.sup.5 is N, NR.sup.2' or CR.sup.2, wherein at least two of Y.sup.1, Y.sup.2, Y.sup.3, Y.sup.4 and Y.sup.5 are independently N, NH or NR.sup.2'; the dashed bonds - - - are selected from single bonds and double bonds so as to provide an aromatic ring system; A is --(CR.sup.4R.sup.4').sub.n--; n is 3, 4, 5 or 6; each p is 1 or 2; Ar is a C.sub.2-C.sub.20 heterocyclyl group or a C.sub.6-C.sub.20 aryl group, wherein the C.sub.2-C.sub.20 heterocyclyl group or the C.sub.6-C.sub.20 aryl group is optionally substituted with 1 to 5 R.sup.6; X is --C(R.sup.13)(R.sup.14)--, --N(CH.sub.2R.sup.14)-- or --NH--, or X is absent; R.sup.1 is H, --OR.sup.11, --NR.sup.11R.sup.12, --NR.sup.11C(O)R.sup.11, --NR.sup.11C(O)OR.sup.11, --NR.sup.11C(O)NR.sup.11R.sup.12, N.sub.3, CN, NO.sub.2, --SR.sup.11, --S(O).sub.pR.sup.a, NR.sup.11S(O).sub.pR.sup.a, --C(.dbd.O)R.sup.11, --C(.dbd.O)OR.sup.11, --C(.dbd.O)NR.sup.11R.sup.12, --C(.dbd.O)SR.sup.11, --S(O).sub.p(OR.sup.11), --SO.sub.2NR.sup.11R.sup.12, --NR.sup.11S(O).sub.p(OR.sup.11), --NR.sup.11SO.sub.pNR.sup.11R.sup.12, --NR.sup.11C(.dbd.NR.sup.11)NR.sup.11R.sup.12, halogen, (C.sub.1-C.sub.8)alkyl, (C.sub.2-C.sub.8)alkenyl, (C.sub.2-C.sub.8)alkynyl, aryl(C.sub.1-C.sub.8)alkyl, C.sub.6-C.sub.20 aryl, C.sub.2-C.sub.20 heterocyclyl, C.sub.2-C.sub.20 heterocyclyl(C.sub.1-C.sub.8)alkyl, (C.sub.3-C.sub.7)cycloalkyl or (C.sub.3-C.sub.7)cycloalkyl(C.sub.1-C.sub.8)alkyl; R.sup.2 is H, CN, NO.sub.2, halogen or (C.sub.1-C.sub.8)alkyl; R.sup.2' is H or (C.sub.1-C.sub.8)alkyl; R.sup.3 is H, --OR.sup.11, --NR.sup.11R.sup.12, --NR.sup.11C(O)R.sup.11, --NR.sup.11C(O)OR.sup.11, --NR.sup.11C(O)NR.sup.11R.sup.12, N.sub.3, CN, NO.sub.2, --SR.sup.11, --S(O).sub.pR.sup.a, --NR.sup.11S(O).sub.pR.sup.a, --C(.dbd.O)R.sup.11, --C(.dbd.O)OR.sup.11, --C(.dbd.O)NR.sup.11R.sup.12, --C(.dbd.O)SR.sup.11, --S(O).sub.p(OR.sup.11), --SO.sub.2NR.sup.11R.sup.12, --NR.sup.11S(O).sub.p(OR.sup.11), --NR.sup.11SO.sub.pNR.sup.11R.sup.12, --NR.sup.11C(.dbd.NR.sup.11)NR.sup.11R.sup.12, halogen, (C.sub.1-C.sub.8)alkyl, (C.sub.2-C.sub.8)alkenyl, (C.sub.2-C.sub.8)alkynyl, aryl(C.sub.1-C.sub.8)alkyl, C.sub.6-C.sub.20 aryl, C.sub.2-C.sub.20 heterocyclyl, C.sub.2-C.sub.20 heterocyclyl(C.sub.1-C.sub.8)alkyl, (C.sub.3-C.sub.7)cycloalkyl or (C.sub.3-C.sub.7)cycloalkyl(C.sub.1-C.sub.8)alkyl; R.sup.3' is H, --OR.sup.11, (C.sub.1-C.sub.8)alkyl, (C.sub.2-C.sub.8)alkenyl, (C.sub.2-C.sub.8)alkynyl, aryl(C.sub.1-C.sub.8)alkyl, C.sub.6-C.sub.20 aryl, C.sub.2-C.sub.20 heterocyclyl, C.sub.2-C.sub.20 heterocyclyl(C.sub.1-C.sub.8)alkyl, (C.sub.3-C.sub.7)cycloalkyl or (C.sub.3-C.sub.7)cycloalkyl(C.sub.1-C.sub.8)alkyl; each R.sup.4 is independently H, --OR.sup.11, --NR.sup.11R.sup.12, --NR.sup.11C(O)R.sup.11, --NR.sup.11C(O)OR.sup.11, --NR.sup.11C(O)NR.sup.11R.sup.12, N.sub.3, CN, NO.sub.2, SR.sup.11, --S(O).sub.pR.sup.a, --NR.sup.11S(O).sub.pR.sup.a, --C(.dbd.O)R.sup.11, --C(.dbd.O)OR.sup.11, --C(.dbd.O)NR.sup.11R.sup.12, --C(.dbd.O)SR.sup.11, --S(O).sub.p(OR.sup.11), --SO.sub.2NR.sup.11R.sup.12, --NR.sup.11S(O).sub.p(OR.sup.11), --NR.sup.11SO.sub.pNR.sup.11R.sup.12, NR.sup.11C(.dbd.NR.sup.11)NR.sup.11R.sup.12, halogen, (C.sub.1-C.sub.8)alkyl, (C.sub.2-C.sub.8)alkenyl, (C.sub.2-C.sub.8)alkynyl, aryl(C.sub.1-C.sub.8)alkyl, C.sub.6-C.sub.20 aryl, C.sub.2-C.sub.20 heterocyclyl, C.sub.2-C.sub.20 heterocyclyl(C.sub.1-C.sub.8)alkyl, (C.sub.3-C.sub.7)cycloalkyl or (C.sub.3-C.sub.7)cycloalkyl(C.sub.1-C.sub.8)alkyl; and each R.sup.4' is independently H, OR.sup.11, (C.sub.1-C.sub.8)alkyl, (C.sub.2-C.sub.8)alkenyl, (C.sub.2-C.sub.8)alkynyl, aryl(C.sub.1-C.sub.8)alkyl, C.sub.6-C.sub.20 aryl, C.sub.2-C.sub.20 heterocyclyl, C.sub.2-C.sub.20 heterocyclyl(C.sub.1-C.sub.8)alkyl, (C.sub.3-C.sub.7)cycloalkyl or (C.sub.3-C.sub.7)cycloalkyl(C.sub.1-C.sub.8)alkyl; each R.sup.6 is independently H, oxo, --OR.sup.11, --NR.sup.11R.sup.12, --NR.sup.11C(O)R.sup.11, --NR.sup.11C(O)OR.sup.11, --NR.sup.11C(O)NR.sup.11R.sup.12, N.sub.3, CN, NO.sub.2, --SR.sup.11, --S(O).sub.pR.sup.a, --NR.sup.11S(O).sub.pR.sup.a, --C(.dbd.O)R.sup.11, --C(.dbd.O)OR.sup.11, --C(.dbd.O)NR.sup.11R.sup.12, --C(.dbd.O)SR.sup.11, --S(O).sub.p(OR.sup.11), --SO.sub.2NR.sup.11R.sup.12, --NR.sup.11S(O).sub.p(OR.sup.11), --NR.sup.11SO.sub.pNR.sup.11R.sup.12, --NR.sup.11C(.dbd.NR.sup.11)NR.sup.11R.sup.12, halogen, (C.sub.1-C.sub.8)alkyl, (C.sub.2-C.sub.8)alkenyl, (C.sub.2-C.sub.8)alkynyl, aryl(C.sub.1-C.sub.8)alkyl, C.sub.6-C.sub.20 aryl, C.sub.2-C.sub.20 heterocyclyl, C.sub.2-C.sub.20 heterocyclyl(C.sub.1-C.sub.8)alkyl, (C.sub.3-C.sub.7)cycloalkyl or (C.sub.3-C.sub.7)cycloalkyl(C.sub.1-C.sub.8)alkyl; R.sup.7 is H, --OR.sup.11, --NR.sup.11R.sup.12, --NR.sup.11C(O)R.sup.11, --NR.sup.11C(O)OR.sup.11, --NR.sup.11C(O)NR.sup.11R.sup.12, N.sub.3, CN, NO.sub.2, --SR.sup.11, --S(O).sub.pR.sup.a, --NR.sup.11S(O).sub.pR.sup.a, --C(.dbd.O)R.sup.11, --C(.dbd.O)OR.sup.11, --C(.dbd.O)NR.sup.11R.sup.12, --C(.dbd.O)SR.sup.11, --S(O).sub.p(OR.sup.11), --SO.sub.2NR.sup.11R.sup.12, --NR.sup.11S(O).sub.p(OR.sup.11), --NR.sup.11SO.sub.pNR.sup.11R.sup.12, --NR.sup.11C(.dbd.NR.sup.11)NR.sup.11R.sup.12, halogen, (C.sub.1-C.sub.8)alkyl, (C.sub.2-C.sub.8)alkenyl, (C.sub.2-C.sub.8)alkynyl, aryl(C.sub.1-C.sub.8)alkyl, C.sub.6-C.sub.20 aryl, C.sub.2-C.sub.20 heterocyclyl, C.sub.2-C.sub.20 heterocyclyl(C.sub.1-C.sub.8)alkyl, (C.sub.3-C.sub.7)cycloalkyl or (C.sub.3-C.sub.7)cycloalkyl(C.sub.1-C.sub.8)alkyl; R.sup.8 is H, --OR.sup.11, --NR.sup.11R.sup.12, --NR.sup.11C(O)R.sup.11, --NR.sup.11C(O)OR.sup.11, --NR.sup.11C(O)NR.sup.11R.sup.12, N.sub.3, CN, NO.sub.2, --SR.sup.11, --S(O).sub.pR.sup.a, --NR.sup.11S(O).sub.pR.sup.a, --C(.dbd.O)R.sup.11, --C(.dbd.O)OR.sup.11, --C(.dbd.O)NR.sup.11R.sup.12, --C(.dbd.O)SR.sup.11, --S(O).sub.p(OR.sup.11), --SO.sub.2NR.sup.11R.sup.12, --NR.sup.11S(O).sub.p(OR.sup.11), --NR.sup.11SO.sub.pNR.sup.11R.sup.12, NR.sup.11C(.dbd.NR.sup.11)NR.sup.11R.sup.12, halogen, (C.sub.1-C.sub.8)alkyl, (C.sub.2-C.sub.8)alkenyl, (C.sub.2-C.sub.8)alkynyl, aryl(C.sub.1-C.sub.8)alkyl, C.sub.6-C.sub.20 aryl, C.sub.2-C.sub.20 heterocyclyl, C.sub.2-C.sub.20 heterocyclyl(C.sub.1-C.sub.8)alkyl, (C.sub.3-C.sub.7)cycloalkyl or (C.sub.3-C.sub.7)cycloalkyl(C.sub.1-C.sub.8)alkyl; R.sup.8' is H, --OR.sup.11, --NR.sup.11R.sup.12, --NR.sup.11C(O)R.sup.11, --NR.sup.11C(O)OR.sup.11, --NR.sup.11C(O)NR.sup.11R.sup.12, N.sub.3, CN, NO.sub.2, --SR.sup.11, --S(O).sub.pR.sup.a, --NR.sup.11S(O).sub.pR.sup.a, --C(.dbd.O)R.sup.11, --C(.dbd.O)OR.sup.11, --C(.dbd.O)NR.sup.11R.sup.12, --C(.dbd.O)SR.sup.11, --S(O).sub.p(OR.sup.11), --SO.sub.2NR.sup.11R.sup.12, --NR.sup.11S(O).sub.p(OR.sup.11), --NR.sup.11SO.sub.pNR.sup.11R.sup.12, NR.sup.11C(.dbd.NR.sup.11)NR.sup.11R.sup.12, halogen, (C.sub.1-C.sub.8)alkyl, (C.sub.2-C.sub.8)alkenyl, (C.sub.2-C.sub.8)alkynyl, aryl(C.sub.1-C.sub.8)alkyl, C.sub.6-C.sub.20 aryl, C.sub.2-C.sub.20 heterocyclyl, C.sub.2-C.sub.20 heterocyclyl(C.sub.1-C.sub.8)alkyl, (C.sub.3-C.sub.7)cycloalkyl or (C.sub.3-C.sub.7)cycloalkyl(C.sub.1-C.sub.8)alkyl; each R.sup.a is independently (C.sub.1-C.sub.8)alkyl, (C.sub.1-C.sub.8)haloalkyl, (C.sub.2-C.sub.8)alkenyl, (C.sub.2-C.sub.8)alkynyl, aryl(C.sub.1-C.sub.8)alkyl, C.sub.6-C.sub.20 aryl, C.sub.2-C.sub.20 heterocyclyl, C.sub.2-C.sub.20 heterocyclyl(C.sub.1-C.sub.8)alkyl, (C.sub.3-C.sub.7)cycloalkyl or (C.sub.3-C.sub.7)cycloalkyl(C.sub.1-C.sub.8)alkyl wherein any (C.sub.1-C.sub.8)alkyl, (C.sub.1-C.sub.8)haloalkyl, (C.sub.2-C.sub.8)alkenyl or (C.sub.2-C.sub.8)alkynyl of R.sup.a is optionally substituted with one or more OH, NH.sub.2, CO.sub.2H, C.sub.2-C.sub.20 heterocyclyl, and wherein any aryl(C.sub.1-C.sub.8)alkyl, C.sub.6-C.sub.20 aryl, C.sub.2-C.sub.20 heterocyclyl, (C.sub.3-C.sub.7)cycloalkyl or (C.sub.3-C.sub.7)cycloalkyl(C.sub.1-C.sub.8)alkyl of R.sup.a is optionally substituted with one or more --OH, --NH.sub.2, CO.sub.2H, C.sub.2-C.sub.20 heterocyclyl or (C.sub.1-C.sub.8)alkyl; each R.sup.11 or R.sup.12 is independently H, (C.sub.1-C.sub.8)alkyl, (C.sub.2-C.sub.8)alkenyl, (C.sub.2-C.sub.8)alkynyl, aryl(C.sub.1-C.sub.8)alkyl, C.sub.6-C.sub.20 aryl, C.sub.2-C.sub.20 heterocyclyl, (C.sub.3-C.sub.7)cycloalkyl, (C.sub.3-C.sub.7)cycloalkyl(C.sub.1-C.sub.8)alkyl, --C(.dbd.O)R.sup.a or --S(O).sub.pR.sup.a; or when R.sup.11 and R.sup.12 are attached to a nitrogen they may optionally be taken together with the nitrogen to which they are both attached to form a 3 to 7 membered heterocyclic ring wherein any one carbon atom of said heterocyclic ring can optionally be replaced with --O--, --S--, --S(O).sub.p--, --NH--, --NR.sup.a-- or --C(O)--; R.sup.13 is H or (C.sub.1-C.sub.8)alkyl; R.sup.14 is H, (C.sub.1-C.sub.8)alkyl, NR.sup.11R.sup.12, NR.sup.11C(O)R.sup.11, NR.sup.11C(O)OR.sup.11, NR.sup.11C(O)NR.sup.11R.sup.12, NR.sup.11S(O).sub.pR.sup.a, --NR.sup.11S(O).sub.p(OR.sup.11) or NR.sup.11SO.sub.pNR.sup.11R.sup.12; and wherein each (C.sub.1-C.sub.8)alkyl, (C.sub.2-C.sub.8)alkenyl, (C.sub.2-C.sub.8)alkynyl, aryl(C.sub.1-C.sub.8)alkyl, C.sub.6-C.sub.20 aryl, C.sub.2-C.sub.20 heterocyclyl, C.sub.2-C.sub.20 heterocyclyl(C.sub.1-C.sub.8)alkyl, (C.sub.3-C.sub.7)cycloalkyl or (C.sub.3-C.sub.7)cycloalkyl(C.sub.1-C.sub.8)alkyl of each R.sup.1, R.sup.2, R.sup.2', R.sup.3, R.sup.3', R.sup.4, R.sup.4'R.sup.6, R.sup.7, R.sup.8, R.sup.8', R.sup.11 or R.sup.12 is independently, optionally substituted with one or more oxo, halogen, hydroxy, --NH.sub.2, CN, N.sub.3, --N(R.sup.a).sub.2, --NHR.sup.a, --SH, --SR.sup.a, --S(O).sub.pR.sup.a, --OR.sup.a, (C.sub.1-C.sub.8)alkyl, (C.sub.1-C.sub.8)haloalkyl, --C(O)R.sup.a, --C(O)H, --C(.dbd.O)OR.sup.a, --C(.dbd.O)OH, --C(.dbd.O)N(R.sup.a).sub.2, --C(.dbd.O)NHR.sup.a, --C(.dbd.O)NH.sub.2, --NHS(O).sub.pR.sup.a, --NR.sup.aS(O).sub.pR.sup.a, --NHC(O)R.sup.a, --NR.sup.aC(O)R.sup.a, --NHC(O)OR.sup.a, --NR.sup.aC(O)OR.sup.a, --NR.sup.aC(O)NHR.sup.a, --NR.sup.aC(O)N(R.sup.a).sub.2, --NR.sup.aC(O)NH.sub.2, --NHC(O)NHR.sup.a, --NHC(O)N(R.sup.a).sub.2, --NHC(O)NH.sub.2, .dbd.NH, .dbd.NOH, .dbd.NOR.sup.a, --NR.sup.aS(O).sub.pNHR.sup.a, --NR.sup.aS(O).sub.pN(R.sup.a).sub.2, --NR.sup.aS(O).sub.pNH.sub.2, --NHS(O).sub.pNHR.sup.a, --NHS(O).sub.pN(R.sup.a).sub.2, --NHS(O).sub.pNH.sub.2, --OC(.dbd.O)R.sup.a, --OP(O)(OH).sub.2 or R.sup.a. 3. The compound of claim 1 wherein the compound of formula I is a compound of formula Ic: ##STR00305## or a pharmaceutically acceptable salt thereof. 4. The compound of claim 1 wherein R.sup.3 and R.sup.3' are each H. 5. The compound of claim 1 wherein n is 3. 6. The compound of claim wherein each R.sup.4 and each R.sup.4' is H. 7. The compound of claim 1 wherein A is --(CH.sub.2).sub.3--. 8. The compound of claim 1 wherein a) Y.sup.1 is N, NH or CH, Y.sup.2 is C, Y.sup.3 is N, Y.sup.4 is N or C and Y.sup.5 is NR.sup.2' or CR.sup.2, wherein at least two of Y.sup.1, Y.sup.2, Y.sup.3, Y.sup.4 and Y.sup.5 are independently N, NH or NR.sup.2'; or b) Y.sup.1 is N, NH or CH, Y.sup.2 is N or C, Y.sup.3 is N or CR.sup.8', Y.sup.4 is N or C, and Y.sup.5 is N, wherein at least two of Y.sup.1, Y.sup.2, Y.sup.3, Y.sup.4 and Y.sup.5 are independently N or NH; or c) Y.sup.1 is N, NH or CH, Y.sup.2 is N or C, Y.sup.3 is CR.sup.8, Y.sup.4 is N or C, and Y.sup.5 is NR.sup.2' or CR.sup.2, wherein at least two of Y.sup.1, Y.sup.2, Y.sup.3, Y.sup.4 and Y.sup.5 are independently N, NH or NR.sup.2'. 9. The compound of claim 1 wherein a) Y.sup.1 is N, Y.sup.2 is C, Y.sup.3 is N, Y.sup.4 is N and Y.sup.5 is CR.sup.2; or b) Y.sup.1 is N, Y.sup.2 is N, Y.sup.3 is CR.sup.8', Y.sup.4 is C, and Y.sup.5 is CR.sup.2. 10. The compound of c aim 1 wherein R.sup.2', R.sup.2 and R.sup.8' are each H. 11. The compound of claim 1 wherein the compound of formula I is a compound of formula I.times.4: ##STR00306## wherein Z is: ##STR00307## or a salt thereof. 12. The compound of claim 1 wherein the compound of formula I is a compound of formula Im: ##STR00308## or a salt thereof. 13. The compound of claim 12 wherein R.sup.2 is H. 14. The compound of claim 1 wherein X is --C(R.sup.13)(R.sup.14)-- or X is absent. 15. The compound of claim 1 wherein R.sup.13 is H and R.sup.14 is --NHS(O).sub.2(C.sub.1-C.sub.3)alkyl. 16. The compound of claim 1 wherein X is absent. 17. The compound of claim 1 wherein R.sup.7 is H or (C.sub.1-C.sub.8)alkyl, wherein (C.sub.1-C.sub.8)alkyl is optionally substituted with one or more oxo, halogen, hydroxy, --NH.sub.2, CN, N.sub.3, --N(R.sup.a).sub.2, --NHR.sup.a, --SH, --SR.sup.a, S(O).sub.pR.sup.a, --OR.sup.a, (C.sub.1-C.sub.8)alkyl, (C.sub.1-C.sub.8)haloalkyl, --C(O)R.sup.a, --C(O)H, --C(.dbd.O)OR.sup.a, --C(.dbd.O)OH, --C(.dbd.O)N(R.sup.a).sub.2, --C(.dbd.O)NHR.sup.a, --C(.dbd.O)NH.sub.2, --NHS(O).sub.pR.sup.a, --NR.sup.aS(O).sub.pR.sup.a, --NHC(O)R.sup.a, --NR.sup.aC(O)R.sup.a, --NHC(O)OR.sup.a, --NR.sup.aC(O)OR.sup.a, --NR.sup.aC(O)NHR.sup.a, --NR.sup.aC(O)N(R.sup.a).sub.2, --NR.sup.aC(O)NH.sub.2, --NHC(O)NHR.sup.a, --NHC(O)N(R.sup.a).sub.2, --NHC(O)NH.sub.2, .dbd.NH, .dbd.NOH, .dbd.NOR.sup.a, --NR.sup.aS(O).sub.pNHR.sup.a, --NR.sup.aS(O).sub.pN(R.sup.a).sub.2, --NR.sup.aS(O).sub.pNH.sub.2, --NHS(O).sub.pNHR.sup.a, --NHS(O).sub.pN(R.sup.a).sub.2, --NHS(O).sub.pNH.sub.2, --OC(.dbd.O)R.sup.a, --OP(O)(OH).sub.2 or R.sup.a. 18. The compound of claim 1 wherein R.sup.7 is H or methyl. 19. The compound of claim 1 wherein R.sup.1 is H, --NR.sup.11R.sup.12, (C.sub.1-C.sub.8)alkyl or C.sub.2-C.sub.20 heterocyclyl wherein (C.sub.1-C.sub.8)alkyl or C.sub.2-C.sub.20 heterocyclyl is optionally substituted with one or more oxo, halogen, hydroxy, --NH.sub.2, CN, N.sub.3, --N(R.sup.a).sub.2, --NHR.sup.a, --SH, --SR.sup.a, --S(O).sub.pR.sup.a, --OR.sup.a, (C.sub.1-C.sub.8)alkyl, (C.sub.1-C.sub.8)haloalkyl, --C(O)R.sup.a, --C(O)H, --C(.dbd.O)OR.sup.a, --C(.dbd.O)OH, --C(.dbd.O)N(R.sup.a).sub.2, --C(.dbd.O)NHR.sup.a, --C(.dbd.O)NH.sub.2, NHS(O).sub.pR.sup.a, --NR.sup.aS(O).sub.pR.sup.a, --NHC(O)R.sup.a, --NR.sup.aC(O)R.sup.a, --NHC(O)OR.sup.a, --NR.sup.aC(O)OR.sup.a, --NR.sup.aC(O)NHR.sup.a, --NR.sup.aC(O)N(R.sup.a).sub.2, --NR.sup.aC(O)NH.sub.2, --NHC(O)NHR.sup.a, --NHC(O)N(R.sup.a).sub.2, --NHC(O)NH.sub.2, .dbd.NH, .dbd.NOH, .dbd.NOR.sup.a, --NR.sup.aS(O).sub.pNHR.sup.a, --NR.sup.aS(O).sub.pN(R.sup.a).sub.2, --NR.sup.aS(O).sub.pNH.sub.2, --NHS(O).sub.pNHR.sup.a, --NHS(O).sub.pN(R.sup.a).sub.2, --NHS(O).sub.pNH.sub.2, --OC(.dbd.O)R.sup.a, --OP(O)(OH).sub.2 or R.sup.a. 20. The compound of claim 1 wherein R.sup.1 is H, (C.sub.1-C.sub.3)alkyl or --NR.sup.11R.sup.12, wherein each R.sup.11 or R.sup.12 is independently H or (C.sub.1-C.sub.3)alkyl; or R.sup.11 and R.sup.12 together with the nitrogen to which they are both attached to form a 3 to 7 membered heterocyclic ring wherein any one carbon atom of said heterocyclic ring can optionally be replaced with --O--, --S--, --S(O).sub.p--, --NH--, --NR.sup.a-- or --C(O)--. 21. The compound of claim 1 wherein R.sup.1 is H, methyl or azetidinyl. 22. The compound of claim 1 wherein R.sup.8 is --NR.sup.11R.sup.12, (C.sub.1-C.sub.8)alkyl or C.sub.2-C.sub.20 heterocyclyl wherein (C.sub.1-C.sub.8)alkyl or C.sub.2-C.sub.20 heterocyclyl is optionally substituted with one or more oxo, halogen, hydroxy, --NH.sub.2, CN, N.sub.3, --N(R.sup.a).sub.2, --NHR.sup.a, --SH, --SR.sup.a, --S(O).sub.pR.sup.a, --OR.sup.a, (C.sub.1-C.sub.8)alkyl, (C.sub.1-C.sub.8)haloalkyl, --C(O)R.sup.a, --C(O)H, --C(.dbd.O)OR.sup.a, --C(.dbd.O)OH, --C(.dbd.O)N(R.sup.a).sub.2, --C(.dbd.O)NHR.sup.a, --C(.dbd.O)NH.sub.2, --NHS(O).sub.pR.sup.a, --NR.sup.aS(O).sub.pR.sup.a, --NHC(O)R.sup.a, --NR.sup.aC(O)R.sup.a, --NHC(O)OR.sup.a, --NR.sup.aC(O)OR.sup.a, --NR.sup.aC(O)NHR.sup.a, --NR.sup.aC(O)N(R.sup.a).sub.2, --NR.sup.aC(O)NH.sub.2, --NHC(O)NHR.sup.a, --NHC(O)N(R.sup.a).sub.2, --NHC(O)NH.sub.2, .dbd.NH, .dbd.NOH, .dbd.NOR.sup.a, --NR.sup.aS(O).sub.pNHR.sup.a, --NR.sup.aS(O).sub.pN(R.sup.a).sub.2, --NR.sup.aS(O).sub.pNH.sub.2, --NHS(O).sub.pNHR.sup.a, --NHS(O).sub.pN(R.sup.a).sub.2, --NHS(O).sub.pNH.sub.2, --OC(.dbd.O)R.sup.a, --OP(O)(OH).sub.2 or R.sup.a. 23. The compound of claim 1 wherein R.sup.8 is (C.sub.1-C.sub.8)alkyl, azetidinyl or pyrrolidinyl, wherein azetidinyl or pyrrolidinyl is optionally substituted with one or more oxo, halogen, hydroxy, --NH.sub.2, CN, N.sub.3, --N(R.sup.a).sub.2, --NHR.sup.a, --SH, --SR.sup.a, --S(O).sub.pR.sup.a, --OR.sup.a, (C.sub.1-C.sub.8)alkyl, (C.sub.1-C.sub.8)haloalkyl, --C(O)R.sup.a, --C(O)H, --C(.dbd.O)OR.sup.a, --C(.dbd.O)OH, --C(.dbd.O)N(R.sup.a).sub.2, --C(.dbd.O)NHR.sup.a, --C(.dbd.O)NH.sub.2, --NHS(O).sub.pR.sup.a, --NR.sup.aS(O).sub.pR.sup.a, --NHC(O)R.sup.a, --NR.sup.aC(O)R.sup.a, --NHC(O)OR.sup.a, --NR.sup.aC(O)OR.sup.a, --NR.sup.aC(O)NHR.sup.a, --NR.sup.aC(O)N(R.sup.a).sub.2, --NR.sup.aC(O)NH.sub.2, --NHC(O)NHR.sup.a, --NHC(O)N(R.sup.a).sub.2, --NHC(O)NH.sub.2, .dbd.NH, .dbd.NOH, .dbd.NOR.sup.a, --NR.sup.aS(O).sub.pNHR.sup.a, --NR.sup.aS(O).sub.pN(R.sup.a).sub.2, --NR.sup.aS(O).sub.pNH.sub.2, --NHS(O).sub.pNHR.sup.a, --NHS(O).sub.pN(R.sup.a).sub.2, --NHS(O).sub.pNH.sub.2, --OC(.dbd.O)R.sup.a, --OP(O)(OH).sub.2 or R.sup.a. 24. The compound of claim 1 wherein R.sup.8 is methyl, azetidinyl or pyrrolidinyl, wherein azetidinyl or pyrrolidinyl is optionally substituted with one or more hydroxy, NH.sub.2 or CN. 25. The compound of claim 1 wherein Ar is a phenyl or 5-6 membered monocyclic heteroaryl, wherein phenyl or 5-6 membered monocyclic heteroaryl is optionally substituted with 1 to 5 R.sup.6. 26. The compound of claim 1 wherein Ar is a phenyl, pyridinyl or thienyl, wherein phenyl, pyridinyl or thienyl is optionally substituted with 1 to 5 R.sup.6. 27. The compound of claim 1 wherein each R.sup.6 is --NR.sup.11S(O).sub.pR.sup.a, halogen, or (C.sub.1-C.sub.8)alkyl. 28. The compound of claim 1 wherein each R.sup.6 is --NHS(O).sub.2CH.sub.3, chloro, bromo or methyl. 29. The compound of claim 1 selected from: ##STR00309## ##STR00310## ##STR00311## ##STR00312## and pharmaceutically acceptable salts thereof. 30. A pharmaceutical composition comprising a therapeutically effective amount of a compound as described in claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. 31. The pharmaceutical composition of claim 30 further comprising at least one therapeutic agent selected from ribavirin, palivizumab, motavizumab, RSV-IGIV, MEDI-557, A-60444, MDT-637, BMS-433771, ALN-RSV01 and ALX-0171 and mixtures thereof.

Details for Patent 8,980,878

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Swedish Orphan Biovitrum Ab (publ)	SYNAGIS	palivizumab	For Injection	103770	06/19/1998		2032-04-17
Swedish Orphan Biovitrum Ab (publ)	SYNAGIS	palivizumab	Injection	103770	07/23/2004		2032-04-17
Hoffmann-la Roche Inc.	PEGASYS COPEGUS COMBINATION PACK	peginterferon alfa-2a and ribavirin		125083	06/04/2004		2032-04-17
Schering Corporation A Subsidiary Of Merck & Co., Inc.	PEGINTRON/ REBETOL COMBO PACK	peginterferon alfa-2b and ribavirin		125196	06/13/2008		2032-04-17