초록 ▼

The present invention relates to a novel class of sulfonamides which are aspartyl protease inhibitors. In one embodiment, this invention relates to a novel class of HIV aspartyl protease inhibitors characterized by specific structural and physicochemical features. This invention also relates to phar

The present invention relates to a novel class of sulfonamides which are aspartyl protease inhibitors. In one embodiment, this invention relates to a novel class of HIV aspartyl protease inhibitors characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting HIV-1 and HIV-2 protease activity and consequently, may be advantageously used as anti-viral agents against the HIV-1 and HIV-2 viruses. This invention also relates to methods for inhibiting the activity of HIV aspartyl protease using the compounds of this invention and methods for screening compounds for anti-HIV activity.

대표청구항 ▼

[ We claim:] [1.] A compound of formula I: [ STR 610 ] wherein: A is selected from the group consisting of Het; --R.sup.1 --Het; --R.sup.1 --C.sub.1 -C.sub.6 alkyl, which is substituted with one to two groups selected from the group consisting of Het and --O--Het; and --R.sup.1 --C.sub.2 -C.sub.6 al

[ We claim:] [1.] A compound of formula I: [ STR 610 ] wherein: A is selected from the group consisting of Het; --R.sup.1 --Het; --R.sup.1 --C.sub.1 -C.sub.6 alkyl, which is substituted with one to two groups selected from the group consisting of Het and --O--Het; and --R.sup.1 --C.sub.2 -C.sub.6 alkenyl, which is substituted with one to two groups selected from the group consisting of Het and --O--Het;each R.sup.1 is independently selected from the group consisting of --C(O)--, --S(O).sub.2, --C(O)--C(O)--, --O--C(O)--, --O--S(O).sub.2, --NR.sup.2 --S(O).sub.2 --, --NR.sup.2 --C(O)-- and --NR.sup.2 --C(O)--C(O)--;each Het is independently selected from the group consisting of 5-7 membered saturated or unsaturated heterocycle, containing one or more heteroatoms selected from O, S and S(O).sub.n, wherein said heterocycle may optionally be benzofused; and wherein any member of said Het may be optionally substituted with one to two substituents selected from the group consisting of oxo, --OR.sup.2, --R.sup.2, --N(R.sup.2) (R.sup.2), --R.sup.2 --OH, --CN, --CO.sub.2 R.sup.2, --C(O) --N(R.sup.2) (R.sup.2), --S(O).sub.2 --N(R.sup.2) (R.sup.2), --N(R.sup.2)--C(O)--R.sup.2, --C(O)--R.sup.2, --S(O).sub.n --R.sup.2, --OCF.sub.3, --S(O).sub.n --Ar, methylenedioxy, --N(R.sup.2)--S(O).sub.2 (R.sup.2), halo, --CF.sub.3, --NO.sub.2, Ar and --O--Ar;each R.sup.2 is independently selected from the group consisting of H and C.sub.1 -C.sub.3 alkyl optionally substituted with Ar; with the proviso that when R.sup.2 is C.sub.1 -C.sub.3 alkyl substituted with Ar, said Ar may not be substituted with an Ar-containing moiety;B, when present, is --N(R.sup.2)--C(R.sup.3) (R.sup.3)--C(O)--;x is 0 or 1;each R.sup.3 is independently selected from the group consisting of H, Het, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.6 cycloalkyl and C.sub.5 -C.sub.6 cycloalkenyl, wherein any member of said R.sup.3, except H, may be optionally substituted with one to two substituents selected from the group consisting of --OR.sup.2, --C(O)--NH--R.sup.2, --S(O).sub.n --N(R.sup.2) (R.sup.2), Het, --CN, --SR.sup.2, --CO.sub.2 R.sup.2, NR.sup.2 --C(O) --R.sup.2 ;each n is independently 1 or 2;D and D' are independently selected from the group consisting of Ar; C.sub.1 -C.sub.4 alkyl, which may be optionally substituted with one to two groups selected from C.sub.3 -C.sub.6 cycloalkyl, --OR.sup.2, --R.sup.3, --O--Ar and Ar; C.sub.2 -C.sub.4 alkenyl, which may be optionally substituted with one to two groups selected from the group consisting of C.sub.3 -C.sub.6 cycloalkyl, --OR.sup.2, --R.sup.3, --O--Ar and Ar; C.sub.3 -C.sub.6 cycloalkyl, which may be optionally substituted with or fused with Ar; and C.sub.5 -C.sub.6 cycloalkenyl, which may be optionally substituted with or fused with Ar;each Ar is independently selected from the group consisting of phenyl; 3-6 membered carbocyclic ring and 5-6 membered heterocyclic ring containing one or more heteroatoms selected from O, S, and S(O).sub.n, wherein said carbocyclic or heterocyclic ring may be saturated or unsaturated and optionally substituted with one to two groups selected from the group consisting of oxo, --OR.sup.2, --R.sup.2, --N(R.sup.2) (R.sup.2), --N(R.sup.2)--C(O)--R.sup.2, C.sub.1 -C.sub.3 alkyl substituted with --OH and optionally substituted with Ar, --CN, --CO.sub.2 R.sup.2, --C(O)--N(R.sup.2) (R.sup.2), halo and --CF.sub.3 ;E is selected from the group consisting of Het; O--Het; Het--Het; C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.6 saturated carbocycle and C.sub.5 -C.sub.6 unsaturated carbocycle, each of which is substituted with one to two Het groups.