Protease inhibiting succinic acid derivatives
AssigneeBio-Mega/Boehringer Ingeleheim Research Inc.
InventorsPierre L. Beaulieu, Ingrid Guse
Life of this patent
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Abstract
Disclosed herein are compounds which inhibit human immunodeficiency virus (HIV) protease activity and inhibit HIV replication in human cells. Thus, the compounds are indicated for the treatment of HIV infections. The compounds can be represented by the formula ##STR1## wherein X is a terminal group, for example, an aryloxycarbonyl, an alkanoyl or an arylalkyl carbamoyl; A is absent or an amino acid or a derived amino acid; either R.sup.1 or R.sup.2 is hydrogen while the other is alkyl or R.sup.1 and R.sup.2 are joined to form a cyclohexane; Q is hydrogen, hydroxy, halo or lower alkoxy; and Y is a terminal group, for example, an alkylamino, alkoxy or an optionally substituted anilino.
Claims10
A compound of formula 1 ##STR7## wherein X is R.sup.3 OC(O), R.sup.3 C(O) or R.sup.3 NHC(O) wherein R.sup.3 is
- (i) lower alkyl,
- (ii) lower cycloalkyl,
- (iii) phenyl;
- phenyl monosubstituted with halo, hydroxy, amino, lower alkyl or lower alkoxy;
- or phenyl disubstituted or trisubstituted with the same or different substituent selected from the group consisting of halo, amino and lower alkyl;
- (iv) phenyl(lower)alkyl or phenyl(lower)alkyl wherein the aromatic portion thereof is monosubstituted with halo, hydroxy, lower alkyl or lower alkoxy,
- (v) phenyl(lower)alkenyl,
- (vi) 1-naphthyl or 2-naphthyl,
- (vii) Het or Het-(lower alkyl) wherein Het represents, a five- or six-membered monocyclic, or a nine- or ten-membered bicyclic, radical containing one or two heteroatoms selected from nitrogen, oxygen and sulfur, the heterocyclic radical being either unsubstituted or having one or two of the same or different substituents selected from the group consisting of halo, hydroxy, amino, lower alkyl or lower alkoxy;
- or
- X is R.sup.3A NHCH.sub.2 C(O) wherein R.sup.3A is lower alkyl or phenyl, or X is R.sup.3B OCH.sub.2 C(O) wherein R.sup.3B is phenyl, phenyl monosubstituted with halo or lower alkyl, or phenyl disubstituted or trisubstituted with the same or different substituent selected from the group of halo and lower alkyl;
- A is absent or A is a divalent radical NR.sup.4 CHR.sup.5 C(O) wherein R.sup.4 is hydrogen or lower alkyl, R.sup.5 is lower alkyl, 1-carboxycyclobut-1-yl, 1-carboxycyclopent-1-yl, or lower alkyl monosubtituted with carboxy, carbamyl, (lower alkoxy)carbonyl, benzyloxycarbonyl, hydroxy, cyano or benzyloxy, and the carbon atom bearing R.sup.5 has the (S) configuration.
- R.sup.1 is lower alkyl and R.sup.2 is hydrogen, or R.sup.1 is hydrogen and R.sup.2 is lower alkyl, or R.sup.1 and R.sup.2 together with the carbon atoms to which they are attached form a 1,2-cyclohexanediyl;
- Q is hydrogen, hydroxy, halo or lower alkoxy;
- and
- Y is (1-8C)alkylamino, (1-8C)alkoxy, phenylamino or phenylamino having one or two of the same or different substituents on the phenyl portion thereof selected from the group consisting of lower alkyl, lower alkoxy, hydroxy, halo, amino or lower alkylamino;
- or a therapeutically acceptable acid addition salt thereof.
Dependencies are inferred from the claim text.