Details for Patent: 6,110,946

Title:	Antivirally active heterocyclic azahexane derivatives
Abstract:	There are described compounds of formula I*, ##STR1## wherein R.sub.1 is lower alkoxycarbonyl, R.sub.2 is secondary or tertiary lower alkyl or lower alkylthio-lower alkyl, R.sub.3 is phenyl that is unsubstituted or substituted by one or more lower alkoxy radicals, or C.sub.4 -C.sub.8 cycloalkyl, R.sub.4 is phenyl or cyclohexyl each substituted in the 4-position by unsaturated heterocyclyl that is bonded by way of a ring carbon atom, has from 5 to 8 ring atoms, contains from 1 to 4 hetero atoms selected from nitrogen, oxygen, sulfur, sulfinyl (--SO--) and sulfonyl (--SO.sub.2 --) and is unsubstituted or substituted by lower alkyl or by phenyl-lower alkyl, R.sub.5, independently of R.sub.2, has one of the meanings mentioned for R.sub.2, and R.sub.6, independently of R.sub.1, is lower alkoxycarbonyl, or salts thereof, provided that at least one salt-forming group is present. The compounds are inhibitors of retroviral aspartate protease and can be used, for example, in the treatment of AIDS. They exhibit outstanding pharmacodynamic properties.
Inventor(s):	Fassler; Alexander (Macclesfield, GB), Bold; Guido (Gipf-Oberfrick, CH), Capraro; Hans-Georg (Rheinfelden, CH), Lang; Marc (Mulhouse, FR), Khanna; Satish Chandra (Bottmingen, CH)
Assignee:	Novartis Finance Corporation (Summit, NJ)
Filing Date:	Jul 01, 1998
Application Number:	09/108,481
Claims:	1. A compound of the formula XX, ##STR42## wherein R.sub.1 is methoxycarbonyl or ethoxycarbonyl and R.sub.2 is tert-butyl, or a salt thereof. 2. A compound of the formula IV, ##STR43## wherein R.sub.1 is methoxycarbonyl or ethoxycarbonyl, R.sub.2 is tert-butyl and R.sub.3 is is phenyl that is unsubstituted or substituted by one or more lower alkoxy radicals, or C.sub.4 -C.sub.8 cycloalkyl. 3. A compound of the formula III* ##STR44## where R.sub.4 is phenyl or cyclohexyl each substituted in the 4-position by unsaturated heterocyclyl that is bonded by way of a ring carbon atom, has from 5 to 8 ring atoms, contains from 1 to 4 hetero atoms selected from nitrogen, oxygen, sulfur, sulfinyl and sulfonyl and is unsubstituted or substituted by lower alkyl or by phenyl-lower alkyl, R.sub.5 is tert-butyl and R.sub.6 is methoxy- or ethoxycarbonyl; or a salt thereof where a salt-forming group is present. 4. A compound of the formula XII, ##STR45## where R.sub.4 is phenyl or cyclohexyl each substituted in the 4-position by unsaturated heterocyclyl that is bonded by way of a ring carbon atom, has from 5 to 8 ring atoms, contains from 1 to 4 hetero atoms selected from nitrogen, oxygen, sulfur, sulfinyl and sulfonyl and is unsubstituted or substituted by lower alkyl or by phenyl-lower alkyl and R.sub.7 is an amino protecting group, or a salt thereof if a salt-forming group is present. 5. A compound of the formula XII*, ##STR46## wherein R.sub.4 is phenyl or cyclohexyl each substituted in the 4-position by unsaturated heterocyclyl that is bonded by way of a ring carbon atom, has from 5 to 8 ring atoms, contains from 1 to 4 hetero atoms selected from nitrogen, oxygen, sulfur, sulfinyl and sulfonyl and is unsubstituted or substituted by lower alkyl or by phenyl-lower alkyl and R.sub.7 is an amino protecting group, or a salt thereof if a salt-forming group is present. 6. A compound of the formula III, ##STR47## wherein R.sub.4 is phenyl or cyclohexyl each substituted in the 4-position by unsaturated heterocyclyl that is bonded by way of a ring carbon atom, has from 5 to 8 ring atoms, contains from 1 to 4 hetero atoms selected from nitrogen, oxygen, sulfur, sulfinyl and sulfonyl and is unsubstituted or substituted by lower alkyl or by phenyl-lower alkyl, R.sub.5 is isopropyl, sec-butyl, tert-butyl or methylthiomethyl, and R.sub.6 is lower alkoxycarbonyl, or a salt thereof, provided that at least one salt-forming group is present. 7. A compound of the formula V, ##STR48## wherein R.sub.1 is lower alkoxycarbonyl, R.sub.2 is secondary or tertiary lower alkyl or lower alkylthio-lower alkyl, R.sub.3 is phenyl that is unsubstituted or substituted by one or more lower alkoxy radicals, or C.sub.4 -C.sub.8 cycloalkyl, and R.sub.4 is phenyl or cyclohexyl each substituted in the 4-position by unsaturated heterocyclyl that is bonded by way of a ring carbon atom, has from 5 to 8 ring atoms, contains from 1 to 4 hetero atoms selected from nitrogen, oxygen, sulfur, sulfinyl and sulfonyl and is unsubstituted or substituted by lower alkyl or by phenyl-lower alkyl, or a salt thereof, provided that at least one salt-forming group is present. 8. A compound of the formula VII, ##STR49## wherein R.sub.3 is phenyl that is unsubstituted or substituted by one or more lower alkoxy radicals, or C.sub.4 -C.sub.8 cycloalkyl, R.sub.4 is phenyl or cyclohexyl each substituted in the 4-position by unsaturated heterocyclyl that is bonded by way of a ring carbon atom, has from 5 to 8 ring atoms, contains from 1 to 4 hetero atoms selected from nitrogen, oxygen, sulfur, sulfinyl and sulfonyl and is unsubstituted or substituted by lower alkyl or by phenyl-lower alkyl, R.sub.5 is secondary or tertiary lower alkyl or lower alkylthio-lower alkyl, and R.sub.6 is lower alkoxycarbonyl, or a salt thereof, provided that at least one salt-forming group is present. 9. A compound of the formula IX, ##STR50## wherein R.sub.3 is phenyl that is unsubstituted or substituted by one or more lower alkoxy radicals, or C.sub.4 -C.sub.8 cycloalkyl, and R.sub.4 is phenyl or cyclohexyl each substituted in the 4-position by unsaturated heterocyclyl that is bonded by way of a ring carbon atom, has from 5 to 8 ring atoms, contains from 1 to 4 hetero atoms selected from nitrogen, oxygen, sulfur, sulfinyl and sulfonyl and is unsubstituted or substituted by lower alkyl or by phenyl-lower alkyl, or a salt thereof, provided that at least one salt-forming group is present. 10. A compound of the formula XXIV, ##STR51## wherein R.sub.13 and R.sub.14 are amino-protecting groups, which are different from one another, R.sub.3 is phenyl that is unsubstituted or substituted by one or more lower alkoxy radicals, or C.sub.4 -C.sub.8 cycloalkyl, and R.sub.4 is phenyl or cyclohexyl each substituted in the 4-position by unsaturated heterocyclyl that is bonded by way of a ring carbon atoms, has from 5 to 8 ring atoms, contains from 1 to 4 hetero atoms selected from nitrogen, oxygen, sulfur, sulfinyl and sulfonyl and is unsubstituted or substituted by lower alkyl or by phenyl-lower alkyl, or a salt thereof, provided that at least one salt-forming group is present. 11. A compound of the formula XXV, ##STR52## where R.sub.14 is an amino-protecting group, R.sub.3 is phenyl that is unsubstituted or substituted by one or more lower alkoxy radicals, or C.sub.4 -C.sub.8 cycloalkyl, and R.sub.4 is phenyl or cyclohexyl each substituted in the 4-position by unsaturated heterocyclyl that is bonded by way of a ring carbon atom, has from 5 to 8 ring atoms, contains from 1 to 4 hetero atoms selected from nitrogen, oxygen, sulfur, sulfinyl and sulfonyl and is unsubstituted or substituted by lower alkyl or by phenyl-lower alkyl, or a salt thereof, provided that at least one salt-forming group is present. 12. A compound of the formula XXVI, ##STR53## wherein R.sub.15 is an amino-protecting group, R.sub.1 is lower alkoxycarbonyl, R.sub.2 is secondary or tertiary lower alkyl or lower alkylthio-lower alkyl, R.sub.3 is phenyl that is unsubstituted or substituted by one or more lower alkoxy radicals, or C.sub.4 -C.sub.8 cycloalkyl, and R.sub.4 is phenyl or cyclohexyl each substituted in the 4-position by unsaturated heterocyclyl that is bonded by way of a ring carbon atom, has from 5 to 8 ring atoms, contains from 1 to 4 hetero atoms selected from nitrogen, oxygen, sulfur, sulfinyl and sulfonyl and is unsubstituted or substituted by lower alkyl or by phenyl alkyl, or a salt thereof, provided that at least one salt-forming group is present .