Claims
- 1. A compound of the formula: ##STR132## wherein: Q, and Q.sub.2 are each independently selected from hydrogen and substituted and unsubstituted alkyl and aryl;
- Q.sub.3 is selected from mercapto and substituted and unsubstituted alkoxyl, aryloxyl, thioether, amino, alkyl, cycloalkyl, saturated and partially saturated heterocycle, and aryl;
- Q.sub.4, Q.sub.5, Q.sub.6, Q.sub.7, and Q.sub.8 are each independently selected from hydrogen, hydroxyl, mercapto, nitro, halogen, --O--J, where J is a substituted or unsubstituted hydrolyzable group, and substituted and unsubstituted alkoxyl, aryloxyl, thioether, sulfinyl, sulfonyl, amino, alkyl, cycloalkyl, saturated and partially saturated heterocycle, aryl, and L.sub.6 C(O)L.sub.4, where L.sub.6 is a single bond, --O or --N, and further where L.sub.4 is alkyl, hydroxyl, alkoxyl or hydrogen; and further wherein any one or more of Q.sub.4, Q.sub.5, Q.sub.6, Q.sub.7, and Q.sub.8 may be a member of a spiro ring, and any two of Q.sub.4, Q.sub.5, Q.sub.6, Q.sub.7, and Q.sub.8 may together be members of a ring;
- E is carbon or nitrogen;
- Q.sub.9 is selected from hydrogen, halogen, hydroxyl, mercapto, and substituted and unsubstituted alkoxyl, aryloxyl, thioether, amino, alkyl, and aryl, where Q.sub.9 may form part of a ring; ##STR133## is a monocyclic or polycyclic carbocycle or heterocycle, which is optionally further substituted, and when ##STR134## is heterocycle, each heterocyclic ring has one to three heteroatoms independently selected from nitrogen, oxygen, and sulfur; and ##STR135## is a monocyclic or polycyclic heterocycle, which is optionally further substituted, and optionally has one or two additional heteroatoms independently selected from nitrogen, oxygen and sulfur, with the proviso that ##STR136## is neither a 5- or 6-membered monocyclic ring, which is optionally further substituted, nor ##STR137## where B.sub.1 and B.sub.2 form part of a ring having from 3 to 10 members, which is optionally further substituted;
- or a prodrug or pharmaceutically acceptable salt of said compound.
- 2. A compound, prodrug, or pharmaceutically acceptable salt according to claim 1, wherein E is carbon.
- 3. A compound, prodrug, or pharmaceutically acceptable salt according to claim 1, wherein Q.sub.3 is substituted or unsubstituted aryl or thioether.
- 4. A compound, prodrug, or pharmaceutically acceptable salt according to claim 3, wherein E is carbon.
- 5. A compound, prodrug, or pharmaceutically acceptable salt according to claim 1, wherein Q.sub.1 is hydrogen and Q.sub.2 is substituted or unsubstituted alkyl.
- 6. A pharmaceutical composition comprising:
- (a) an active ingredient that is:
- (i) a compound of the formula: ##STR138## wherein: Q.sub.1 and Q.sub.2 are each independently selected from hydrogen and substituted and unsubstituted alkyl and aryl;
- Q.sub.3 is selected from mercapto and substituted and unsubstituted alkoxyl, aryloxyl, thioether, amino, alkyl, cycloalkyl, saturated and partially saturated heterocycle, and aryl;
- Q.sub.4, Q.sub.5, Q.sub.6, Q.sub.7, and Q.sub.8 are each independently selected from hydrogen, hydroxyl, mercapto, nitro, halogen, --O--J, where J is a substituted or unsubstituted hydrolyzable group, and substituted and unsubstituted alkoxyl, aryloxyl, thioether, sulfinyl, sulfonyl, amino, alkyl, cycloalkyl, saturated and partially saturated heterocycle, aryl, and L.sub.6 C(O)L.sub.4, where L.sub.6 is a single bond, --O or --N, and further where L.sub.4 is alkyl, hydroxyl, alkoxyl or hydrogen; and further wherein any one or more of Q.sub.4, Q.sub.5, Q.sub.6, Q.sub.7, and Q.sub.8 may be a member of a spiro ring, and any two of Q.sub.4, Q.sub.5, Q.sub.6, Q.sub.7, and Q.sub.8 may together be members of a ring;
- E is carbon or nitrogen;
- Q.sub.9 is selected from hydrogen, halogen, hydroxyl, mercapto, and substituted and unsubstituted alkoxyl, aryloxyl, thioether, amino, alkyl, and aryl, where Q.sub.9 may form part of a ring; ##STR139## is a monocyclic or polycyclic carbocycle or heterocycle, which is optionally further substituted, and when ##STR140## is heterocycle, each heterocyclic ring has one to three heteroatoms independently selected from nitrogen, oxygen, and sulfur; and ##STR141## is a monocyclic or polycyclic heterocycle, which is optionally further substituted, and optionally has one or two additional heteroatoms independently selected from nitrogen, oxygen and sulfur, with the proviso that ##STR142## is neither a 5- or 6-membered monocyclic ring, which is optionally further substituted, nor ##STR143## where B.sub.1 and B.sub.2 form part of a ring having from 3 to 10 members, which is optionally further substituted; or
- (ii) a prodrug or pharmaceutically acceptable salt of said compound; and
- (b) a pharmaceutically acceptable carrier.
- 7. A pharmaceutical composition according to claim 6, wherein E is carbon.
- 8. A pharmaceutical composition according to claim 6, wherein Q.sub.3 is substituted or unsubstituted aryl or thioether.
- 9. A pharmaceutical composition according to claim 8, wherein E is carbon.
- 10. A pharmaceutical composition according to claim 6, wherein Q.sub.1 is hydrogen and Q.sub.2 is substituted or unsubstituted alkyl.
- 11. A method of inhibiting HIV protease, comprising administering to a host an effective amount of:
- a compound of the formula: ##STR144## wherein: Q.sub.1 and Q.sub.2 are each independently selected from hydrogen and substituted and unsubstituted alkyl and aryl;
- Q.sub.3 is selected from mercapto and substituted and unsubstituted alkoxyl, aryloxyl, thioether, amino, alkyl, cycloalkyl, saturated and partially saturated heterocycle, and aryl;
- Q.sub.4, Q.sub.5, Q.sub.6, Q.sub.7, and Q.sub.8 are each independently selected from hydrogen, hydroxyl, mercapto, nitro, halogen, --O--J, where J is a substituted or unsubstituted hydrolyzable group, and substituted and unsubstituted alkoxyl, aryloxyl, thioether, sulfinyl, sulfonyl, amino, alkyl, cycloalkyl, saturated and partially saturated heterocycle, aryl, and L.sub.6 C(O)L.sub.4, where L.sub.6 is a single bond, --O or --N, and further where L.sub.4 is alkyl, hydroxyl, alkoxyl or hydrogen; and further wherein any one or more of Q.sub.4, Q.sub.5, Q.sub.6, Q.sub.7, and Q.sub.8 may be a member of a spiro ring, and any two of Q.sub.4, Q.sub.5, Q.sub.6, Q.sub.7, and Q.sub.8 may together be members of a ring;
- E is carbon or nitrogen;
- Q.sub.9 is selected from hydrogen, halogen, hydroxyl, mercapto, and substituted and unsubstituted alkoxyl, aryloxyl, thioether, amino, alkyl, and aryl, where Q.sub.9 may form part of a ring; ##STR145## is a monocyclic or polycyclic carbocycle or heterocycle, which is optionally further substituted, and when ##STR146## is heterocycle, each heterocyclic ring has one to three heteroatoms independently selected from nitrogen, oxygen, and sulfur; and ##STR147## is a monocyclic or polycyclic heterocycle, which is optionally further substituted, and optionally has one or two additional heteroatoms independently selected from nitrogen, oxygen and sulfur, with the proviso that ##STR148## is neither a 5- or 6-membered monocyclic ring, which is optionally further substituted, nor ##STR149## where B.sub.1 and B.sub.2 form part of a ring having from 3 to 10 members, which is optionally further substituted;
- or a prodrug or pharmaceutically acceptable salt of said compound.
- 12. A method according to claim 11, wherein E is carbon.
- 13. A method according to claim 11, wherein Q.sub.3 is substituted or unsubstituted aryl or thioether.
- 14. A method according to claim 13, wherein E is carbon.
- 15. A method according to claim 11, wherein Q.sub.1 is hydrogen and Q.sub.2 is substituted or unsubstituted alkyl.
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a division of U.S. patent application Ser. No. 08/190,764, filed on Feb. 2, 1994, now U.S. Pat. No. 5,484,926 which is a continuation-in-part of each of U.S. patent application Ser. Nos. (i) 08/133,543 abandoned and (ii) 08/133,696, now U.S. Pat. No. 5,497,934 filed on Oct. 7, 1993, and a CIP of 08/137,254, filed Oct. 18, 1993, now abandoned which is a CIP of 07/995,621, filed Dec. 22, 1992, now abandoned. The disclosures of the two parent applications, Ser. Nos. 08/133,543 and 08/133,696 (including the specification and claims as originally filed), are specifically incorporated by reference herein, except for the "Background of the Invention" section of the specification of each application, with the caveat that the definitions of preferences, terms, variables, labels and the like used in each application are applicable only to the corresponding disclosure from that application.
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Related Publications (1)
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Oct 1993 |
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Divisions (1)
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190764 |
Feb 1994 |
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Continuation in Parts (2)
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133543 |
Oct 1993 |
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995621 |
Dec 1992 |
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