|Title:||.alpha.- and .beta.-amino acid hydroxyethylamino sulfonamides useful as retroviral protease inhibitors|
|Abstract:||.alpha.- and .beta.-amino acid hydroxyethylamino sulfonamide compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease.|
|Inventor(s):||Vazquez; Michael L. (Gurnee, IL), Mueller; Richard A. (Glencoe, IL), Talley; John J. (Brentwood, MO), Getman; Daniel P. (Chestertfield, MO), DeCrescenzo; Gary A. (St. Peters, MO), Freskos; John N. (Clayton, MO), Bertenshaw; Deborah E. (Brentwood, MO), Heintz; Robert M. (Ballwin, MO)|
|Assignee:||G. D. Searle & Co. (Chicago, IL)|
1. A compound represented by the formula: ##STR827##
or a pharmaceutically acceptable salt, prodrug, or ester thereof, wherein
P.sup.1 represents alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, cycloalkylcarbonyl, cycloalkylalkoxycarbonyl, cycloalkylalkanoyl, alkanoyl, aralkanoyl, aroyl, aryloxycarbonyl, aryloxycarbonylalkyl, aryloxyalkanoyl, heterocyclylcarbonyl, heterocyclyloxycarbonyl, heterocyclylalkanoyl, heterocyclylalkoxycarbonyl, heteroaralkanoyl, heteroaralkoxycarbonyl, heteroaryloxycarbonyl, heteroaroyl, alkyl, alkenyl, cycloalkyl, aryl, aralkyl, aryloxyalkyl, heteroaryloxyalkyl, hydroxyalkyl, aminocarbonyl, aminoalkanoyl, and mono- and disubstituted aminocarbonyl and mono- and disubstituted aminoalkanoyl radical wherein the substituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl, and heterocycloalkyalkyl radicals; or where said aminoalkanoyl radicals is disubstituted, said substituents along with the nitrogen atom to which they are attached form a heterocycloalkyl or heteroaryl radical;
P.sup.2 is hydrogen;
R.sup.2 is an alkyl, aryl, cycloalkyl, cycloalkylalkyl or aralkyl radical, which radicals are optionally substituted with a group selected from alkyl and halogen radicals, nitro, cyano, CF.sub.3, --OR.sup.9, --SR.sup.9, wherein R.sup.9 is a hydrogen, alkyl or halogen radical;
R.sup.3 is a hydrogen, alkyl, haloalkyl alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, heteroaralkyl, aminoalkyl or mono- or disubstituted aminoalkyl radical, wherein said substituents are selected from the group consisting of alkyl, aryl, arakyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl, and heterocycloalkylalkyl radicals, or where the aminoalkyl radical is disubstituted, said substituents along with the nitrogen atom to which they are attached, form a heterocycloalkyl or a heteroaryl radical; and
R.sup.4 is a radical as defined by R.sup.3 except for hydrogen.
2. A compound of claim 1 wherein P.sup.1 is heteroclyloxycarbonyl.
3. A compound of claim 2 wherein the heterocycloxycarbonyl is selected from the following: ##STR828##
4. A compound of claim 3 which is: ##STR829##
5. A compound of claim 3 which is: ##STR830##
6. A compound of claim 3 which is: ##STR831##
7. A compound of claim 3 which is: ##STR832##
8. A compound of claim 3 which is: ##STR833##
9. A compound of claim 3 which is: ##STR834##
10. A compound of claim 3 which is: ##STR835##
11. A compound of claim 3 which is: ##STR836##
12. Method of treating a retroviral infection comprising administering an effective amount of a compound of claim 2.
13. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
14. Method of inhibiting a retrovirus protease comprising administering a protease inhibiting amount of a composition of claim 13.
15. Method of claim 14 wherein the retrovirals protease is HIV protease.
16. Method of treating a retrovirus infection comprising administering an effective amount of a composition of claim 13.
17. Method of claim 16 wherein the retrovirals infection is an HIV infection.
18. Method for treating AIDS comprising administering an effective amount of a composition of claim 13.
Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.