You’re using a public version of DrugPatentWatch with 5 free searches available | Register to unlock more free searches. CREATE FREE ACCOUNT

Last Updated: March 28, 2024

Details for Patent: 5,648,497


✉ Email this page to a colleague

« Back to Dashboard


Title: Retroviral protease inhibiting compounds
Abstract:A retroviral protease inhibiting compound of the formula A--X--B is disclosed. Also disclosed are a composition and method for inhibiting a retroviral protease and for treating an HIV infection. Also disclosed are processes and intermediates useful for the preparation of the retroviral protease inhibitors.
Inventor(s): Kempf; Dale J. (Libertyville, IL), Norbeck; Daniel W. (Lindenhurst, IL), Codacovi; Lynn M. (Antioch, IL), Sham; Hing L. (Gurnee, IL), Wittenberger; Steven J. (Mundelein, IL)
Assignee: Abbott Laboraotries (Abbott Park, IL)
Filing Date:Mar 24, 1995
Application Number:08/410,623
Claims:1. A compound of the formula: ##STR17## wherein R.sub.2 and R.sub.3 are independently selected from C.sub.3 -to-C.sub.7 -cycloalkyl-C.sub.1 -to-C.sub.6 -alkyl and (C.sub.6 -monocyclic or C.sub.9 - or C.sub.10 -bicyclic)aryl-C.sub.1 -to-C.sub.6 -alkyl; and

(a) A is thiazolyl-C.sub.1 -to-C.sub.6 -alkyl-R.sub.9 --C(O)--NH--CH(R.sub.5)--C(O)-- or (substituted-thiazolyl)-C.sub.1 -to-C.sub.6 -alkyl-R.sub.9 --C(O)--NH--CH(R.sub.5)--C(O)-- wherein R.sub.9 is --O--, --NH-- or --N(C.sub.1 -to-C.sub.6 -loweralkyl)- and R.sub.5 is C.sub.1 -to-C.sub.6 -loweralkyl and B is thiazolyl-C.sub.1 -to-C.sub.6 -alkyl-O--C(O)--, thiazolyl-C.sub.1 -to-C.sub.6 -alkyl-NH--C(O)--, thiazolyl-C.sub.1 -to-C.sub.6 -alkyl-N(C.sub.1 -to-C.sub.6 -loweralkyl)-C(O)--, (substituted-thiazolyl)-C.sub.1 -to-C.sub.6 -alkyl-O--C(O)--, (substituted-thiazolyl)-C.sub.1 -to-C.sub.6 -alkyl-NH--C(O)-- or (substituted-thiazolyl)-C.sub.1 -to-C.sub.6 -alkyl-N(C.sub.1 -to-C.sub.6 -loweralkyl)-C(O)-- and wherein at each occurrence substituted-thiazolyl is independently selected from a thiazolyl ring substituted with one or two substituents independently selected from C.sub.1 -to-C.sub.6 -loweralkyl, hydroxy, halo, amino, C.sub.1 -to-C.sub.6 -alkylamino, di-C.sub.1 -to-C.sub.6 -alkylamino, C.sub.1 -to-C.sub.6 -alkoxy, halo-C.sub.1 -to-C.sub.6 -alkyl, unsubstituted-C.sub.3 -to-C.sub.7 -cycloalkyl, unsubstituted (C.sub.6 -monocyclic or C.sub.9 - or C.sub.10 -bicyclic)aryl, unsubstituted (C.sub.6 -monocyclic or C.sub.9 - or C.sub.10 -bicyclic)aryl-C.sub.1 -to-C.sub.6 -alkyl, --COOH and --SO.sub.3 H; or

(b) A is thiazolyl-C.sub.1 -to-C.sub.6 -alkyl-O--C(O)--, thiazolyl-C.sub.1 -to-C.sub.6 -alkyl-NH--C(O)--, thiazolyl-C.sub.1 -to-C.sub.6 -alkyl-N(C.sub.1 -to-C.sub.6 -loweralkyl)-C(O)--, (substituted-thiazolyl)-C.sub.1 -to-C.sub.6 -alkyl-O--C(O)--, (substituted-thiazolyl)-C.sub.1 -to-C.sub.6 -alkyl-NH--C(O)-- or (substituted-thiazolyl)-C.sub.1 -to-C.sub.6 -alkyl-N(C.sub.1 -to-C.sub.6 -loweralkyl)-C(O)-- and B is thiazolyl-C.sub.1 -to-C.sub.6 -alkyl-R.sub.9 --C(O)--NH--CH(R.sub.5)--C(O)-- or (substituted-thiazolyl)-C.sub.1 -to-C.sub.6 -alkyl-R.sub.9 -C(O)--NH--CH(R.sub.5)--C(O)-- wherein R.sub.9 is --O--, --NH-- or --N(C.sub.1 -to-C.sub.6 -loweralkyl)- and R.sub.5 is C.sub.1 -to-C.sub.6 -loweralkyl and wherein at each occurrence substituted-thiazolyl is independently selected from a thiazolyl ring substituted with one or two substituents independently selected from C.sub.1 -to-C.sub.6 -loweralkyl, hydroxy, halo, amino, C.sub.1 -to-C.sub.6 -alkylamino, di-C.sub.1 -to-C.sub.6 -alkylamino, C.sub.1 -to-C.sub.6 -alkoxy, halo-C.sub.1 -to-C.sub.6 -alkyl, unsubstituted-C.sub.3 -to-C.sub.7 -cycloalkyl, unsubstituted (C.sub.6 -monocyclic or C.sub.9 - or C.sub.10 -bicyclic)aryl, unsubstituted (C.sub.6 -monocyclic or C.sub.9 - or C.sub.10 -bicyclic)aryl-C.sub.1 -to-C.sub.6 -alkyl, --COOH and --SO.sub.3 H;

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 wherein A is thiazolyl-C.sub.1 -to-C.sub.6 -alkyl-R.sub.9 --C(O)--NH--CH(R.sub.5)--C(O)-- or (substituted-thiazolyl)-C.sub.1 -to-C.sub.6 -alkyl-R.sub.9 -C(O)--NH--CH(R.sub.5)--C(O)-- wherein R.sub.9 is --O--, --NH-- or --N(C.sub.1 -to-C.sub.6 -loweralkyl)- and R.sub.5 is C.sub.1 -to-C.sub.6 -loweralkyl and B is thiazolyl-C.sub.1 -to-C.sub.6 -alkyl-O--C(O)--, thiazolyl-C.sub.1 -to-C.sub.6 -alkyl-NH--C(O)--, thiazolyl-C.sub.1 -to-C.sub.6 -alkyl-N(C.sub.1 -to-C.sub.6 -loweralkyl)-C(O)--, (substituted-thiazolyl)-C.sub.1 -to-C.sub.6 -alkyl-O--C(O)--, (substituted-thiazolyl)-C.sub.1 -to-C.sub.6 -alkyl-NH--C(O)-- or (substituted-thiazolyl)-C.sub.1 -to-C.sub.6 -alkyl-N(C.sub.1 -to-C.sub.6 -loweralkyl)-C(O)-- and wherein at each occurrence substituted-thiazolyl is independently selected from a thiazolyl ring substituted with one or two substituents independently selected from C.sub.1 -to-C.sub.6 -loweralkyl, hydroxy, halo, amino, C.sub.1 -to-C.sub.6 -alkylamino, di-C.sub.1 -to-C.sub.6 -alkylamino, C.sub.1 -to-C.sub.6 -alkoxy, halo-C.sub.1 -to-C.sub.6 -alkyl, unsubstituted-C.sub.3 -to-C.sub.7 -cycloalkyl, unsubstituted (C.sub.6 -monocyclic or C.sub.9 - or C.sub.10 -bicyclic)aryl, unsubstituted (C.sub.6 -monocyclic or C.sub.9 - or C.sub.10 -bicyclic)aryl-C.sub.1 -to-C.sub.6 -alkyl, --COOH and --SO.sub.3 H.

3. The compound of claim 2 wherein R.sub.2 and R.sub.3 are benzyl, A is thiazolyl-C.sub.1 -to-C.sub.6 -alkyl-R.sub.9 --C(O)--NH--CH(R.sub.5)--C(O)-- or (substituted-thiazolyl)-C.sub.1 -to-C.sub.6 -alkyl-R.sub.9 --O(O)--NH--CH(R.sub.5)--C(O)-- wherein R.sub.9 is --O-- or --N(CH.sub.3)-- and R.sub.5 is C.sub.1 -to-C.sub.6 -loweralkyl and B is thiazolyl-C.sub.1 -to-C.sub.6 -alkyl-O--C(O)-- or (substituted-thiazolyl)-C.sub.1 -to-C.sub.6 -alkyl-O--C(O)-- and wherein at each occurrence substituted-thiazolyl is as defined therein.

4. The compound of claim 3 wherein R.sub.5 is isopropyl and at each occurrence substituted-thiazolyl is independently amino-substituted thiazolyl or C.sub.1 -to-C.sub.6 -loweralkyl-substituted thiazolyl.

5. The compound of claim 1 wherein A is thiazolyl-C.sub.1 -to-C.sub.6 -alkyl-O--C(O)--, thiazolyl-C.sub.1 -to-C.sub.6 -alkyl-NH--C(O)--, thiazolyl-C.sub.1 -to-C.sub.6 -alkyl-N(C.sub.1 -to-C.sub.6 -loweralkyl)-C(O)--, (substituted-thiazolyl)-C.sub.1 -to-C.sub.6 -alkyl-O--C(O)--, (substituted-thiazolyl)-C.sub.1 -to-C.sub.6 -alkyl-NH--C(O)-- or (substituted-thiazolyl)-C.sub.1 -to-C.sub.6 -alkyl-N(C.sub.1 -to-C.sub.6 -loweralkyl)-C(O)-- and B is thiazolyl-C.sub.1 -to-C.sub.6 -alkyl-R.sub.9 --C(O)--NH--CH(R.sub.5)--C(O)-- or (substituted-thiazolyl)-C.sub.1 -to-C.sub.6 -alkyl-R.sub.9 --C(O)--NH--CH(R.sub.5)--C(O)-- wherein R.sub.9 is --O--, --NH-- or --N(C.sub.1 -to-C.sub.6 -loweralkyl)- and R.sub.5 is C.sub.1 -to-C.sub.6 -loweralkyl and wherein at each occurrence substituted-thiazolyl is independently selected from a thiazolyl ring substituted with one or two substituents independently selected from C.sub.1 -to-C.sub.6 -loweralkyl, hydroxy, halo, amino, C.sub.1 -to-C.sub.6 -alkylamino, di-C.sub.1 -to-C.sub.6 -alkylamino, C.sub.1 -to-C.sub.6 -alkoxy, halo-C.sub.1 -to-C.sub.6 -alkyl, unsubstituted -C.sub.3 -to-C.sub.7 -cycloalkyl, unsubstituted (C.sub.6 -monocyclic or C.sub.9 - or C.sub.10 -bicyclic)aryl, unsubstituted (C.sub.6 -monocyclic or C.sub.9 - or C.sub.10 -bicyclic)aryl-C.sub.1 -to-C.sub.6 -alkyl, --COOH and --SO.sub.3 H.

6. The compound of claim 5 wherein R.sub.2 and R.sub.3 are benzyl, A is thiazolyl-C.sub.1 -to-C.sub.6 -alkyl-O--C(O)-- or (substituted-thiazolyl)-C.sub.1 -to-C.sub.6 -alkyl-O--C(O)-- and B is thiazolyl-C.sub.1 -to-C.sub.6 -alkyl-R.sub.9 --C(O)--NH--CH(R.sub.5)--C(O)-- or (substituted-thiazolyl)-C.sub.1 -to-C.sub.6 -alkyl-R.sub.9 --C(O)--NH--CH(R.sub.5)--C(O)-- wherein R.sub.9 is --O-- or --N(CH.sub.3)-- and R.sub.5 is C.sub.1 -to-C.sub.6 -loweralkyl and wherein at each occurrence substituted-thiazolyl is as defined therein.

7. The compound of claim 6 wherein R.sub.5 is isopropyl and at each occurrence substituted-thiazolyl is independently amino-substituted thiazolyl or C.sub.1 -to-C.sub.6 -loweralkyl-substituted thiazolyl.

8. The compound (2S,3S,5S)-2-(N-(N-((N-Methyl-N-((2-amino-4-thiazolyl)methyl)amino)carbony l)valinyl)amino)-5-(N-((5-thiazolyl)-methoxycarbonyl)amino)-1,6-diphenyl-3- hydroxyhexane; or a pharmaceutically acceptable salt thereof.

Make Better Decisions: Try a trial or see plans & pricing

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 verification 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.