Inhibitors of HIV reverse transcriptase

• US 5,308,854 A
• Filed: 11/04/1992
• Issued: 05/03/1994
• Est. Priority Date: 06/18/1990
• Status: Expired due to Term

• Current Assignee: Merck Sharp & Dohme Corporation (Merck & Co., Inc.)
• Original Assignee: Merck & Co., Inc.
• Inventors: Wai, John S., Hoffman, Jacob M. Jr., Saari, Walfred S., Rooney, Clarence S.
• Primary Examiner(s): Fan, Jane T.
• Application Number:
  US07/971,691
• Time in Patent Office: 545 Days
• Field of Search: 514/338, 546/270
• US Class Current: 514/338
• CPC Class Codes: C07D 213/64 attached in position 2 or 6
• CPC Class Codes: C07D 213/69 Two or more oxygen atoms
• CPC Class Codes: C07D 213/74 Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 413/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links

Abstract

Novel aminopyridones inhibit HIV reverse transcriptase, and are useful in the prevention or treatment of infection by HIV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, anti-infectives, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.

Claims

1. A compound of the formula:

##STR27## wherein;

X is NH, O, or S;

Z is O or S;

n is 1-4;

R₁ is

(i) C_1-8 alkyl, unsubstituted or substituted with one or two of C_1-3 alkoxy, halo, C_1-4 alkylamino, C_1-4 -di-alkylamino, or C_1-3 alkylthio;

(ii) C_1-3 alkylthio;

(iii) C_1-3 alkoxy;

or

(iv) halo;

R₂ is H, methyl or ethyl, unsubstituted or substituted with one or two of methoxy, methylamino, dimethylamino or methylthio;

R₃ is H or C_1-8 alkyl;

--◯

is 2-benzoxazolyl, unsubstituted or substituted with one or more of methyl, halogen or hydroxyl.

2. A compound of claim 1, wherein 2-benzoxazolyl is unsubstituted, or substituted as 7-methyl-2-benzoxazolyl, 4,7-dimethyl-2-benzoxazolyl, 7-chloro-2-benzoxazolyl, or 4,7-dichloro-2-benzoxazolyl.

3. A pharmaceutical composition useful for inhibiting HIV reverse transcriptase, comprising an effective amount of a compound as in any of claims 1 or 2, and a pharmaceutically acceptable carrier.

4. A pharmaceutical composition useful for preventing or treating infection of HIV or for teating AIDS or ARC, comprising an effective amount of a compound as in any of claims 1 or 2, and a pharmaceutically acceptable carrier.