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US 8,044,091 B2Granted
Phospho-indoles as HIV inhibitors
AssigneeIdenix Pharmaceuticals, Inc.
InventorsRichard Storer, Cyril Dousson, Francois-Rene Alexandre, Arlene Roland
Life of this patent
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Abstract
3-phosphoindole compounds for the treatment of retroviral infections, and particularly for HIV, are described. Also included are compositions comprising the 3-phosphoindole derivatives alone or in combination with one or more other anti-retroviral agents, processes for their preparation, and methods of manufacturing a medicament incorporating these compounds.
Claims25
A compound of Formula (B):
- or a pharmaceutically acceptable salt, prodrug, N-oxide, quaternary amine, stereochemical isomer or tautomer thereof, wherein:
- Y is O-alkyl;
- W is O;
- R1 is selected from the group consisting of H, R2, C(═O)R2, C(═O)—O—R2, C(═O)—S—R2, C(═O)—NH—R2, C(═O)—NR2R2, C(═O)—NH-A-(amino acid residue), A-(amino acid residue)-R2, S(O)n—R3, S(O)2—NR2R2, any of which may optionally be substituted by one or more C1-6 alkyl, OH, alkoxy, aryl, halo, CN, NO2, or NR2R2;
- each R2 is independently H;
- OH;
- halogen;
- optionally substituted, branched or unbranched alkyl;
- optionally substituted, branched or unbranched alkenyl;optionally substituted, branched or unbranched alkynyl;
- 3-14 membered carbocycle;
- alkylheterocycle;
- acyl;
- carboxamido;
- carbamoyl;
- alkoxy;
- optionally substituted aryl;
- optionally substituted aralkyl;
- optionally substituted alkylaryl;
- O-alkyl;
- O-alkenyl;
- O-alkynyl;
- O-alkaryl;
- O-aralkyl;
- O-carbocycle;
- O-heterocycle;
- O-aryl;
- CF3;
- CN;
- S(O)n—R3;
- N(R3)(R3);
- NH—S(O)n—R3;
- NHC(═W)-aryl;
- NHC(═W)-alkyl;
- NHC(═W)-heterocycle;
- CH2—S(O)n—R3;
- C(═W)R3;
- C(═W)NR3R3;
- C(alkyl)2-S(O)nR3;
- CH(alkyl)-S(O)nR3;
- C(alkyl)2-NH2;
- CH(alkyl)-N(alkyl)R3;
- CR3R2—NR3R3;
- CH2N(alkyl)R3;CH(alkyl)-NHR3;
- C(alkyl)2-NHR3;
- C(alkyl)2-N(alkyl)R3;
- CH2—C(═W)H;
- CH2—C(═W)alkyl;
- CR3R3—C(═W)R3;
- A-R3;
- C(R3)2—C(═W)R3;
- CH2—C(═W)H;
- CH2—C(═W)alkenyl;
- CH(alkenyl)-C(═W)H;
- A-S(O)R3;
- CH(NH)—S(O)nR3;
- or A-N(NH)R3;
- wherein said optional substitution comprises one or more of:
- a substituted or unsubstituted heterocycle;
- C(═W)O-aryl;
- C(═W)O-alkyl;
- C(═W)NH2;
- C(═W)NH-alkyl;
- C(═W)NH-aryl;
- C(═W)N-di-alkyl;
- C(═W)N(alkyl)-aryl;
- α-amino acid;
- α-amino ester;
- α-amino-carboxamide;
- β-amino acid;
- β-amino ester;
- or β-amino-carboxamide;
- each R3 is independently H;
- OH;
- C1-6 alkyl;
- C2-6 alkenyl;
- C2-6 alkynyl;
- alkoxy;
- CF3;
- CN;
- amino;
- NR2R2;
- O-alkyl;
- O-alkenyl;
- O-alkynyl;
- C(R2)(R2)—S(O)nNH2;
- C(R2)(R2)—S(O)nCF3;
- C(R2)(R2)—NH2;
- A-heterocycle;
- C(R2)(R2)—NR2R2;
- C(R2)(R2)—C(═W)R2;
- aryl;
- carbocycle;
- heterocycle;
- cycloalkyl;
- alkaryl;
- alkylheterocycle;
- aralkyl;
- or heterocycle-alkyl;
- any of which may be unsubstituted or substituted with one or more of the following taken in any combination:
- halo;
- OH;
- OR2;
- SR2;
- COOH;
- carboxylic acid ester;
- C(═W)R2;
- C(═W)OR2;
- C(═W)OR3;
- C(═W)SR2;
- A-C(═W)NH2;
- C(═W)NR2R3;
- NR2R2;
- NR2R3;
- NR2—S(O)nR3;
- NR2—C(═W)—C1-6alkyl;
- S(O)nR3;
- C1-6alkoxy;
- C1-6 thioether;
- amino acid residue;
- NH-A-(amino acid residue);
- C(═W)NH-A-(amino acid residue);
- and wherein when said optional substitution comprises a substituted heterocycle, then substitution is selected from the group consisting of:
- C(═W)O-aryl;
- C(═W)O-alkyl;
- C(═W)NH2;
- C(═W)NH-aryl;
- C(═W)NH-alkyl;
- C(═W)N-di-alkyl;
- C(═W)N(alkyl)-aryl;
- α-amino acid;
- α-amino ester;
- α-amino-carboxamide;
- β-amino acid;
- β-amino ester;
- β-amino-carboxamide;
- halo;
- or cyano, taken alone or in any combination;
- each n is independently 0, 1 or 2;
- A is a disubstituted spacer selected from the group consisting of:
- C1-6 alkylene, branched or unbranched, and optionally having one or more heteroatoms, aryl, cycloalkyl or heterocyclyl functions in or attached to the chain;
- C2-12 alkenylene, branched or unbranced, and optionally having one or more heteroatoms, aryl, cycloalkyl or heterocyclyl functions in or attached to the chain;
- C2-12 alkynylene, branched or unbranced, and optionally having one or more heteroatoms, aryl, cycloalkyl or heterocyclyl functions in or attached to the chain;
- optionally substituted arylene;
- O-alkylene, branched or unbranched, and optionally having one or more heteroatoms, aryl, cycloalkyl or heterocyclyl functions in or attached to the chain;
- aralkylene, branched or unbranched, and optionally having one or more heteroatoms, aryl, cycloalkyl or heterocyclyl functions in or attached to the chain;
- optionally substituted cycloalkyl;
- and optionally substituted heterocycle;
- wherein “A” may be joined by any desired linkage or any combination of desired linkages;
- R6′ and R7′ are each independently H;
- R4′ and R5′ are each independently Cl, F, Br, I, methyl, ethyl or CF3;
- Z is —C(═O)NH2;
- and
- R2″, R3″, R4″, R5″, and R6″ are each independently selected from the group consisting of hydrogen, halogen, NO2, CN, OR2, SR2, NH2, NR2R3, N(R2)—C(═W)—C1-4 alkyl, N(R2)—SO2—C1-4 alkyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, CF3, CR2R2—S(O)n—R3, CR2R2NR2R3, C—OH, CR2R2—C(═W)R2, acyl, C(═W)R2, C(═W)OR2, C(═W)SR2, C(═W)—NR2R3, C(═W)NH(CH2)p-(amino acid residue), amino residue, and A-(amino acid residue), any of which optionally may be substituted.
150 more elements
Dependencies are inferred from the claim text.