Composition and antiviral activity of substituted azaindoleoxoacetic piperazine derivatives

A compound of Formula I, including pharmaceutically acceptable salts thereof,

• 2393
• wherein:
• Q is selected from the group consisting of:
• 2394
• R1, R2, R3, and R4, are independently selected from the group consisting of hydrogen, halogen, cyano, nitro, COR56, XR57 C(O)R7, C(O)NR55R56, B, D, and E with the proviso that at least one of R1-R4 is selected from B or E;
• wherein—represents a carbon-carbon bond or does not exist;
• m is 1 or 2;
• R5 is hydrogen or (CH2)nCH3, —C(O)(CH2)nCH3, —C(O)O(CH2)nCH3, —C(O) (CH2)nN(CH3)2 wherein n is 0-5;
• R6is O or does not exist;
• A is selected from the group consisting of C1-6alkoxy, aryl and heteroaryl;
• in which said aryl is phenyl or napthyl;
• said heteroaryl is selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, triazinyl, furanyl, thienyl, pyrrolyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, quinolinyl, isoquinolinyl, benzofuranyl, benzothienyl, benzoimidazolyl and benzothiazolyl;
• and said aryl or heteroaryl is optionally substituted with one or two of the same or different members selected from the group consisting of amino, nitro, cyano, hydroxy, C1-6alkoxy, —C(O)NH2, C1-6alkyl, —NHC(O)CH3, halogen and trifluoromethyl;
• 2395
• B is selected from the group consisting of —C(=NR46)(R47), C(O)NR40R41, aryl, heteroaryl, heteroalicyclic, S(O)2R8, C(O)R7, XR8a, (C1-6)alkylNR40R41, (C1-6)alkylCOOR8b;
• wherein said aryl, heteroaryl, and heteroalicyclic are optionally substituted with one to three same or different halogens or from one to three same or different substituents selected from the group F;
• wherein aryl is napthyl or substituted phenyl;
• wherein heteroaryl is a mono or bicyclic system which contains from 3 to 7 ring atoms for a mono cyclic system and up to 12 atoms in a fused bicyclic system, including from 1 to 4 heteroatoms;
• wherein heteroalicyclic is a 3 to 7 membered mono cyclic ring which may contain from 1 to 2 heteroatoms in the ring skeleton and which may be fused to a benzene or pyridine ring;
• q is 0, 1, or 2;
• D is selected from the group consisting of (C1-6)alkyl and (C2-6)alkenyl;
• wherein said (C1-6)alkyl and (C2-6)alkenyl are optionally substituted with one to three same or different halogens or from one to three same or different substituents selected from the group consisting of C(O)NR55R56, hydroxy, cyano and XR57;
• E is selected from the group consisting of (C1-6)alkyl and (C2-6)alkenyl;
• wherein said (C1-6)alkyl and (C2-6)alkenyl are independently optionally substituted with a member selected from the group consisting of phenyl, heteroaryl, SMe, SPh, —C(O)NR56R57, C(O)R57, SO2(C1-6)alkyl and S02Ph;
• wherein heteroaryl is a monocyclic system which contains from 3 to 7 ring atoms, including from 1 to 4 heteroatoms;
• F is selected from the group consisting of (C1-6)alkyl, (C3-7)cycloalkyl, aryl, heteroaryl, heteroalicyclic, hydroxy, (C1-6)alkoxy, aryloxy, (C1-6)thioalkoxy, cyano, halogen, nitro, —C(O)R57, benzyl, —NR42C(O)—(C1-6)alkyl, —NR42C(O)—(C3-6)cycloalkyl, —NR42C(O)-aryl, —NR42C(O)-heteroaryl, —NR42C(O)-heteroalicyclic, a 4, 5, or 6 membered ring cyclic N-lactam, —NR42S(O)2—(C1-6)alkyl, —NR42S(O)2—(C3-6cycloallkyl, —NR42S(O)2-aryl, —NR42S(O)2-heteroaryl, —NR42S(O)2-heteroalicyclic, S(O)2(C1-6)alkyl, S(O)2aryl, —S(O)2 NR42R43, NR42R43, (C1-6)alkylC(O)NR42R43, C(O)NR42R43, NHC(O)NR42R43, OC(O)NR42R43, NHC(O)OR54, (C1-6)alkylNR42R43, COOR54 and (C1-6)alkylCOOR54;
• wherein said (C1-6)alkyl, (C3-7)cycloalkyl, aryl, heteroaryl, heteroalicyclic, (C1-6)alkoxy, and aryloxy, are optionally substituted with one to nine same or different halogens or from one to five same or different substituents selected from the group G;
• wherein aryl is phenyl;
• heteroaryl is a monocyclic system which contains from 3 to 7 ring atoms, including from 1 to 4 heteroatoms;
• heteroalicyclic is selected from the group consisting of aziridine, azetidine, pyrrolidine, piperazine, piperidine, tetrahydrofuran, tetrahydropyran, azepine, and morpholine;
• G is selected from the group consisting of (C1-6)alkyl, (C3-7)cycloalkyl, aryl, heteroaryl, heteroalicyclic, hydroxy, (C1-6)alkoxy, aryloxy, cyano, halogen, nitro, —C(O)R57, benzyl, —NR48C(O)—(C1-6)alkyl, —NR48C(O)—(C3-6)cycloalkyl, —NR48C(O)-aryl, —NR48C(O)-heteroaryl, —NR48C(O)-heteroalicyclic, a 4, 5, or 6 membered ring cyclic N-lactam, —NR48S(O)2—(C1-6)alkyl, —NR48S(O)2—(C3-6)cycloalkyl, —NR48S(O)2-aryl, —NR48S(O)2-heteroaryl, —NR48S(O)2-heteroalicyclic, sulfinyl, sulfonyl, sulfonamide, NR48R49, (C1-6)alkyl C(O)NR48R49, C(O)NR48R49, NHC(O)NR48R49, OC(O)NR48R49, NHC(O)OR54, (C1-6)alkylNR48R49, COOR54, and (C1-6)alkylCOOR54;
• wherein aryl is phenyl;
• heteroaryl is a monocyclic system which contains from 3 to 7 ring atoms, including from 1 to 4 heteroatoms;
• heteroalicyclic is selected from the group consisting of aziridine, azetidine, pyrrolidine, piperazine, piperidine, tetrahydrofuran, tetrahydropyran, azepine, and morpholine;
• R7 is selected from the group consisting of aryl, heteroaryl, and heteroalicyclic;
• wherein said aryl, heteroaryl, and heteroalicyclic are optionally substituted with one to three same or different halogens or with from one to three same or different substituents selected from the group F;
• wherein for R7, R8, R8a, R8b aryl is phenyl;
• heteroaryl is a mono or bicyclic system which contains from 3 to 7 ring atoms for mono cyclic systems and up to 10 atoms in a bicyclic system, including from 1 to 4 heteroatoms;
• wherein heteroalicyclic is selected from the group consisting of aziridine, azetidine, pyrrolidine, piperazine, piperidine, tetrahydrofuran, tetrahydropyran, azepine, and morpholine;
• R8 is selected from the group consisting of hydrogen, (C1-6)alkyl, (C3-7)cycloalkyl, (C2-6)alkenyl, (C3-7)cycloalkenyl, (C2-6)alkynyl, aryl, heteroaryl, and heteroalicyclic;
• wherein said (C1-6)alkyl, (C3-7)cycloalkyl, (C2-6)alkenyl, (C3-7)cycloalkenyl, (C2-6)alkynyl, aryl, heteroaryl, and heteroalicyclic are optionally substituted with one to six same or different halogens or from one to five same or different substituents selected from the group F;
• R8a is a member selected from the group consisting of aryl, heteroaryl, and heteroalicyclic;
• wherein each member is independently optionally substituted with one to six same or different halogens or from one to five same or different substituents selected from the group F;
• R8b is selected from the group consisting of hydrogen, (C1-6)alkyl and phenyl;
• R9, R10, R11, R12, R13, R14, R15, R16, are each independently selected from the group consisting of hydrogen and (C1-6)alkyl;
• wherein said (C1-6)alkyl is optionally substituted with one to three same or different halogens;
• X is selected from the group consisting of NH or NCH3, O, and S;
• R40 and R41 are independently selected from the group consisting of (a) hydrogen;
• (b) (C1-6)alkyl or (C3-7)cycloalkyl substituted with one to three same or different halogens or from one to two same or different substituents selected from the group F;
• and (c) (C1-6)alkoxy, aryl, heteroaryl or heteroalicyclic;
• or R40 and R41 taken together with the nitrogen to which they are attached form a member selected from the group consisting of aziridine, azetidine, pyrrolidine, piperazine, 4-NMe piperazine, piperidine, azepine, and morpholine;
• and wherein said aryl, heteroaryl, and heteroalicyclic are optionally substituted with one to three same or different halogens or from one to two same or different substituents selected from the group F;
• wherein for R40 and R41 aryl is phenyl;
• heteroaryl is a monocyclic system which contains from 3 to 6 ring atoms, including from 1 to 4 heteroatoms;
• heteroalicyclic is selected from the group consisting of aziridine, azetidine, pyrrolidine, piperazine, piperidine, tetrahydrofuran, tetrahydropyran, azepine, and morpholine;
• provided when B is C(O)NR40R41, at least one of R40 and R41 is not selected from groups (a) or (b);
• R42 and R43 are independently selected from the group consisting of hydrogen, (C1-6)alkyl, allyl, (C1-6)alkoxy, (C3-7)cycloalkyl, aryl, heteroaryl and heteroalicyclic;
• or R42 and R43 taken together with the nitrogen to which they are attached form a member selected from the group consisting of aziridine, azetidine, pyrrolidine, piperazine, 4-NMe piperazine, piperidine, azepine, and morpholine;
• and wherein said (C1-6)alkyl, (C1-6)alkoxy, (C3-7)cycloalkyl, aryl, heteroaryl, and heteroalicyclic are optionally substituted with one to three same or different halogens or from one to two same or different substituents selected from the group G;
• wherein for R42 and R43 aryl is phenyl;
• heteroaryl is a monocyclic system which contains from 3 to 6 ring atoms, including from 1 to 4 heteroatoms;
• heteroalicyclic is a member selected from the group consisting of aziridine, azetidine, pyrrolidine, piperazine, piperidine, tetrahydrofuran, tetrahydropyran, azepine, and morpholine;
• Ra and Rb are each independently H, (C1-6)alkyl or phenyl;
• R46 is selected from the group consisting of H, OR57, and NR55R56;
• R47 is selected from the group consisting of H, amino, halogen, phenyl, and (C1-6)alkyl;
• R48 and R49 are independently selected from the group consisting of hydrogen, (C1-6)alkyl and phenyl;
• R50 is selected from the group consisting of H, (C1-6)alkyl, (C3-6)cycloalkyl, and benzyl;
• wherein each of said (C1-6)alkyl, (C3-7)cycloalkyl and benzyl are optionally substituted with one to three same or different halogen, amino, OH, CN or NO2;
• R54 is selected from the group consisting of hydrogen and (C1-6)alkyl;
• R54 is (C1-6)alkyl;
• R55 and R56 are independently selected from the group consisting of hydrogen and (C1-6)alkyl;
• and
• R57 is selected from the group consisting of hydrogen, (C1-6)alkyl and phenyl.