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HIV integrase inhibitors

  • US 6,306,891 B1
  • Filed: 06/01/1999
  • Issued: 10/23/2001
  • Est. Priority Date: 06/03/1998
  • Status: Expired due to Fees
First Claim
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1. A compound of structural formula (I):

  • and tautomers and pharmaceutically acceptable salts thereof, wherein;

    A is a five-membered heteroaromatic ring containing 1 or 2 nitrogen atoms and substituted on carbon or nitrogen by R1, R2 and R8;

    the heteroaromatic ring may optionally be fused with a phenyl ring to form a fused ring system, provided that when A is a fused ring system, the nitrogen-containing heteroaromatic ring is substituted by the dioxobutyric acid/ester moiety;

    R1 is selected from;

    (1) —

    H, (2) —

    C1-5 alkyl, (3) —

    CF3, (4) -halo, (5) —

    NO2, (6) —

    N(R4)(R5), (7) —

    R6, (8) —

    C2-5 alkenyl-R3, (9) —

    C2-5 alkynyl-R3, (10) —

    O—

    R6, (11) —

    O—

    C1-6 alkyl, and (12) —

    C(O)CH2C(O)C(O)OR7;

    R2 is selected from;

    (1) —

    H, (2) —

    R3, (3) —

    C1-6 alkyl, (4) —

    C1-6 alkyl substituted with R3, (5) —

    O—

    R6, (6) —

    O—

    C1-6 alkyl-OR6, (7) —

    S(O)n-R6, (8) —

    C1-6 alkyl (OR6)(R4), (9) —

    C1-6 alkyl-N(R4)(R6), (10) —

    C1-6 alkyl S(O)n-R6, (11) —

    C1-6 alkyl C(O)—

    R6, (12) —

    C1-6 alkyl C(S)—

    R6, (13) —

    C1-6 alkyl NR4C(O)—

    R6, and (14) —

    C1-6 alkyl-C(O)N(R4)(R5);

    each R3 is independently selected from;

    (1) a 5 or 6 membered aromatic or heteroaromatic ring, containing 0, 1, 2, 3, or 4 heteroatoms selected from oxygen, nitrogen and sulfur, unsubstituted or substituted on a nitrogen or carbon atom by 1 to 5 substituents selected from;

    (a) halogen, (b) C1-6 alkyl, (c) C1-6 alkyloxy-, (d) phenyl, (e) —

    CF3, (f) —

    OCF3, (g) —

    CN, (h) hydroxy, (i) phenyloxy, and (j) substituted phenyloxy with 1, 2, or 3 substituents selected from;

    (i) halogen, (ii) C1-6 alkyl, (iii) —

    CF3, and (iv) hydroxy;

    (2) a 3 to 6 membered saturated ring containing 0 or 1 heteroatoms selected from oxygen, nitrogen or sulfur, unsubstituted or substituted with 1 to 5 substituents selected from;

    (a) halogen, (b) C1-6 alkyl, (c) C1-6 alkyloxy-, (d) —

    CF3, (e) —

    OCF3, (f) —

    CN, (g) ═

    O, and (h) hydroxy;

    (3) unsubstituted or substituted hexahydrothieno[3,4-d]imidazolyl with one or two substituents selected from;

    (a) oxo, (b) halogen, (c) C1-6 alkyl, (d) C1-6 alkyloxy-, (e) —

    CF3, (f) —

    OCF3, (g) —

    CN, and (h) hydroxy;

    (4) a 5 or 6 membered aromatic or heteroaromatic ring, containing 0, 1, or 2 heteroatoms selected from oxygen, nitrogen and sulfur, fused with a phenyl ring;

    wherein the ring system is unsubstituted or substituted on a nitrogen or carbon atom by 1 to 3 substituents selected from;

    (a) -halogen, (b) —

    C1-6 alkyl, (c) —

    C1-6 alkyloxy-, (d) —

    CF3, (e) —

    OCF3, (f) —

    CN, and (g) -hydroxy;

    (5) a 3 to 6 membered saturated ring containing 0 or 1 heteroatoms selected from oxygen, nitrogen or sulfur, fused with a phenyl ring, unsubstituted or substituted with 1 or 2 substituents selected from;

    (a) halogen, (b) C1-6 alkyl, (c) C1-6 alkyloxy-, (d) —

    CF3, (e) —

    OCF3, (f) —

    CN, (g) ═

    O, and (h) hydroxy; and

    (6) a 5 to 6 membered ring containing 0, 1 or 2 heteroatoms selected from oxygen, nitrogen or sulfur, containing 2 or 3 double bonds, unsubstituted or substituted with 1 or 2 substituents selected from;

    (a) halogen, (b) C1-6 alkyl, (c) C1-6 alkyloxy-, (d) —

    CF3, (e) —

    OCF3, (f) —

    CN, (g) ═

    O, and (h) hydroxy;

    each R4 is independently selected from;

    (1) —

    H, (2) —

    C1-3 alkyl, (3) —

    CF3, (4) —

    R3, (5) —

    C2-3 alkenyl, (6) —

    C1-3 alkyl-R3, (7) —

    C2-3 alkenyl-R3, (8) —

    S(O)n

    R3, and (9) —

    C(O)—

    R3;

    each R5 is independently selected from;

    (1) —

    H, (2) —

    C1-3 alkyl, (3) —

    CF3, (4) —

    R3, (5) —

    C2-3 alkenyl, (6) —

    C1-3 alkyl-R3, (7) —

    C2-3 alkenyl-R3, (8) —

    S(O)n

    R3, and (9) —

    C(O)—

    R3;

    each R6 is independently selected from;

    (1) —

    C1-3 alkyl-R3, and (2) —

    R3;

    R7 is selected from;

    (1) —

    H, and (2) C1-6 alkyl;

    R8 is selected from;

    (1) —

    H, (2) C1-6 alkyl-oxy, and (3) C1-6 alkyl; and

    each n is independently selected from 0, 1 and 2; and

    further provided that when R7 is C1-6 alkyl, then R2 is not —

    H or —

    C1-6 alkyl.

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