Benzimidazole and benzotriazole derivatives as non nucleoside reverse transcriptase Inhibitors, Pharmaceutical compositions containing same and use in preparation of a Medicament for the Treatment or prophylaxis of HIV infection or AIDS - 1

摘要

The compounds of Formula 1 are inhibitors of HIV reverse transcriptase, in which Q, R2, R3, R4, T1, T2, and T3 are defined in this paper.The compounds of Formula 1, and their pharmaceutically acceptable Salts and prodrugs, are useful in the inhibition of HIV reverse transcriptase, prophylaxis and Treatment of infection by HIV and in the Prevention, delay the onset or progression, and Treatment of AIDS.The compounds and their salts can be used as ingredients in Pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or Vaccines claim 1: a compound of the formula (1) or a pharmaceutically acceptable Salt thereof, in which t1 and T2 and T3 are each independently h, c1-4 alkyl, halogen, CN, CH = CH NS, C (OR) raOr 1 - (CH2) 2N (RA) RB; R2 and r3se each independently selected from the group consisting of: (1) h, (2), 3 (3) C (o) n (RA) RB, c1-4 alkyl (4), (5) (CF3, 6) or c1-4 alkyl, and (7) ocf3; R6 is as in the Formula 2 to 10 (- 10) * ch2ch2oh; J1 and J2 are each independently h, Logeno, CN, NO2, c1-4 alkyl, CF3, Oh, or c1-4 alkyl, ocf3, C (o) n (RA) (RA or RB, c), co2ra, so2ra,So2n (RA or RB; J3) is H, halogen, CN, c1-4 alkyl, o-alkyl Oh, Oxo, c1-4, CF3, ocf3, C (o) NH2, C (o) CH3, N (H) C (o) n (RA, RB, C (o) co2ra, so2ra) ra, RB, or so2n (RA); l is n or n oxide; Q is: (1) - ch (R4) - (2) - C (R4) = C (R5) - (3) - (4) - ch - ch (R5), (4) - C (R4) = C (R5) - CH2 - (5) - ch - ch (R4) (R5) - CH2 - (6) - C (R = C (R4) 5) - ch = CH - (7) - ch - ch (R4) (R5) - ch = CH - (8) - C (R4) = C (R5) - ch2ch2 - (9) - ch - ch (R4) - ch2ch2 (R5),(10) - C (R) = N - (11) - n = C (R4) - or (12) - n = N -; in which the leftmost atom of q is the Atom that binds directly to benzo condensate; R4 and R5 are selected independently for each from a group consisting of: (1) h, (2) alkyl C1 - 4, (3) or c1-4 alkyl, CF3 (4), (5) Ocf3,And (6) Halogen; R7 and R8 are each independently selected from the group consisting of: (1) H (2) o (3), 3 NS, 5 (4) (5) (6) NO2, c1-4 alkyl, o-alkyl (7) C1 4, (8) or (CH2) 2 - 3N (RA), Rb (9) or (CH2) 1 - 3C (or ra, CF3) (10) (11) (12) ocf3, or 1 - (CH2) 2cf3 (12) n (RC, RD, (13) n - (RA)) 2 - (CH2) 3N (RC) Rd,(14) C and (OR) n RB ra (RA); each is independently H or alkyl c1-4; each RB is independently H or alkyl c1-4; each RC is independently H or alkyl Rd C1 - 4; each is independently H or alkyl of C1 - 4; and alternative and independent each pair of RC and RD with the N atom of the Both are United to form a saturated monocyclic Ring that is selected from the GroupThe remains of stituido formulas (11), and with the condition that (a) when q is - n = C (R4) - R4 and R6 H is different, so it's not like formula (12).Claim 1: a compound of the formula (1) in which t1 and T2 and T3 are each independently h, c1-4 alkyl, halogen, CN, cn CH = CH - C (o), RA, or 1 - (CH2) 2N (RA) RB; R2 and select each r3se One independently from the Group consisting of: (1) h, (2), 3 (3) (c) (RB, RA (n) 4) c1-4 alkyl, CF3 (5), (6) or c1-4 alkyl, and (7) ocf3; l is n or n oxide; Q is: (1) - (4) -, CH(2) - C (R4) = C (R5) - (3) - ch - ch (R4) (R5) - (4) - C (R4) = C (R5) - CH2 - (5) - ch - ch (R4) (R5) - CH2 -, (6) - C (R4) = C (R5) - ch = CH - (7) - ch - ch (R4) (R5) - ch = CH - (8) - C (R4) = C (R5) - ch2ch2 - (9) - ch (R4) CH (R5) - ch2ch2 - (10) - C (R) = N - (11) - n = CH -(12) or - n = N -; in which the leftmost atom of q is the Atom that binds directly to benzo condensate; R4 and R5 are each independently selected from the group consisting of: (1) h, (2) alkyl C1 - 4 (3), or c1-4 alkyl, CF3 (4), (5) and (6) ocf3, halogen; R7 and R8 is s Eleccionan each independently from a group consisting of: (1) H (2) o(3), 3 NS, 5 (4) (5) NO2, c1-4 alkyl (6), (7) or c1-4 alkyl, (8) or (CH2) 2 - 3N (RA), Rb (9) or (CH2) - 3C (1 or) RA (10) ocf3 CF3, (11), (12) or (CH2) 1 - 2cf3, (12) n (RC) Rd, (13) (RA) - 2 - (CH2) 3N (RC) Rd,(14) C and (OR) n RB ra (RA); each is independently H or alkyl c1-4; each RB is independently H or alkyl c1-4; each RC is independently H or alkyl Rd C1 - 4; each is independently H or alkyl of C1 - 4; each Alternative and independent couple of RC and RD with the N Atom to the qu And both are United to form a saturated monocyclic Ring that is selected from the Group constItuido by Remnants of formulas (2), r9p is PO (OH) or -. M + (OR -); PO 2.2m + (OR -); PO 2 m2 +; acid or a Salt of formula (3) or (4); M + is a monovalent counterion pharmaceutically acceptable; m2 + is a divalent counterion pharmaceutically acceptable; R15 is H or alkyl c1-4, r16a and r16b are each independently H or alkyl c1-4, is H or alkyl R19 and R20 C1 - 4; S H o r22a c1-4 alkyl; and r22b are each independently H or c1-4 alkyl; and D is a number.Or equal to 2, 3 or 4, and with the condition that (a) when q is - n = C (R4), then H is R4.