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US-20260124209-A1 - INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION

US20260124209A1US 20260124209 A1US20260124209 A1US 20260124209A1US-20260124209-A1

Abstract

Methods of treatment or prevention of HIV infection in a subject are set forth. The methods involve the administration of a compound of Formula (I), including pharmaceutically acceptable salts of a compound of Formula (I), to a subject in need of such treatment or prevention of HIV infection:

Inventors

  • Manoj Patel
  • Kyle E. Parcella
  • Michael S. Bowsher
  • Christiana Iwuagwu
  • Eric P. Gillis
  • B Narasimhulu NAIDU

Assignees

  • VIIV Healthcare UK (No.5) Limited

Dates

Publication Date
20260507
Application Date
20251218

Claims (20)

  1. 1 . A method of treatment of HIV infection in a subject, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I): or a pharmaceutically acceptable salt thereof, wherein: Z is CH or N; G 1 is selected from G 1a is selected from the group consisting of —OH, —F, —Cl, —CN, —C 1-4 alkyl optionally substituted with 1, 2 or 3 —F, and —C 1-3 alkyl optionally substituted with one substituent selected from the group consisting of —N(C 1-2 alkyl) 2 , —NH(C 1-2 alkyl), and a heterocycle selected from the group consisting of azetidine, pyrrolidine, piperidine, and morpholine, wherein said heterocycle is optionally substituted with 1, 2, 3 or 4 substituents independently selected from the group consisting of —CH 3 and —F; G 2 is selected from the group consisting of —H, —F, —Cl, —OCH 3 , —CH 3 , —CHF 2 , cyclopropyl, G 3 is selected from the group consisting of —H, —Cl, —CN, —CHO, —C(O)C 1-2 alkyl; —C 1-3 alkyl optionally substituted with 1, 2 or 3 —F; —C 1-3 alkyl optionally substituted with one substituent select from the group consisting of —OH, —OC 1-2 alkyl and —CN; —C 3-4 cycloalkyl optionally substituted with 1, 2 or 3 —F; and —NH—C 1-3 alkyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of —OCH 3 and —F; or G 3 is —NH(C 1-4 alkyl-G 3a ), wherein G 3a is a heterocycle selected from the group consisting of oxetane, tetrahydrofuran, and tetrahydro-2H-pyran, wherein said heterocycle is optionally substituted with one substituent selected from the group consisting of —CH 3 , —F, —OC 1-3 alkyl and —OC 3-4 cycloalkyl; or G 3 is selected from the group consisting of: G 3b is selected from the group consisting of —NH(C 1-2 alkyl), —N(C 1-2 alkyl) 2 , —NH(CH 2 CH 2 OC 1-3 alkyl), —N(C 1-2 alkyl)(CH 2 CH 2 OC 1-3 alkyl) and —NH(CH 2 CH 2 R 8 ); G 3c is selected from the group consisting of —H, —CN, —OC 1-3 alkyl, —C 3-6 cycloalkyl, —NHC(O)C 1-3 alkyl, —NH(C 1-2 alkyl), —N(C 1-2 alkyl) 2 , —R 8 , an aromatic heterocycle selected from the group consisting of phenyl, pyridine, thiazole, pyrazole and imidazole, wherein said aromatic heterocycle is optionally substituted with one —CH 3 group; and a non-aromatic heterocycle selected from the group consisting of wherein said non-aromatic heterocycle is optionally independently substituted with 1 or 2 substituents selected from the group consisting of —F, —CH 3 , —CF 3 , —CHF 2 , —OC 1-2 alkyl and —C(O)C 1-2 alkyl; G 4 is a heterocycle selected from the group consisting of pyridine, pyrimidine, pyrazole, imidazole, oxetane, tetrahydrofuran, tetrahydro-2H-pyran, azetidine, pyrrolidine and piperidine, wherein said heterocycle is optionally substituted with —CH 2 CH 2 OC 1-3 alkyl; or G 4 is selected from the group consisting of: X is selected from the group consisting of —OR 1 , —Cl, —Br, phenyl, pyridine, pyrazole, imidazole, pyrrolidin-2-one, 2,5-dihydro-pyrrole, 4-methyl-7-(methylamino)-2H-chromen-2-one, —NR 1 R 2 , —R 6 , —R 7 , and —R 8 ; Y is selected from the group consisting of —NR 1 R 2 , —R 6 , —R 7 , and —R 8 ; R 1 is selected from the group consisting of —H, phenyl, pyridine, —R 4 , and —C 1-4 alkyl optionally substituted with 1, 2 or 3 —F, 1 or 2 —OC 1-3 alkyl groups, or one —CN group; —C 3-4 cycloalkyl optionally substituted with 1 or 2 —F or a —OCH 3 group; oxetane optionally substituted with one —CH 3 group; tetrahydrofuran optionally substituted with one —CH 3 group; and tetrahydro-2H-pyran optionally substituted with one —CH 3 group; R 2 is selected from the group consisting of —H, —C 1-4 alkyl optionally substituted with 1, 2 or 3 —F, 1 or 2 —OC 1-3 alkyl groups, or one —CN group; —C 3-4 cycloalkyl optionally substituted with 1 or 2 substituents independently selected from the group consisting of —F and —OCH 3 ; and oxetane optionally substituted with one —CH 3 group; R 4 is selected from the group consisting of —(CH 2 CH 2 O), CH 2 CH 2 N(R 5 ) 2 and —(CH 2 CH 2 O) n R 5 ; n is 2, 3, 4, 5, 6, 7 or 8; each R 5 is independently selected from the group consisting of —H, —C 1-4 alkyl and —C 3-4 cycloalkyl; R 6 is a heterocycle selected from the group consisting of azetidine, pyrrolidine, piperidine, piperazine, and morpholine, wherein said heterocycle is optionally substituted with 1, 2, 3 or 4 —F, one —OH group, 1 or 2 —OC 1-4 alkyl groups, 1 or 2 —CH 3 groups, one —C 1-3 alkyl group optionally substituted with 1, 2 or 3 —F, one —CH 3 group optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of —F, —OH and —OC 1-3 alkyl, or —CH 2 pyridine optionally substituted with 1 or 2 —CH 3 groups; R 7 is a heterocycle selected from the group consisting of azetidine, pyrrolidine, piperidine, piperazine, and morpholine, wherein said heterocycle is optionally substituted with one substituent selected from the group consisting of —CO 2 H, —S(O 2 )R 10 , —N(R 9 ) 2 , —NR 9 SO 2 R 10 , —NR 9 COR 10 , —C(O)R 5 , —C(O)R 6 , a heterocycle selected from the group consisting of 1,2,4-oxadiazole, isoxazole, pyrazole, imidazole and thiazole, wherein said heterocycle is optionally substituted with one R 10 group, and a heterocycle selected from the group consisting of oxetane, tetrahydrofuran and tetrahydro-2H-pyran, wherein said heterocycle is optionally substituted with one —CH 3 group; each R 8 is independently a heterocycle selected from the group consisting of wherein said heterocycle is optionally substituted with 1, 2, 3 or 4 substituents independently selected from the group consisting of —F, —CF 3 , —OCH 3 , —CHF 2 , —CH 2 F and —C 1-4 alkyl; each R 9 is independently selected from the group consisting of —H, —CH 3 , —C 2-3 alkyl optionally substituted with 1, 2 or 3 —F, and —C 3-4 cycloalkyl optionally substituted with 1 or 2 —F; R 10 is selected from the group consisting of —CH 3 , —CH 2 F, —CHF 2 , —CF 3 , —C 2-3 alkyl optionally substituted with 1, 2 or 3 —F, and —C 3-4 cycloalkyl optionally substituted with 1 or 2 —F; G 5 is selected from the group consisting of —C 1-3 alkyl optionally substituted with 1, 2 or 3 —F, and —C 3-4 cycloalkyl optionally substituted with 1 or 2 —F; G 6 is selected from the group consisting of —F, —Cl, —CH 3 , and —OCH 3 ; G 7 is selected from the group consisting of G 7a is selected from the group consisting of —H and —F; G 7b is selected from the group consisting of —H, —CH 3 and —F; G 7c is selected from the group consisting of —C 1-2 alkyl optionally substituted with 1, 2 or 3 —F, and —C 3-4 cycloalkyl optionally substituted with 1 or 2 —F; G 8 and G 9 are independently selected from the group consisting of —H, —F, —Cl, —CH 3 and —OCH 3 ; G 10 is selected from the group consisting of —H and —F; and G 11 is selected from the group consisting of —H, —F, —CH 3 and —OCH 3 , or a pharmaceutically acceptable salt thereof.
  2. 2 . The method according to claim 1 , satisfying at least one condition selected from the group consisting of (i) or (ii): (i) G 3 is selected from the group consisting of —CH 3 , G 3c is selected from the group consisting of H, —OCH 3 , and a non-aromatic heterocycle selected from the group consisting of wherein said non-aromatic heterocycle is optionally independently substituted with 1 or 2 substituents selected from the group consisting of —F, —CH 3 , —CF 3 , —CHF 2 and —OC 1-2 alkyl; and (ii) G 4 is selected from the group consisting of: X is selected from the group consisting of —OR 1 and —R 8 ; R 1 is selected from the group consisting of H and —C 1-4 alkyl optionally substituted with 1, 2 or 3 —F, 1 or 2 —OC 1-3 alkyl groups, or one —CN group; and R 8 is a heterocycle selected from the group consisting of wherein said heterocycle is optionally substituted with 1, 2, 3 or 4 substituents independently selected from the group consisting of —F and —C 1-4 alkyl.
  3. 3 . The method according to claim 1 , wherein the compound is a compound of Formula (II): or a pharmaceutically acceptable salt thereof, wherein: G 1a is selected from the group consisting of —F, —CHF 2 , —CH 2 F and —CH 3 ; G 2 is selected from the group consisting of —H, —CH 3 and —CHF 2 ; G 3 is selected from the group consisting of —H, —C 1-3 alkyl optionally substituted with 1, 2 or 3 —F; —C 3-4 cycloalkyl optionally substituted with 1, 2 or 3 —F; —NH—C 1-3 alkyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of —OCH 3 and —F; —C 1-3 alkyl-azetidine optionally substituted with 1, 2 or 3 —F; and —C 1-3 alkyl-morpholine optionally substituted with 1, 2, 3 or 4 substituents independently selected from the group consisting of —C 1-3 alkyl and —F; G 4 is selected from the group consisting of wherein G 4B is selected from the group consisting of —CH 2 —O—CH 3 , and a heterocycle selected from group consisting of wherein said heterocycle is optionally substituted with 1, 2, 3 or 4 substituents independently selected from group consisting of —F and —C 1-3 alkyl.
  4. 4 . The method according to claim 3 , wherein G 1a is selected from the group consisting of —F and —CH 3 ; and/or G 2 is —H and wherein G 7 is selected from the group consisting of wherein G 7a is —H and G 7b is —H, or G 7a is F and G 7b is F; and G 7c is selected from the group consisting of —C 1-2 alkyl optionally substituted with 1, 2 or 3 —F, and —C 3-4 cycloalkyl.
  5. 5 . The method according to claim 3 , wherein G 3 is selected from the group consisting of —CH 3 , —CHF 2 , —NH—CH 2 CH 2 OCH 3 , —NHCH 2 CH 3 , —CH 2 -azetidine substituted with 2 —F, and —C 1-2 alkyl-morpholine optionally substituted with 1, 2, 3 or 4 substituents independently selected from the group consisting of —CH 3 and F and wherein G 4 is wherein G 4B selected from the group consisting of —CH 2 —O—CH 3 , and a heterocycle selected from the group consisting of wherein said heterocycle is optionally substituted with 1, 2, 3 or 4 substituents independently selected from group consisting of —F and —C 1-3 alkyl.
  6. 6 . The method according to claim 3 , wherein the compound is a compound of Formula (IIb)
  7. 7 . A method of treatment of HIV infection in a subject, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound which is or a pharmaceutically acceptable salt thereof.
  8. 8 . The method according to claim 7 , wherein the compound of Formula (I) or pharmaceutically acceptable salt thereof is administered as a free compound.
  9. 9 . The method according to claim 7 , wherein the compound of Formula (I) or pharmaceutically acceptable salt thereof is administered as a pharmaceutically acceptable salt.
  10. 10 . The method according to claim 7 , wherein the compound is a crystalline compound characterized by having at least four diffraction angles, when measured using Cu K α radiation, selected from a group consisting of about 5.1, 5.6, 6.9, 7.6, 8.2, 8.7, 9.1, 9.8, 11.1, 11.3, 11.9, 13.2, 13.9, 14.4, 14.7, 15.2, 15.4, 16.0, 16.6, 16.8, 17.2, 17.5, 18.4, 18.7, 19.1, 19.4, 19.9, 20.3, 20.5, 21.0, 21.4, 22.0, 22.6, 23.8, 24.0, 24.4, 24.7, 25.1, 25.8, 26.2, 26.8, 27.0, 27.6, 27.9, 28.5, 28.8, 29.2, 29.8, 30.1, 31.1, 31.3, 31.9, 32.5, 32.7, 33.2, 34.1, 34.8, 35.4, 36.1, 37.7, 38.7, 39.0, 39.5, and 39.7 degrees ±0.2° 2θ.
  11. 11 . The method according to claim 7 , wherein the compound is a crystalline compound and is characterized by a DSC thermogram having a melting onset of about 216° C.
  12. 12 . The method according to claim 7 , wherein a pharmaceutical composition is administered, the pharmaceutical composition comprising a) the compound or pharmaceutically acceptable salt thereof, and b) a pharmaceutically acceptable excipient.
  13. 13 . The method according to claim 7 , wherein the compound or pharmaceutically acceptable salt thereof is administered to said subject orally, subcutaneously, or intramuscularly.
  14. 14 . The method according to claim 7 , the method further comprising administering to said subject an agent used for treatment or prevention of AIDS or HIV infection selected from the group consisting of nucleoside HIV reverse transcriptase inhibitors, non-nucleoside HIV reverse transcriptase inhibitors, HIV protease inhibitors, HIV fusion inhibitors, HIV attachment inhibitors, CCR5 inhibitors, CXCR4 inhibitors, HIV budding or maturation inhibitors, and HIV integrase inhibitors.
  15. 15 . A method of prevention of HIV infection in a subject, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I): or a pharmaceutically acceptable salt thereof, wherein: Z is CH or N; G 1 is selected from G 1a is selected from the group consisting of —OH, —F, —Cl, —CN, —C 1-4 alkyl optionally substituted with 1, 2 or 3 —F, and —C 1-3 alkyl optionally substituted with one substituent selected from the group consisting of —N(C 1-2 alkyl) 2 , —NH(C 1-2 alkyl), and a heterocycle selected from the group consisting of azetidine, pyrrolidine, piperidine, and morpholine, wherein said heterocycle is optionally substituted with 1, 2, 3 or 4 substituents independently selected from the group consisting of —CH 3 and —F; G 2 is selected from the group consisting of —H, —F, —Cl, —OCH 3 , —CH 3 , —CHF 2 , cyclopropyl, G 3 is selected from the group consisting of —H, —Cl, —CN, —CHO, —C(O)C 1-2 alkyl; —C 1-3 alkyl optionally substituted with 1, 2 or 3 —F; —C 1-3 alkyl optionally substituted with one substituent select from the group consisting of —OH, —OC 1-2 alkyl and —CN; —C 3-4 cycloalkyl optionally substituted with 1, 2 or 3 —F; and —NH—C 1-3 alkyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of —OCH 3 and —F; or G 3 is —NH(C 1-4 alkyl-G 3a ), wherein G 3a is a heterocycle selected from the group consisting of oxetane, tetrahydrofuran, and tetrahydro-2H-pyran, wherein said heterocycle is optionally substituted with one substituent selected from the group consisting of —CH 3 , —F, —OC 1-3 alkyl and —OC 3-4 cycloalkyl; or G 3 is selected from the group consisting of: G 3b is selected from the group consisting of —NH(C 1-2 alkyl), —N(C 1-2 alkyl) 2 , —NH(CH 2 CH 2 OC 1-3 alkyl), —N(C 1-2 alkyl)(CH 2 CH 2 OC 1-3 alkyl) and —NH(CH 2 CH 2 R 8 ); G 3c is selected from the group consisting of —H, —CN, —OC 1-3 alkyl, —C 3-6 cycloalkyl, —NHC(O)C 1-3 alkyl, —NH(C 1-2 alkyl), —N(C 1-2 alkyl) 2 , —R 8 , an aromatic heterocycle selected from the group consisting of phenyl, pyridine, thiazole, pyrazole and imidazole, wherein said aromatic heterocycle is optionally substituted with one —CH 3 group; and a non-aromatic heterocycle selected from the group consisting of wherein said non-aromatic heterocycle is optionally independently substituted with 1 or 2 substituents selected from the group consisting of —F, —CH 3 , —CF 3 , —CHF 2 , —OC 1-2 alkyl and —C(O)C 1-2 alkyl; G 4 is a heterocycle selected from the group consisting of pyridine, pyrimidine, pyrazole, imidazole, oxetane, tetrahydrofuran, tetrahydro-2H-pyran, azetidine, pyrrolidine and piperidine, wherein said heterocycle is optionally substituted with —CH 2 CH 2 OC 1-3 alkyl; or G 4 is selected from the group consisting of: X is selected from the group consisting of —OR 1 , —Cl, —Br, phenyl, pyridine, pyrazole, imidazole, pyrrolidin-2-one, 2,5-dihydro-pyrrole, 4-methyl-7-(methylamino)-2H-chromen-2-one, —NR 1 R 2 , —R 6 , —R 7 , and —R 8 ; Y is selected from the group consisting of —NR 1 R 2 , —R 6 , —R 7 , and —R 8 ; R 1 is selected from the group consisting of —H, phenyl, pyridine, —R 4 , and —C 1-4 alkyl optionally substituted with 1, 2 or 3 —F, 1 or 2 —OC 1-3 alkyl groups, or one —CN group; —C 3-4 cycloalkyl optionally substituted with 1 or 2 —F or a —OCH 3 group; oxetane optionally substituted with one —CH 3 group; tetrahydrofuran optionally substituted with one —CH 3 group; and tetrahydro-2H-pyran optionally substituted with one —CH 3 group; R 2 is selected from the group consisting of —H, —C 1-4 alkyl optionally substituted with 1, 2 or 3 —F, 1 or 2 —OC 1-3 alkyl groups, or one —CN group; —C 3-4 cycloalkyl optionally substituted with 1 or 2 substituents independently selected from the group consisting of —F and —OCH 3 ; and oxetane optionally substituted with one —CH 3 group; R 4 is selected from the group consisting of —(CH 2 CH 2 O) n CH 2 CH 2 N(R 5 ) 2 and —(CH 2 CH 2 O) n R 5 ; n is 2, 3, 4, 5, 6, 7 or 8; each R 5 is independently selected from the group consisting of —H, —C 1-4 alkyl and —C 3-4 cycloalkyl; R 6 is a heterocycle selected from the group consisting of azetidine, pyrrolidine, piperidine, piperazine, and morpholine, wherein said heterocycle is optionally substituted with 1, 2, 3 or 4 —F, one —OH group, 1 or 2 —OC 1-4 alkyl groups, 1 or 2 —CH 3 groups, one —C 1-3 alkyl group optionally substituted with 1, 2 or 3 —F, one —CH 3 group optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of —F, —OH and —OC 1-3 alkyl, or —CH 2 pyridine optionally substituted with 1 or 2 —CH 3 groups; R 7 is a heterocycle selected from the group consisting of azetidine, pyrrolidine, piperidine, piperazine, and morpholine, wherein said heterocycle is optionally substituted with one substituent selected from the group consisting of —CO 2 H, —S(O 2 )R 10 , —N(R 9 ) 2 , —NR 9 SO 2 R 10 , —NR 9 COR 10 , —C(O)R 5 , —C(O)R 6 , a heterocycle selected from the group consisting of 1,2,4-oxadiazole, isoxazole, pyrazole, imidazole and thiazole, wherein said heterocycle is optionally substituted with one R 10 group, and a heterocycle selected from the group consisting of oxetane, tetrahydrofuran and tetrahydro-2H-pyran, wherein said heterocycle is optionally substituted with one —CH 3 group; each R 8 is independently a heterocycle selected from the group consisting of wherein said heterocycle is optionally substituted with 1, 2, 3 or 4 substituents independently selected from the group consisting of —F, —CF 3 , —OCH 3 , —CHF 2 , —CH 2 F and —C 1-4 alkyl; each R 9 is independently selected from the group consisting of —H, —CH 3 , —C 2-3 alkyl optionally substituted with 1, 2 or 3 —F, and —C 3-4 cycloalkyl optionally substituted with 1 or 2 —F; R 10 is selected from the group consisting of —CH 3 , —CH 2 F, —CHF 2 , —CF 3 , —C 2-3 alkyl optionally substituted with 1, 2 or 3 —F, and —C 3-4 cycloalkyl optionally substituted with 1 or 2 —F; G 5 is selected from the group consisting of —C 1-3 alkyl optionally substituted with 1, 2 or 3 —F, and —C 3-4 cycloalkyl optionally substituted with 1 or 2 —F; G 6 is selected from the group consisting of —F, —Cl, —CH 3 , and —OCH 3 ; G 7 is selected from the group consisting of G 7a is selected from the group consisting of —H and —F; G 7b is selected from the group consisting of —H, —CH 3 and —F; G 7c is selected from the group consisting of —C 1-2 alkyl optionally substituted with 1, 2 or 3 —F, and —C 3-4 cycloalkyl optionally substituted with 1 or 2 —F; G 8 and G 9 are independently selected from the group consisting of —H, —F, —Cl, —CH 3 and —OCH 3 ; G 10 is selected from the group consisting of —H and —F; and G 11 is selected from the group consisting of —H, —F, —CH 3 and —OCH 3 , or a pharmaceutically acceptable salt thereof.
  16. 16 . The method according to claim 15 , satisfying at least one condition selected from the group consisting of (i) or (ii): (i) G 3 is selected from the group consisting of —CH 3 , G 3c is selected from the group consisting of H, —OCH 3 , and a non-aromatic heterocycle selected from the group consisting of wherein said non-aromatic heterocycle is optionally independently substituted with 1 or 2 substituents selected from the group consisting of —F, —CH 3 , —CF 3 , —CHF 2 and —OC 1-2 alkyl; and (ii) G 4 is selected from the group consisting of: X is selected from the group consisting of —OR 1 and —R 8 ; R 1 is selected from the group consisting of H and —C 1-4 alkyl optionally substituted with 1, 2 or 3 —F, 1 or 2 —OC 1-3 alkyl groups, or one —CN group; and R 8 is a heterocycle selected from the group consisting of wherein said heterocycle is optionally substituted with 1, 2, 3 or 4 substituents independently selected from the group consisting of —F and —C 1-4 alkyl.
  17. 17 . The method according to claim 15 , wherein the compound is a compound of Formula (II): or a pharmaceutically acceptable salt thereof, wherein: G 1a is selected from the group consisting of —F, —CHF 2 , —CH 2 F and —CH 3 ; G 2 is selected from the group consisting of —H, —CH 3 and —CHF 2 ; G 3 is selected from the group consisting of —H, —C 1-3 alkyl optionally substituted with 1, 2 or 3 —F; —C 3-4 cycloalkyl optionally substituted with 1, 2 or 3 —F; —NH—C 1-3 alkyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of —OCH 3 and —F; —C 1-3 alkyl-azetidine optionally substituted with 1, 2 or 3 —F; and —C 1-3 alkyl-morpholine optionally substituted with 1, 2, 3 or 4 substituents independently selected from the group consisting of —C 1-3 alkyl and —F; G 4 is selected from the group consisting of wherein G 4B is selected from the group consisting of —CH 2 —O—CH 3 , and a heterocycle selected from group consisting of wherein said heterocycle is optionally substituted with 1, 2, 3 or 4 substituents independently selected from group consisting of —F and —C 1-3 alkyl.
  18. 18 . The method according to claim 17 , wherein G 1a is selected from the group consisting of —F and —CH 3 ; and/or G 2 is —H and wherein G 7 is selected from the group consisting of wherein G 7a is —H and G 7b is —H, or G 7a is F and G 7b is F; and G 7c is selected from the group consisting of —C 1-2 alkyl optionally substituted with 1, 2 or 3 —F, and —C 3-4 cycloalkyl.
  19. 19 . The method according to claim 17 , wherein G 3 is selected from the group consisting of —CH 3 , —CHF 2 , —NH—CH 2 CH 2 OCH 3 , —NHCH 2 CH 3 , —CH 2 -azetidine substituted with 2 —F, and —C 1-2 alkyl-morpholine optionally substituted with 1, 2, 3 or 4 substituents independently selected from the group consisting of —CH 3 and F and wherein G 4 is wherein G 4B selected from the group consisting of —CH 2 —O—CH 3 , and a heterocycle selected from the group consisting of wherein said heterocycle is optionally substituted with 1, 2, 3 or 4 substituents independently selected from group consisting of —F and —C 1-3 alkyl.
  20. 20 . The method according to claim 17 , wherein the compound is a compound of Formula (IIb)

Description

CROSS REFERENCE TO RELATED APPLICATIONS The present application is a divisional application of U.S. patent application Ser. No. 19/043,910, filed Feb. 3, 2025, which is hereby incorporated by reference herein in its entirety, and claims the benefit of priority in U.S. Provisional Patent Application No. 63/549,602, filed Feb. 5, 2024, which is hereby incorporated by reference herein in its entirety. FIELD OF THE INVENTION The invention relates to compounds, compositions, and methods for the treatment or prevention of human immunodeficiency virus (HIV) infection. More particularly, the invention provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection. BACKGROUND OF THE INVENTION Acquired immunodeficiency syndrome (AIDS) is the result of infection by HIV. HIV continues to be a major global public health issue. In 2015, an estimated 36.7 million people were living with HIV (including 1.8 million children)—a global HIV prevalence of 0.8%. The vast majority of this number live in low- and middle-income countries. In the same year, 1.1 million people died of AIDS-related illnesses. Current therapy for HIV-infected individuals consists of a combination of approved anti-retroviral agents. Close to four dozen drugs are currently approved for HIV infection, either as single agents, fixed dose combinations or single tablet regimens; the latter two containing 2-4 approved agents. These agents belong to a number of different classes, targeting either a viral enzyme or the function of a viral protein during the virus replication cycle. Thus, agents are classified as either nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleotide reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase strand transfer inhibitors (INSTIs), or entry inhibitors (one, maraviroc, targets the host CCR5 protein, while the other, enfuvirtide, is a peptide that targets the gp41 region of the viral gp160 protein). In addition, a pharmacokinetic enhancer (cobicistat) can be used in combinations with antiretroviral agents (ARVs) that require boosting. Despite the armamentarium of agents and drug combinations, there remains a medical need for new anti-retroviral agents. High viral heterogeneity, drug-associated toxicity, tolerability problems, and poor adherence can all lead to treatment failure and may result in the selection of viruses with mutations that confer resistance to one or more antiretroviral agents or even multiple drugs from an entire class (Beyrer, C., Pozniak A. HIV drug resistance—an emerging threat to epidemic control. N. Engl. J. Med. 2017, 377, 1605-1607; Gupta, R. K., Gregson J., et al. HIV-1 drug resistance before initiation or re-initiation of first-line antiretroviral therapy in low-income and middle-income countries: a systematic review and meta-regression analysis. Lancet Infect. Dis. 2017, 18, 346-355; Zazzi, M., Hu, H., Prosperi, M. The global burden of HIV-1 drug resistance in the past 20 years. PeerJ. 2018, DOI 10.7717/peerj.4848). As a result, new drugs are needed that are easier to take, have high genetic barriers to the development of resistance and have improved safety over current agents. In this panoply of choices, novel mechanisms of action (MOAs) that can be used as part of the preferred antiretroviral therapy (ART) can still have a major role to play since they should be effective against viruses resistant to current agents. Maximum benefits to HIV infected patients might be achieved if anti-HIV drugs with new mechanisms of action are discovered which have benefits which facilitate long term compliance and safety. Certain potentially therapeutic compounds, including capsid inhibitors, have been described and are set forth in Blair, Wade S. et. al. Antimicrobial Agents and Chemotherapy (2009), 53 (12), 5080-5087, Blair, Wade S. et al. PLoS Pathogens (2010), 6 (12), e1001220, Thenin-Houssier, Suzie; Valente, Susana T. Current HIV Research, 2016, 14, 270-282, and published PCT Patent applications with the following numbers: WO 2012/065062, WO 2013/006738, WO 2013/006792, WO 2014/110296, WO 2014/110297, WO 2014/110298, WO 2014/134566, WO 2015/130964, WO 2015130966, WO 2016/033243, WO 2018/035359, and WO 2018/203235, WO 2019/198024, WO 2020/254985, WO 2020/031112, WO 2020/053811, WO 2020/058844, WO 2020/084480, WO 2020/084491, WO 2020/084492, WO 2020/089778, WO 2020/095177, WO 2020/095176, WO 2020/157692, WO 2020/222108, WO 2020/222108, WO 2020/254985. WO 2021/064677, WO 2021/064570, WO 2021/064571, WO 2021/070054, WO 2021/176366, and WO 2021/176367. What is now needed are additional compounds which are novel and useful in the treatment of HIV. Additionally, these compounds should provide advantages for pharmaceutical uses, for example, with regard to one or more of their mechanisms of action, binding, inhibition efficacy, target selectivity, solubility, safety profiles, or bioavail