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US 2025/0026759 A1Published application
Tetrahydroquinazoline derivatives as selective cytotoxic agents
AssigneeMerck Sharp & Dohme Corp.
InventorsMichael J. Breslin, Antonella Converso, Abdellatif El Marrouni, Ashley Forster, David N. Hunter, Anthony W. Shaw, William D. Shipe, Yunlong Zhang
Life of this patent
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Abstract
The present disclosure is directed to tetrahydroquinazoline derivatives of Formula I and their use for selectively killing HIV infected GAG-POL expressing cells without concomitant cytotoxicity to HIV naïve cells, and for the treatment or prophylaxis of infection by HIV, or for the treatment, prophylaxis or delay in the onset or progression of AIDS or AIDS Related Complex (ARC).
Claims21
A compound of Formula I:
- or a pharmaceutically acceptable salt thereof, wherein:
- X is N(R3) or C(R3);
- W is —C1-6 alkyl-, —(C0-6 alkyl)O—, —(C1-6 alkyl)amino-, or —(C1-6 alkyl)aminocarbonyl-, wherein W is substituted by 0, 1, or 2 R5 substituents;
- each R5 independently is halo, C1-4 alkyl or C1-4 fluoroalkyl;
- R1 is halo, C1-6 alkyl, (C3-12)heterocycloalkyl(C0-4 alkyl), or (C3-12)cycloalkyl(C0-4 alkyl);
- R2 is hydrogen, halo, or C1-10 alkyl;
- R3 is hydrogen, halo, or C1-10 alkyl;
- R4 is selected from:
- a) a 5-membered heteroaryl having at least one nitrogen atom,
- b) a mono-, bicyclic- or tricyclic, 7- to 14-membered heteroaryl comprising at least one aromatic heteroatom containing ring, wherein said 7- to 14-member heteroaryl comprises at least one nitrogen atom, or
- c) a ketone containing ring system selected from triazolinonyl, 2,4-dihydro-3H-1,2,4-triazoly-3-onyl, dihydropyrrolo[3, 4-b]pyrrolonyl, imidazolidinonyl, 1,3-dihydro-2H-benzo[d]imidazole-2-onyl, dihydrobenzo[d]imidazolinonyl, 1,3-dihydroimidazo[4,5-c]pyridinonyl, oxazolo[5,4-c]pyridine-2-onyl, 1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-onyl, 1,3-dihydroimidazo[4,5-b]pyridine-2-onyl, isoindolinonyl, 4,5-dihydropyrrolo[3,4-b]pyrrolonyl, 4,5-dihydropyrrolo[3,4-b]pyrrol-6(2H)onyl, benzo[d]oxazolonyl, benzo[d]oxazol-2-onyl, 1,4,5,6-tetrahydrocyclopenta[c]pyrazolonyl, and 1,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-4-onyl;
- wherein R4 is substituted by 0, 1, 2, or 3 R4a substituents;
- each R4a independently is selected from:
- C1-6 alkyl,
- C1-10 fluoroalkyl,
- amino,
- cyano,
- halo,
- hydroxy,
- (C1-10 alkyloxy)C0-10 alkyl,
- C1-10 fluoroalkyloxy,
- —(C1-10 alkyl)OH,
- (C1-6 alkyl)1-2 amino(C0-10 alkyl),
- amino(C1-10 alkyl),
- aminocarbonyl(C0-10 alkyl),
- (C3-12)cycloalkyl(C0-6 alkyl),
- (C5-6)heteroaryl(C0-6 alkyl),
- (C6-14)aryl(C0-6 alkyl),
- —(C0-4 alkyl)carbonyl, and
- —(C0-5 alkyl)-(S(═O)2NH2);
- wherein R4a is substituted by 0, 1, 2, or 3 R4b substituents;
- and
- each R4b independently is C1-10 alkyloxy, C1-6 alkyl, C1-10 fluoroalkyl, amino, hydroxy, halo, or cyano.
30 more elements
Dependencies are inferred from the claim text.