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US 7,115,601 B2Granted
HIV integrase inhibitors
AssigneeBristol-Myers Squibb Company
InventorsB. Narasimhulu Naidu, Margaret E. Sorenson
Life of this patent
Estimating the term…
Abstract
Compounds of the present disclosure are spirocycle-substituted pyrimidinecarboxamides. Also disclosed are pharmaceutical compositions comprising the compounds, and methods of using the compounds. The compounds are useful for treating HIV infection and AIDS.
Claims11
A compound of formula (I)
- or a pharmaceutically acceptable salt thereof, wherein
- R1 is selected from hydrogen, alkenyl, alkoxyalkyl, alkyl, and arylalkyl;
- R2 is a 3- to 8-membered saturated or partially unsaturated ring containing one to three heteroatoms selected from N, O, and S(O)n, wherein n is 0, 1, or 2;
- wherein said ring is attached through a nitrogen atom, and wherein said ring is substituted by a 3- to 10-membered monocyclic or bicyclic spirocycle containing from zero to three heteroatoms selected from N, O, and S(O)n, wherein n is 0, 1, or 2;
- and wherein said ring and said spirocycle are each optionally substituted with one to three substituents independently selected from alkoxy, alkyl, alkylcarbonyl, aryl, halo, heteroaryl, heterocyclyl, —NRaRb, oxo, thiooxo, and trialkylsilyl;
- R3 and R4 are independently selected from hydrogen, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl;
- and
- Ra and Rb are independently selected from hydrogen, alkyl, aryl, and arylalkyl.
5 more elements
A compound of formula (II),
- or a pharmaceutically acceptable salt thereof, wherein
- R1 is selected from hydrogen, alkenyl, alkoxyalkyl, alkyl, and arylalkyl;
- R3 and R4 are independently selected from hydrogen, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl;
- R7 and R8, together with the nitrogen atom to which they are attached, form a 3- to 8-membered saturated or partially unsaturated ring containing zero to two additional heteroatoms selected from N, O, and S(O)n, wherein n is 0, 1, or 2;
- wherein said ring is substituted by a 3- to 10-membered monocyclic or bicyclic spirocycle containing from zero to three heteroatoms selected from N, O, and S(O)n, wherein n is 0, 1, or 2;
- and wherein said ring and said spirocycle are each optionally substituted with one to three substituents independently selected from alkoxy, alkyl, alkylcarbonyl, aryl, halo, heteroaryl, heterocyclyl, —NRaRb, oxo, thiooxo, and trialkylsilyl;
- and
- Ra and Rb are independently selected from hydrogen, alkyl, aryl, and arylalkyl.
5 more elements
A compound selected from
- 2-(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)-N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-4-pyrimidinecarboxamide;
- 2-(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)-N-[(4-fluoro-3-methylphenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-4-pyrimidinecarboxamide;
- N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-8-yl)-4-pyrimidinecarboxamide;
- N-[(4-fluoro-3-methylphenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-8-yl)-4-pyrimidinecarboxamide;
- N-[(4-fluoro-3-methylphenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-2-(2-methyl-1-oxo-2,8-diazaspiro[4.5]dec-8-yl)-6-oxo-4-pyrimidinecarboxamide;
- N-[(4-fluoro-3-methylphenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-2-(3-oxa-8-azaspiro[5.5]undec-8-yl)-6-oxo-4-pyrimidinecarboxamide;
- N-[4-fluoro-3-methylphenyl)methyl]-2-(1,3-diethyl-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-8-yl)-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-4-pyrimidinecarboxamide;
- N-[4-fluoro-3-methylphenyl)methyl]-1,6-dihydro-2-(2,4-dioxo-1,3,8-triazaspiro[4.5]dec-8-yl)-5-hydroxy-1-methyl-6-oxo-4-pyrimidinecarboxamide;
- N-[(4-fluoro-3-methylphenyl)methyl]-2-(3,4-benzo-2-oxo-8-azaspiro[4.5]decan-2-yl)-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-4-pyrimidinecarboxamide;
- N-[(4-fluoro-3-methylphenyl)methyl]-2-(8-azaspiro[4.5]dec-8-yl)-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-4-pyrimidinecarboxamide;
- N-[(4-fluoro-3-methylphenyl)methyl]-2-[3-[[(4-fluoro-3-methylphenyl)methyl]amino]spiro[1H-indene-1,4′-piperidin]-1′-yl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-4-pyrimidinecarboxamide;
- N-[(4-fluoro-3-methylphenyl)methyl]-2-(8-azaspiro[4.5]dec-8-yl)-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-4-pyrimidinecarboxamide;
- N-(4-fluoro-3-methylbenzyl)-5-hydroxy-1-methyl-6-oxo-2-(1-ethanone)-2,8-diazaspiro[4.5]dec-8-yl)-1,6-dihydropyrimidine-4-carboxamide;
- N-(4-fluoro-3-methylbenzyl)-5-hydroxy 1-methyl-6-oxo-2-(1-trimethylsilane-6-azaspiro[4.3]oct-6-yl)-1,6-dihydropyrimidine-4-carboxamide;
- N-(4-fluoro-3-methylbenzyl)-5-hydroxy-1-methyl-6-oxo-2-(6-azaspiro[4.3]oct-6-yl)-1,6-dihydropyrimidine-4-carboxamide;
- and
- N-[(4-fluoro-3-methylphenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-2-(1-oxa-8-azaspiro[4.5]dec-8-yl)-6-oxo-4-pyrimidinecarboxamide.
14 more elements
A compound selected from
- N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(7-azaspiro[4.5]dec-7-yl)-4-pyrimidinecarboxamide;
- N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(6-oxa-9-azaspiro[4.5]dec-9-yl)-4-pyrimidinecarboxamide;
- N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(2-oxa-7-azaspiro[4.5]dec-7-yl)-4-pyrimidinecarboxamide;
- N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(1,3-dioxo-2,7-diazaspiro[4.5]dec-7-yl)-4-pyrimidinecarboxamide;
- N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(2-oxo-1,7-diazaspiro[4.5]dec-7-yl)-4-pyrimidinecarboxamide;
- N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(2,4-dioxo-1,3,8-triazaspiro[4.5]dec-8-yl)-4-pyrimidinecarboxamide;
- N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(8-azaspiro[4.5]dec-8-yl)-4-pyrimidinecarboxamide;
- N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(1-oxa-8-azaspiro[4.5]dec-8-yl)-4-pyrimidinecarboxamide;
- N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(1-oxo-2,8-diazaspiro[4.5]dec-8-yl)-4-pyrimidinecarboxamide;
- N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(2-oxo-1,3,8-triazaspiro[4.5]dec-8-yl)-4-pyrimidinecarboxamide;
- N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(1,3,8-triazaspiro[4.5]deca-1,3-dien-8-yl)-4-pyrimidinecarboxamide;
- N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(3-oxa-9-azaspiro[5.5]undec-9-yl)-4-pyrimidinecarboxamide;
- N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(1-oxa-9-azaspiro[5.5]undec-9-yl)-4-pyrimidinecarboxamide;
- N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(1-oxa-3,8-diazaspiro[4.5]dec-2-en-8-yl)-4-pyrimidinecarboxamide;
- N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(1-oxa-4,9-diazaspiro[5.5]undec-9-yl)-4-pyrimidinecarboxamide;
- N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(5-oxo-1-oxa-4,9-diazaspiro[5.5]undec-9-yl)-4-pyrimidinecarboxamide;
- N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(1,4,9-triazaspiro[5.5]undec-9-yl)-4-pyrimidinecarboxamide;
- and
- N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-2-(5-oxo-1,4,9-triazaspiro[5.5]undec-9-yl)-4-pyrimidinecarboxamide.
16 more elements
Dependencies are inferred from the claim text.