Claims for Patent: 5,563,142

Summary for Patent: 5,563,142

Title:	Diaromatic substituted compounds as anti-HIV-1 agents
Abstract:	The present invention includes diaromatic substituted heterocyclic compounds (III) (III) which are useful in treating individuals infected with the HIV virus.
Inventor(s):	John R. Palmer, Donna L. Romero, Paul A. Aristoff, Richard C. Thomas, Herman W. Smith
Assignee:	Pharmacia and Upjohn Co
Application Number:	US08/198,428
Patent Claims:	1. A diaromatic substituted compound of formula (III) ##STR31## where R1 is --CH2 -- or --CO--; where Z is ##STR32## where n12 is 1 and n13 is 1, ##STR33## where Y3 is --N(Y3-1)-- where Y3-1 is C1 -C4 alkyl and n12 and n13 are as defined above;where R6 is --N═; where R7 is --N(R7-5)(R7-6) where R7-5 isC1 --C6 alkyl, --CH2 --cyclopropyl, --CH2 --CH2 F, and where R7-6 is --H; where R8 is --CR8-1 ═where R8-1 is --H or --F; where R9 is --CR9-1 ═where R9-1 is --H or --F; where R10 is --CR10-1 ═where R10-1 is --H or --F; where Aryl/Heteroaryl is a substituent selected from the group of substituents of formula (7) ##STR34## where . . . . is a double bond; where Q1 is --NX11 -- where X11 is --H; where X14 is --H,--O--CH2 --φ, --O--CH2 --COOR14-10 where R14-10 is--H, C1 -C4 alkyl, --CH2 --φ, C1 -C6 alkyl, --F, --Cl, Br, --O--SO2 --X14-11 where X14-11 is C1 -C4 alkyl, --NO2, --NH2, --N3, --NH--SO2 --X14-1 where X14-1 is C1 -C6 alkyl, --N═C(X14-4)--N(X14-7)(X14-8) where(a) X14-4 is --H or C1 -C4 alkyl and where X14-7 and X14-8 are the same or different and are C1 -C6 alkyl, --N(X14-2)--CO--X14-9 where X14-2 is --H or C1 -C4 alkyl and where X14-9 is--H, C1 -C4 alkyl or --φ where X14-2 is defined above; where n7 is 0 or 1; where X6 is --H,--OH, --O--CH2 --φ, --CHO, C1 -C3 alkoxy, --O--SO2 --X6-12 where X6-12 is C1 -C4 alkyl, --C.tbd.N, --O--(CH2)n3 --N(X6-3)(X6-4) where n3 is 2 thru 5, where X6-3 is --H or where X6-3 and X6-4 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl, N-morpholinyl or 1-aziridinyl, --(CH2)n24 --OH, where n24 is 1, --NH--SO2 --X6-7 where X6-7 is C1 -C4 alkyl, enantiomers, pharmaceutically acceptable salts, hydrates and solvates thereof. 2. A diaromatic substituted compound (III) according to claim 1 where R1 is --CO--. 3. A diaromatic substituted compound (III) according to claim 1 where Z is ##STR35## 4. A diaromatic substituted compound (III) according to claim 1 where R7 is --N(R7-5)(R7-6) where R7-5 is C1 -C4 alkyl. 5. A diaromatic substituted compound (III) according to claim 4 where C1 -C4 alkyl is --CH2 --CH3, --CH(CH3)2 or --C(CH3)3. 6. A diaromatic substituted compound (III) according to claim 1 which is1-[indolyl-2-carbonyl]-4-[3-(ethylamino)-2-pyridinyl]piperazine, 1-[indolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine, 1-[indolyl-2-carbonyl]-4-[3-(N,N-diethylamino)-2-pyridinyl]piperazine, 1-[indolyl-2-methyl]-4-[3-(ethylamino)-2-pyridinyl]piperazine, 1-[5-fluoroindolyl-2-carbonyl]-4-[3-(propylamino)-2-pyridinyl]piperazine, 1-[5-chloroindoyl-2-carbonyl]-4-[3-(ethylamino)-2-pyridinyl]piprazine, 1-[5-fluoroindolyl-2-carbonyl]-4-[3-(ethylamino)-2-pyridinyl]piperazine, 1-[5-ethylindolyl-2-carbonyl]-4-[3-(ethylamino)-2-pyridinyl]piperazine, 1-[5-fluoroindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]-piperazine, 1-[indolyl-2-carbonyl]-4-[3-(cyclopropylmethylamino)-2-pyridinyl]piperazine 1-[5-fluoroindolyl-2-methyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine, 1-[5-benzyloxyindolyl-2-carbonyl]-4-(3-ethylamino-2-pyridinyl)piperazine, 1-[5-benzyloxyindolyl-2-carbonyl]-4-[3-(1-methylethyl)amino-2-pyridinyl]-piperazine, 1-[indolyl-2-methyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine, 1-[indolyl-2-carbonyl]-4-[3-(1,1-dimethylethylamino)-2-pyridinyl]piperazine 1-[5-fluoroindolyl-2-carbonyl]-4-[3-(1,1-dimethylethylamino)-2-pyridinyl]piperazine, 1-[5-(ethoxycarbonylmethoxy)indolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine, 1-(5-fluoroindolyl-2-carbonyl)-4-[3-methylamino-2-pyridinyl]piperazine, 1-(indolyl-2-carbonyl)-4-[3-(methylamino)-2-pyridinyl]piperazine, 1-[5-(benzyloxycarbonylmethoxy)indolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine, 1-[5-(carboxymethoxy)indolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine, 1-[(5N-(N',N'-dimethylaminomethylene)aminoindolyl)carbonyl]-4-(3-(1-methylethylamino)-2-pyridinyl)piperazine, 1-[6-methoxyindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine, 1-[4-methoxyindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine, 1-[5-methylindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine, 1-[5-fluoro-6-methoxyindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine, 1-[5-bromoindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine, 1-[5-bromo-6-methoxyindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine, 1-[indolyl-2-carbonyl]-4-[3-(1-methylpropyl)amino-2-pyridinyl]piperazine, 1-[indolyl-2-carbonyl]-4-[3-(1-ethylpropyl)amino-2-pyridinyl]piperazine, 1-[5-aminoindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine, 1-[5-fluoroindolyl-2-carbonyl]-4-[3-(2',2'-dimethylpropylamino)-2-pyridinyl]piperazine, 1-[5-nitroindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine, 1-[5-acetamidoindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine, 1-[5-methanesulfonamidoindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine, 1-[6-formylindoyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine, 1-[5-azido-2-indolycarbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine, 1-[indolyl-2-carbonyl]-4-[3-(2-fluoroethylamino)-2-pyridinyl]piperazine, 1-[6-hydroxymethylindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine, 1-[6-hydroxymethylindolyl-2-carbonyl]-4-[3-(ethylamino)-2-pyridinyl]piperazine, 1-(indolyl-2-carbonyl)-4-(N-methyl-N-(3-(1-methylethylamino)-2-pyridinyl)amino)piperidine, 1-(6-cyanoindolyl-2-carbonyl)-4-[3-(ethylamino)-2-pyridinyl]piperazine, 1-(6-cyanoindolyl-2-carbonyl)-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine, 1-[5-nitroindolyl-2-carbonyl]-4-[3-(1,1-dimethylethylamino)-2-pyridinyl]piperazine, 1-[(5-(N',N'-dimethylaminomethylene)aminoindolyl-2-carbonyl]-4-[3-(1,1-dimethylethylamino)-2-pyridinyl]piperazine. 7. A diaromatic substituted compound (III) according to claim 6 which is1-[indolyl-2-carbonyl]-4-[3-(ethylamino)-2-pyridinyl]piperazine, 1-[indolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine, 1-[5-fluoroindolyl-2-carbonyl]-4-[3-(ethylamino)-2-pyridinyl]piperazine, 1-[5-fluoroindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine, 1-[5-fluoroindolyl-2-methyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine, 1-[indolyl-2-carbonyl]-4-[3-(1,1-dimethylethylamino)-2-pyridinyl]piperazine 1-[5-fluoroindolyl-2-carbonyl]-4-[3-(1,1-dimethylethylamino)-2-pyridinyl]piperazine, 1-[5-(carboxymethoxy)indolyl-2-carbonyl]-4-[3-(1-methylethyl- amino)-2-pyridinyl]piperazine, 1-[(5N-(N',N'-dimethylaminomethylene)aminoindolyl)carbonyl]-4-(3-(1-methylethylamino)-2-pyridinyl)piperazine, 1-[indolyl-2-carbonyl]-4-[3-(1-ethylpropyl)amino-2-pyridinyl]piperazine and 1-[5-methanesulfonamidoindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine. 8. A diaromatic substituted compound (III) according to claim 6 which is 1-[5-methanesulfonamidoindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine. 9. A diaromatic substituted compounds (III) according to claim 1 where the pharmaceutically acceptable salt is an acid addition salt. 10. A diaromatic substituted compounds (III) according to claim 9 where the acid addition salt is selected from the group consisting of methanesulfonic, hydrochloric, hydrobromic, sulfuric, phosphoric, nitric, benzoic, citric, tartaric, fumaric, maleic, p-toluenesulfonic, benzenesulfonic, CH3 --(CH2)n --COOH where n is 0 thru 4 and HOOC--(CH2)n --COOH where n is as defined above. 11. A diaromatic substituted compound (III) according to claim 8 which is 1-[5-methanesulfonamidoindolyl-2-carbonyl]-4-[3-(1-methylethylamino)-2-pyridinyl]piperazine monomethanesulfonate salt.