Substituted pyrido[2,3-B]pyrazines as IP receptor agonists

摘要

The present invention provides substituted pyrido[2,3-b]pyrazines which activate the IP receptor. Activating the IP receptor signaling pathway is useful to treat many forms of PAH, pulmonary fibrosis and exert beneficial effects in fibrotic conditions of various organs in animal models and in patients. Pharmaceutical compositions comprising such substituted pyride[2,3-b]pyrazines are also encompassed.

主权项

1. A compound selected from the group consisting of
(rac)-6-(2,3-di-p-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazin-6-yl)hexanoic acid; (S)-6-(2,3-di-p-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazin-6-yl)hexanoic acid; (R)-6-(2,3-di-p-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazin-6-yl)hexanoic acid (rac)-7-(7-(2-Hydroxypropan-2-yl)-6-oxo-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; (R)-7-(7-(2-hydroxypropan-2-yl)-6-oxo-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; (S)-7-(7-(2-hydroxypropan-2-yl)-6-oxo-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(7-Ethyl-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(7-Methyl-2-phenyl-3-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; (rac)-7-(6-Ethyl-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; (R)-7-(6-Ethyl-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; (S)-7-(6-Ethyl-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(6-Methyl-2-phenyl-3-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(3-o-Tolyl-2-p-tolyl-7,8-dihydropyrido[3,2-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(2-o-Tolyl-3-p-tolyl-7,8-dihydropyrido[3,2-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(2-(2-Fluorophenyl)-3-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(2-(4-Fluorophenyl)-3-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(2-(3-Fluorophenyl)-3-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(2-(4-Methoxyphenyl)-3-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; (rac)-7-(8-Methoxy-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; (R)-7-(8-methoxy-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; (S)-7-(8-methoxy-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(2,3-Bis(2,4-difluorophenyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(2,3-Bis(6-methylpyridin-3-yl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(2-(6-Methylpyridin-3-yl)-3-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(3-(6-Methylpyridin-3-yl)-2-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 9-(6-Oxo-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)nonanoic acid; 9-(2,3-Di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)nonanoic acid; (rac)-7-(7-(2-hydroxypropan-2-yl)-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; (R)-7-(7-(2-hydroxypropan-2-yl)-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; (S)-7-(7-(2-hydroxypropan-2-yl)-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 6-(2,3-Di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)hexanoic acid; (R)-7-(7-hydroxy-6-oxo-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; (S)-7-(7-hydroxy-6-oxo-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 8-(6-Oxo-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)octanoic acid; 7-(2,3-Di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-methoxyheptanamide; 7-(2,3-Di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N,N-dimethylheptanamide; 7-(2,3-Di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-hydroxy-N-methylheptanamide; 6-(2,3-Di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-hydroxyhexanamide; (R)-7-(8-Hydroxy-2,3-di-p-tolyl-7,8-dihydropyrido[3,2-b]pyrazin-5(6H)-yl)-N-(methylsulfonyl)heptanamide; (S)-7-(8-Hydroxy-2,3-di-p-tolyl-7,8-dihydropyrido[3,2-b]pyrazin-5(6H)-yl)-N-(methylsulfonyl)heptanamide; (R)—N-(Benzylsulfonyl)-7-(8-hydroxy-2,3-di-p-tolyl-7,8-dihydropyrido[3,2-b]pyrazin-5(6H)-yl)heptanamide; (S)—N-(Benzylsulfonyl)-7-(8-hydroxy-2,3-di-p-tolyl-7,8-dihydropyrido[3,2-b]pyrazin-5(6H)-yl)heptanamide; 7-(2,3-Di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-(methylsulfonyl)heptanamide; 7-(7-Piperidin-1-yl)-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; rac-7-(8-Methoxy-8-methyl-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(8-Hydroxy-8-methyl-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; rac-7-(2,3-Di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-3-hydroxyheptanoic acid; (R)-7-(8-Methoxy-8-methyl-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; (S)-7-(8-Methoxy-8-methyl-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; (R)-7-(2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-3-hydroxyheptanoic acid; (S)-7-(2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-3-hydroxyheptanoic acid; 7-(2,3-Bis(4-chlorophenyl)-6-oxo-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(2-(4-Chlorophenyl)-6-oxo-3-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(3-(4-Chlorophenyl)-6-oxo-2-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; N-(Benzylsulfonyl)-7-(2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; N-Benzyl-7-(2,3-di-p-tolyl-7,8-dihydro pyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; 7-(2,3-Di-p-tolyl-7,8-dihydro pyrido[2,3-b]pyrazin-5(6H)-yl)-N-(phenyl sulfonyl)heptanamide; 7-(2,3-Di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-isopropylheptanamide; 7-(2,3-Di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-methylheptanamide; 7-(2,3-Di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-phenylheptanamide; 7-(2,3-Di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-hydroxyheptanamide; 7-(2,3-Di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-(isopropylsulfonyl)heptanamide; (rac)-7-(7-hydroxy-7-methyl-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; (R)-7-(7-hydroxy-7-methyl-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanic acid; (S)-7-(7-hydroxy-7-mehtyl-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanix acid; (rac)-7-(7-(dimethylamino)-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; (R)-7-(7-(dimethylamino)-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl) heptanic acid; (S)-7-(7-dimethylamino)-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanic acid; 7-(3-(4-chlorophenyl)-2-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(2-(4-chlorophenyl)-3-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(2,3-bis(4-chlorophenyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(6-oxo-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(2-(4-chlorophenyl)-6-oxo-3-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(3-(4-chlorophenyl)-6-oxo-2-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(7-hydroxy-6-oxo-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(2-(4-chlorophenyl)-7-hydroxy-6-oxo-3-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(3-(4-chlorophenyl)-7-hydroxy-6-oxo-2-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(2,3-bis(4-chlorophenyl)-7-hydroxy-6-oxo-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(7-hydroxy-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(2-(4-chlorophenyl)-7-hydroxy-3-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(3-(4-chlorophenyl)-7-hydroxy-2-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(2,3-bis(4-chlorophenyl)-7-hydroxy-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(8-hydroxy-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(2-(4-chlorophenyl)-8-hydroxy-3-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(3-(4-chlorophenyl)-8-hydroxy-2-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(2,3-bis(4-chlorophenyl)-8-hydroxy-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; 7-(2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-(phenylsulfonyl)heptanamide; 7-(2-(4-chlorophenyl)-3-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-(phenylsulfonyl)heptanamide; 7-(3-(4-chlorophenyl)-2-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-(phenylsulfonyl)heptanamide; 7-(2,3-bis(4-chlorophenyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-(phenylsulfonyl)heptanamide; 7-(6-oxo-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-(phenylsulfonyl)heptanamide; 7-(2-(4-chlorophenyl)-6-oxo-3-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-(phenylsulfonyl)heptanamide; 7-(3-(4-chlorophenyl)-6-oxo-2-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-(phenylsulfonyl)heptanamide; 7-(2,3-bis(4-chlorophenyl)-6-oxo-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-(phenylsulfonyl)heptanamide; 7-(7-hydroxy-6-oxo-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-(phenylsulfonyl)heptanamide; 7-(2-(4-chlorophenyl)-7-hydroxy-6-oxo-3-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-(phenylsulfonyl)heptanamide; 7-(3-(4-chlorophenyl)-7-hydroxy-6-oxo-2-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-(phenylsulfonyl)heptanamide; 7-(2,3-bis(4-chlorophenyl)-7-hydroxy-6-oxo-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-(phenylsulfonyl)heptanamide; 7-(7-hydroxy-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-(phenylsulfonyl)heptanamide; 7-(2-(4-chlorophenyl)-7-hydroxy-3-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-(phenylsulfonyl)heptanamide; 7-(3-(4-chlorophenyl)-7-hydroxy-2-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-(phenylsulfonyl)heptanamide; 7-(2,3-bis(4-chlorophenyl)-7-hydroxy-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-(phenylsulfonyl)heptanamide; 7-(8-hydroxy-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-(phenylsulfonyl)heptanamide; 7-(2-(4-chlorophenyl)-8-hydroxy-3-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-(phenylsulfonyl)heptanamide; 7-(3-(4-chlorophenyl)-8-hydroxy-2-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-(phenylsulfonyl)heptanamide; 7-(2,3-bis(4-chlorophenyl)-8-hydroxy-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-(phenylsulfonyl)heptanamide; N-(benzylsulfonyl)-7-(2,3-bis(4-chlorophenyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; N-(benzylsulfonyl)-7-(2-(4-chlorophenyl)-3-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; N-(benzylsulfonyl)-7-(3-(4-chlorophenyl)-2-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; N-(benzylsulfonyl)-7-(6-oxo-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; N-(benzylsulfonyl)-7-(3-(4-chlorophenyl)-6-oxo-2-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; N-(benzylsulfonyl)-7-(7-hydroxy-6-oxo-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; N-(benzylsulfonyl)-7-(3-(4-chlorophenyl)-7-hydroxy-6-oxo-2-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; N-(benzylsulfonyl)-7-(7-hydroxy-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; N-(benzylsulfonyl)-7-(3-(4-chlorophenyl)-7-hydroxy-2-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; N-(benzylsulfonyl)-7-(8-hydroxy-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; N-(benzylsulfonyl)-7-(3-(4-chlorophenyl)-8-hydroxy-2-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; 7-(2-(4-chlorophenyl)-3-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-phenylheptanamide; 7-(3-(4-chlorophenyl)-2-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-phenylheptanamide; 7-(2,3-bis(4-chlorophenyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-phenylheptanamide; 7-(6-oxo-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-phenylheptanamide; 7-(2-(4-chlorophenyl)-6-oxo-3-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-phenylheptanamide; 7-(3-(4-chlorophenyl)-6-oxo-2-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-phenylheptanamide; 7-(2,3-bis(4-chlorophenyl)-6-oxo-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-phenylheptanamide; 7-(7-hydroxy-6-oxo-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-phenylheptanamide; 7-(2-(4-chlorophenyl)-7-hydroxy-6-oxo-3-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-phenylheptanamide; 7-(3-(4-chlorophenyl)-7-hydroxy-6-oxo-2-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-phenylheptanamide; 7-(2,3-bis(4-chlorophenyl)-7-hydroxy-6-oxo-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-phenylheptanamide; 7-(7-hydroxy-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-phenylheptanamide; 7-(2-(4-chlorophenyl)-7-hydroxy-3-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-phenylheptanamide; 7-(3-(4-chlorophenyl)-7-hydroxy-2-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-phenylheptanamide; 7-(2,3-bis(4-chlorophenyl)-7-hydroxy-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-phenylheptanamide; 7-(8-hydroxy-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-phenylheptanamide; 7-(2-(4-chlorophenyl)-8-hydroxy-3-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-phenylheptanamide; 7-(3-(4-chlorophenyl)-8-hydroxy-2-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-phenylheptanamide; 7-(2,3-bis(4-chlorophenyl)-8-hydroxy-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-phenylheptanamide; N-benzyl-7-(2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; N-benzyl-7-(2-(4-chlorophenyl)-3-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; N-benzyl-7-(3-(4-chlorophenyl)-2-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; N-benzyl-7-(2,3-bis(4-chlorophenyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; N-benzyl-7-(6-oxo-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; N-benzyl-7-(2-(4-chlorophenyl)-6-oxo-3-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; N-benzyl-7-(3-(4-chlorophenyl)-6-oxo-2-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; N-benzyl-7-(2,3-bis(4-chlorophenyl)-6-oxo-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; N-benzyl-7-(7-hydroxy-6-oxo-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; N-benzyl-7-(2-(4-chlorophenyl)-7-hydroxy-6-oxo-3-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; N-benzyl-7-(3-(4-chlorophenyl)-7-hydroxy-6-oxo-2-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; N-benzyl-7-(2,3-bis(4-chlorophenyl)-7-hydroxy-6-oxo-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; N-benzyl-7-(7-hydroxy-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; N-benzyl-7-(2-(4-chlorophenyl)-7-hydroxy-3-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; N-benzyl-7-(3-(4-chlorophenyl)-7-hydroxy-2-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; N-benzyl-7-(2,3-bis(4-chlorophenyl)-7-hydroxy-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; N-benzyl-7-(8-hydroxy-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; N-benzyl-7-(2-(4-chlorophenyl)-8-hydroxy-3-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; N-benzyl-7-(3-(4-chlorophenyl)-8-hydroxy-2-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; N-benzyl-7-(2,3-bis(4-chlorophenyl)-8-hydroxy-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanamide; 7-(2-(4-chlorophenyl)-3-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-(methylsulfonyl)heptanamide; 7-(3-(4-chlorophenyl)-2-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-(methylsulfonyl)heptanamide; 7-(2,3-bis(4-chlorophenyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-(methylsulfonyl)heptanamide; 7-(2-(4-chlorophenyl)-3-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-(isopropylsulfonyl)heptanamide; 7-(3-(4-chlorophenyl)-2-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-(isopropylsulfonyl)heptanamide; 7-(2,3-bis(4-chlorophenyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-(isopropylsulfonyl)heptanamide; 7-(2-(4-chlorophenyl)-3-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-methylheptanamide; 7-(3-(4-chlorophenyl)-2-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-methylheptanamide; 7-(2,3-bis(4-chlorophenyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-methylheptanamide; 7-(2-(4-chlorophenyl)-3-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-isopropylheptanamide; 7-(3-(4-chlorophenyl)-2-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-isopropylheptanamide; 7-(2,3-bis(4-chlorophenyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-isopropylheptanamide; 7-(2-(4-chlorophenyl)-3-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-hydroxyheptanamide; 7-(3-(4-chlorophenyl)-2-(p-tolyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-hydroxyheptanamide; 6-(5-methyl-2,3-di-p-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazin-6-yl)hexanoic acid; 6-(5-isopropyl-2,3-di-p-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazin-6-yl)hexanoic acid; 5-(2,3-di-p-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazin-6-yl)pentanoic acid; 5-(5-methyl-2,3-di-p-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazin-6-yl)pentanoic acid; 5-(5-isopropyl-2,3-di-p-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazin-6-yl)pentanoic acid; 7-(2,3-di-p-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazin-6-yl)heptanoic acid; 7-(5-methyl-2-phenyl-3-(p-tolyl)-5,6,7,8-tetrahydropyrido[2,3-b]pyrazin-6-yl)heptanoic acid; 7-(5-isopropyl-2,3-di-p-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazin-6-yl)heptanoic acid; 6-(7-hydroxy-2,3-di-p-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazin-6-yl)hexanoic acid; 6-(7-hydroxy-5-methyl-2,3-di-p-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazin-6-yl)hexanoic acid; 6-(7-hydroxy-5-isopropyl-2,3-di-p-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazin-6-yl)hexanoic acid; 5-(7-hydroxy-2,3-di-p-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazin-6-yl)pentanoic acid; 5-(7-hydroxy-5-methyl-2,3-di-p-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazin-6-yl)pentanoic acid; 5-(7-hydroxy-5-isopropyl-2,3-di-p-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazin-6-yl)pentanoic acid; 7-(7-hydroxy-2,3-di-p-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazin-6-yl)heptanoic acid; 7-(7-hydroxy-5-methyl-2-phenyl-3-(p-tolyl)-5,6,7,8-tetrahydropyrido[2,3-b]pyrazin-6-yl)heptanoic acid; 7-(7-hydroxy-5-isopropyl-2,3-di-p-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazin-6-yl)heptanoic acid; 6-(8-hydroxy-2,3-di-p-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazin-6-yl)hexanoic acid; 6-(8-hydroxy-5-methyl-2,3-di-p-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazin-6-yl)hexanoic acid; 6-(8-hydroxy-5-isopropyl-2,3-di-p-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazin-6-yl)hexanoic acid; 5-(8-hydroxy-2,3-di-p-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazin-6-yl)pentanoic acid; 5-(8-hydroxy-5-methyl-2,3-di-p-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazin-6-yl)pentanoic acid; 5-(8-hydroxy-5-isopropyl-2,3-di-p-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazin-6-yl)pentanoic acid; 7-(8-hydroxy-2,3-di-p-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazin-6-yl)heptanoic acid; 7-(8-hydroxy-5-methyl-2,3-di-p-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazin-6-yl)heptanoic acid; 7-(8-hydroxy-5-isopropyl-2,3-di-p-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazin-6-yl)heptanoic acid; and 7-(2,3-bis(4-chlorophenyl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)-N-hydroxyheptanamide; or a pharmaceutically acceptable salt thereof.