IP receptor agonist heterocyclic compounds

摘要

The present invention provides heterocyclic derivatives 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 derivatives 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 or (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 or (S)-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; (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 or (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; (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 or (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 or R or S)-7-(7-hydroxy-7-methyl-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid; (rac or R or S)-7-(7-(dimethylamino)-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic 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-(3-(4-chlorophenyl)-6-oxo-2-(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-(3-(4-chlorophenyl)-7-hydroxy-6-oxo-2-(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-(3-(4-chlorophenyl)-7-hydroxy-2-(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; N-(benzylsulfonyl)-7-(3-(4-chlorophenyl)-8-hydroxy-2-(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.