Antiviral inhibition of capsid proteins

A compound or its pharmaceutically acceptable salt having the formula I:

• 3
• wherein:
• (a) R1 represents hydrogen, halogen, cyano, trifluoromethyl, trichloromethyl, nitro, —OR8, —SR8,, —NHR8, —NR8R9, —NHCOOH, —NHCH2COOH, —NHCHR8COOH, —NHCR8R9COOH, —NR8COOR9, —COOR8 or a hydrocarbon group comprising a straight chained, branched or cyclic group each containing up to 9 carbon atoms;
• (b) R2 represents hydrogen, halogen, cyano, trifluoromethyl, trichloromethyl, nitro, —OR8, —SR8,, —NHR8, —NR8R9, —NHCOOH, —NHCH2COOH, —NHCHR8COOH, —NHCR8R9COOH, —NR8COOR9, —COOR8 or a hydrocarbon group comprising a straight chained, branched or cyclic group each containing up to 9 carbon atoms;
• (c) R3 represents hydrogen, halogen, cyano, trifluoromethyl, trichloromethyl, nitro, —OR8, —SR8,, —NHR8, —NR8R9, —NHCOOH, —NHCH2COOH, —NHCHR8COOH, —NHCR8R9COOH, —NR8COOR9, —COOR8 or a hydrocarbon group comprising a straight chained, branched or cyclic group each containing up to 9 carbon atoms;
• (d) R4 represents hydrogen, halogen, cyano, trifluoromethyl, trichloromethyl, nitro, —OR8, —SR8,, —NHR8, —NR8R9, —NHCOOH, —NHCH2COOH, —NHCHR8COOH, —NHCR8R9COOH, —NR8COOR9, —COOR8 or a hydrocarbon group comprising a straight chained, branched or cyclic group each containing up to 9 carbon atoms;
• (e) R5 represents hydrogen, halogen, cyano, trifluoromethyl, trichloromethyl, nitro, —OR8, —SR8,, —NHR8, —NR8R9, —NHCOOH, —NHCH2COOH, —NHCHR8COOH, —NHCR8R9COOH, —NR8COOR9, —COOR8 or a hydrocarbon group comprising a straight chained, branched or cyclic group each containing up to 9 carbon atoms;
• (f) Halogen is limited to fluoro, chloro, bromo, and iodo;
• (g) R8 and R9 are independently methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, sec-butyl, t-butyl, pentyl, hexyl, neo-pentyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclopropylethyl, cyclobutylmethyl, cyclobutylethyl, cyclopentylmethyl, cyclohexylmethyl, or cyclohexylethyl;
• (h) The letters n, m, and p represent independently any integer from 1 to 6;
• (i) R6 and R7 are independently selected from the group consisting of hydrogen or a hydrocarbon group comprising a straight chained, branched or cyclic group each containing up to 6 carbon atoms;
• (j) X is selected from the group consisting of O or S;
• (k) Y is heterocyclic, carbocyclic,or optionally substituted phenyl;
• (l) Heterocyclic is selected from any stable 5, 6, or 7-membered monocyclic or bicyclic or 7, 8, 9, or 10-membered bicyclic heterocyclic ring which is saturated, partially unsaturated or unsaturated (aromatic), and which consists of carbon atoms and 1, 2, 3, or 4 heteroatoms independently selected from the group consisting of N, NH, O and S and including any bicyclic group in which any of the above-defined heterocyclic rings is fused to a benzene ring. The nitrogen and sulfur heteroatoms may optionally be oxidized. The heterocyclic ring may be attached to its pendant group at any heteroatom or carbon atom which results in a stable structure. The heterocyclic rings described herein may be substituted on carbon or on a nitrogen atom if the resulting compound is stable. If specifically noted, a nitrogen in the heterocycle may optionally be quaternized. It is preferred that when the total number of S and O atoms in the heterocycle exceeds 1, then these heteroatoms are not adjacent to one another. As used herein, the term “aromatic heterocyclic system” is intended to mean a stable 5- to 7-membered monocyclic or bicyclic or 7- to 10-membered bicyclic heterocyclic aromatic ring which consists of carbon atoms and from 1 to 4 heteroatoms independently selected from the group consisting of N, O and S. Examples of heterocycles include, but are not limited to, 1H-indazole, 2-pyrrolidonyl, 2H,6H-1,5,2-dithiazinyl, 2H-pyrrolyl, 3H-indolyl, 4- piperidonyl, 4aH-carbazole, 4H-quinolizinyl, 6H-1,2,5-thiadiazinyl, acridinyl, azocinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazalonyl, carbazolyl, 4aH-carbazolyl, β-carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, 2H,6H-1,5,2-dithiazinyl, dihydrofuro[2,3-b]tetrahydrofuran, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolenyl, indolinyl, indolizinyl, indolyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl (benzimidazolyl), isothiazolyl, isoxazolyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl., oxazolyl, oxazolidinylperimidinyl, phenanthridinyl, phenanthrolinyl, phenarsazinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, pteridinyl, piperidonyl, 4-piperidonyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridooxazole, pyridoimidazole, pyridothiazole, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, carbolinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4- thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thiophenyl, triazinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, tetrazolyl, and xanthenyl. Preferred heterocycles include, but are not limited to, pyridinyl, thiophenyl, furanyl, indazolyl, benzothiazolyl, benzimidazolyl, benzothiaphenyl, benzofuranyl, benzoxazolyl, benzisoxazolyl, quinolinyl, isoquinolinyl, imidazolyl, indolyl, isoidolyl, piperidinyl, piperidonyl, 4-piperidonyl, piperonyl, pyrrazolyl, 1,2,4-triazolyl, 1,2,3-triazolyl, tetrazolyl, thiazolyl, oxazolyl, pyrazinyl, and pyrimidinyl, and fused ring and spiro compounds containing the above heterocycles;
• (m) carbocyclic is intended to mean any stable 3, 4, 5, 6, or 7-membered monocyclic or bicyclic or 7, 8, 9, 10, 11, 12, or 13-membered bicyclic or tricyclic, any of which may be saturated, partially unsaturated, or aromatic. Examples of such carbocycles include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, adamantyl, cyclooctyl,;
• [3.3.0] bicyclooctane, [4.3.0]bicyclononane, [4.4.0]bicyclodecane (decalin), [2.2.2]bicyclooctane, fluorenyl, phenyl, naphthyl, indanyl, adamantyl, or tetrahydronaphthyl (tetralin);
• (n) Substituted phenyl is defined by Structure II
• 4
• wherein:
• (o) R10 represents hydrogen, halogen, cyano, trifluoromethyl, trichloromethyl, nitro, —OR8, —SR8, —NHR8, —NR8R9, —NHCOOH, —NHCH2COOH, —NR8COOR9, —COOR8 or a hydrocarbon group comprising a straight chained, branched or cyclic group each containing up to 9 carbon atoms;
• (p) R11 independently represents hydrogen, halogen, cyano, trifluoromethyl, trichloromethyl, nitro, —OR8, —SR8,, —NHR8, —NR8R9, —NHCOOH, —NHCH2COOH, —NR8COOR9, —COOR8 or a hydrocarbon group comprising a straight chained, branched or cyclic group each containing up to 9 carbon atoms;
• (q) R12 independently represents hydrogen, halogen, cyano, trifluoromethyl, trichloromethyl, nitro, —OR8, —SR8,, —NHR8, —NR8R9, —NHCOOH, ——NHCH2COOH, —NR8COOR9, —COOR8 or a hydrocarbon group comprising a straight chained, branched or cyclic group each containing up to 9 carbon atoms;
• (r) R13 independently represents hydrogen, halogen, cyano, trifluoromethyl, trichloromethyl, nitro, —OR8, —SR8,, —NHR8, —NR8R9, —NHCOOH, —NHCH2COOH, —NR8COOR9, —COOR8 or a hydrocarbon group comprising a straight chained, branched or cyclic group each containing up to 9 carbon atoms;
• (s) R14 independently represents hydrogen, halogen, cyano, trifluoromethyl, trichloromethyl, nitro, —OR8, —SR8,, —NHR8, —NR8R9, —NHCOOH, —NHCH2COOH, —NR8COOR9, —COOR8 or a hydrocarbon group comprising a straight chained, branched or cyclic group each containing up to 9 carbon atoms;
• (t) R8 and R9 are independently methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, sec-butyl, t-butyl, pentyl, hexyl, neo-pentyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclopropylethyl, cyclobutylmethyl, cyclobutylethyl, cyclopentylmethyl, cyclohexylmethyl, or cyclohexylethyl;
• (u) Halogen is limited to fluoro, chloro, bromo, and iodo.