JP2007531749A5 - - Google Patents

Description

In the above formula, the core ring is unsubstituted or H, halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _{1- 6} alkoxy, hydroxy -C _{1 to 6} alkyl, C _{1 to 6} alkyl, substituted C _{1 to 6} alkyl, C _{1 to 6} alkoxy, substituted C _{1 to 6} alkoxy, C _{6 or 10} aryl, pyridyl, Pirimi Jill, thienyl , Furanyl, thiazolyl, oxazolyl, phenoxy, thiophenoxy, sulfonamide, urea, thiourea, amide, keto, carboxyl, carbamyl, sulfide, sulfoxide, sulfone, amino, alkoxyamino, alkyloxyheterocycle, alkylamino, alkylcarboxy, Carbonyl, spirocyclic cyclopropyl, spirocyclic cyclobutyl, spirocyclic cyclopentyl, or B cyclic cyclohexyl by may be substituted;
Alternatively, Q is R ¹ -R ² and R ¹ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, phenyl, pyridine, pyrazine, pyrimidine, pyridazine, pyrrole, Furan, thiophene, thiazole, oxazole, imidazole, isoxazole, pyrazole, isothiazole, naphthyl, quinoline, isoquinoline, quinoxaline, benzothiazole, benzothiophene, benzofuran, indole, or benzimidazole, each with up to 3 NR ⁶ R ⁷ , halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _{1- 6} alkyl or up to 5 substituents C _{1 to 6} a be optionally substituted with fluoro, Kill, may be optionally substituted with optionally C _{1 to 6} alkoxy which may be optionally substituted with up to 5 fluoro; R ² is, H, phenyl, pyridine, pyrazine, pyrimidine, pyridazine, Pyrrole, furan, thiophene, thiazole, oxazole, imidazole, isoxazole, pyrazole, isothiazole, naphthyl, quinoline, isoquinoline, quinoxaline, benzothiazole, benzothiophene, benzofuran, indole, or benzimidazole, each up to 3 NR ⁶ R ⁷ , halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, optionally substituted with up to 5 fluoro Optionally substituted by C _1-6 alkyl, optionally substituted by up to 5 fluoro, or optionally substituted by C _1-6 alkoxy;
R ⁴ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, phenyl, or benzyl, where phenyl or benzyl is a maximum of 3 halo, cyano, nitro Hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, up to 5 fluoro Optionally substituted by C _1-6 alkyl optionally substituted by, or C _1-6 alkoxy optionally substituted by up to 5 fluoro;
R ⁵ is H, C _1-6 alkyl, C (O) NR ⁶ R ⁷ , C (S) NR ⁶ R ⁷ , C (O) R ⁸ , C (O) OR ⁸ , S (O) ₂ R ⁸ or (CO) CHR ²¹ NH (CO) R ²² ;
R ⁶ and R ⁷ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl, wherein the phenyl is a maximum of 3 halo, cyano, optionally nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, hydroxy -C _{1 to 6} alkyl, by up to 5 fluoro in it may be optionally substituted with optionally substituted C _{1 to 6} alkyl optionally or up to 5 substituents C _{1 to 6} alkoxy which may be optionally substituted with fluoro; or R ⁶ and R ⁷ together with the nitrogen to which they are attached forms indolinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl;
R ⁸ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are 1-3 by halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl Optionally substituted; or R ⁸ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or by up to 5 fluoro, C _{6 or 10} aryl optionally substituted by optionally substituted C _1-6 alkoxy; or R ⁸ is optionally substituted by up to 5 fluoro groups. May be C _1-6 alkyl; or R ⁸ is a tetrahydrofuran ring bonded through the C ₃ or C ₄ position of the tetrahydrofuran ring; or R ⁸ is bonded through the C ₄ position of the tetrapyranyl ring. Is a tetrapyranyl ring;
Y is a sulfonimide having the formula —C (O) NHS (O) ₂ R ⁹ and R ⁹ is C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl , All of which may be optionally substituted 1-3 times with halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl, or R ⁹ may have up to 3 halo, cyano, nitro , Hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, or up to 5 good C _{1 to 6} alkyl which may be optionally substituted with fluoro, optionally optionally substituted with up to 5 substituents C _{1 to 6} alkoxy which may be optionally substituted with fluoro C _{6 or} be ₁₀ aryl; or R ⁹ is the highest 5 fluoro groups, NR ⁶ R ^7, an NR ^1a R ^1b, or (CO) optionally C _{1 to 6} alkyl which may be optionally substituted with OH,, or R ⁹ is halo, cyano, nitro, Is an aromatic heterocycle optionally substituted up to two times by hydroxyl or C _1-6 alkoxy; or Y is a carboxylic acid, or a pharmaceutically acceptable salt, solvate, or Is a prodrug;
R ^1a and R ^1b are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl, all of which are halo, cyano, nitro, C _1-6 Optionally substituted 1-3 times by alkoxy, amide, or phenyl,
Alternatively, R ^1a and R ^1b are each independently H, and up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _{1 to 6} alkoxy, optionally by 5 fluoro hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or at the highest, C _{6 or 10} aryl optionally substituted by optionally substituted C _1-6 alkoxy,
Alternatively, R ^1a and R ^1b are each independently H, a heterocyclic ring, which includes 1 to 4 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. Or a 7-membered saturated or unsaturated heterocyclic molecule,
Alternatively, NR ^1a R ^1b is a 3-6 membered alicyclic secondary amine, which optionally has 1 to 3 heteroatoms incorporated into the ring, and is halo, cyano, nitro, Optionally substituted 1-3 times by C _1-6 alkoxy, amide, or phenyl,
Or NR ^1a R ^1b is a heteroaryl selected from the group consisting of:

In the above formula, R ^1c is H, halo, C _1-6 alkyl, C _3-6 cycloalkyl, C _1-6 alkoxy, C _3-6 cycloalkoxy, NO ₂ , N (R ^1d ) ₂ , NH ( CO) R ^1d , or NH (CO) NHR ^1d , each R ^1d is independently H, C _1-6 alkyl, or C _3-6 cycloalkyl,
Or R ^1c is NH (CO) OR ^1e and R ^1e is C _1-6 alkyl or C _3-6 cycloalkyl;
p = 0 or 1;
V is selected from O, S, or NH;
When V is O or S, W is selected from O, NR ¹⁵ , or CR ¹⁵ ; when V is NH, W is selected from NR ¹⁵ or CR ¹⁵ and R ¹⁵ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or C _1-6 alkyl optionally substituted with up to 5 fluoro;
The dashed line represents an optional double bond;
R ²¹ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are halo, cyano, nitro, hydroxy, C _1-6 alkoxy, up to 5 fluoro Optionally substituted by C _1-6 alkyl, optionally substituted by phenyl, or optionally substituted 1-3 times by phenyl; or R ²¹ is up to 3 halo, cyano, nitro, hydroxy By, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, or up to 5 fluoro C _1-6 alkyl optionally substituted, C _{6 or 10} optionally substituted with C _1-6 alkoxy optionally substituted with up to 5 fluoro Is aryl; Alternatively or R ²¹ is pyridyl, Pirimi Jill, pyrazinyl, thienyl, furanyl, thiazolyl, there oxazolyl, phenoxy, or thiophenoxy;
R ²² is C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl, all of which are optionally substituted with halo, cyano, nitro, hydroxy, up to 5 fluoro Optionally substituted _C1-6 alkyl, or optionally substituted 1-3 times by phenyl;
However, a compound having formula I does not include a compound having formula II, III, or IV as defined below. ]

[In the above formula,
a) R ¹ and R ² are each independently H, halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl or up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro, it is optionally substituted with up to 5 fluoro which may be C _{1 to 6} alkoxy, C _{6 or 10} aryl, pyridyl, Pirimi Jill, thienyl, furanyl, thiazolyl, oxazolyl, phenoxy, ^{_{thiophenoxy, S (O) 2 NR 6}} R 7, NHC (O) NR 6 R ⁷ , NHC (S) NR ⁶ R ⁷ , C (O) NR ⁶ R ⁷ , NR ⁶ R ⁷ , C (O) R ⁸ , C (O) OR ⁸ , NHC (O) R ⁸ , NHC (O ) OR ⁸ , SO _m R ⁸ , NHS (O) ₂ R ⁸ , CH _n NR ⁶ R ⁷ , OCH _n NR ⁶ R ⁷ , or OCH _n R ⁹ (R ⁹ is imidazolyl or pyrazolyl); Rules for R ¹ and R ² Said thienyl, Pirimi Jill, furanyl, thiazolyl, and oxazolyl are up to two halo, cyano, nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl alkyl, C _{4 to 10} alkyl cycloalkyl alkyl, C of _2-6 alkenyl, C _{1 to 6} alkoxy, optionally by 5 fluoro hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or at the highest, It may be optionally substituted with optionally C _{1 to 6} alkoxy optionally substituted by selection; the C _{6 or 10} aryl of R ¹ and R ² defined, pyridyl, phenoxy and thiophenoxy is best in three halo, cyano, nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydro Shi -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or up to five which may _{C. 1 to} substituted optionally by fluoro, Optionally substituted by ₆ alkoxy;
b) m = 0, 1, or 2;
c) R ⁴ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, phenyl, or benzyl, wherein the phenyl or benzyl is a maximum of 3 halo, cyano , Nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, up to 5 Optionally substituted by C _1-6 alkyl, optionally substituted by fluoro, or optionally substituted by C _1-6 alkoxy, optionally substituted by up to 5 fluoro ;
d) R ⁵ is H, C _1-6 alkyl, C (O) NR ⁶ R ⁷ , C (S) NR ⁶ R ⁷ , C (O) R ⁸ , C (O) OR ⁸ , S (O) ₂ R ⁸ or (CO) CHR ²¹ NH (CO) R ²² ;
e) R ⁶ and R ⁷ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl, said phenyl being at most 3 halo, cyano, nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, hydroxy -C _{1 to 6} alkyl or up to 5 fluoro, Optionally substituted by C _1-6 alkyl, optionally substituted by up to 5 fluoro, optionally substituted by C _1-6 alkoxy, optionally substituted by up to 5 fluoro; or R ⁶ and R ⁷ together with the nitrogen to which they are attached form indolinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl;
f) R ⁸ is C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl, all of these by halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl Optionally substituted 1-3 times; or R ⁸ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{2 to 6} alkenyl, 5 C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl or up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro, at the highest C _{6 or 10} aryl optionally substituted by C _1-6 alkoxy optionally substituted by fluoro; or R ⁸ is optionally substituted by up to 5 fluoro groups Is replaced with It is also good C _{1 to 6} alkyl; or R ⁸ is an tetrahydrofuran ring attached via a C ₃ or C ₄ position of the tetrahydrofuran ring; or R ⁸ is, via the C ₄ position of Tetorapiraniru ring A bound tetrapyranyl ring;
g) Y is a sulfonimide having the formula —C (O) NHS (O) ₂ R ⁹ , where R ⁹ is C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl All of which may be optionally substituted 1 to 3 times by halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl, or R ⁹ may have up to 3 halo, cyano, , Nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, or up to 5 C _1-6 alkyl optionally substituted by ₁ fluoro, optionally substituted by C _1-6 alkoxy optionally substituted by up to 5 fluoro C _{6 or 10} aryl; or R ⁹ is the highest Or C _9-6 alkyl, NR ⁶ R ⁷ , or (CO) OH, optionally substituted by 5 fluoro groups, or R ⁹ is halo, cyano, nitro, hydroxyl, or C An aromatic heterocycle optionally substituted up to 2 times by _1-6 alkoxy; or Y is a carboxylic acid, or a pharmaceutically acceptable salt, solvate or prodrug thereof;
h) R ¹⁰ and R ¹¹ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{6 or 10} aryl, hydroxy-C _1-6 alkyl, C _1-6 alkyl optionally substituted by up to 5 fluoro, (CH ₂ ) _n NR ⁶ R ⁷ , (CH ₂ ) _n C (O) OR ¹⁴ (R ¹⁴ is H, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, or C _{4 to 10} alkylcycloalkyl), all of which halo, 1 to 3 cyano, nitro, hydroxy, C _{1 to 6} alkoxy or by phenyl, Optionally substituted once; or R ¹⁴ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, in up to 5 fluoro Which may be optionally substituted with optionally C _{1 to 6} alkoxy substituted optionally which may be C _{1 to 6} alkyl optionally substituted, or the best, by 5 fluoro What C _{6 or 10} aryl; said C _{6 or 10} aryl as defined for R ¹⁰ and R ¹¹ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or, Optionally substituted by C _1-6 alkoxy optionally substituted by up to 5 fluoro; or R ¹⁰ and R ¹¹ together with the carbon to which they are attached. Become cyclopropi , Cyclobutyl, cyclopentyl, or cyclohexyl; or R ¹⁰ and R ¹¹ are combined as O;
i) p = 0 or 1;
j) R ¹² and R ¹³ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{6 or 10} aryl, hydroxy-C _1-6 alkyl, C _1-6 alkyl optionally substituted by up to 5 fluoro, (CH ₂ ) _n NR ⁶ R ⁷ , (CH ₂ ) _n C (O) OR ¹⁴ (R ¹⁴ is H, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkyl cycloalkyl), 1-3 times all of which halo, cyano, nitro, hydroxy, C _{1 to 6} alkoxy or by phenyl, Optionally substituted; or R ¹⁴ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, by up to 5 fluoro Optionally substituted with meaning selected C _{1 to 6} alkyl or up to 5 substituents C _{6 or} be optionally substituted with optionally C _{1 to 6} alkoxy which may be optionally substituted with fluoro, It is ₁₀ aryl; wherein C _{6 or 10} aryl provisions of R ¹² and R ^13, up to three halo, cyano, nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, _{C. 4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or at the highest, Optionally substituted by C _1-6 alkoxy optionally substituted by 5 fluoro; or R ¹² and R ¹³ together with the carbon to which they are attached. Cyclopropyl, Si Forms chlorobutyl, cyclopentyl, or cyclohexyl; or R ¹² and R ¹³ are each independently C _1-6 alkyl optionally substituted by (CH ₂ ) _n OR ⁸ ;
k) R ²⁰ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{6 or 10} aryl, hydroxy-C _1-6 alkyl, up to 5 fluoro C _1-6 alkyl optionally substituted, or (CH ₂ ) _n NR ⁶ R ⁷ , (CH ₂ ) _n C (O) OR ¹⁴ (R ¹⁴ is H, C _1-6 alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkyl cycloalkyl), all of which halo, cyano, nitro, hydroxy, C _{1 to 6} alkoxy or substituted optionally 1-3 times by phenyl, Or R ¹⁴ may be up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C ₆ alkoxy, hydroxy -C _1-6 alkyl, optionally substituted with up to 5 fluoro There be which may be C _{6 or 10} aryl optionally substituted with optionally C _{1 to 6} alkoxy which may be optionally substituted with 5 fluoro also good C _{1 to 6} alkyl or up and; R Said C _{6 or 10} aryl as defined for ¹² and R ¹³ is a maximum of 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl optionally or up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro, by up to 5 fluoro, Optionally substituted by optionally substituted C _1-6 alkoxy;
l) n = 1-4;
m) V is selected from O, S, or NH;
n) when V is O or S, W is selected from O, NR ¹⁵ , or CR ¹⁵ ; when V is NH, W is selected from NR ¹⁵ or CR ¹⁵ and R ¹⁵ is H C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or C _1-6 alkyl optionally substituted by up to 5 fluoro;
o) The dashed line represents an optional double bond;
p) R ²¹ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are halo, cyano, nitro, hydroxy, C _1-6 alkoxy, up to 5 Optionally substituted by fluoro of C _1-6 alkyl, or optionally substituted 1-3 times by phenyl; or R ²¹ is up to 3 halo, cyano, nitro Hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, up to 5 fluoro optionally substituted with C _{1 to 6} alkyl or substituted optionally with up to 5 substituents C _{1 to 6} alkoxy which may be optionally substituted with fluoro C _6, by _or Oh in ₁₀ aryl ; Or R ²¹ is pyridyl, Pirimi Jill, pyrazinyl, thienyl, furanyl, thiazolyl, there oxazolyl, phenoxy, or thiophenoxy;
q) R ²² is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are optionally selected by halo, cyano, nitro, hydroxy, up to 5 fluoro C _1-6 alkyl, which may be substituted, or optionally substituted 1-3 times with phenyl. ]

In the above formula, R ^1c is H, halo, C _1-6 alkyl, C _3-6 cycloalkyl, C _1-6 alkoxy, C _3-6 cycloalkoxy, NO ₂ , N (R ^1d ) ₂ , NH ( CO) R ^1d , or NH (CO) NHR ^1d , each R ^1d is independently H, C _1-6 alkyl, or C _3-6 cycloalkyl;
Or R ^1c is NH (CO) OR ^1e and R ^1e is C _1-6 alkyl or C _3-6 cycloalkyl;
b) W is O or NH;
c) V is selected from O, S, or NH;
d) when V is O or S, W is selected from O, NR ¹⁵ , or CR ¹⁵ ; when V is NH, W is selected from NR ¹⁵ or CR ¹⁵ and R ¹⁵ is H C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or C _1-6 alkyl optionally substituted by up to 5 fluoro;
e) R ² is a bicyclic secondary amine having the structure:

In the above formula, R ²¹ and R ²² are each independently H, halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6. Alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, optionally substituted by up to 5 fluoro, optionally substituted by C _1-6 alkyl, up to 5 fluoro which may be C _{1 to 6} alkoxy, C _{6 or 10} aryl, pyridyl, Pirimi Jill, thienyl, furanyl, thiazolyl, oxazolyl, phenoxy, ^{_{thiophenoxy, S (O) 2 NR 6}} R 7, NHC (O) NR ⁶ R ⁷ , NHC (S) NR ⁶ R ⁷ , C (O) NR ⁶ R ⁷ , NR ⁶ R ⁷ , C (O) R ⁸ , C (O) OR ⁸ , NHC (O) R ⁸ , NHC ( _{^{O) oR 8, SO m R}} 8 (m = 0,1 or 2), or NHS (O) be ₂ R ^8; the thienyl, Pirimi Jill provisions of R ²¹ and R ^22, furanyl, thiazolyl, Contact Yo Fine oxazolyl is up to two halo, cyano, nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or up to five which may _{C. 1 to} substituted optionally by fluoro, may be optionally substituted with ₆ alkoxy; said C _{6 or 10} aryl provisions of R ²¹ and R ^22, pyridyl, phenoxy and thiophenoxy is up to three halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, optional with up to 5 fluoro so Optionally substituted by C _1-6 alkyl, which may be substituted, or C _1-6 alkoxy, optionally substituted by up to 5 fluoro;
Wherein R ¹⁰ and R ¹¹ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{6 or 10} aryl, hydroxy-C _1-6 alkyl , C _1-6 alkyl, (CH ₂ ) _n NR ⁶ R ⁷ , or (CH ₂ ) _n C (O) OR ¹⁴ (R ¹⁴ is optionally substituted with up to 5 fluoro H, C _1-6 alkyl, C _3-7 cycloalkyl or C _4-10 alkyl cycloalkyl), which are all 1- to halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl. May be optionally substituted three times; or R ¹⁴ may be up to three halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl , C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, up to 5 C _1-6 alkyl optionally substituted by Luoro, C ₆ optionally substituted by C _1-6 alkoxy optionally substituted by up to 5 fluoro C _{6 Or} C _{6 or 10} aryl as defined for R ¹² and R ¹³ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _{4 10} alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or up, Optionally substituted by 5 fluoro and optionally substituted by C _1-6 alkoxy; or R ¹⁰ and R ¹¹ together with the carbon to which they are attached. Cyclop Pills, cyclobutyl, cyclopentyl or cyclohexyl to form,; or R ¹⁰ and R ¹¹ are coalesced as O;
Where p = 0 or 1;
Wherein R ¹² and R ¹³ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{6 or 10} aryl, hydroxy-C _1-6 alkyl C _1-6 alkyl, optionally substituted with up to 5 fluoro, (CH ₂ ) _n NR ⁶ R ⁷ , (CH ₂ ) _n C (O) OR ¹⁴ (R ¹⁴ is H , C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl), which are all 1- to halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl. May be optionally substituted three times; or R ¹⁴ may be up to three halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl , C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, up to 5 fluors C _1-6 alkyl optionally substituted by b, optionally substituted by C _1-6 alkoxy optionally substituted by up to 5 fluoro C _{6 Or} C _{6 or 10} aryl as defined for R ¹² and R ¹³ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _{4 10} alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or up, Optionally substituted by 5 fluoro and optionally substituted by C _1-6 alkoxy; or R ¹² and R ¹³ together with the carbon to which they are attached. Cyclopropi To form cyclobutyl, cyclopentyl, or cyclohexyl;
Wherein R ²⁰ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{6 or 10} aryl, hydroxy-C _1-6 alkyl, up to 5 fluoro C _1-6 alkyl, optionally substituted by (CH ₂ ) _n NR ⁶ R ⁷ , or (CH ₂ ) _n C (O) OR ¹⁴ (R ¹⁴ is H, C _1-6 alkyl All of which are optionally substituted 1 to 3 times by halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl), C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl) Or R ¹⁴ may be up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl. , optionally by 5 fluoro C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, with the highest Optionally substituted C _{1 to 6} alkyl or up to 5 amino which may be C _{6 or 10} aryl optionally substituted with optionally C _{1 to 6} alkoxy which may be optionally substituted with fluoro, Yes; said C _{6 or 10} aryl as defined for R ¹² and R ¹³ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkylcyclo alkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or up to five, Optionally substituted by C _1-6 alkoxy optionally substituted by fluoro;
Where n = 0-4;
In the formula, R ⁶ and R ⁷ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl, and the phenyl has a maximum of 3 Halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, hydroxy-C _1-6 alkyl, up to 5 fluoro Optionally substituted by C _1-6 alkyl, optionally substituted by, or C _1-6 alkoxy, optionally substituted by up to 5 fluoro; or R ⁶ and R ⁷ together with the nitrogen to which they are attached form indolinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl;
Or R ² is R ^2a R ^2b when W = NH, V = O,
R ^2a is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, phenyl, pyridine, pyrazine, pyrimidine, pyridazine, pyrrole, furan, thiophene, thiazole, oxazole, imidazole, isoxazole, Pyrazole, isothiazole, naphthyl, quinoline, isoquinoline, quinoxaline, benzothiazole, benzothiophene, benzofuran, indole, or benzimidazole, each up to 3 NR ^2c R ^2d , halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, optionally up to 5 fluoro Optionally substituted C _1-6 alkyl, or up to 5 fluoro Optionally substituted by C _1-6 alkoxy optionally substituted by;
R ^2b is H, phenyl, pyridine, pyrazine, pyrimidine, pyridazine, pyrrole, furan, thiophene, thiazole, oxazole, imidazole, isoxazole, pyrazole, isothiazole, naphthyl, quinoline, isoquinoline, quinoxaline, benzothiazole, benzothiophene, Benzofuran, indole, or benzimidazole, each up to 3 NR ^2c R ^2d , halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl , C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, 5 fluoro up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or at the highest, the good C _{1 to 6} alkoxy which may be optionally substituted with It may be substituted with meaning selected;
R ^2c and R ^2d are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl, wherein the phenyl is a maximum of 3 halos. , Cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, hydroxy-C _1-6 alkyl, optional up to 5 fluoro Optionally substituted by C _1-6 alkyl optionally substituted, or C _1-6 alkoxy optionally substituted by up to 5 fluoro; or R ^2c And R ^2d together with the nitrogen to which they are attached form indolinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl;
f) R ⁴ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl, said phenyl being up to 3 halo, cyano, nitro, hydroxy Optional, by C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, up to 5 fluoro Optionally substituted C _1-6 alkyl, or optionally substituted by up to 5 fluoro, optionally substituted by C _1-6 alkoxy;
g) R ⁵ is H, C _1-6 alkyl, C (O) NR ⁶ R ⁷ , C (S) NR ⁶ R ⁷ , C (O) R ⁸ , C (O) OR ⁸ , or S (O ) ₂ R ⁸ ;
h) R ⁸ is C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl, all of these by halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl Optionally substituted 1-3 times; or R ⁸ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{2 to 6} alkenyl, 5 C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or at the highest, C _{6 or 10} aryl optionally substituted by C _1-6 alkoxy optionally substituted by fluoro;
i) The dashed line represents an optional double bond. ]

[In the above formula,
R ⁴ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, phenyl, or benzyl, where phenyl or benzyl is a maximum of 3 halo, cyano, nitro Hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, up to 5 fluoro Optionally substituted by C _1-6 alkyl optionally substituted by, or C _1-6 alkoxy optionally substituted by up to 5 fluoro;
R ⁵ is C _1-6 alkyl, C (O) NR ⁶ R ⁷ , C (S) NR ⁶ R ⁷ , C (O) R ⁸ , C (O) OR ⁸ , S (O) ₂ R ⁸ , Or (CO) CHR ²¹ NH (CO) R ²² ;
R ⁶ and R ⁷ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl, wherein the phenyl is a maximum of 3 halo, cyano, optionally nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, hydroxy -C _{1 to 6} alkyl, by up to 5 fluoro in it may be optionally substituted with optionally substituted C _{1 to 6} alkyl optionally or up to 5 substituents C _{1 to 6} alkoxy which may be optionally substituted with fluoro; or R ⁶ and R ⁷ together with the nitrogen to which they are attached forms indolinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl;
R ⁸ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are 1-3 by halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl Optionally substituted; or R ⁸ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or by up to 5 fluoro, C _{6 or 10} aryl optionally substituted by optionally substituted C _1-6 alkoxy; or R ⁸ is optionally substituted by up to 5 fluoro groups. May be C _1-6 alkyl; or R ⁸ is a tetrahydrofuran ring bonded through the C ₃ or C ₄ position of the tetrahydrofuran ring; or R ⁸ is bonded through the C ₄ position of the tetrapyranyl ring. Is a tetrapyranyl ring;
Y is a sulfonimide having the formula —C (O) NHS (O) ₂ R ⁹ , where R ⁹ is C _1-3 alkyl, C _3-7 cycloalkyl, or up to 2 halo, cyano, Nitro, hydroxy, C _1-3 alkyl, C _3-7 cycloalkyl, or phenyl optionally substituted by C _1-3 alkoxy, or Y is a carboxylic acid ;
V is selected from OH, SH, or NH ₂ ;
The dashed line represents an optional double bond;
R ²¹ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are halo, cyano, nitro, hydroxy, C _1-6 alkoxy, up to 5 fluoro Optionally substituted by C _1-6 alkyl, optionally substituted by phenyl, or optionally substituted 1-3 times by phenyl; or R ²¹ is up to 3 halo, cyano, nitro, hydroxy C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, optional up to 5 fluoro C _1-6 alkyl optionally substituted, _or C _{6 or 10} optionally substituted with C _1-6 alkoxy optionally substituted with up to 5 fluoro. Is aryl; Alternatively or R ²¹ is pyridyl, Pirimi Jill, pyrazinyl, thienyl, furanyl, thiazolyl, there oxazolyl, phenoxy, or thiophenoxy;
R ²² is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are optionally substituted by halo, cyano, nitro, hydroxy, up to 5 fluoro C _1-6 alkyl, which may optionally be substituted, or optionally substituted 1 to 3 times by phenyl. ]

Wherein the core ring is unsubstituted or H, halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _{1- 6} alkoxy, hydroxy -C _{1 to 6} alkyl, C _{1 to 6} alkyl, substituted C _{1 to 6} alkyl, C _{1 to 6} alkoxy, substituted C _{1 to 6} alkoxy, C _{6 or 10} aryl, pyridyl, Pirimi Jill, thienyl , Furanyl, thiazolyl, oxazolyl, phenoxy, thiophenoxy, sulfonamide, urea, thiourea, amide, keto, carboxyl, carbamyl, sulfide, sulfoxide, sulfone, amino, alkoxyamino, alkyloxyheterocycle, alkylamino, alkylcarboxy, Carbonyl, spirocyclic cyclopropyl, spirocyclic cyclobutyl, spirocyclic cyclopentyl, or B cyclic cyclohexyl by may be substituted;
Or Q is R ¹ -R ² and R ¹ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, phenyl, pyridine, pyrazine, pyrimidine, pyridazine, pyrrole, furan , Thiophene, thiazole, oxazole, imidazole, isoxazole, pyrazole, isothiazole, naphthyl, quinoline, isoquinoline, quinoxaline, benzothiazole, benzothiophene, benzofuran, indole, benzimidazole, each with up to 3 NR ⁶ R ⁷ , halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl , up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or, It may be optionally substituted with optionally C _{1 to 6} alkoxy which may be optionally substituted with 5 fluoro at high; R ² is, H, phenyl, pyridine, pyrazine, pyrimidine, pyridazine, pyrrole, Furan, thiophene, thiazole, oxazole, imidazole, isoxazole, pyrazole, isothiazole, naphthyl, quinoline, isoquinoline, quinoxaline, benzothiazole, benzothiophene, benzofuran, indole, benzimidazole, each with up to 3 NR ⁶ R ⁷ , halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 Alkyl, optionally substituted with up to 5 fluoro Optionally substituted by C _1-6 alkyl, or C _1-6 alkoxy optionally substituted by up to 5 fluoro;
R ⁴ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, phenyl, or benzyl, where phenyl or benzyl is a maximum of 3 halo, cyano, nitro Hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, up to 5 fluoro Optionally substituted by C _1-6 alkyl optionally substituted by, or C _1-6 alkoxy optionally substituted by up to 5 fluoro;
R ⁵ is C _1-6 alkyl, C (O) NR ⁶ R ⁷ , C (S) NR ⁶ R ⁷ , C (O) R ⁸ , C (O) OR ⁸ , S (O) ₂ R ⁸ , Or (CO) CHR ²¹ NH (CO) R ²² ;
R ⁶ and R ⁷ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl, wherein the phenyl is a maximum of 3 halo, cyano, optionally nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, hydroxy -C _{1 to 6} alkyl, by up to 5 fluoro in it may be optionally substituted with optionally substituted C _{1 to 6} alkyl optionally or up to 5 substituents C _{1 to 6} alkoxy which may be optionally substituted with fluoro; or R ⁶ and R ⁷ together with the nitrogen to which they are attached forms indolinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl;
R ⁸ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are 1-3 by halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl Optionally substituted; or R ⁸ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or by up to 5 fluoro, C _{6 or 10} aryl optionally substituted by optionally substituted C _1-6 alkoxy; or R ⁸ is optionally substituted by up to 5 fluoro groups. May be C _1-6 alkyl; or R ⁸ is a tetrahydrofuran ring bonded through the C ₃ or C ₄ position of the tetrahydrofuran ring; or R ⁸ is bonded through the C ₄ position of the tetrapyranyl ring. Is a tetrapyranyl ring;
Y is, R ⁹ is C _{1 to 6} alkyl, COOR ^9; or Y is the formula -C (O) NHS (O) sulfonimide is ₂ R ^9, R ⁹ is _{C. 1 to} Optionally substituted by ₃ alkyl, C _3-7 cycloalkyl, or up to 2 halo, cyano, nitro, hydroxy, C _1-3 alkyl, C _3-7 cycloalkyl, or C _1-3 alkoxy Optionally phenyl, or Y is a carboxylic acid ;
V and W are each independently selected from O, S, or NH;
The dashed line represents an optional double bond;
R ²¹ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are halo, cyano, nitro, hydroxy, C _1-6 alkoxy, up to 5 fluoro Optionally substituted by C _1-6 alkyl, optionally substituted by phenyl, or optionally substituted 1-3 times by phenyl; or R ²¹ is up to 3 halo, cyano, nitro, hydroxy Optional, by C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, up to 5 fluoro C _1-6 alkyl optionally substituted, C _{6 or 10} aryl optionally substituted by C _1-6 alkoxy optionally substituted by up to 5 fluoro Yes; yes Is or R ²¹ is pyridyl, Pirimi Jill, pyrazinyl, thienyl, furanyl, thiazolyl, there oxazolyl, phenoxy, or thiophenoxy;
R ²² is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are optionally substituted with halo, cyano, nitro, hydroxy, up to 5 fluoro. Optionally substituted _C1-6 alkyl, or optionally substituted 1-3 times by phenyl].

In the above formula, the core ring is unsubstituted or H, halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _{1- 6} alkoxy, hydroxy -C _{1 to 6} alkyl, C _{1 to 6} alkyl, substituted C _{1 to 6} alkyl, C _{1 to 6} alkoxy, substituted C _{1 to 6} alkoxy, C _{6 or 10} aryl, pyridyl, Pirimi Jill, thienyl , Furanyl, thiazolyl, oxazolyl, phenoxy, thiophenoxy, sulfonamide, urea, thiourea, amide, keto, carboxyl, carbamyl, sulfide, sulfoxide, sulfone, amino, alkoxyamino, alkyloxyheterocycle, alkylamino, alkylcarboxy, Carbonyl, spirocyclic cyclopropyl, spirocyclic cyclobutyl, spirocyclic cyclopentyl, or B cyclic cyclohexyl may be substituted by,
Or Q is R ¹ -R ² and R ¹ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, phenyl, pyridine, pyrazine, pyrimidine, pyridazine, pyrrole, furan , Thiophene, thiazole, oxazole, imidazole, isoxazole, pyrazole, isothiazole, naphthyl, quinoline, isoquinoline, quinoxaline, benzothiazole, benzothiophene, benzofuran, indole, or benzimidazole, each with up to 3 NR ⁶ R ⁷ , halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl or up to 5 substituents C _{1 to 6} Al be optionally substituted with fluoro, Le or may be optionally substituted with optionally C _{1 to 6} alkoxy substituted optionally up at the 5 fluoro,; R ² is, H, phenyl, pyridine, pyrazine, pyrimidine, pyridazine , Pyrrole, furan, thiophene, thiazole, oxazole, imidazole, isoxazole, pyrazole, isothiazole, naphthyl, quinoline, isoquinoline, quinoxaline, benzothiazole, benzothiophene, benzofuran, indole, or benzimidazole, each up to 3 NR ⁶ R ⁷ , halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy- C _1-6 alkyl, optionally placed with up to 5 fluoro It may be optionally substituted with conversion which may C _{1 to 6} alkyl optionally or up to 5 substituents C _{1 to 6} alkoxy which may be optionally substituted with fluoro;
R ⁴ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, phenyl, or benzyl, where phenyl or benzyl is a maximum of 3 halo, cyano, nitro Hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, up to 5 fluoro Optionally substituted by C _1-6 alkyl optionally substituted by, or C _1-6 alkoxy optionally substituted by up to 5 fluoro;
R ⁵ is H, C _1-6 alkyl, C (O) NR ⁶ R ⁷ , C (S) NR ⁶ R ⁷ , C (O) R ⁸ , C (O) OR ⁸ , S (O) ₂ R ⁸ or (CO) CHR ²¹ NH (CO) R ²² ;
R ⁶ and R ⁷ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl, wherein the phenyl is a maximum of 3 halo, cyano, optionally nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, hydroxy -C _{1 to 6} alkyl, by up to 5 fluoro in it may be optionally substituted with optionally substituted C _{1 to 6} alkyl optionally or up to 5 substituents C _{1 to 6} alkoxy which may be optionally substituted with fluoro; or R ⁶ and R ⁷ together with the nitrogen to which they are attached forms indolinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl;
R ⁸ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are 1-3 by halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl Optionally substituted; or R ⁸ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or by up to 5 fluoro, C _{6 or 10} aryl optionally substituted by optionally substituted C _1-6 alkoxy; or R ⁸ is optionally substituted by up to 5 fluoro groups. May be C _1-6 alkyl; or R ⁸ is a tetrahydrofuran ring bonded through the C ₃ or C ₄ position of the tetrahydrofuran ring; or R ⁸ is bonded through the C ₄ position of the tetrapyranyl ring. Is a tetrapyranyl ring;
Y is a sulfonimide having the formula —C (O) NHS (O) ₂ R ⁹ and R ⁹ is C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl , All of which may be optionally substituted 1-3 times with halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl, or R ⁹ may have up to 3 halo, cyano, nitro , Hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, or up to 5 good C _{1 to 6} alkyl which may be optionally substituted with fluoro, optionally optionally substituted with up to 5 substituents C _{1 to 6} alkoxy which may be optionally substituted with fluoro C _{6 or} be ₁₀ aryl; or R ⁹ is the highest 5 fluoro good C _{1 to 6} alkyl which may be optionally substituted with groups, a ^{NR 6 R 7, NR 1a R} 1b , or (CO) OH,, or R ⁹ is halo, cyano, nitro, Hydroxyl or an aromatic heterocycle optionally substituted up to 2 times with C _1-6 alkoxy; or Y is a carboxylic acid, or a pharmaceutically acceptable salt, solvate, or Is a prodrug;
R ^1a and R ^1b are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl, all of which are halo, cyano, nitro, C _1-6 Optionally substituted 1-3 times by alkoxy, amide, or phenyl,
Alternatively, R ^1a and R ^1b are each independently H, and up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _{1 to 6} alkoxy, optionally by 5 fluoro hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or at the highest, C _{6 or 10} aryl optionally substituted by optionally substituted C _1-6 alkoxy,
Alternatively, R ^1a and R ^1b are each independently H, a heterocyclic ring, which includes 1 to 4 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. Or a 7-membered saturated or unsaturated heterocyclic molecule,
Alternatively, NR ^1a R ^1b is a 3-6 membered alicyclic secondary amine, which optionally has 1 to 3 heteroatoms incorporated into the ring, and is halo, cyano, nitro, Optionally substituted 1 to 3 times by C _1-6 alkoxy, amide or phenyl,
Or NR ^1a R ^1b is a heteroaryl selected from the group consisting of:

In the above formula, R ^1c is H, halo, C _1-6 alkyl, C _3-6 cycloalkyl, C _1-6 alkoxy, C _3-6 cycloalkoxy, NO ₂ , N (R ^1d ) ₂ , NH ( CO) R ^1d , or NH (CO) NHR ^1d , each R ^1d is independently H, C _1-6 alkyl, or C _3-6 cycloalkyl,
Or R ^1c is NH (CO) OR ^1e and R ^1e is C _1-6 alkyl or C _3-6 cycloalkyl;
p = 0 or 1;
V is selected from O, S, or NH;
When V is O or S, W is selected from O, NR ¹⁵ , or CR ¹⁵ ; when V is NH, W is selected from NR ¹⁵ or CR ¹⁵ and R ¹⁵ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or C _1-6 alkyl optionally substituted with up to 5 fluoro;
The dashed line represents an optional double bond;
R ²¹ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are halo, cyano, nitro, hydroxy, C _1-6 alkoxy, up to 5 fluoro Optionally substituted by C _1-6 alkyl, optionally substituted by phenyl, or optionally substituted 1-3 times by phenyl; or R ²¹ is up to 3 halo, cyano, nitro, hydroxy By, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, or up to 5 fluoro C _1-6 alkyl optionally substituted, C _{6 or 10} optionally substituted with C _1-6 alkoxy optionally substituted with up to 5 fluoro Is aryl; Alternatively or R ²¹ is pyridyl, Pirimi Jill, pyrazinyl, thienyl, furanyl, thiazolyl, there oxazolyl, phenoxy, or thiophenoxy;
R ²² is C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl, all of which are optionally substituted with halo, cyano, nitro, hydroxy, up to 5 fluoro C _1-6 alkyl, which may be substituted, or optionally substituted 1-3 times with phenyl. ].

[In the above formula,
R ¹ and R ² are each independently H, halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _{1 6} alkoxy, hydroxy -C _{1 to 6} alkyl or up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro, it is optionally substituted with up to 5 fluoro good C _{1 to 6} alkoxy, C _{6 or 10} aryl, pyridyl, Pirimi Jill, thienyl, furanyl, thiazolyl, oxazolyl, phenoxy, ^{_{thiophenoxy, S (O) 2 NR 6}} R 7, NHC (O) NR 6 R 7 , NHC (S) NR ⁶ R ⁷ , C (O) NR ⁶ R ⁷ , NR ⁶ R ⁷ , C (O) R ⁸ , C (O) OR ⁸ , NHC (O) R ⁸ , NHC (O) OR ⁸ , SO _m R ⁸ , NHS (O) ₂ R ⁸ , CH _n NR ⁶ R ⁷ , OCH _n NR ⁶ R ⁷ , or OCH _n R ⁹ (R ⁹ is imidazolyl or pyrazolyl); R ¹ the provisions of and R ² Said thienyl, Pirimi Jill, furanyl, thiazolyl, and oxazolyl are up to two halo, cyano, nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 6} alkenyl, optionally by 5 fluoro C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or at the highest, in substituted it may be optionally substituted with also a good C _{1 to 6} alkoxy; said C _{6 or 10} aryl of R ¹ and R ² defined, pyridyl, phenoxy and thiophenoxy is the highest three halo, cyano, nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, optionally substituted optionally by 5 fluoro optionally optionally substituted C _{1 to 6} alkyl or a maximum, by up to 5 fluoro C _{1 to 6} Optionally substituted by alkoxy;
m = 0, 1, or 2;
R ⁴ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, phenyl, or benzyl, where phenyl or benzyl is a maximum of 3 halo, cyano, nitro Hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, up to 5 fluoro Optionally substituted by C _1-6 alkyl optionally substituted by, or C _1-6 alkoxy optionally substituted by up to 5 fluoro;
R ⁵ is H, C _1-6 alkyl, C (O) NR ⁶ R ⁷ , C (S) NR ⁶ R ⁷ , C (O) R ⁸ , C (O) OR ⁸ , S (O) ₂ R ⁸ or (CO) CHR ²¹ NH (CO) R ²² ;
R ⁶ and R ⁷ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl, wherein the phenyl is a maximum of 3 halo, any cyano, nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, hydroxy -C _{1 to 6} alkyl or up by 5 fluoro Optionally substituted C _1-6 alkyl, optionally substituted by C _1-6 alkoxy optionally substituted by up to 5 fluoro; or R ⁶ and R ⁷ together with the nitrogen to which they are attached form indolinyl, pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl;
R ⁸ is C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl, all of which are 1- to halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl. Optionally substituted three times; or R ⁸ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl , C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl or up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro, up to 5 fluoro, C _{6 or 10} aryl optionally substituted by C _1-6 alkoxy optionally substituted by; or R ⁸ is optionally substituted by up to 5 fluoro groups Have been It is also good C _{1 to 6} alkyl; or R ⁸ is an tetrahydrofuran ring attached via a C ₃ or C ₄ position of the tetrahydrofuran ring; or R ⁸ is, via the C ₄ position of Tetorapiraniru ring A bound tetrapyranyl ring;
Y is a sulfonimide having the formula —C (O) NHS (O) ₂ R ⁹ and R ⁹ is C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl , All of which may be optionally substituted 1-3 times with halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl, or R ⁹ may have up to 3 halo, cyano, nitro , Hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, or up to 5 good C _{1 to 6} alkyl which may be optionally substituted with fluoro, optionally optionally substituted with up to 5 substituents C _{1 to 6} alkoxy which may be optionally substituted with fluoro C _{6 or} be ₁₀ aryl; or R ⁹ is the highest 5 fluoro good C _{1 to 6} alkyl which may be optionally substituted with groups is NR ⁶ R ^7, or (CO) OH, or R ⁹ is halo, cyano, nitro, hydroxyl, or C _1, An aromatic heterocycle optionally substituted up to 2 times with up to ₆ alkoxy; or Y is a carboxylic acid, or a pharmaceutically acceptable salt, solvate or prodrug thereof;
R ¹⁰ and R ¹¹ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{6 or 10} aryl, hydroxy-C _1-6 alkyl, at most C _1-6 alkyl optionally substituted by 5 fluoro, (CH ₂ ) _n NR ⁶ R ⁷ , (CH ₂ ) _n C (O) OR ¹⁴ (R ¹⁴ is H, C _{1 6} alkyl, C _{3 to 7} cycloalkyl, or C _{4 to 10} alkylcycloalkyl), all of which halo, cyano, nitro, hydroxy, optionally three times C _{1 to 6} alkoxy or by phenyl, Optionally substituted; or R ¹⁴ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{2 ~ 6} alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, up to 5 fluoro Optionally substituted by C _1-6 alkyl, optionally substituted by up to 5 fluoro, optionally substituted by C _1-6 alkoxy. _{6 or 10} aryl; said C _{6 or 10} aryl as defined for R ¹⁰ and R ¹¹ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or, Optionally substituted by C _1-6 alkoxy optionally substituted by up to 5 fluoro; or R ¹⁰ and R ¹¹ together with the carbon to which they are attached. Become cyclopropi To form cyclobutyl, cyclopentyl, or cyclohexyl; or R ¹⁰ and R ¹¹ are coalesced as O;
p = 0 or 1;
R ¹² and R ¹³ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{6 or 10} aryl, hydroxy-C _1-6 alkyl, at most C _1-6 alkyl optionally substituted by 5 fluoro, (CH ₂ ) _n NR ⁶ R ⁷ , (CH ₂ ) _n C (O) OR ¹⁴ (R ¹⁴ is H, C _{1 ~ 6alkyl} , _{C3-7cycloalkyl} , _{C4-10alkylcycloalkyl} ), all of which are optionally 1-3 times by halo, cyano, nitro, hydroxy, _C1-6 alkoxy, or phenyl Or R ¹⁴ may be up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{2-6 6} alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, up to 5 fluoros C _1-6 alkyl optionally substituted, or C ₆ optionally substituted with C _1-6 alkoxy optionally substituted with up to 5 fluoro, _or It is ₁₀ aryl; wherein C _{6 or 10} aryl provisions of R ¹² and R ^13, up to three halo, cyano, nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, _{C. 4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or at the highest, Optionally substituted by C _1-6 alkoxy optionally substituted by 5 fluoro; or R ¹² and R ¹³ together with the carbon to which they are attached. Cyclopropyl, Si Robuchiru, cyclopentyl or cyclohexyl to form,; or R ¹² and R ¹³ are each independently, (CH ₂₎ by _n OR ⁸ be a good C _{1 to 6} alkyl substituted optionally;
R ²⁰ is optionally selected from H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{6 or 10} aryl, hydroxy-C _1-6 alkyl, up to 5 fluoro C _1-6 alkyl optionally substituted with (CH ₂ ) _n NR ⁶ R ⁷ , (CH ₂ ) _n C (O) OR ¹⁴ (R ¹⁴ is H, C _1-6 alkyl, C _{3 7-cycloalkyl,} C _{4 to 10} alkyl cycloalkyl), all of which halo, cyano, nitro, hydroxy, C _{1 to 6} alkoxy, or substituted optionally 1-3 times by phenyl Well; or R ¹⁴ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _{1- 6} alkoxy, hydroxy -C _{1 to 6} alkyl, optionally substituted by up to 5 fluoro It is which may be C _{6 or 10} aryl optionally substituted with optionally C _{1 to 6} alkoxy which may be optionally substituted with optionally C _{1 to 6} alkyl or up, depending on the five fluoro and; R Said C _{6 or 10} aryl as defined for ¹² and R ¹³ is a maximum of 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl optionally or up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro, by up to 5 fluoro, Optionally substituted by optionally substituted C _1-6 alkoxy;
n = 1-4;
V is selected from O, S, or NH;
When V is O or S, W is selected from O, NR ¹⁵ , or CR ¹⁵ ; when V is NH, W is selected from NR ¹⁵ or CR ¹⁵ and R ¹⁵ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or C _1-6 alkyl optionally substituted with up to 5 fluoro;
The dashed line represents an optional double bond;
R ²¹ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are halo, cyano, nitro, hydroxy, C _1-6 alkoxy, up to 5 fluoro Optionally substituted by C _1-6 alkyl, optionally substituted by phenyl, or optionally substituted 1-3 times by phenyl; or R ²¹ is up to 3 halo, cyano, nitro, hydroxy C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, optional up to 5 fluoro C _1-6 alkyl optionally substituted, _or C _{6 or 10} optionally substituted with C _1-6 alkoxy optionally substituted with up to 5 fluoro. Is aryl; Or R ²¹ is pyridyl, Pirimi Jill, pyrazinyl, thienyl, furanyl, thiazolyl, oxazolyl, there phenoxy or thiophenoxy;
R ²² is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are optionally substituted by halo, cyano, nitro, hydroxy, up to 5 fluoro C _1-6 alkyl, which may optionally be substituted, or optionally substituted 1 to 3 times by phenyl. ].

[In the above formula,
R ¹ and R ² are each independently H, halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _{1 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro, by up to 5 fluoro may be optionally substituted C _{1 to 6} alkoxy, C _{6 or 10} aryl, pyridyl, Pirimi Jill, thienyl, furanyl, thiazolyl, oxazolyl, phenoxy, ^{_{thiophenoxy, S (O) 2 NR 6}} R 7, NHC (O) NR 6 R 7, NHC (S) NR ⁶ R ⁷ , C (O) NR ⁶ R ⁷ , NR ⁶ R ⁷ , C (O) R ⁸ , C (O) OR ⁸ , NHC (O) R ⁸ , NHC (O) OR ⁸ , SO _m R ⁸ , NHS (O) ₂ R ⁸ , CH _n NR ⁶ R ⁷ , OCH _n NR ⁶ R ⁷ , or OCH _n R ¹⁶ (R ¹⁶ is imidazolyl or pyrazolyl), the thienyl, Pirimi , Furanyl, thiazolyl, and oxazolyl, in defining R ¹ and R ^2, up to two halo, cyano, nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkyl cycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro, up to five may be optionally substituted with optionally C _{1 to 6} alkoxy which may be optionally substituted with fluoro, said C _{6 or 10} aryl, pyridyl, phenoxy and thiophenoxy is of R ¹ and R ² by convention, up to three halo, cyano, nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, optionally substituted optionally by 5 fluoro optionally optionally substituted C _{1 to 6} alkyl or a maximum, by up to 5 fluoro C _{1 to 6} Optionally substituted by alkoxy,
m = 0, 1, or 2,
R ⁴ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, phenyl, or benzyl, where phenyl or benzyl is a maximum of 3 halo, cyano, nitro Hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, up to 5 fluoro Optionally substituted by C _1-6 alkyl, optionally substituted by, or C _1-6 alkoxy, optionally substituted by up to 5 fluoro,
R ⁵ is H, C _1-6 alkyl, C (O) NR ⁶ R ⁷ , C (S) NR ⁶ R ⁷ , C (O) R ⁸ , C (O) OR ⁸ , S (O) ₂ R ⁸ or (CO) CHR ²¹ NH (CO) R ²² ;
R ⁶ and R ⁷ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl, wherein the phenyl is a maximum of 3 halo, cyano, optionally nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, hydroxy -C _{1 to 6} alkyl, by up to 5 fluoro in an optionally substituted C _{1 to 6} alkyl, it may be optionally substituted with up to 5 substituents C _{1 to 6} alkoxy which may be optionally substituted with fluoro, or R ⁶ and R ⁷ together with their binding partner nitrogen forms indolinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl,
R ⁸ is C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl, any of which are optional by halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl Optionally substituted 1 to 3 times, or R ⁸ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl , C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, 5 fluoro up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or at the highest, C _{6 or 10} aryl optionally substituted by C _1-6 alkoxy optionally substituted by or R ⁸ is optionally substituted by up to 5 fluoro groups Have been A good C _{1 to 6} alkyl or R ^8, is a tetrahydrofuran ring linked via the C ₃ position or C ₄ position of the tetrahydrofuran ring, or R ⁸ is, via the C ₄ position of Tetorapiraniru ring A bound tetrapyranyl ring,
Y is a sulfonimide of the formula -C (O) NHS (O) 2 R 9, R 9 is C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, these Are all optionally substituted 1 to 3 times by halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl, or R ⁹ is up to 3 halo, cyano, nitro, hydroxy Optional, by C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, up to 5 fluoro C _1-6 alkyl optionally substituted, _or C _{6 or 10} optionally substituted with C _1-6 alkoxy optionally substituted with up to 5 fluoro. aryl, or R ⁹ is 5 fluoro at the highest Any is optional substituted with C _{1 to 6} alkyl, NR ⁶ R ^7, or (CO) OH, or R ⁹ is halo, cyano, nitro, hydroxyl or by C _{1 to 6} alkoxy by Is an aromatic heterocycle which is optionally substituted at most twice, or Y is a carboxylic acid or a pharmaceutically acceptable salt, solvate or prodrug thereof,
R ¹⁰ and R ¹¹ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{6 or 10} aryl, hydroxy-C _1-6 alkyl, up to C _1-6 alkyl, optionally substituted with 5 fluoro, (CH ₂ ) _n NR ⁶ R ⁷ , or (CH ₂ ) _n C (O) OR ¹⁴ , wherein R ¹⁴ is H , C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are optionally once with halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl Substituted 3 times or R ¹⁴ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 depending ₆ alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, in up to 5 fluoro Optionally substituted with C _{1 to 6} alkyl or up to 5 substituents C _{6 or} be optionally substituted with optionally C _{1 to 6} alkoxy which may be optionally substituted with fluoro, ₁₀ aryl, said C _{6 or 10} aryl, as defined by R ¹⁰ and R ¹¹ , up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _{4 10} alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro at the highest Optionally substituted by 5-6 fluoro, optionally substituted by C _1-6 alkoxy, or R ¹⁰ and R ¹¹ together with their binding partner carbon. , Cyclopropi , Cyclobutyl, cyclopentyl, or cyclohexyl, or R ¹⁰ and R ¹¹ are combined as O;
p = 0 or 1,
R ¹² and R ¹³ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{6 or 10} aryl, hydroxy-C _1-6 alkyl, at most C _1-6 alkyl, optionally substituted with 5 fluoro, (CH ₂ ) _n NR ⁶ R ⁷ , or (CH ₂ ) _n C (O) OR ¹⁴ , wherein R ¹⁴ is H , C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are optionally once with halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl Substituted 3 times or R ¹⁴ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 depending ₆ alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, in up to 5 fluoro Optionally substituted with C _{1 to 6} alkyl or up to 5 substituents C _{6 or} be optionally substituted with optionally C _{1 to 6} alkoxy which may be optionally substituted with fluoro, a ₁₀ aryl, said C _{6 or 10} aryl, in the provision of R ¹² and R ^13, up to three halo, cyano, nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 10} alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or up, Optionally substituted by 5 fluoro and optionally substituted by C _1-6 alkoxy, or R ¹² and R ¹³ together with their binding partner carbon. Cyclo Form propyl, cyclobutyl, cyclopentyl, or cyclohexyl, or R ¹² and R ¹³ are each independently C _1-6 alkyl optionally substituted by (CH ₂ ) _n OR ⁸ ,
R ²⁰ is optionally selected from H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{6 or 10} aryl, hydroxy-C _1-6 alkyl, up to 5 fluoro C _1-6 alkyl optionally substituted with (CH ₂ ) _n NR ⁶ R ⁷ , or (CH ₂ ) _n C (O) OR ¹⁴ , wherein R ¹⁴ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are optionally substituted 1 to 3 times optionally by halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl Or R ¹⁴ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 Alkoxy, hydroxy-C _1-6 alkyl, optionally substituted by up to 5 fluoro C _1-6 alkyl, or C _{6 or 10} aryl optionally substituted by up to 5 fluoro, optionally substituted by C _1-6 alkoxy, said C _{6 or 10} aryl, as defined for R ¹² and R ¹³ , up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, optionally substituted with up to 5 fluoro, optionally with C _1-6 alkyl, up to 5 fluoro Optionally substituted by C _1-6 alkoxy, which may be substituted with
n = 1 to 4,
V is selected from O, S, or NH;
When V is O or S, W is selected from O, NR ¹⁵ , or CR ^15; when V is NH, W is selected from NR ¹⁵ or CR ¹⁵ ; R ¹⁵ is H, C _{1 to 6} alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or C _1-6 alkyl optionally substituted by up to 5 fluoro,
The dashed line represents an optional double bond,
R ²¹ is C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl, all of which are halo, cyano, nitro, hydroxy, C _1-6 alkoxy, up to 5 Optionally substituted by fluoro of C _1-6 alkyl, or optionally substituted by phenyl 1 to 3 times, or R ²¹ is up to 3 halo, cyano, nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, by up to 5 fluoro C _1-6 alkyl optionally substituted, C _{6 or 10} optionally substituted with C _1-6 alkoxy optionally substituted with up to 5 fluoro Is aryl, Rui R ²¹ is pyridyl, Pirimi Jill, pyrazinyl, thienyl, furanyl, thiazolyl, oxazolyl, phenoxy, or thiophenoxy,,
R ²² is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are optionally substituted by halo, cyano, nitro, hydroxy, up to 5 fluoro Optionally substituted 1 to 3 times by optionally substituted C _1-6 alkyl, or phenyl. ]

In the above formula, R ²¹ and R ²² are each independently H, halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6. alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl or up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro, optionally by up to 5 fluoro, substituted which may C _{1 to 6} alkoxy optionally, C _{6 or 10} aryl, pyridyl, Pirimi Jill, thienyl, furanyl, thiazolyl, oxazolyl, phenoxy, ^{_{thiophenoxy, S (O) 2 NR 6}} R 7, NHC (O) NR ⁶ R ⁷ , NHC (S) NR ⁶ R ⁷ , C (O) NR ⁶ R ⁷ , NR ⁶ R ⁷ , C (O) R ⁸ , C (O) OR ⁸ , NHC (O) R ⁸ , NHC _{^{(O) oR 8, SO m}} R 8 (m = 0,1, or 2), or NHS (O) be ₂ R ^8; wherein thienyl provisions of R ²¹ and R ^22, Pirimi Jill, furanyl, thiazolyl , And oxazolyl up to two halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy , hydroxy -C _{1 to 6} alkyl, optionally substituted optionally by 5 fluoro optionally optionally substituted C _{1 to 6} alkyl or a maximum, by up to 5 fluoro C ₁ may be optionally substituted with ₆ alkoxy; said C _{6 or 10} aryl provisions of R ²¹ and R ^22, pyridyl, phenoxy and thiophenoxy is up to three halo, cyano, nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, by up to 5 fluoro Assignment Optionally substituted C _1-6 alkyl, or optionally substituted with up to 5 fluoro, optionally substituted with C _1-6 alkoxy;
Wherein R ¹⁰ and R ¹¹ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{6 or 10} aryl, hydroxy-C _1-6 alkyl , Or C _1-6 alkyl, (CH ₂ ) _n NR ⁶ R ⁷ , or (CH ₂ ) _n C (O) OR ¹⁴ (R ¹⁴ is optionally substituted with up to 5 fluoro , H, C _1-6 alkyl, C _3-7 cycloalkyl or C _4-10 alkyl cycloalkyl), all of which are 1 by halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl. Optionally substituted 3 times; or R ¹⁴ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkylcyclo alkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl or, High at 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro, it is optionally substituted with up to 5 substituents C _{1 to 6} alkoxy which may be optionally substituted with fluoro be a good C _{6 or 10} aryl optionally; said C _{6 or 10} aryl provisions of R ¹² and R ^13, up to three halo, cyano, nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to five may be _{C. 1 to} substituted optionally by fluoro Optionally substituted by ₆ alkyl, or C _1-6 alkoxy optionally substituted by up to 5 fluoro; or R ¹⁰ and R ¹¹ are attached Together with carbon Te cyclopropyl, form a cyclobutyl, cyclopentyl or cyclohexyl; or R ¹⁰ and R ¹¹ are coalesced as O;
Where p = 0 or 1;
Wherein R ¹² and R ¹³ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{6 or 10} aryl, hydroxy-C _1-6 alkyl C _1-6 alkyl, optionally substituted with up to 5 fluoro, (CH ₂ ) _n NR ⁶ R ⁷ , (CH ₂ ) _n C (O) OR ¹⁴ (R ¹⁴ is H _Are C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl), all of which are 1-3 by halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl Optionally substituted once; or R ¹⁴ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, up to 5 fluoro Good C ₆ be optionally substituted with optionally C _{1 to 6} alkoxy substituted optionally which may be C _{1 to 6} alkyl substituted optionally with up by 5 fluoro I _Or C _{6 or 10} aryl as defined for R ¹² and R ¹³ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _{4 10} alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or up, Optionally substituted by 5 fluoro and optionally substituted by C _1-6 alkoxy; or R ¹² and R ¹³ together with the carbon to which they are attached. Cyclopropyl, Forming Robuchiru, cyclopentyl, or cyclohexyl;
Wherein R ²⁰ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{6 or 10} aryl, hydroxy-C _1-6 alkyl, up to 5 fluoro C _1-6 alkyl, optionally substituted by (CH ₂ ) _n NR ⁶ R ⁷ , or (CH ₂ ) _n C (O) OR ¹⁴ (R ¹⁴ is H, C _1-6 alkyl All of which are optionally substituted 1 to 3 times by halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl), C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl) Or R ¹⁴ may be up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _{1 to 6} alkoxy, substituted hydroxy -C _{1 to 6} alkyl, by up to 5 fluoro optionally Which may be C _{1 to 6} alkyl, up to five which may be C _{6 or 10} aryl optionally substituted with optionally C _{1 to 6} alkoxy which may be optionally substituted with fluoro; The C _{6 or 10} aryl as defined for R ¹² and R ¹³ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or by up to 5 fluoro, Optionally substituted by optionally substituted C _1-6 alkoxy;
Where n = 0-4;
In the formula, R ⁶ and R ⁷ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl, and the phenyl has a maximum of 3 Halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, hydroxy-C _1-6 alkyl, up to 5 fluoro Optionally substituted by C _1-6 alkyl, optionally substituted by up to 5 fluoro, optionally substituted by C _1-6 alkoxy, optionally substituted by up to 5 fluoro; or R ⁶ and R ⁷ together with the nitrogen to which they are attached form indolinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl;
Or R ² is R ^2a R ^2b when W = NH, V = O,
R ^2a is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, phenyl, pyridine, pyrazine, pyrimidine, pyridazine, pyrrole, furan, thiophene, thiazole, oxazole, imidazole, isoxazole, Pyrazole, isothiazole, naphthyl, quinoline, isoquinoline, quinoxaline, benzothiazole, benzothiophene, benzofuran, indole, benzimidazole, each up to 3 NR ^2c R ^2d , halo, cyano, nitro, hydroxy, C _{1 6} alkyl, optionally substituted with C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 fluoro C _1-6 alkyl, optionally up to 5 fluoro Optionally substituted by optionally substituted C _1-6 alkoxy;
R ^2b is H, phenyl, pyridine, pyrazine, pyrimidine, pyridazine, pyrrole, furan, thiophene, thiazole, oxazole, imidazole, isoxazole, pyrazole, isothiazole, naphthyl, quinoline, isoquinoline, quinoxaline, benzothiazole, benzothiophene, Benzofuran, indole, or benzimidazole, each up to 3 NR ^2c R ^2d , halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl , C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl or up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro, up to 5 fluoro, the good C _{1 to 6} alkoxy which may be optionally substituted with It may be substituted with meaning selected;
R ^2c and R ^2d are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl, wherein the phenyl is a maximum of 3 halos. , Cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, hydroxy-C _1-6 alkyl, optional up to 5 fluoro Optionally substituted by C _1-6 alkyl optionally substituted, or C _1-6 alkoxy optionally substituted by up to 5 fluoro; or R ^2c And R ^2d together with the nitrogen to which they are attached form indolinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl;
R ⁴ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl, said phenyl being up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, optionally up to 5 fluoro Optionally substituted by C _1-6 alkyl, which may be substituted, or C _1-6 alkoxy, optionally substituted by up to 5 fluoro;
R ⁵ is H, C _1-6 alkyl, C (O) NR ⁶ R ⁷ , C (S) NR ⁶ R ⁷ , C (O) R ⁸ , C (O) OR ⁸ , or S (O) ₂ R ⁸ ;
R ⁸ is C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl, which are all 1- to halo, cyano, nitro, hydroxy, C _1-6 alkoxy or phenyl Optionally substituted three times; or R ⁸ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl , C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, 5 fluoro up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or at the highest, C _{6 or 10} aryl optionally substituted by C _1-6 alkoxy optionally substituted by:
The dashed line represents an optional double bond. ]

[In the above formula,
R ¹ and R ² are each independently H, halo, cyano, hydroxy, C _1-3 alkyl, or C _1-3 alkoxy;
R ⁵ is H, C (O) OR ⁸ , or C (O) NHR ⁸ ;
R ⁸ is C _1-6 alkyl, C _5-6 cycloalkyl, or 3-tetrahydrofuryl;
R ⁹ may be optionally substituted by C _1-3 alkyl, C _3-5 cycloalkyl, or up to 2 halo, cyano, hydroxy, C _1-3 alkyl, or C _1-3 alkoxy Good phenyl ;
W is selected from O or NH;
The dashed line represents an optional double bond. ]

Instead of cyclopentanol to use 2,3-dihydro-1H-isoindole instead in Step 4 of Example 1-2 and form the chloroformate reagent in Step 2 of Example 2-1. According to the procedure described in Examples 1-2 and 2-1, except that 2-fluoroethanol was used, (1S, 4R, 6S, 14S, 18R) -18- (1,3-dihydro-isoindole-2 -Carbonyloxy) -2,15-dioxo-14- ( 2-fluoro-ethoxycarbonylamino ) -3,16-diaza-tricyclo [14.3.0.0 ^4,6 ] nonadeca-7-ene-4-carboxylic acid (compound AR00320076) was synthesized. MS m / e 601.1 (M ⁺⁺ 1).

By following a procedure similar to step 1 of Example 2-1, (1S, 4R, 6S, 14S, 18R) -14- (2-amino-3-methyl-butyrylamino) -18- (3,4-dihydro -1H-isoquinoline-2-carbonyloxy) -2,15-dioxo-3,16-diaza-tricyclo [14.3.0.0 ^4,6 ] nonadeca-7-ene-4-carboxylic acid (compound AR00 298990) was prepared . MS m / e 624.2 (M ⁺⁺ 1).

In the above formula, the core ring is unsubstituted or H, halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _{1- 6} alkoxy, hydroxy -C _{1 to 6} alkyl, C _{1 to 6} alkyl, substituted C _{1 to 6} alkyl, C _{1 to 6} alkoxy, substituted C _{1 to 6} alkoxy, C _{6 or 10} aryl, pyridyl, Pirimi Jill, thienyl , Furanyl, thiazolyl, oxazolyl, phenoxy, thiophenoxy, sulfonamide, urea, thiourea, amide, keto, carboxyl, carbamyl, sulfide, sulfoxide, sulfone, amino, alkoxyamino, alkyloxyheterocycle, alkylamino, alkylcarboxy, Carbonyl, spirocyclic cyclopropyl, spirocyclic cyclobutyl, spirocyclic cyclopentyl, or B cyclic cyclohexyl may be substituted by,
Or Q is R ¹ -R ² and R ¹ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, phenyl, pyridine, pyrazine, pyrimidine, pyridazine, pyrrole, furan , Thiophene, thiazole, oxazole, imidazole, isoxazole, pyrazole, isothiazole, naphthyl, quinoline, isoquinoline, quinoxaline, benzothiazole, benzothiophene, benzofuran, indole, benzimidazole, each with up to 3 NR ⁶ R ⁷ , halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl , up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or, It may be optionally substituted with optionally C _{1 to 6} alkoxy which may be optionally substituted with 5 fluoro at high; R ² is, H, phenyl, pyridine, pyrazine, pyrimidine, pyridazine, pyrrole, Furan, thiophene, thiazole, oxazole, imidazole, isoxazole, pyrazole, isothiazole, naphthyl, quinoline, isoquinoline, quinoxaline, benzothiazole, benzothiophene, benzofuran, indole, benzimidazole, each with up to 3 NR ⁶ R ⁷ , halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 Alkyl, optionally substituted with up to 5 fluoro Optionally substituted by C _1-6 alkyl, or C _1-6 alkoxy optionally substituted by up to 5 fluoro;
R ⁴ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, phenyl, or benzyl, where phenyl or benzyl is a maximum of 3 halo, cyano, nitro Hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, up to 5 fluoro Optionally substituted by C _1-6 alkyl optionally substituted by, or C _1-6 alkoxy optionally substituted by up to 5 fluoro;
R ⁵ is C _1-6 alkyl, C (O) NR ⁶ R ⁷ , C (S) NR ⁶ R ⁷ , C (O) R ⁸ , C (O) OR ⁸ , S (O) ₂ R ⁸ , Or (CO) CHR ²¹ NH (CO) R ²² ;
R ⁶ and R ⁷ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl, wherein the phenyl is a maximum of 3 halo, cyano, optionally nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, hydroxy -C _{1 to 6} alkyl, by up to 5 fluoro in it may be optionally substituted with optionally substituted C _{1 to 6} alkyl optionally or up to 5 substituents C _{1 to 6} alkoxy which may be optionally substituted with fluoro; or R ⁶ and R ⁷ together with the nitrogen to which they are attached forms indolinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl;
R ⁸ is C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl, all of which are 1-3 by halo, cyano, nitro, hydroxy, C _1-6 alkoxy or phenyl. Optionally substituted; or R ⁸ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or by up to 5 fluoro, C _{6 or 10} aryl optionally substituted by optionally substituted C _1-6 alkoxy; or R ⁸ is optionally substituted by up to 5 fluoro groups. Even if Good C _1-6 alkyl; or R ⁸ is a tetrahydrofuran ring attached through the C ₃ or C ₄ position of the tetrahydrofuran ring; or R ⁸ is attached through the C ₄ position of the tetrapyranyl ring A tetrapyranyl ring;
Y is COOR ⁹ and R ⁹ is C _1-6 alkyl;
p = 0 or 1;
V is selected from O, S, or NH;
When V is O or S, W is selected from O, NR ¹⁵ , or CR ¹⁵ ; when V is NH, W is selected from NR ¹⁵ or CR ¹⁵ and R ¹⁵ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or C _1-6 alkyl optionally substituted with up to 5 fluoro;
The dashed line represents an optional double bond;
R ²¹ is C _1-6 alkyl, C _3-7 cycloalkyl or C _4-10 alkyl cycloalkyl, all of which are halo, cyano, nitro, hydroxy, C _1-6 alkoxy, up to 5 fluoro Optionally substituted by C _1-6 alkyl, optionally substituted by phenyl, or optionally substituted 1-3 times by phenyl; or R ²¹ is up to 3 halo, cyano, nitro, hydroxy Optional, by C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, up to 5 fluoro C _1-6 alkyl optionally substituted, _or C _{6 or 10} optionally substituted with C _1-6 alkoxy optionally substituted with up to 5 fluoro. In aryl Ri; or alternatively R ²¹ is pyridyl, Pirimi Jill, pyrazinyl, thienyl, furanyl, thiazolyl, oxazolyl, there phenoxy or thiophenoxy;
R ²² is C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl, all of which are optionally substituted with halo, cyano, nitro, hydroxy, up to 5 fluoro C _1-6 alkyl, which may be substituted, or optionally substituted 1-3 times with phenyl. ].

[In the above formula:
R ⁴ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, phenyl, or benzyl, where phenyl or benzyl is a maximum of 3 halo, cyano, nitro Hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, up to 5 fluoro Optionally substituted by C _1-6 alkyl optionally substituted by, or C _1-6 alkoxy optionally substituted by up to 5 fluoro;
R ⁵ is H, C _1-6 alkyl, C (O) NR ⁶ R ⁷ , C (S) NR ⁶ R ⁷ , C (O) R ⁸ , C (O) OR ⁸ , S (O) ₂ R ⁸ or (CO) CHR ²¹ NH (CO) R ²² ;
R ⁶ and R ⁷ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl, wherein the phenyl is a maximum of 3 halo, cyano, optionally nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, hydroxy -C _{1 to 6} alkyl, by up to 5 fluoro Optionally substituted by C _1-6 alkyl, optionally substituted by up to 5 fluoro, or optionally substituted by C _1-6 alkoxy optionally substituted by up to 5 fluoro; or R ⁶ and R ⁷ together with the nitrogen to which they are attached form indolinyl, pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl;
R ⁸ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are 1-3 by halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl Optionally substituted; or R ⁸ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or by up to 5 fluoro, C _{6 or 10} aryl optionally substituted by optionally substituted C _1-6 alkoxy; or R ⁸ is optionally substituted by up to 5 fluoro groups. C _{1 ~ 6} alkyl; or R ⁸ is a tetrahydrofuran ring bonded through the C ₃ or C ₄ position of the tetrahydrofuran ring; or R ⁸ is bonded through the C ₄ position of the tetrapyranyl ring A tetrapyranyl ring;
Y is COOR ⁹ and R ⁹ is C _1-6 alkyl;
p = 0 or 1;
V is selected from OH, SH, or NH ₂ ;
The dashed line represents an optional double bond;
R ²¹ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are halo, cyano, nitro, hydroxy, C _1-6 alkoxy, up to 5 fluoro Optionally substituted by C _1-6 alkyl, optionally substituted by phenyl, or optionally substituted 1-3 times by phenyl; or R ²¹ is up to 3 halo, cyano, nitro, hydroxy Optional, by C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, up to 5 fluoro C _1-6 alkyl optionally substituted, C _{6 or 10} aryl optionally substituted by C _1-6 alkoxy optionally substituted by up to 5 fluoro Yes; yes Is or R ²¹ is pyridyl, Pirimi Jill, pyrazinyl, thienyl, furanyl, thiazolyl, there oxazolyl, phenoxy, or thiophenoxy;
R ²² is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are optionally substituted by halo, cyano, nitro, hydroxy, up to 5 fluoro C _1-6 alkyl, which may optionally be substituted, or optionally substituted 1 to 3 times by phenyl. ].

Claims (224)

A compound having formula I.

[In the above formula,
Q is a core ring selected from:

In the above formula, the core ring is unsubstituted or H, halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _{1- 6} alkoxy, hydroxy-C _1-6 alkyl, C _1-6 alkyl, substituted C _1-6 alkyl, C _1-6 alkoxy, substituted C _1-6 alkoxy, C _{6 or 10} aryl, pyridyl, pyrimidyl, thienyl, furanyl , Thiazolyl, oxazolyl, phenoxy, thiophenoxy, sulfonamide, urea, thiourea, amide, keto, carboxyl, carbamyl, sulfide, sulfoxide, sulfone, amino, alkoxyamino, alkyloxyheterocycle, alkylamino, alkylcarboxy, carbonyl, Spirocyclic cyclopropyl, spirocyclic cyclobutyl, spirocyclic cyclopentyl, or B cyclic cyclohexyl by may be substituted;
Alternatively, Q is R ¹ -R ² and R ¹ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, phenyl, pyridine, pyrazine, pyrimidine, pyridazine, pyrrole, Furan, thiophene, thiazole, oxazole, imidazole, isoxazole, pyrazole, isothiazole, naphthyl, quinoline, isoquinoline, quinoxaline, benzothiazole, benzothiophene, benzofuran, indole, or benzimidazole, each with up to 3 NR ⁶ R ⁷ , halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _{1- 6} alkyl or up to 5 substituents C _{1 to 6} a be optionally substituted with fluoro, Kill, may be optionally substituted with optionally C _{1 to 6} alkoxy which may be optionally substituted with up to 5 fluoro; R ² is, H, phenyl, pyridine, pyrazine, pyrimidine, pyridazine, Pyrrole, furan, thiophene, thiazole, oxazole, imidazole, isoxazole, pyrazole, isothiazole, naphthyl, quinoline, isoquinoline, quinoxaline, benzothiazole, benzothiophene, benzofuran, indole, or benzimidazole, each up to 3 NR ⁶ R ⁷ , halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, optionally substituted with up to 5 fluoro Optionally substituted by C _1-6 alkyl, optionally substituted by up to 5 fluoro, or optionally substituted by C _1-6 alkoxy;
R ⁴ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, phenyl, or benzyl, where phenyl or benzyl is a maximum of 3 halo, cyano, nitro Hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, up to 5 fluoro Optionally substituted by C _1-6 alkyl optionally substituted by, or C _1-6 alkoxy optionally substituted by up to 5 fluoro;
R ⁵ is H, C _1-6 alkyl, C (O) NR ⁶ R ⁷ , C (S) NR ⁶ R ⁷ , C (O) R ⁸ , C (O) OR ⁸ , S (O) ₂ R ⁸ or (CO) CHR ²¹ NH (CO) R ²² ;
R ⁶ and R ⁷ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl, wherein the phenyl is a maximum of 3 halo, cyano, optionally nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, hydroxy -C _{1 to 6} alkyl, by up to 5 fluoro in it may be optionally substituted with optionally substituted C _{1 to 6} alkyl optionally or up to 5 substituents C _{1 to 6} alkoxy which may be optionally substituted with fluoro; or R ⁶ and R ⁷ together with the nitrogen to which they are attached forms indolinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl;
R ⁸ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are 1-3 by halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl Optionally substituted; or R ⁸ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or by up to 5 fluoro, C _{6 or 10} aryl optionally substituted by optionally substituted C _1-6 alkoxy; or R ⁸ is optionally substituted by up to 5 fluoro groups. May be C _1-6 alkyl; or R ⁸ is a tetrahydrofuran ring bonded through the C ₃ or C ₄ position of the tetrahydrofuran ring; or R ⁸ is bonded through the C ₄ position of the tetrapyranyl ring. Is a tetrapyranyl ring;
Y is a sulfonimide having the formula —C (O) NHS (O) ₂ R ⁹ and R ⁹ is C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl , All of which may be optionally substituted 1-3 times with halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl, or R ⁹ may have up to 3 halo, cyano, nitro , Hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, or up to 5 good C _{1 to 6} alkyl which may be optionally substituted with fluoro, optionally optionally substituted with up to 5 substituents C _{1 to 6} alkoxy which may be optionally substituted with fluoro C _{6 or} be ₁₀ aryl; or R ⁹ is the highest 5 fluoro groups, NR ⁶ R ^7, an NR ^1a R ^1b, or (CO) optionally C _{1 to 6} alkyl which may be optionally substituted with OH,, or R ⁹ is halo, cyano, nitro, Is an aromatic heterocycle optionally substituted up to two times by hydroxyl or C _1-6 alkoxy; or Y is a carboxylic acid, or a pharmaceutically acceptable salt, solvate, or Is a prodrug;
R ^1a and R ^1b are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl, all of which are halo, cyano, nitro, C _1-6 Optionally substituted 1-3 times by alkoxy, amide, or phenyl,
Alternatively, R ^1a and R ^1b are each independently H, and up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _{1 to 6} alkoxy, optionally by 5 fluoro hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or at the highest, C _{6 or 10} aryl optionally substituted by optionally substituted C _1-6 alkoxy,
Alternatively, R ^1a and R ^1b are each independently H, a heterocyclic ring, which includes 1 to 4 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur. Or a 7-membered saturated or unsaturated heterocyclic group,
Alternatively, NR ^1a R ^1b is a 3-6 membered alicyclic secondary amine, which optionally has 1 to 3 heteroatoms incorporated into the ring, and is halo, cyano, nitro, Optionally substituted 1-3 times by C _1-6 alkoxy, amide, or phenyl,
Or NR ^1a R ^1b is a heteroaryl selected from the group consisting of:

Wherein R ^1c is H, halo, C _1-6 alkyl, C _3-6 cycloalkyl, C _1-6 alkoxy, C _3-6 cycloalkoxy, NO ₂ , N (R ^1d ) ₂ , NH ( CO) R ^1d , or NH (CO) NHR ^1d , each R ^1d is independently H, C _1-6 alkyl, or C _3-6 cycloalkyl,
Or R ^1c is NH (CO) OR ^1e and R ^1e is C _1-6 alkyl or C _3-6 cycloalkyl;
p = 0 or 1;
V is selected from O, S, or NH;
When V is O or S, W is selected from O, NR ¹⁵ , or CR ¹⁵ ; when V is NH, W is selected from NR ¹⁵ or CR ¹⁵ and R ¹⁵ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or C _1-6 alkyl optionally substituted with up to 5 fluoro;
The dashed line represents an optional double bond;
R ²¹ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are halo, cyano, nitro, hydroxy, C _1-6 alkoxy, up to 5 fluoro Optionally substituted by C _1-6 alkyl, optionally substituted by phenyl, or optionally substituted 1-3 times by phenyl; or R ²¹ is up to 3 halo, cyano, nitro, hydroxy By, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, or up to 5 fluoro C _1-6 alkyl optionally substituted, C _{6 or 10} optionally substituted with C _1-6 alkoxy optionally substituted with up to 5 fluoro Is aryl; Alternatively, R ²¹ is pyridyl, pyrimidyl, pyrazinyl, thienyl, furanyl, thiazolyl, oxazolyl, phenoxy, or thiophenoxy;
R ²² is C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl, all of which are optionally substituted with halo, cyano, nitro, hydroxy, up to 5 fluoro Optionally substituted _C1-6 alkyl, or optionally substituted 1-3 times by phenyl;
However, the compound of the formula I does not include a compound having the following formula II, III, or IV.

[In the above formula,
(aa) R ¹ and R ² are each independently H, halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl C _1-6 alkoxy, hydroxy-C _1-6 alkyl, or optionally substituted by up to 5 fluoro, optionally substituted by C _1-6 alkyl, up to 5 fluoro C _1-6 alkoxy, C _{6 or 10} aryl, pyridyl, pyrimidyl, thienyl, furanyl, thiazolyl, oxazolyl, phenoxy, thiophenoxy, S (O) ₂ NR ⁶ R ⁷ , NHC (O) NR ⁶ R ⁷ , NHC (S) NR ⁶ R ⁷ , C (O) NR ⁶ R ⁷ , NR ⁶ R ⁷ , C (O) R ⁸ , C (O) OR ⁸ , NHC (O) R ⁸ , NHC (O) OR ⁸ , SO _m R ⁸ , NHS (O) ₂ R ⁸ , CH _n NR ⁶ R ⁷ , OCH _n NR ⁶ R ⁷ , or OCH _n R ⁹ (R ⁹ is imidazolyl or pyrazolyl); R of regulations ¹ and R ² Said thienyl, pyrimidyl, furanyl, thiazolyl, and oxazolyl are of up to two halo, cyano, nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 6} alkenyl, optionally by 5 fluoro C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or at the highest, Optionally substituted by C _1-6 alkoxy, optionally substituted by: and said C _{6 or 10} aryl, pyridyl, phenoxy, and thiophenoxy as defined for R ¹ and R ² are at most 3 number of halo, cyano, nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydro Carboxymethyl -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or up to five which may _{C. 1 to} substituted optionally by fluoro, Optionally substituted by ₆ alkoxy;
(bb) m = 0, 1, or 2;
(cc) R ⁴ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, phenyl, or benzyl, wherein phenyl or benzyl is a maximum of 3 halo, cyano, nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, with up to 5 Optionally substituted by C _1-6 alkyl optionally substituted by ₁ fluoro, or C _1-6 alkoxy optionally substituted by up to 5 fluoro Often;
(dd) R ⁵ is H, C _1-6 alkyl, C (O) NR ⁶ R ⁷ , C (S) NR ⁶ R ⁷ , C (O) R ⁸ , C (O) OR ⁸ , S (O ) ₂ R ⁸ , or (CO) CHR ²¹ NH (CO) R ²² ;
(ee) R ⁶ and R ⁷ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl, and the phenyl is a maximum of 3 Halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, hydroxy-C _1-6 alkyl, or up to 5 Optionally substituted by C _1-6 alkyl, optionally substituted by fluoro, optionally substituted by up to 5 fluoro, optionally substituted by C _1-6 alkoxy; or R ⁶ and R ⁷ together with the nitrogen to which they are attached form indolinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl;
(ff) R ⁸ is C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl, all of which are halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl Optionally substituted 1-3 times by; or R ⁸ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl or up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro, at the highest 5 C _{6 or 10} aryl optionally substituted by C _1-6 alkoxy optionally substituted by ₁ fluoro; or R ⁸ is optionally substituted by up to 5 fluoro groups Replaced by selection Be a good C _{1 to 6} alkyl optionally; or R ⁸ is an tetrahydrofuran ring attached via a C ₃ or C ₄ position of the tetrahydrofuran ring; or R ⁸ is, via the C ₄ position of Tetorapiraniru ring A tetrapyranyl ring bonded together;
(gg) Y is a formula -C (O) NHS (O) sulfonimide is ₂ R ^9, R ⁹ is C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl or C _{4 to 10} alkyl cycloalkyl, Alkyl, all of which may be optionally substituted 1 to 3 times with halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl, or R ⁹ is up to 3 halo, Cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, or at most C _1-6 alkyl optionally substituted with 5 fluoro, optionally substituted with C _1-6 alkoxy optionally substituted with up to 5 fluoro It is a good C _{6 or 10} aryl; or R ⁹ is most In 5 fluoro groups by which may be C _{1 to 6} alkyl optionally substituted, an NR ⁶ R ⁷ or, (CO) OH or R ^9, is selected from halo, cyano, nitro, hydroxyl or C, An aromatic heterocycle optionally substituted up to 2 times by _1-6 alkoxy; or Y is a carboxylic acid, or a pharmaceutically acceptable salt, solvate or prodrug thereof;
(hh) R ¹⁰ and R ¹¹ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{6 or 10} aryl, hydroxy-C _1-6 alkyl C _1-6 alkyl, optionally substituted with up to 5 fluoro, (CH ₂ ) _n NR ⁶ R ⁷ , (CH ₂ ) _n C (O) OR ¹⁴ (R ¹⁴ is H , C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl), which are all 1- to halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl. May be optionally substituted three times; or R ¹⁴ may be up to three halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl , C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, with up to five fluoro Accordingly optionally optionally substituted C _{1 to 6} alkyl or up to 5 substituents be optionally substituted with optionally C _{1 to 6} alkoxy which may be optionally substituted with fluoro C _{6, Or} C _{10 or 10} aryl as defined for R ¹⁰ and R ¹¹ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _{4 10} alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or up, Optionally substituted by 5 fluoro and optionally substituted by C _1-6 alkoxy; or R ¹⁰ and R ¹¹ together with the carbon to which they are attached. Cyclopro Le, cyclobutyl, cyclopentyl or cyclohexyl to form,; or R ¹⁰ and R ¹¹ are coalesced as O;
(ii) p = 0 or 1;
(jj) R ¹² and R ¹³ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{6 or 10} aryl, hydroxy-C _1-6 alkyl C _1-6 alkyl, optionally substituted with up to 5 fluoro, (CH ₂ ) _n NR ⁶ R ⁷ , (CH ₂ ) _n C (O) OR ¹⁴ (R ¹⁴ is H _Are C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl), all of which are 1-3 by halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl Optionally substituted once; or R ¹⁴ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{2 to 6} depending alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, in up to 5 fluoro Optionally substituted with C _{1 to 6} alkyl or up to 5 substituents C _{6 or} be optionally substituted with optionally C _{1 to 6} alkoxy which may be optionally substituted with fluoro, It is ₁₀ aryl; wherein C _{6 or 10} aryl provisions of R ¹² and R ^13, up to three halo, cyano, nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, _{C. 4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or at the highest, Optionally substituted by C _1-6 alkoxy optionally substituted by 5 fluoro; or R ¹² and R ¹³ together with the carbon to which they are attached. Cyclopropyl, Cyclobutyl, cyclopentyl or cyclohexyl to form,; or R ¹² and R ¹³ are each independently, (CH ₂₎ by _n OR ⁸ be a good C _{1 to 6} alkyl substituted optionally;
(kk) R ²⁰ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{6 or 10} aryl, hydroxy-C _1-6 alkyl, up to 5 fluoro C _1-6 alkyl optionally substituted by, or (CH ₂ ) _n NR ⁶ R ⁷ , (CH ₂ ) _n C (O) OR ¹⁴ (R ¹⁴ is H, C _1-6 alkyl All of which are optionally substituted 1 to 3 times by halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl), C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl) Or R ¹⁴ may be up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, optionally substituted with up to 5 fluoro Good C _{1 to 6} alkyl optionally or at the highest, the 5 fluoro be which may be C _{6 or 10} aryl optionally substituted with optionally C _{1 to 6} alkoxy substituted optionally; The C _{6 or 10} aryl as defined for R ¹² and R ¹³ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl or up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro, by up to 5 fluoro Optionally substituted by optionally substituted C _1-6 alkoxy;
(ll) n = 1-4;
(mm) V is selected from O, S, or NH;
(nn) when V is O or S, W is selected from O, NR ¹⁵ , or CR ¹⁵ ; when V is NH, W is selected from NR ¹⁵ or CR ¹⁵ and R ¹⁵ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or C _1-6 alkyl optionally substituted with up to 5 fluoro;
(oo) dashed line represents an optional double bond;
(pp) R ²¹ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are halo, cyano, nitro, hydroxy, C _1-6 alkoxy, up to 5 C _1-6 alkyl optionally substituted by ₁ fluoro, or optionally substituted 1-3 times by phenyl; or R ²¹ is a maximum of 3 halo, cyano, nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to five C _1-6 alkyl optionally substituted with fluoro, or C _1-6 alkoxy optionally substituted with up to 5 fluoro, optionally substituted with C _1-6 alkoxy _{6 or 10} aryl Or R ²¹ is pyridyl, pyrimidyl, pyrazinyl, thienyl, furanyl, thiazolyl, oxazolyl, phenoxy, or thiophenoxy;
(qq) R ²² is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are optionally selected by halo, cyano, nitro, hydroxy, up to 5 fluoro Optionally substituted with 1 to 3 times C _1-6 alkyl, optionally substituted with phenyl. ]] The compound of claim 1, wherein the core ring is of the formula:

The compound of claim 1, wherein the core ring is of the formula:

The compound of claim 1, wherein the core ring is of the formula:

2. A compound according to claim 1 which is formula Ia.

2. A compound according to claim 1 of formula Ib.

2. A compound according to claim 1 of formula Ic.

2. A compound according to claim 1 of formula Id.

2. A compound according to claim 1 of formula Ie.

The compound of claim 1, which is of formula If.

2. A compound according to claim 1 which is of formula Ig.

2. A compound according to claim 1 of formula Ih.

2. A compound according to claim 1 of formula Ii.

2. A compound according to claim 1 of formula Ij.

2. A compound according to claim 1 of formula Iz.

Y is a sulfonimide having the formula —C (O) NHS (O) ₂ R ⁹ , where R ⁹ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, and NR ^2. The compound of claim 1, selected from the group consisting of ^1a R ^1b , wherein R ^1a and R ^1b are each independently H, C _1-6 alkyl, or C _3-7 cycloalkyl. Y is a sulfonimide having the formula —C (O) NHS (O) ₂ R ⁹ , where R ⁹ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, and NR 3. The compound of claim 2, selected from the group consisting of ^1a R ^1b , wherein R ^1a and R ^1b are each independently H, C _1-6 alkyl, or C _3-7 cycloalkyl. Y is a sulfonimide having the formula —C (O) NHS (O) ₂ R ⁹ , where R ⁹ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, and NR is selected from the group consisting of ^1a R ^1b, R ^1a and R ^1b are each independently, H, a C _{1 to 6} alkyl or C _{3 to 7} cycloalkyl, a compound according to claim 3. Y is a sulfonimide having the formula —C (O) NHS (O) ₂ R ⁹ , where R ⁹ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, and NR ^5. The compound of claim 4, selected from the group consisting of ^1a R ^1b , wherein R ^1a and R ^1b are each independently H, C _1-6 alkyl, or C _3-7 cycloalkyl. 2. The compound of claim 1, wherein the C13-C14 double bond is cis. The compound according to claim 1, wherein the C13-C14 double bond is trans. a) the compound of claim 1;
b) to treat hepatitis C virus infection in an individual, to treat hepatic fibrosis in an individual, or to enhance liver function in an individual having hepatitis C virus infection, comprising a pharmaceutically acceptable carrier. Pharmaceutical composition. 23. A pharmaceutical composition according to claim 22 in a formulation free of any alcohol and any poly-ol. 24. A pharmaceutical composition according to claim 23, wherein the formulation does not comprise any sugar alcohol and any poly (ethylene glycol) (PEG). 23. A pharmaceutical composition according to claim 22 in an aqueous formulation that does not include any excipients that reduce polarity in the aqueous formulation. 23. A pharmaceutical composition according to claim 22 in a tablet formulation. 23. A pharmaceutical composition according to claim 22 in a caplet formulation. 23. A pharmaceutical composition according to claim 22 in a capsule formulation. a) the compound of claim 1;
b) A pharmaceutical composition for treating hepatitis C virus infection in an individual, comprising a pharmaceutically acceptable carrier. 30. A pharmaceutical composition according to claim 29 for realizing a sustained viral response. 30. A pharmaceutical composition according to claim 29 for treating hepatitis C virus infection in an individual in combination with an effective amount of a nucleoside analog. 32. The pharmaceutical composition according to claim 31, wherein the nucleoside analogue is selected from ribavirin, levovirin, viramidine, L-nucleoside, and isatribin. 30. The pharmaceutical composition of claim 29 for treating hepatitis C virus infection in an individual in combination with an effective amount of an NS5B RNA dependent RNA polymerase inhibitor. 30. A pharmaceutical composition according to claim 29 for treating hepatitis C virus infection in an individual in combination with an effective amount of thymosin- [alpha]. 35. The pharmaceutical composition of claim 34, wherein thymosin-α in an amount of about 1.0 mg to about 1.6 mg is administered subcutaneously twice a week. 30. The pharmaceutical composition of claim 29 for treating hepatitis C virus infection in an individual in combination with an effective amount of interferon-γ (IFN-γ). 37. The pharmaceutical composition of claim 36, wherein an amount of about 10 [mu] g to about 300 [mu] g of IFN- [gamma] is administered subcutaneously. 30. The pharmaceutical composition according to claim 29 for treating hepatitis C virus infection in an individual in combination with an effective amount of interferon-α (IFN-α). 39. The pharmaceutical composition according to claim 38, wherein the IFN- [alpha] is mono-PEG (30 kD, linear) consensus IFN- [alpha] and is administered at an administration interval of every 8 to 14 days. 39. The pharmaceutical composition according to claim 38, wherein IFN- [alpha] is monoPEG (30 kD, linear) consensus IFN- [alpha] and is administered at an administration interval of once every 7 days. 39. The pharmaceutical composition according to claim 38, wherein IFN- [alpha] is INFERGEN consensus IFN- [alpha]. 3'-azidothymidine, 2 ', 3'-dideoxyinosine, 2', 3'-dideoxycytidine, 2-, 3-didehydro-2 ', 3'-dideoxythymidine, combivir, abacavir, adefovir dipoxyl, cidofovir, 30. A pharmaceutical composition according to claim 29 for treating hepatitis C virus infection in an individual in combination with an effective amount of a drug selected from and an inosine monophosphate dehydrogenase inhibitor. a) the compound of claim 1;
b) A pharmaceutical composition for treating liver fibrosis in an individual, comprising a pharmaceutically acceptable carrier. 44. A pharmaceutical composition according to claim 43 for treating liver fibrosis in an individual in combination with an effective amount of a nucleoside analog. 45. The pharmaceutical composition of claim 44, wherein the nucleoside analog is selected from ribavirin, levovirin, viramidine, L-nucleoside, and isatoribine. 44. A pharmaceutical composition according to claim 43 for treating liver fibrosis in an individual in combination with an effective amount of an NS5B RNA dependent RNA polymerase inhibitor. 44. A pharmaceutical composition according to claim 43 for treating liver fibrosis in an individual in combination with an effective amount of thymosin-α. 48. The pharmaceutical composition of claim 47, wherein thymosin-α in an amount of about 1.0 mg to about 1.6 mg is administered subcutaneously twice a week. 44. The pharmaceutical composition of claim 43, for treating liver fibrosis in an individual in combination with an effective amount of interferon-γ (IFN-γ). 50. The pharmaceutical composition of claim 49, wherein IFN- [gamma] is administered subcutaneously in an amount of about 10 [mu] g to about 300 [mu] g. 44. The pharmaceutical composition of claim 43, for treating liver fibrosis in an individual in combination with an effective amount of interferon-α (IFN-α). 52. The pharmaceutical composition of claim 51, wherein IFN- [alpha] is monoPEG (30 kD, linear) consensus IFN- [alpha] and is administered at an administration interval of every 8-14 days. 52. The pharmaceutical composition of claim 51, wherein IFN- [alpha] is monoPEG (30 kD, linear) consensus IFN- [alpha] and is administered at an administration interval of once every 7 days. 52. The pharmaceutical composition according to claim 51, wherein the IFN-α is INFERGEN consensus IFN-α. 3'-azidothymidine, 2 ', 3'-dideoxyinosine, 2', 3'-dideoxycytidine, 2-, 3-didehydro-2 ', 3'-dideoxythymidine, combivir, abacavir, adefovir dipoxyl, cidofovir, 44. A pharmaceutical composition according to claim 43 for treating liver fibrosis in an individual in combination with an effective amount of a drug selected from and an inosine monophosphate dehydrogenase inhibitor. a) the compound of claim 1;
b) A pharmaceutical composition for enhancing liver function in an individual having hepatitis C virus infection, comprising a pharmaceutically acceptable carrier. 57. The pharmaceutical composition of claim 56 for enhancing liver function in an individual having hepatitis C virus infection in combination with an effective amount of a nucleoside analog. 58. The pharmaceutical composition of claim 57, wherein the nucleoside analog is selected from ribavirin, levovirin, viramidine, L-nucleoside, and isatoribine. 57. The pharmaceutical composition of claim 56 for enhancing liver function in an individual having hepatitis C virus infection in combination with an effective amount of an NS5B RNA dependent RNA polymerase inhibitor. 57. A pharmaceutical composition according to claim 56 for enhancing liver function in an individual having hepatitis C virus infection in combination with an effective amount of thymosin- [alpha]. 61. The pharmaceutical composition of claim 60, wherein thymosin- [alpha] is administered subcutaneously twice a week in an amount of about 1.0 mg to about 1.6 mg. 57. A pharmaceutical composition according to claim 56 for enhancing liver function in an individual having hepatitis C virus infection in combination with an effective amount of interferon-γ (IFN-γ). 64. The pharmaceutical composition of claim 62, wherein an amount of about 10 [mu] g to about 300 [mu] g of IFN- [gamma] is administered subcutaneously. 57. The pharmaceutical composition according to claim 56 for enhancing liver function in an individual having hepatitis C virus infection in combination with an effective amount of interferon-α (IFN-α). 65. The pharmaceutical composition of claim 64, wherein IFN- [alpha] is monoPEG (30 kD, linear) consensus IFN- [alpha] and is administered at an administration interval of every 8-14 days. 65. The pharmaceutical composition of claim 64, wherein IFN- [alpha] is monoPEG (30 kD, linear) consensus IFN- [alpha] and is administered at an administration interval of once every 7 days. 65. The pharmaceutical composition of claim 64, wherein the IFN-α is INFERGEN consensus IFN-α. 3'-azidothymidine, 2 ', 3'-dideoxyinosine, 2', 3'-dideoxycytidine, 2-, 3-didehydro-2 ', 3'-dideoxythymidine, combivir, abacavir, adefovir dipoxyl, cidofovir and 57. A pharmaceutical composition according to claim 56 for enhancing liver function in an individual having hepatitis C virus infection in combination with an effective amount of a drug selected from an inosine monophosphate dehydrogenase inhibitor. Compound having formula XI

[In the above formula,
(a) R ^1a and R ^1b are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl, all of which are halo, cyano, nitro, C Optionally substituted 1 to 3 times by 1 to ₆ alkoxy, amide, or phenyl;
Alternatively, R ^1a and R ^1b are each independently H, and up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _{1 to 6} alkoxy, optionally by 5 fluoro hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or at the highest, C _{6 or 10} aryl optionally substituted by optionally substituted C _1-6 alkoxy;
Alternatively, R ^1a and R ^1b are each independently H or a heterocycle, the heterocycle containing 1 to 4 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur Or a 7-membered, saturated or unsaturated heterocyclic group;
Alternatively, NR ^1a R ^1b is a 3-6 membered alicyclic secondary amine, which optionally has 1 to 3 heteroatoms incorporated into the ring, and is halo, cyano, nitro, Optionally substituted 1-3 times by C _1-6 alkoxy, amide, or phenyl;
Or NR ^1a R ^1b is a heteroaryl selected from the group consisting of:

Wherein R ^1c is H, halo, C _1-6 alkyl, C _3-6 cycloalkyl, C _1-6 alkoxy, C _3-6 cycloalkoxy, NO ₂ , N (R ^1d ) ₂ , NH ( CO) R ^1d , or NH (CO) NHR ^1d , each R ^1d is independently H, C _1-6 alkyl, or C _3-6 cycloalkyl;
Or R ^1c is NH (CO) OR ^1e and R ^1e is C _1-6 alkyl or C _3-6 cycloalkyl;
(b) W is O or NH;
(c) V is selected from O, S, or NH;
(d) when V is O or S, W is selected from O, NR ¹⁵ , or CR ¹⁵ ; when V is NH, W is selected from NR ¹⁵ or CR ¹⁵ and R ¹⁵ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or C _1-6 alkyl optionally substituted with up to 5 fluoro;
(e) R ² is a bicyclic secondary amine having the structure:

In the above formula, R ²¹ and R ²² are each independently H, halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6. Alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, optionally substituted by up to 5 fluoro, optionally substituted by C _1-6 alkyl, up to 5 fluoro C _1-6 alkoxy, C _{6 or 10} aryl, pyridyl, pyrimidyl, thienyl, furanyl, thiazolyl, oxazolyl, phenoxy, thiophenoxy, S (O) ₂ NR ⁶ R ⁷ , NHC (O) NR ⁶ R ⁷ , NHC (S) NR ⁶ R ⁷ , C (O) NR ⁶ R ⁷ , NR ⁶ R ⁷ , C (O) R ⁸ , C (O) OR ⁸ , NHC (O) R ⁸ , NHC (O) OR ⁸ , SO _m R ⁸ (m = 0, 1, or 2), or NHS (O) ₂ R ⁸ ; the thienyl, pyrimidyl, furanyl, thiazolyl, and R ²¹ and R ²² as defined above Fine oxazolyl is up to two halo, cyano, nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or up to five which may _{C. 1 to} substituted optionally by fluoro, Optionally substituted by ₆ alkoxy; said C _{6 or 10} aryl, pyridyl, phenoxy and thiophenoxy as defined for R ²¹ and R ²² is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, optionally up to 5 fluoro Optionally substituted by C _1-6 alkyl, which may be substituted, or C _1-6 alkoxy, optionally substituted by up to 5 fluoro;
Wherein R ¹⁰ and R ¹¹ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{6 or 10} aryl, hydroxy-C _1-6 alkyl , C _1-6 alkyl, (CH ₂ ) _n NR ⁶ R ⁷ , or (CH ₂ ) _n C (O) OR ¹⁴ (R ¹⁴ is optionally substituted with up to 5 fluoro H, C _1-6 alkyl, C _3-7 cycloalkyl or C _4-10 alkyl cycloalkyl), which are all 1- to halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl. May be optionally substituted three times; or R ¹⁴ may be up to three halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl , C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, up to 5 C _1-6 alkyl optionally substituted by Luoro, C ₆ optionally substituted by C _1-6 alkoxy optionally substituted by up to 5 fluoro C _{6 Or} C _{6 or 10} aryl as defined for R ¹² and R ¹³ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _{4 10} alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or up, Optionally substituted by 5 fluoro and optionally substituted by C _1-6 alkoxy; or R ¹⁰ and R ¹¹ together with the carbon to which they are attached. Cyclop Pills, cyclobutyl, cyclopentyl or cyclohexyl to form,; or R ¹⁰ and R ¹¹ are coalesced as O;
Where p = 0 or 1;
Wherein R ¹² and R ¹³ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{6 or 10} aryl, hydroxy-C _1-6 alkyl C _1-6 alkyl, optionally substituted with up to 5 fluoro, (CH ₂ ) _n NR ⁶ R ⁷ , (CH ₂ ) _n C (O) OR ¹⁴ (R ¹⁴ is H , C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl), which are all 1- to halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl. May be optionally substituted three times; or R ¹⁴ may be up to three halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl , C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, up to 5 fluors C _1-6 alkyl optionally substituted by b, optionally substituted by C _1-6 alkoxy optionally substituted by up to 5 fluoro C _{6 Or} C _{6 or 10} aryl as defined for R ¹² and R ¹³ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _{4 10} alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or up, Optionally substituted by 5 fluoro and optionally substituted by C _1-6 alkoxy; or R ¹² and R ¹³ together with the carbon to which they are attached. Cyclopropi To form cyclobutyl, cyclopentyl, or cyclohexyl;
Wherein R ²⁰ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{6 or 10} aryl, hydroxy-C _1-6 alkyl, up to 5 fluoro C _1-6 alkyl, optionally substituted by (CH ₂ ) _n NR ⁶ R ⁷ , or (CH ₂ ) _n C (O) OR ¹⁴ (R ¹⁴ is H, C _1-6 alkyl All of which are optionally substituted 1 to 3 times by halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl), C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl) Or R ¹⁴ may be up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl. , optionally by 5 fluoro C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, with the highest Optionally substituted C _{1 to 6} alkyl or up to 5 amino which may be C _{6 or 10} aryl optionally substituted with optionally C _{1 to 6} alkoxy which may be optionally substituted with fluoro, Yes; said C _{6 or 10} aryl as defined for R ¹² and R ¹³ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkylcyclo alkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or up to five, Optionally substituted by C _1-6 alkoxy optionally substituted by fluoro;
Where n = 0-4;
In the formula, R ⁶ and R ⁷ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl, and the phenyl has a maximum of 3 Halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, hydroxy-C _1-6 alkyl, up to 5 fluoro Optionally substituted by C _1-6 alkyl, optionally substituted by, or C _1-6 alkoxy, optionally substituted by up to 5 fluoro; or R ⁶ and R ⁷ together with the nitrogen to which they are attached form indolinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl;
Or R ² is R ^2a R ^2b when W = NH, V = O,
R ^2a is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, phenyl, pyridine, pyrazine, pyrimidine, pyridazine, pyrrole, furan, thiophene, thiazole, oxazole, imidazole, isoxazole, Pyrazole, isothiazole, naphthyl, quinoline, isoquinoline, quinoxaline, benzothiazole, benzothiophene, benzofuran, indole, or benzimidazole, each up to 3 NR ^2c R ^2d , halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, optionally up to 5 fluoro Optionally substituted C _1-6 alkyl, or up to 5 fluoro Optionally substituted by C _1-6 alkoxy optionally substituted by;
R ^2b is H, phenyl, pyridine, pyrazine, pyrimidine, pyridazine, pyrrole, furan, thiophene, thiazole, oxazole, imidazole, isoxazole, pyrazole, isothiazole, naphthyl, quinoline, isoquinoline, quinoxaline, benzothiazole, benzothiophene, Benzofuran, indole, or benzimidazole, each up to 3 NR ^2c R ^2d , halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl , C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, 5 fluoro up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or at the highest, the good C _{1 to 6} alkoxy which may be optionally substituted with It may be substituted with meaning selected;
R ^2c and R ^2d are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl, wherein the phenyl is a maximum of 3 halos. , Cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, hydroxy-C _1-6 alkyl, optional up to 5 fluoro Optionally substituted by C _1-6 alkyl optionally substituted, or C _1-6 alkoxy optionally substituted by up to 5 fluoro; or R ^2c And R ^2d together with the nitrogen to which they are attached form indolinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl;
(f) R ⁴ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl, said phenyl being up to 3 halo, cyano, nitro, By hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, up to 5 fluoro Optionally substituted C _1-6 alkyl, or optionally substituted by up to 5 fluoro, optionally substituted by C _1-6 alkoxy;
(g) R ⁵ is H, C _1-6 alkyl, C (O) NR ⁶ R ⁷ , C (S) NR ⁶ R ⁷ , C (O) R ⁸ , C (O) OR ⁸ , or S ( O) ₂ R ⁸ ;
(h) R ⁸ is C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl, all of which are halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl Optionally substituted 1-3 times by; or R ⁸ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or at the highest, 5 C _{6 or 10} aryl optionally substituted by C _1-6 alkoxy optionally substituted by ₁ fluoro;
(i) The dashed line represents an optional double bond. ]. 70. The compound of claim 69 having the formula XII.

[In the above formula,
(a) R ^1a and R ^1b are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl, all of which are halo, cyano, nitro, C Optionally substituted 1 to 3 times by 1 to ₆ alkoxy, amide, or phenyl;
Or R ^1a and R ^1b are each independently H or heteroaryl selected from the group consisting of:

Wherein R ^1c is H, halo, C _1-6 alkyl, C _3-6 cycloalkyl, C _1-6 alkoxy, C _3-6 cycloalkoxy, NO ₂ , N (R ^1d ) ₂ , NH ( CO) R ^1d , or NH (CO) NHR ^1d , each R ^1d is independently H, C _1-6 alkyl, or C _3-6 cycloalkyl;
Alternatively, NR ^1a R ^1b is a 3-6 membered alicyclic secondary amine, which optionally has 1 to 3 heteroatoms incorporated into the ring, and is halo, cyano, nitro, Optionally substituted 1-3 times by C _1-6 alkoxy, amide, or phenyl;
(b) R ²¹ and R ²² are each independently H, halo, cyano, hydroxy, C _1-3 alkyl, or C _1-3 alkoxy;
(c) R ⁵ is H, C (O) NR ⁶ R ⁷ , C (O) R ⁸ , or C (O) OR ⁸ ;
(d) R ⁶ and R ⁷ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl;
(e) R ⁸ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or 3-tetrahydrofuryl;
(f) R ¹⁰ and R ¹¹ are each independently H, halo, C _1-3 alkyl, or R ¹⁰ and R ¹¹ together with the carbon to which they are attached are cyclopropyl, cyclobutyl , Cyclopentyl, or cyclohexyl;
(g) R ¹² and R ¹³ are each independently H, halo, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{6 or 10} aryl, hydroxy-C _{1- 6} alkyl, or C _1-6 alkyl optionally substituted with up to 5 halogen atoms;
(h) The dashed line represents an optional double bond. ] 70. The compound of claim 69 having the formula XIII.

[In the above formula,
(a) R ^1a and R ^1b are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl, all of which are halo, cyano, nitro, C Optionally substituted 1 to 3 times by 1 to ₆ alkoxy, amide, or phenyl;
Or R ^1a and R ^1b are each independently H or heteroaryl selected from the group consisting of:

Wherein R ^1c is H, halo, C _1-6 alkyl, C _3-6 cycloalkyl, C _1-6 alkoxy, C _3-6 cycloalkoxy, NO ₂ , N (R ^1d ) ₂ , NH ( CO) R ^1d , or NH (CO) NHR ^1d , each R ^1d is independently H, C _1-6 alkyl, or C _3-6 cycloalkyl;
Alternatively, NR ^1a R ^1b is a 3-6 membered alicyclic secondary amine, which optionally has 1 to 3 heteroatoms incorporated into the ring, and is halo, cyano, nitro, Optionally substituted 1-3 times by C _1-6 alkoxy, amide, or phenyl;
(b) R ²¹ and R ²² are each independently H, halo, cyano, hydroxy, C _1-3 alkyl, or C _1-3 alkoxy;
(c) R ⁵ is H, C (O) NR ⁶ R ⁷ , C (O) R ⁸ , or C (O) OR ⁸ ;
(d) R ⁶ and R ⁷ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl;
(e) R ⁸ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or 3-tetrahydrofuryl;
(f) The dashed line represents an optional double bond. ]. 70. The compound of claim 69, having the formula XIV.

[In the above formula,
(a) R ^1a and R ^1b are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl, all of which are halo, cyano, nitro, C ₁ Optionally substituted 1-3 times by alkoxy- ₆ , amide, or phenyl;
Or R ^1a and R ^1b are each independently H or heteroaryl selected from the group consisting of:

Wherein R ^1c is H, halo, C _1-6 alkyl, C _3-6 cycloalkyl, C _1-6 alkoxy, C _3-6 cycloalkoxy, NO ₂ , N (R ^1d ) ₂ , NH ( CO) R ^1d , or NH (CO) NHR ^1d , each R ^1d is independently H, C _1-6 alkyl, or C _3-6 cycloalkyl;
Alternatively, NR ^1a R ^1b is a 3-6 membered alicyclic secondary amine, which optionally has 1 to 3 heteroatoms incorporated into the ring, and is halo, cyano, nitro, Optionally substituted 1-3 times by C _1-6 alkoxy, amide, or phenyl;
(b) R ^2a is up to 3 NR ^2c R ^2d , halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl or up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro, optionally by up to 5 fluoro, substituted C _{6 or 10} aryl optionally substituted by optionally substituted C _1-6 alkoxy;
R ^2c and R ^2d are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl, wherein the phenyl is a maximum of 3 halos. , Cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, hydroxy-C _1-6 alkyl, optional up to 5 fluoro Optionally substituted by C _1-6 alkyl, optionally substituted by up to 5 fluoro, optionally substituted by C _1-6 alkoxy; or R ^2c and R ^2d together with the nitrogen to which they are attached forms indolinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl;
Or R ^2a is a 5- or 6-membered unsaturated heteroaryl, or such defined heteroaryl fused to another ring, which may be a heterocycle or any other ring;
(c) R ⁵ is H, C (O) NR ⁶ R ⁷ , C (O) R ⁸ , or C (O) OR ⁸ ;
(d) R ⁶ and R ⁷ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl;
(e) R ⁸ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or 3-tetrahydrofuryl;
(f) The dashed line represents an optional double bond. ]. a) the compound of claim 69;
b) to treat hepatitis C virus infection in an individual, to treat hepatic fibrosis in an individual, or to enhance liver function in an individual having hepatitis C virus infection, comprising a pharmaceutically acceptable carrier. Pharmaceutical composition. 74. A pharmaceutical composition according to claim 73 in a formulation that does not contain any alcohol and any poly-ol. 75. The pharmaceutical composition of claim 74 , wherein the formulation does not comprise any sugar alcohol and any poly (ethylene glycol) (PEG). 74. The pharmaceutical composition of claim 73 , in an aqueous formulation that does not include any excipients that reduce polarity in the aqueous formulation. 74. A pharmaceutical composition according to claim 73 in a tablet formulation. 74. A pharmaceutical composition according to claim 73 in a caplet formulation. 74. A pharmaceutical composition according to claim 73 in a capsule formulation. a) the compound of claim 69;
b) A pharmaceutical composition for treating hepatitis C virus infection in an individual, comprising a pharmaceutically acceptable carrier. 81. A pharmaceutical composition according to claim 80 for realizing a sustained viral response. 81. A pharmaceutical composition according to claim 80 for treating hepatitis C virus infection in an individual in combination with an effective amount of a nucleoside analog. 83. The pharmaceutical composition of claim 82 , wherein the nucleoside analog is selected from ribavirin, levovirin, viramidine, L-nucleoside, and isatoribine. 81. The pharmaceutical composition of claim 80 for treating hepatitis C virus infection in an individual in combination with an effective amount of an NS5B RNA dependent RNA polymerase inhibitor. 81. A pharmaceutical composition according to claim 80 for treating hepatitis C virus infection in an individual in combination with an effective amount of thymosin- [alpha]. 86. The pharmaceutical composition of claim 85 , wherein thymosin- [alpha] is administered subcutaneously twice a week in an amount of about 1.0 mg to about 1.6 mg. 81. A pharmaceutical composition according to claim 80 for treating hepatitis C virus infection in an individual in combination with an effective amount of interferon-y (IFN-y). 90. The pharmaceutical composition of claim 87 , wherein IFN- [gamma] is administered subcutaneously in an amount of about 10 [mu] g to about 300 [mu] g. 81. The pharmaceutical composition of claim 80 for treating hepatitis C virus infection in an individual in combination with an effective amount of interferon-α (IFN-α). 90. The pharmaceutical composition of claim 89 , wherein the IFN- [alpha] is monoPEG (30 kD, linear) consensus IFN- [alpha] and is administered at an administration interval of every 8-14 days. 90. The pharmaceutical composition of claim 89 , wherein the IFN- [alpha] is monoPEG (30 kD, linear) consensus IFN- [alpha] and is administered at an administration interval of once every 7 days. 90. The pharmaceutical composition of claim 89 , wherein the IFN- [alpha] is INFERGEN consensus IFN- [alpha]. 3'-azidothymidine, 2 ', 3'-dideoxyinosine, 2', 3'-dideoxycytidine, 2-, 3-didehydro-2 ', 3'-dideoxythymidine, combivir, abacavir, adefovir dipoxyl, cidofovir, 81. A pharmaceutical composition according to claim 80 for treating hepatitis C virus infection in an individual in combination with an effective amount of a drug selected from and an inosine monophosphate dehydrogenase inhibitor. a) the compound of claim 69;
b) A pharmaceutical composition for treating liver fibrosis in an individual, comprising a pharmaceutically acceptable carrier. 95. The pharmaceutical composition of claim 94 for treating liver fibrosis in an individual in combination with an effective amount of a nucleoside analog. 96. The pharmaceutical composition of claim 95 , wherein the nucleoside analog is selected from ribavirin, levovirin, viramidine, L-nucleoside, and isatoribine. 95. The pharmaceutical composition of claim 94 for treating liver fibrosis in an individual in combination with an effective amount of an NS5B RNA dependent RNA polymerase inhibitor. 95. The pharmaceutical composition of claim 94 for treating liver fibrosis in an individual in combination with an effective amount of thymosin- [alpha]. 99. The pharmaceutical composition of claim 98 , wherein thymosin-α in an amount of about 1.0 mg to about 1.6 mg is administered subcutaneously twice a week. 95. The pharmaceutical composition of claim 94 for treating liver fibrosis in an individual in combination with an effective amount of interferon-γ (IFN-γ). 101. The pharmaceutical composition of claim 100 , wherein IFN- [gamma] is administered subcutaneously in an amount of about 10 [mu] g to about 300 [mu] g. 95. The pharmaceutical composition of claim 94 for treating liver fibrosis in an individual in combination with an effective amount of interferon- [alpha] (IFN- [alpha]). 103. The pharmaceutical composition of claim 102 , wherein IFN- [alpha] is monoPEG (30 kD, linear) consensus IFN- [alpha] and is administered at an administration interval of every 8-14 days. 103. The pharmaceutical composition according to claim 102 , wherein the IFN- [alpha] is monoPEG (30 kD, linear) consensus IFN- [alpha] and is administered at an administration interval of once every 7 days. 103. The pharmaceutical composition of claim 102 , wherein IFN- [alpha] is INFERGEN consensus IFN- [alpha]. 3'-azidothymidine, 2 ', 3'-dideoxyinosine, 2', 3'-dideoxycytidine, 2-, 3-didehydro-2 ', 3'-dideoxythymidine, combivir, abacavir, adefovir dipoxyl, cidofovir, 95. A pharmaceutical composition according to claim 94 for treating liver fibrosis in an individual in combination with an effective amount of a drug selected from and an inosine monophosphate dehydrogenase inhibitor. a) the compound of claim 69;
b) A pharmaceutical composition for enhancing liver function in an individual having hepatitis C virus infection, comprising a pharmaceutically acceptable carrier. 108. The pharmaceutical composition of claim 107 for enhancing liver function in an individual having hepatitis C virus infection in combination with an effective amount of a nucleoside analog. 109. The pharmaceutical composition of claim 108 , wherein the nucleoside analog is selected from ribavirin, levovirin, viramidine, L-nucleoside, and isatoribine. 108. The pharmaceutical composition of claim 107 for enhancing liver function in an individual having hepatitis C virus infection in combination with an effective amount of an NS5B RNA-dependent RNA polymerase inhibitor. 108. The pharmaceutical composition according to claim 107 for enhancing liver function in an individual having hepatitis C virus infection in combination with an effective amount of thymosin- [alpha]. 112. The pharmaceutical composition of claim 111 , wherein thymosin- [alpha] is administered subcutaneously twice a week in an amount of about 1.0 mg to about 1.6 mg. 108. The pharmaceutical composition of claim 107 for enhancing liver function in an individual having hepatitis C virus infection in combination with an effective amount of interferon-γ (IFN-γ). 114. The pharmaceutical composition of claim 113 , wherein IFN- [gamma] is administered subcutaneously in an amount of about 10 [mu] g to about 300 [mu] g. 108. The pharmaceutical composition of claim 107 , for enhancing liver function in an individual having hepatitis C virus infection in combination with an effective amount of interferon-α (IFN-α). 116. The pharmaceutical composition of claim 115 , wherein the IFN- [alpha] is monoPEG (30 kD, linear) consensus IFN- [alpha] and is administered at an administration interval of every 8-14 days. 116. The pharmaceutical composition of claim 115 , wherein IFN-α is monoPEG (30 kD, linear) consensus IFN-α and is administered at an administration interval of once every 7 days. 116. The pharmaceutical composition of claim 115 , wherein IFN-α is INFERGEN consensus IFN-α. 3'-azidothymidine, 2 ', 3'-dideoxyinosine, 2', 3'-dideoxycytidine, 2-, 3-didehydro-2 ', 3'-dideoxythymidine, combivir, abacavir, adefovir dipoxyl, cidofovir and 108. The pharmaceutical composition of claim 107 for enhancing liver function in an individual having hepatitis C virus infection in combination with an effective amount of a drug selected from an inosine monophosphate dehydrogenase inhibitor. Compound having formula XVIII

[In the above formula,
(a) R ¹ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, phenyl, pyridine, pyrazine, pyrimidine, pyridazine, pyrrole, furan, thiophene, thiazole, oxazole, imidazole, Isoxazole, pyrazole, isothiazole, naphthyl, quinoline, isoquinoline, quinoxaline, benzothiazole, benzothiophene, benzofuran, indole, or benzimidazole, each up to 3 NR ⁵ R ⁶ , halo, cyano, nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, by up to 5 fluoro Optionally substituted C _1-6 alkyl, or up to 5 fluoro Optionally substituted by C _1-6 alkoxy optionally substituted by;
(b) R ² is H, phenyl, pyridine, pyrazine, pyrimidine, pyridazine, pyrrole, furan, thiophene, thiazole, oxazole, imidazole, isoxazole, pyrazole, isothiazole, naphthyl, quinoline, isoquinoline, quinoxaline, benzothiazole, Benzothiophene, benzofuran, indole, or benzimidazole, each up to 3 NR ⁵ R ⁶ , halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or at the highest, 5 the good C _{1 to 6} alkoxy which may be optionally substituted with number of fluoro It may be substituted with meaning selected;
(c) R ³ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl, said phenyl being up to 3 halo, cyano, nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, by up to 5 fluoro Optionally substituted C _1-6 alkyl, or optionally substituted by up to 5 fluoro, optionally substituted by C _1-6 alkoxy;
(d) R ⁴ is C _1-6 alkyl, C (O) NR ⁵ R ⁶ , C (S) NR ⁵ R ⁶ , C (O) R ⁷ , C (O) OR ⁷ , or S (O) ₂ R ⁷ ;
(e) R ⁵ and R ⁶ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl, and the phenyl is at most 3 Halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, hydroxy-C _1-6 alkyl, or up to 5 Optionally substituted by C _1-6 alkyl, optionally substituted by fluoro, optionally substituted by up to 5 fluoro, optionally substituted by C _1-6 alkoxy; or R ⁵ and R ⁶ together with the nitrogen to which they are attached form indolinyl, pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl;
(f) R ⁷ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl Optionally substituted 1-3 times; or R ⁷ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{2 to 6} alkenyl, 5 C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or at the highest, C _{6 or 10} aryl optionally substituted by C _1-6 alkoxy optionally substituted by fluoro of
(g) R ⁸ is optionally substituted with C _1-3 alkyl, C _3-4 cycloalkyl, or up to two halo, cyano, hydroxy, C _1-3 alkyl, or C _1-3 alkoxy. Optionally phenyl;
(h) the dashed line represents an optional double bond],
Or a pharmaceutically acceptable salt thereof. R ¹ is phenyl, benzothiazole, benzothiophene, benzofuran, or benzimidazole, each up to 1-2 NR ⁵ R ⁶ , halo, cyano, nitro, hydroxy, C _1-2 alkyl, C _{3 7-cycloalkyl,} C _{4 to 10} alkylcycloalkyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or, Optionally substituted by C _1-6 alkoxy optionally substituted by up to 5 fluoro;
R ² is H, phenyl, pyridine, pyrimidine, thiazole, oxazole, isoxazole, or pyrazole, each of up to 1 to 2 NR ⁵ R ⁶ , halo, cyano, nitro, hydroxy, C _1-6 Alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, optionally substituted with up to 5 fluoro Optionally substituted by C _1-6 alkyl, or C _1-6 alkoxy optionally substituted by up to 5 fluoro;
R ³ is H;
R ⁴ is C _1-6 alkyl, C (O) NR ⁵ R ⁶ , C (S) NR ⁵ R ⁶ , C (O) R ⁷ , C (O) OR ⁷ , or S (O) ₂ R ⁷ Is;
R ⁵ and R ⁶ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl, said phenyl being at most 2 halo, Optionally by cyano, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, hydroxy-C _1-6 alkyl, or up to 5 fluoro optionally substituted C _{1 to 6} alkyl or up to may be optionally substituted with optionally C _{1 to 6} alkoxy which may be optionally substituted with 5 fluoro; or R ⁵ and R ⁶ together with the nitrogen to which they are attached form indolinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl;
R ⁷ is C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl, all of which are 1- to halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl Optionally substituted 3 times; or R ⁷ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl , C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, 5 fluoro up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or at the highest, C _{6 or 10} aryl optionally substituted by C _1-6 alkoxy optionally substituted by:
R ⁸ may be optionally substituted with C _1-3 alkyl, C _3-4 cycloalkyl, or up to 2 halo, cyano, hydroxy, C _1-3 alkyl, or C _1-3 alkoxy 124. The compound of claim 123, wherein the compound is a good phenyl; the dashed line represents an optional double bond. R ¹ is phenyl, benzothiazole, or benzothiophene, each optionally substituted by up to _1-2 halo, hydroxy, C _1-2 alkyl, up to 5 fluoro Optionally substituted by C _1-6 alkyl, or C _1-6 alkoxy optionally substituted by up to 5 fluoro;
R ² is either a H, or up to 1-2 halo, hydroxy, C _{1 to 3} alkyl, alkyl or up which may be optionally substituted with five fluoro C _{1 to 3,} Alkyl, or phenyl optionally substituted by C _1-6 alkoxy optionally substituted by up to 5 fluoro;
R ³ is H;
R ⁴ is C _1-6 alkyl, C (O) NR ⁵ R ⁶ , C (O) R ⁷ , or C (O) OR ⁷ ;
R ⁵ is H and R ⁶ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl, said phenyl being at most 2 halo, Optionally by cyano, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, hydroxy-C _1-6 alkyl, or up to 5 fluoro Optionally substituted C _1-6 alkyl, optionally substituted with up to 5 fluoro, optionally substituted with C _1-6 alkoxy;
R ⁷ is C _1-6 alkyl or C _3-7 cycloalkyl, which may all be optionally substituted 1-3 times with halo or phenyl; or R ⁷ is at most 1 Halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, or Optionally substituted by C _1-6 alkyl optionally substituted by up to 5 fluoro, or C _1-6 alkoxy optionally substituted by up to 5 fluoro. Optionally C _{6 or 10} aryl;
R ⁸ may be optionally substituted with C _1-3 alkyl, C _3-4 cycloalkyl, or up to 2 halo, cyano, hydroxy, C _1-3 alkyl, or C _1-3 alkoxy 121. The compound of claim 120 , wherein the compound is a good phenyl; the dashed line represents an optional double bond. a) the compound of claim 120 ;
b) to treat hepatitis C virus infection in an individual, to treat hepatic fibrosis in an individual, or to enhance liver function in an individual having hepatitis C virus infection, comprising a pharmaceutically acceptable carrier. Pharmaceutical composition. 124. The pharmaceutical composition of claim 123 , in a formulation that does not include any alcohol and any poly-ol. 125. The pharmaceutical composition of claim 124 , wherein the formulation does not comprise any sugar alcohol and any poly (ethylene glycol) (PEG). 124. The pharmaceutical composition of claim 123 , in an aqueous formulation that does not include any excipients that reduce polarity in the aqueous formulation. Tablet Formulation A pharmaceutical composition according to claim 123. 124. The pharmaceutical composition of claim 123 , in a caplet formulation. 124. The pharmaceutical composition of claim 123 , in a capsule formulation. a) the compound of claim 120 ;
b) A pharmaceutical composition for treating hepatitis C virus infection in an individual, comprising a pharmaceutically acceptable carrier. 135. The pharmaceutical composition of claim 130 , for realizing a sustained virus response. 132. The pharmaceutical composition of claim 130 , for treating hepatitis C virus infection in an individual in combination with an effective amount of a nucleoside analog. 135. The pharmaceutical composition of claim 132 , wherein the nucleoside analog is selected from ribavirin, levovirin, viramidine, L-nucleoside, and isatoribine. 132. The pharmaceutical composition of claim 130 , for treating hepatitis C virus infection in an individual in combination with an effective amount of an NS5B RNA dependent RNA polymerase inhibitor. 134. The pharmaceutical composition of claim 130 for treating hepatitis C virus infection in an individual in combination with an effective amount of thymosin-α. 138. The pharmaceutical composition of claim 135 , wherein thymosin-α in an amount of about 1.0 mg to about 1.6 mg is administered subcutaneously twice a week. 134. The pharmaceutical composition of claim 130 , for treating hepatitis C virus infection in an individual in combination with an effective amount of interferon-γ (IFN-γ). 138. The pharmaceutical composition of claim 137 , wherein an amount of about 10 [mu] g to about 300 [mu] g of IFN- [gamma] is administered subcutaneously. 131. The pharmaceutical composition of claim 130 for treating hepatitis C virus infection in an individual in combination with an effective amount of interferon-α (IFN-α). 140. The pharmaceutical composition of claim 139 , wherein IFN- [alpha] is monoPEG (30 kD, linear) consensus IFN- [alpha] and is administered at an administration interval of every 8-14 days. 140. The pharmaceutical composition of claim 139 , wherein IFN-α is monoPEG (30 kD, linear) consensus IFN-α and is administered at an administration interval of once every 7 days. 140. The pharmaceutical composition of claim 139 , wherein IFN-α is INFERGEN consensus IFN-α. 3'-azidothymidine, 2 ', 3'-dideoxyinosine, 2', 3'-dideoxycytidine, 2-, 3-didehydro-2 ', 3'-dideoxythymidine, combivir, abacavir, adefovir dipoxyl, cidofovir, 134. A pharmaceutical composition according to claim 130 for treating hepatitis C virus infection in an individual in combination with an effective amount of a drug selected from and an inosine monophosphate dehydrogenase inhibitor. a) the compound of claim 120 ;
b) A pharmaceutical composition for treating liver fibrosis in an individual, comprising a pharmaceutically acceptable carrier. 145. The pharmaceutical composition of claim 144 , for treating liver fibrosis in an individual in combination with an effective amount of a nucleoside analog. 146. The pharmaceutical composition of claim 145 , wherein the nucleoside analog is selected from ribavirin, levovirin, viramidine, L-nucleoside, and isatoribine. 145. The pharmaceutical composition of claim 144 , for treating liver fibrosis in an individual in combination with an effective amount of an NS5B RNA dependent RNA polymerase inhibitor. 145. The pharmaceutical composition of claim 144 , for treating liver fibrosis in an individual in combination with an effective amount of thymosin-α. 149. The pharmaceutical composition of claim 148 , wherein thymosin-α in an amount of about 1.0 mg to about 1.6 mg is administered subcutaneously twice a week. 145. The pharmaceutical composition of claim 144 for treating liver fibrosis in an individual in combination with an effective amount of interferon-γ (IFN-γ). 165. The pharmaceutical composition of claim 150 , wherein IFN- [gamma] is administered subcutaneously in an amount of about 10 [mu] g to about 300 [mu] g. 145. The pharmaceutical composition of claim 144 , for treating liver fibrosis in an individual in combination with an effective amount of interferon-α (IFN-α). 153. The pharmaceutical composition of claim 152 , wherein the IFN-α is monoPEG (30 kD, linear) consensus IFN-α and is administered at an administration interval of every 8-14 days. 153. The pharmaceutical composition of claim 152 , wherein the IFN-α is monoPEG (30 kD, linear) consensus IFN-α and is administered at an administration interval of once every 7 days. 153. The pharmaceutical composition of claim 152 , wherein IFN-α is INFERGEN consensus IFN-α. 3'-azidothymidine, 2 ', 3'-dideoxyinosine, 2', 3'-dideoxycytidine, 2-, 3-didehydro-2 ', 3'-dideoxythymidine, combivir, abacavir, adefovir dipoxyl, cidofovir, 145. The pharmaceutical composition of claim 144 , for treating liver fibrosis in an individual in combination with an effective amount of a drug selected from and an inosine monophosphate dehydrogenase inhibitor. a) the compound of claim 120 ;
b) A pharmaceutical composition for enhancing liver function in an individual having hepatitis C virus infection, comprising a pharmaceutically acceptable carrier. 158. The pharmaceutical composition of claim 157 for enhancing liver function in an individual having hepatitis C virus infection in combination with an effective amount of a nucleoside analog. 159. The pharmaceutical composition of claim 158 , wherein the nucleoside analog is selected from ribavirin, levovirin, viramidine, L-nucleoside, and isatoribine. 158. The pharmaceutical composition of claim 157 for enhancing liver function in an individual having hepatitis C virus infection in combination with an effective amount of an NS5B RNA dependent RNA polymerase inhibitor. 158. The pharmaceutical composition of claim 157 for enhancing liver function in an individual having hepatitis C virus infection in combination with an effective amount of thymosin-α. 164. The pharmaceutical composition of claim 161 , wherein thymosin-α in an amount of about 1.0 mg to about 1.6 mg is administered subcutaneously twice a week. 158. The pharmaceutical composition of claim 157 for enhancing liver function in an individual having hepatitis C virus infection in combination with an effective amount of interferon-γ (IFN-γ). 164. The pharmaceutical composition of claim 163 , wherein IFN-γ in an amount of about 10 μg to about 300 μg is administered subcutaneously. 158. The pharmaceutical composition of claim 157 for enhancing liver function in an individual having hepatitis C virus infection in combination with an effective amount of interferon-α (IFN-α). 166. The pharmaceutical composition of claim 165 , wherein the IFN-α is monoPEG (30 kD, linear) consensus IFN-α and is administered at an administration interval of every 8-14 days. 166. The pharmaceutical composition of claim 165 , wherein the IFN-α is mono PEG (30 kD, linear) consensus IFN-α and is administered at an administration interval of once every 7 days. 165. The pharmaceutical composition of claim 165 , wherein IFN-α is INFERGEN consensus IFN-α. 3'-azidothymidine, 2 ', 3'-dideoxyinosine, 2', 3'-dideoxycytidine, 2-, 3-didehydro-2 ', 3'-dideoxythymidine, combivir, abacavir, adefovir dipoxyl, cidofovir and 158. The pharmaceutical composition of claim 157 for enhancing liver function in an individual having hepatitis C virus infection in combination with an effective amount of a drug selected from an inosine monophosphate dehydrogenase inhibitor. A compound of the formula

[In the above formula,
(a) Z is a group arranged to hydrogen bond to the NS3 protease His57 imidazole moiety and hydrogen bond to the NS3 protease Gly137 nitrogen atom;
(b) P1 _′ has a nonpolar interaction with at least one NS3 protease S1 ′ pocket selected from the group consisting of Lys136, Gly137, Ser139, His57, Gly58, Gln41, Ser42, and Phe43 A group placed on
(c) L is a linking group consisting of 1 to 5 atoms selected from the group consisting of carbon, oxygen, nitrogen, hydrogen, and sulfur;
(d) P2 is selected from the group consisting of unsubstituted aryl, substituted aryl, unsubstituted heteroaryl, substituted heteroaryl, unsubstituted heterocycle, and substituted heterocycle; P2 is His57, Arg155, Val78, Asp79, Gln80 , And at least one NS3 protease selected from the group consisting of Asp81 and positioned by L to perform a nonpolar interaction with the S2 pocket portion;
(e) the dashed line represents an optional double bond;
(f) R ⁵ is selected from the group consisting of H, C (O) NR ⁶ R ⁷ , and C (O) OR ⁸ ;
(g) R ⁶ and R ⁷ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl, and the phenyl is at most 3 Halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, hydroxy-C _1-6 alkyl, up to 5 fluoro Optionally substituted by C _1-6 alkyl, optionally substituted by up to 5 fluoro, optionally substituted by C _1-6 alkoxy, optionally substituted by up to 5 fluoro; or R ⁶ and R ⁷ together with the nitrogen to which they are attached form indolinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl;
(h) R ⁸ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of these by halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl Optionally substituted 1-3 times; or R ⁸ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro, up to five C _{6 or 10} aryl optionally substituted by C _1-6 alkoxy optionally substituted by fluoro; or R ⁸ is optionally substituted by up to 5 fluoro groups C _1-optionally substituted Be ₆ alkyl; or R ⁸ is an tetrahydrofuran ring attached via a C ₃ or C ₄ position of the tetrahydrofuran ring; or R ⁸ is attached via a C ₄ position of Tetorapiraniru ring Tetorapiraniru A ring;
However, this compound does not include compounds having the formula II, III or IV.

In the above formula,
(aa) R ¹ and R ² are each independently H, halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl C _1-6 alkoxy, hydroxy-C _1-6 alkyl, or optionally substituted by up to 5 fluoro, optionally substituted by C _1-6 alkyl, up to 5 fluoro C _1-6 alkoxy, C _{6 or 10} aryl, pyridyl, pyrimidyl, thienyl, furanyl, thiazolyl, oxazolyl, phenoxy, thiophenoxy, S (O) ₂ NR ⁶ R ⁷ , NHC (O) NR ⁶ R ⁷ , NHC (S) NR ⁶ R ⁷ , C (O) NR ⁶ R ⁷ , NR ⁶ R ⁷ , C (O) R ⁸ , C (O) OR ⁸ , NHC (O) R ⁸ , NHC (O) OR ⁸ , SO _m R ⁸ , NHS (O) ₂ R ⁸ , CH _n NR ⁶ R ⁷ , OCH _n NR ⁶ R ⁷ , or OCH _n R ⁹ (R ⁹ is imidazolyl or pyrazolyl); R of regulations ¹ and R ² Said thienyl, pyrimidyl, furanyl, thiazolyl, and oxazolyl are of up to two halo, cyano, nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 6} alkenyl, optionally by 5 fluoro C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or at the highest, Optionally substituted by C _1-6 alkoxy, optionally substituted by: and said C _{6 or 10} aryl, pyridyl, phenoxy, and thiophenoxy as defined for R ¹ and R ² are at most 3 number of halo, cyano, nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydro Carboxymethyl -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or up to five which may _{C. 1 to} substituted optionally by fluoro, Optionally substituted by ₆ alkoxy;
(bb) m = 0, 1, or 2;
(cc) R ⁴ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, phenyl, or benzyl, wherein phenyl or benzyl is a maximum of 3 halo, cyano, nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, with up to 5 Optionally substituted by C _1-6 alkyl optionally substituted by ₁ fluoro, or C _1-6 alkoxy optionally substituted by up to 5 fluoro Often;
(dd) R ⁵ is H, C _1-6 alkyl, C (O) NR ⁶ R ⁷ , C (S) NR ⁶ R ⁷ , C (O) R ⁸ , C (O) OR ⁸ , S (O ) ₂ R ⁸ , or (CO) CHR ²¹ NH (CO) R ²² ;
(ee) R ⁶ and R ⁷ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl, and the phenyl is a maximum of 3 Halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, hydroxy-C _1-6 alkyl, or up to 5 Optionally substituted by C _1-6 alkyl, optionally substituted by fluoro, optionally substituted by up to 5 fluoro, optionally substituted by C _1-6 alkoxy; or R ⁶ and R ⁷ together with the nitrogen to which they are attached form indolinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl;
(ff) R ⁸ is C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl, all of which are halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl Optionally substituted 1-3 times by; or R ⁸ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl or up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro, at the highest 5 C _{6 or 10} aryl optionally substituted by C _1-6 alkoxy optionally substituted by ₁ fluoro; or R ⁸ is optionally substituted by up to 5 fluoro groups Replaced by selection Be a good C _{1 to 6} alkyl optionally; or R ⁸ is an tetrahydrofuran ring attached via a C ₃ or C ₄ position of the tetrahydrofuran ring; or R ⁸ is, via the C ₄ position of Tetorapiraniru ring A tetrapyranyl ring bonded together;
(gg) Y is a formula -C (O) NHS (O) sulfonimide is ₂ R ^9, R ⁹ is C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl or C _{4 to 10} alkyl cycloalkyl, Alkyl, all of which may be optionally substituted 1 to 3 times with halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl, or R ⁹ is up to 3 halo, Cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, or at most C _1-6 alkyl optionally substituted with 5 fluoro, optionally substituted with C _1-6 alkoxy optionally substituted with up to 5 fluoro It is a good C _{6 or 10} aryl; or R ⁹ is most In 5 fluoro groups by which may be C _{1 to 6} alkyl optionally substituted, an NR ⁶ R ⁷ or, (CO) OH or R ^9, is selected from halo, cyano, nitro, hydroxyl or C, An aromatic heterocycle optionally substituted up to 2 times by _1-6 alkoxy; or Y is a carboxylic acid, or a pharmaceutically acceptable salt, solvate or prodrug thereof;
(hh) R ¹⁰ and R ¹¹ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{6 or 10} aryl, hydroxy-C _1-6 alkyl C _1-6 alkyl, optionally substituted with up to 5 fluoro, (CH ₂ ) _n NR ⁶ R ⁷ , (CH ₂ ) _n C (O) OR ¹⁴ (R ¹⁴ is H , C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl), which are all 1- to halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl. May be optionally substituted three times; or R ¹⁴ may be up to three halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl , C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, with up to five fluoro Accordingly optionally optionally substituted C _{1 to 6} alkyl or up to 5 substituents be optionally substituted with optionally C _{1 to 6} alkoxy which may be optionally substituted with fluoro C _{6, Or} C _{10 or 10} aryl as defined for R ¹⁰ and R ¹¹ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _{4 10} alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or up, Optionally substituted by 5 fluoro and optionally substituted by C _1-6 alkoxy; or R ¹⁰ and R ¹¹ together with the carbon to which they are attached. Cyclopro Le, cyclobutyl, cyclopentyl or cyclohexyl to form,; or R ¹⁰ and R ¹¹ are coalesced as O;
(ii) p = 0 or 1;
(jj) R ¹² and R ¹³ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{6 or 10} aryl, hydroxy-C _1-6 alkyl C _1-6 alkyl, optionally substituted with up to 5 fluoro, (CH ₂ ) _n NR ⁶ R ⁷ , (CH ₂ ) _n C (O) OR ¹⁴ (R ¹⁴ is H _Are C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl), all of which are 1-3 by halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl Optionally substituted once; or R ¹⁴ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{2 to 6} depending alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, in up to 5 fluoro Optionally substituted with C _{1 to 6} alkyl or up to 5 substituents C _{6 or} be optionally substituted with optionally C _{1 to 6} alkoxy which may be optionally substituted with fluoro, It is ₁₀ aryl; wherein C _{6 or 10} aryl provisions of R ¹² and R ^13, up to three halo, cyano, nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, _{C. 4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or at the highest, Optionally substituted by C _1-6 alkoxy optionally substituted by 5 fluoro; or R ¹² and R ¹³ together with the carbon to which they are attached. Cyclopropyl, Cyclobutyl, cyclopentyl or cyclohexyl to form,; or R ¹² and R ¹³ are each independently, (CH ₂₎ by _n OR ⁸ be a good C _{1 to 6} alkyl substituted optionally;
(kk) R ²⁰ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{6 or 10} aryl, hydroxy-C _1-6 alkyl, up to 5 fluoro C _1-6 alkyl optionally substituted by, or (CH ₂ ) _n NR ⁶ R ⁷ , (CH ₂ ) _n C (O) OR ¹⁴ (R ¹⁴ is H, C _1-6 alkyl All of which are optionally substituted 1 to 3 times by halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl), C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl) Or R ¹⁴ may be up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, optionally substituted with up to 5 fluoro Good C _{1 to 6} alkyl optionally or at the highest, the 5 fluoro be which may be C _{6 or 10} aryl optionally substituted with optionally C _{1 to 6} alkoxy substituted optionally; The C _{6 or 10} aryl as defined for R ¹² and R ¹³ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl or up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro, by up to 5 fluoro Optionally substituted by optionally substituted C _1-6 alkoxy;
(ll) n = 1-4;
(mm) V is selected from O, S, or NH;
(nn) when V is O or S, W is selected from O, NR ¹⁵ , or CR ¹⁵ ; when V is NH, W is selected from NR ¹⁵ or CR ¹⁵ and R ¹⁵ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or C _1-6 alkyl optionally substituted with up to 5 fluoro;
(oo) dashed line represents an optional double bond;
(pp) R ²¹ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are halo, cyano, nitro, hydroxy, C _1-6 alkoxy, up to 5 C _1-6 alkyl optionally substituted by ₁ fluoro, or optionally substituted 1-3 times by phenyl; or R ²¹ is a maximum of 3 halo, cyano, nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to five C _1-6 alkyl optionally substituted with fluoro, or C _1-6 alkoxy optionally substituted with up to 5 fluoro, optionally substituted with C _1-6 alkoxy _{6 or 10} aryl Or R ²¹ is pyridyl, pyrimidyl, pyrazinyl, thienyl, furanyl, thiazolyl, oxazolyl, phenoxy, or thiophenoxy;
(qq) R ²² is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are optionally selected by halo, cyano, nitro, hydroxy, up to 5 fluoro Optionally substituted with 1 to 3 times C _1-6 alkyl, optionally substituted with phenyl. ] 171. The compound of claim 170 , wherein L consists of 2-5 atoms. 171. The compound of claim 170 , wherein L comprises a -WC (= V)-group and V and W are each independently selected from O, S, or NH. 171. The compound of claim 170 , wherein L is selected from the group consisting of esters, amides, carbamates, thioesters, and thioamides. The P2 is further positioned by L to effect hydrogen bonding interaction with at least one NS3 protease S2 pocket portion selected from the group consisting of His57, Arg155, Val78, Asp79, Gln80, and Asp81. 170. The compound according to 170 . 171. The compound of claim 170 , wherein the C13-C14 double bond is cis. 171. The compound of claim 170 , wherein the C13-C14 double bond is trans. 171. The compound of claim 170 , wherein P2 is of the formula

171. The compound of claim 170 of the formula:

178. The compound of claim 178 , wherein L consists of 2-5 atoms. 179. The compound of claim 178 , wherein L comprises a -WC (= V)-group and V and W are each independently selected from O, S, or NH. 179. The compound of claim 178 , wherein L is selected from the group consisting of esters, amides, carbamates, thioesters, and thioamides. The P2 is further positioned by L to effect hydrogen bonding interaction with at least one NS3 protease S2 pocket portion selected from the group consisting of His57, Arg155, Val78, Asp79, Gln80, and Asp81. 178. The compound according to 178 . 178. The compound of claim 178 , wherein the C13-C14 double bond is cis. 178. The compound of claim 178 , wherein the C13-C14 double bond is trans. 171. The compound of claim 170 of the formula:

186. The compound of claim 185 , wherein L consists of 2-5 atoms. 186. The compound of claim 185 , wherein L comprises a -WC (= V)-group and V and W are each independently selected from O, S, or NH. 186. The compound of claim 185 , wherein L is selected from the group consisting of esters, amides, carbamates, thioesters, and thioamides. The P2 is further positioned by L to effect hydrogen bonding interaction with at least one NS3 protease S2 pocket portion selected from the group consisting of His57, Arg155, Val78, Asp79, Gln80, and Asp81. 185. The compound according to 185 . 186. The compound of claim 185 , wherein the C13-C14 double bond is cis. 186. The compound of claim 185 , wherein the C13-C14 double bond is trans. Compound having the formula

[In the above formula,
Q is a core ring selected from:

Wherein the core ring is unsubstituted or H, halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _{1 6} alkoxy, hydroxy -C _{1 to 6} alkyl, C _{1 to 6} alkyl, substituted C _{1 to 6} alkyl, C _{1 to 6} alkoxy, substituted C _{1 to 6} alkoxy, C _{6 or 10} aryl, pyridyl, pyrimidyl, thienyl, Furanyl, thiazolyl, oxazolyl, phenoxy, thiophenoxy, sulfonamide, urea, thiourea, amide, keto, carboxyl, carbamyl, sulfide, sulfoxide, sulfone, amino, alkoxyamino, alkyloxyheterocycle, alkylamino, alkylcarboxy, carbonyl , Spirocyclic cyclopropyl, spirocyclic cyclobutyl, spirocyclic cyclopentyl, or It may be substituted by pyro cyclic cyclohexyl;
Or Q is R ¹ -R ² and R ¹ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, phenyl, pyridine, pyrazine, pyrimidine, pyridazine, pyrrole, furan , Thiophene, thiazole, oxazole, imidazole, isoxazole, pyrazole, isothiazole, naphthyl, quinoline, isoquinoline, quinoxaline, benzothiazole, benzothiophene, benzofuran, indole, or benzimidazole, each with up to 3 NR ⁶ R ⁷ , halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro, Other may be optionally substituted with optionally C _{1 to 6} alkoxy which may be optionally substituted with up to 5 fluoro; R ² is, H, phenyl, pyridine, pyrazine, pyrimidine, pyridazine, Pyrrole, furan, thiophene, thiazole, oxazole, imidazole, isoxazole, pyrazole, isothiazole, naphthyl, quinoline, isoquinoline, quinoxaline, benzothiazole, benzothiophene, benzofuran, indole, benzimidazole, each with up to 3 NR ⁶ R ⁷ , halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _{1 ~ 6} alkyl, optionally substituted with up to 5 fluoro Optionally substituted by C _1-6 alkyl, or C _1-6 alkoxy optionally substituted by up to 5 fluoro;
R ⁴ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, phenyl, or benzyl, where phenyl or benzyl is a maximum of 3 halo, cyano, nitro Hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, up to 5 fluoro Optionally substituted by C _1-6 alkyl optionally substituted by, or C _1-6 alkoxy optionally substituted by up to 5 fluoro;
R ⁵ is C _1-6 alkyl, C (O) NR ⁶ R ⁷ , C (S) NR ⁶ R ⁷ , C (O) R ⁸ , C (O) OR ⁸ , S (O) ₂ R ⁸ , Or (CO) CHR ²¹ NH (CO) R ²² ;
R ⁶ and R ⁷ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl, wherein the phenyl is a maximum of 3 halo, cyano, optionally nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, hydroxy -C _{1 to 6} alkyl, by up to 5 fluoro in it may be optionally substituted with optionally substituted C _{1 to 6} alkyl optionally or up to 5 substituents C _{1 to 6} alkoxy which may be optionally substituted with fluoro; or R ⁶ and R ⁷ together with the nitrogen to which they are attached forms indolinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl;
R ⁸ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are 1-3 by halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl Optionally substituted; or R ⁸ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or by up to 5 fluoro, C _{6 or 10} aryl optionally substituted by optionally substituted C _1-6 alkoxy; or R ⁸ is optionally substituted by up to 5 fluoro groups. May be C _1-6 alkyl; or R ⁸ is a tetrahydrofuran ring bonded through the C ₃ or C ₄ position of the tetrahydrofuran ring; or R ⁸ is bonded through the C ₄ position of the tetrapyranyl ring. Is a tetrapyranyl ring;
Y is COOR ^{9 wherein} R ⁹ is C _1-6 alkyl;
V is selected from O, S, or NH;
When V is O or S, W is selected from O, NR ¹⁵ , or CR ¹⁵ ; when V is NH, W is selected from NR ¹⁵ or CR ¹⁵ and R ¹⁵ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or C _1-6 alkyl optionally substituted with up to 5 fluoro;
The dashed line represents an optional double bond;
R ²¹ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are halo, cyano, nitro, hydroxy, C _1-6 alkoxy, up to 5 fluoro Optionally substituted by C _1-6 alkyl, optionally substituted by phenyl, or optionally substituted 1-3 times by phenyl; or R ²¹ is up to 3 halo, cyano, nitro, hydroxy C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, optional up to 5 fluoro C _1-6 alkyl optionally substituted, _or C _{6 or 10} optionally substituted with C _1-6 alkoxy optionally substituted with up to 5 fluoro. Is aryl; Or R ²¹ is pyridyl, pyrimidyl, pyrazinyl, thienyl, furanyl, thiazolyl, oxazolyl, phenoxy, or thiophenoxy;
R ²² is C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl, all of which are optionally substituted with halo, cyano, nitro, hydroxy, up to 5 fluoro C _1-6 alkyl, which may be substituted, or optionally substituted 1-3 times with phenyl. ]. 193. The compound of claim 192 , of the formula

Compound having the formula

[In the above formula,
R ⁴ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, phenyl, or benzyl, where phenyl or benzyl is a maximum of 3 halo, cyano, nitro Hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, up to 5 fluoro Optionally substituted by C _1-6 alkyl optionally substituted by, or C _1-6 alkoxy optionally substituted by up to 5 fluoro;
R ⁵ is C _1-6 alkyl, C (O) NR ⁶ R ⁷ , C (S) NR ⁶ R ⁷ , C (O) R ⁸ , C (O) OR ⁸ , S (O) ₂ R ⁸ , Or (CO) CHR ²¹ NH (CO) R ²² ;
R ⁶ and R ⁷ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl, wherein the phenyl is a maximum of 3 halo, cyano, optionally nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, hydroxy -C _{1 to 6} alkyl, by up to 5 fluoro in it may be optionally substituted with optionally substituted C _{1 to 6} alkyl optionally or up to 5 substituents C _{1 to 6} alkoxy which may be optionally substituted with fluoro; or R ⁶ and R ⁷ together with the nitrogen to which they are attached forms indolinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl;
R ⁸ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are 1-3 by halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl Optionally substituted; or R ⁸ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or by up to 5 fluoro, C _{6 or 10} aryl optionally substituted by optionally substituted C _1-6 alkoxy; or R ⁸ is optionally substituted by up to 5 fluoro groups. May be C _1-6 alkyl; or R ⁸ is a tetrahydrofuran ring bonded through the C ₃ or C ₄ position of the tetrahydrofuran ring; or R ⁸ is bonded through the C ₄ position of the tetrapyranyl ring. Is a tetrapyranyl ring;
Y is a sulfonimide having the formula —C (O) NHS (O) ₂ R ⁹ , where R ⁹ is C _1-3 alkyl, C _3-7 cycloalkyl, or up to 2 halo, cyano, Nitro, hydroxy, C _1-3 alkyl, C _3-7 cycloalkyl, or phenyl optionally substituted by C _1-3 alkoxy, or Y is a carboxylic acid;
V is selected from OH, SH, or NH ₂ ;
The dashed line represents an optional double bond;
R ²¹ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are halo, cyano, nitro, hydroxy, C _1-6 alkoxy, up to 5 fluoro Optionally substituted by C _1-6 alkyl, optionally substituted by phenyl, or optionally substituted 1-3 times by phenyl; or R ²¹ is up to 3 halo, cyano, nitro, hydroxy C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, optional up to 5 fluoro C _1-6 alkyl optionally substituted, _or C _{6 or 10} optionally substituted with C _1-6 alkoxy optionally substituted with up to 5 fluoro. Is aryl; Alternatively, R ²¹ is pyridyl, pyrimidyl, pyrazinyl, thienyl, furanyl, thiazolyl, oxazolyl, phenoxy, or thiophenoxy;
R ²² is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are optionally substituted by halo, cyano, nitro, hydroxy, up to 5 fluoro C _1-6 alkyl, which may optionally be substituted, or optionally substituted 1 to 3 times by phenyl. ]. 195. The compound of claim 194 , of the formula

Y is a sulfonimide having the formula —C (O) NHS (O) ₂ R ⁹ , where R ⁹ is C _1-3 alkyl, C _3-7 cycloalkyl, or up to 2 halo, cyano, nitro, hydroxy, C _{1 to 3} alkyl, C _{3 to 7} cycloalkyl or phenyl which may be optionally substituted with C _{1 to 3} alkoxy,, V is selected from OH and NH _2, wherein Item 195. The compound according to item 195 . Compound having the formula

[In the above formula,
Q is a core ring selected from:

Wherein the core ring is unsubstituted or H, halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, C _1-6 alkyl, substituted C _1-6 alkyl, C _1-6 alkoxy, substituted C _1-6 alkoxy, C _{6 or 10} aryl, pyridyl, pyrimidyl, Thienyl, furanyl, thiazolyl, oxazolyl, phenoxy, thiophenoxy, sulfonamide, urea, thiourea, amide, keto, carboxyl, carbamyl, sulfide, sulfoxide, sulfone, amino, alkoxyamino, alkyloxyheterocycle, alkylamino, alkylcarboxy , Carbonyl, spirocyclic cyclopropyl, spirocyclic cyclobutyl, spirocyclic cyclopentyl, Others may be substituted by spirocyclic cyclohexyl;
Or Q is R ¹ -R ² and R ¹ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, phenyl, pyridine, pyrazine, pyrimidine, pyridazine, pyrrole, furan , Thiophene, thiazole, oxazole, imidazole, isoxazole, pyrazole, isothiazole, naphthyl, quinoline, isoquinoline, quinoxaline, benzothiazole, benzothiophene, benzofuran, indole, benzimidazole, each with up to 3 NR ⁶ R ⁷ , halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl , up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or, It may be optionally substituted with optionally C _{1 to 6} alkoxy which may be optionally substituted with 5 fluoro at high; R ² is, H, phenyl, pyridine, pyrazine, pyrimidine, pyridazine, pyrrole, Furan, thiophene, thiazole, oxazole, imidazole, isoxazole, pyrazole, isothiazole, naphthyl, quinoline, isoquinoline, quinoxaline, benzothiazole, benzothiophene, benzofuran, indole, benzimidazole, each with up to 3 NR ⁶ R ⁷ , halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 Alkyl, optionally substituted with up to 5 fluoro Optionally substituted by C _1-6 alkyl, or C _1-6 alkoxy optionally substituted by up to 5 fluoro;
R ⁴ is H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, phenyl, or benzyl, where phenyl or benzyl is a maximum of 3 halo, cyano, nitro Hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, up to 5 fluoro Optionally substituted by C _1-6 alkyl optionally substituted by, or C _1-6 alkoxy optionally substituted by up to 5 fluoro;
R ⁵ is C _1-6 alkyl, C (O) NR ⁶ R ⁷ , C (S) NR ⁶ R ⁷ , C (O) R ⁸ , C (O) OR ⁸ , S (O) ₂ R ⁸ , Or (CO) CHR ²¹ NH (CO) R ²² ;
R ⁶ and R ⁷ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl, wherein the phenyl is a maximum of 3 halo, cyano, optionally nitro, hydroxy, C _{1 to 6} alkyl, C _{3 to 7} cycloalkyl, C _{4 to 10} alkylcycloalkyl, C _{2 to 6} alkenyl, hydroxy -C _{1 to 6} alkyl, by up to 5 fluoro in it may be optionally substituted with optionally substituted C _{1 to 6} alkyl optionally or up to 5 substituents C _{1 to 6} alkoxy which may be optionally substituted with fluoro; or R ⁶ and R ⁷ together with the nitrogen to which they are attached forms indolinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl;
R ⁸ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are 1-3 by halo, cyano, nitro, hydroxy, C _1-6 alkoxy, or phenyl Optionally substituted; or R ⁸ is up to 3 halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{2 to 6} alkenyl, C _{1 to 6} alkoxy, hydroxy -C _{1 to 6} alkyl, up to 5 substituents C _{1 to 6} alkyl which may be optionally substituted with fluoro or by up to 5 fluoro, C _{6 or 10} aryl optionally substituted by optionally substituted C _1-6 alkoxy; or R ⁸ is optionally substituted by up to 5 fluoro groups. May be C _1-6 alkyl; or R ⁸ is a tetrahydrofuran ring bonded through the C ₃ or C ₄ position of the tetrahydrofuran ring; or R ⁸ is bonded through the C ₄ position of the tetrapyranyl ring. Is a tetrapyranyl ring;
Y is, R ⁹ is C _{1 to 6} alkyl, COOR ^9; or Y is the formula -C (O) NHS (O) sulfonimide is ₂ R ^9, R ⁹ is _{C. 1 to} Optionally substituted by ₃ alkyl, C _3-7 cycloalkyl, or up to 2 halo, cyano, nitro, hydroxy, C _1-3 alkyl, C _3-7 cycloalkyl, or C _1-3 alkoxy Optionally phenyl, or Y is a carboxylic acid;
V and W are each independently selected from O, S, or NH;
The dashed line represents an optional double bond;
R ²¹ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are halo, cyano, nitro, hydroxy, C _1-6 alkoxy, up to 5 fluoro Optionally substituted by C _1-6 alkyl, optionally substituted by phenyl, or optionally substituted 1-3 times by phenyl; or R ²¹ is up to 3 halo, cyano, nitro, hydroxy Optional, by C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, up to 5 fluoro C _1-6 alkyl optionally substituted, C _{6 or 10} aryl optionally substituted by C _1-6 alkoxy optionally substituted by up to 5 fluoro Yes; yes Or R ²¹ is pyridyl, pyrimidyl, pyrazinyl, thienyl, furanyl, thiazolyl, oxazolyl, phenoxy, or thiophenoxy;
R ²² is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are optionally substituted by halo, cyano, nitro, hydroxy, up to 5 fluoro C _1-6 alkyl, which may optionally be substituted, or optionally substituted 1 to 3 times by phenyl. ]. L is, -OCH ₂ - and -NHCH ₂ - are selected from the group consisting of A compound according to claim 171. 181. The compound of claim 171 , wherein L is selected from the group consisting of -CH = CH- and -C≡C-. L _{is, -SCH 2 -, - SO 2} -, and is selected from the group consisting of -CH ₂ SO-, compound of Claim 171. L is selected from the group consisting of -WC (= V) -NH- and -WC (= V) -O-, and V and W are each independently selected from O, S, or NH. Item 171. The compound according to Item 171 . L is, -OCH ₂ - and -NHCH ₂ - are selected from the group consisting of A compound according to claim 179. 180. The compound of claim 179 , wherein L is selected from the group consisting of -CH = CH- and -C≡C-. L _{is, -SCH 2 -, - SO 2} -, and is selected from the group consisting of -CH ₂ SO-, compound of Claim 179. L is selected from the group consisting of -WC (= V) -NH- and -WC (= V) -O-, and V and W are each independently selected from O, S, or NH. Item 179. The compound according to Item 179 . L is, -OCH ₂ - and -NHCH ₂ - are selected from the group consisting of A compound according to claim 186. 187. The compound of claim 186 , wherein L is selected from the group consisting of -CH = CH- and -C≡C-. L _{is, -SCH 2 -, - SO 2} -, and is selected from the group consisting of -CH ₂ SO-, compound of Claim 186. L is selected from the group consisting of -WC (= V) -NH- and -WC (= V) -O-, and V and W are each independently selected from O, S, or NH. Item 186. The compound according to item 186 . 171. The compound of claim 170 , wherein L is a linking group consisting of 1 to 5 atoms selected from the group consisting of nitrogen, hydrogen, and sulfur. 171. The compound of claim 170 , wherein P2 is selected from the group consisting of unsubstituted heterocycle and substituted heterocycle. 175. The compound of claim 174 , wherein L is a linking group consisting of 1 to 5 atoms selected from the group consisting of nitrogen, hydrogen, and sulfur. 175. The compound of claim 174 , wherein P2 is selected from the group consisting of unsubstituted heterocycle and substituted heterocycle. 179. The compound of claim 178 , wherein L is a linking group consisting of 1 to 5 atoms selected from the group consisting of nitrogen, hydrogen, and sulfur. 179. The compound of claim 178 , wherein P2 is selected from the group consisting of unsubstituted heterocycle and substituted heterocycle. 184. The compound of claim 182 , wherein L is a linking group consisting of 1 to 5 atoms selected from the group consisting of nitrogen, hydrogen, and sulfur. 184. The compound of claim 182 , wherein P2 is selected from the group consisting of unsubstituted heterocycle and substituted heterocycle. 186. The compound of claim 185 , wherein L is a linking group consisting of 1 to 5 atoms selected from the group consisting of nitrogen, hydrogen, and sulfur. 186. The compound of claim 185 , wherein P2 is selected from the group consisting of unsubstituted heterocycle and substituted heterocycle. 189. The compound of claim 189 , wherein L is a linking group consisting of 1 to 5 atoms selected from the group consisting of nitrogen, hydrogen, and sulfur. 189. The compound of claim 189 , wherein P2 is selected from the group consisting of unsubstituted heterocycle and substituted heterocycle. 70. The compound of claim 69, having the following formula XII.

[In the above formula,
(a) R ^1a and R ^1b are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are halo, cyano, nitro, C _{1- 6} may be optionally substituted 1-3 times with alkoxy, amide, or phenyl;
Or R ^1a and R ^1b are each independently H or heteroaryl selected from the group consisting of:

(In the above formula, R ^1c is H, halo, C _1-6 alkyl, C _3-6 cycloalkyl, C _1-6 alkoxy, C _3-6 cycloalkoxy, NO ₂ , N (R ^1d ) ₂ , NH (CO) R ^1d , or NH (CO) NHR ^1d , each R ^1d is independently H, C _1-6 alkyl, or C _3-6 cycloalkyl);
Alternatively, NR ^1a R ^1b is a 3-6 membered alicyclic secondary amine, which optionally has 1 to 3 heteroatoms incorporated into the ring, and is halo, cyano, nitro, Optionally substituted 1-3 times by C _1-6 alkoxy, amide, or phenyl;
(b) R ²¹ and R ²² are each independently H, halo, cyano, nitro, hydroxy, C _1-3 alkyl, C _1-3 alkoxy;
(c) R ⁵ is H, C (O) NR ⁶ R ⁷ , C (O) R ⁸ , or C (O) OR ⁸ ;
(d) R ⁶ and R ⁷ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl;
(e) R ⁸ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or 3-tetrahydrofuryl;
(f) R ¹⁰ and R ¹¹ are each independently H, halo, C _1-3 alkyl, or R ¹⁰ and R ¹¹ together with the carbon to which they are attached are cyclopropyl, Form cyclobutyl, cyclopentyl, or cyclohexyl;
(g) R ¹² and R ¹³ are each independently H, halo, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _{6 or 10} aryl, hydroxy-C _{1- 6} alkyl, or C _1-6 alkyl optionally substituted with up to 5 halogen atoms;
(h) The dashed line represents an optional double bond. ] 70. The compound of claim 69 having the following formula XIII:

[In the above formula,
(a) R ^1a and R ^1b are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, or C _4-10 alkyl cycloalkyl, all of which are halo, cyano, nitro, C Optionally substituted 1 to 3 times by 1 to ₆ alkoxy, amide, or phenyl;
Or R ^1a and R ^1b are each independently H or heteroaryl selected from the group consisting of:

(In the above formula, R ^1c is H, halo, C _1-6 alkyl, C _3-6 cycloalkyl, C _1-6 alkoxy, C _3-6 cycloalkoxy, NO ₂ , N (R ^1d ) ₂ , NH (CO) R ^1d , or NH (CO) NHR ^1d , each R ^1d is independently H, C _1-6 alkyl, or C _3-6 cycloalkyl);
Alternatively, NR ^1a R ^1b is a 3-6 membered alicyclic secondary amine, which optionally has 1 to 3 heteroatoms incorporated into the ring, and is halo, cyano, nitro, Optionally substituted 1-3 times by C _1-6 alkoxy, amide, or phenyl;
(b) R ²¹ and R ²² are each independently H, halo, cyano, hydroxy, C _1-3 alkyl, or C _1-3 alkoxy;
(c) R ⁵ is H, C (O) NR ⁶ R ⁷ , C (O) R ⁸ , or C (O) OR ⁸ ;
(d) R ⁶ and R ⁷ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl;
(e) R ⁸ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or 3-tetrahydrofuryl;
(f) The dashed line represents an optional double bond. ] 70. The compound of claim 69, having the following formula XIV.

[In the above formula,
(a) R ^1a and R ^1b are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, all of which are halo, cyano, nitro, C _{1- 6} may be optionally substituted 1-3 times with alkoxy, amide, or phenyl;
Or R ^1a and R ^1b are each independently H or heteroaryl selected from the group consisting of:

(In the above formula, R ^1c is H, halo, C _1-6 alkyl, C _3-6 cycloalkyl, C _1-6 alkoxy, C _3-6 cycloalkoxy, NO ₂ , N (R ^1d ) ₂ , NH (CO) R ^1d , or NH (CO) NHR ^1d , each R ^1d is independently H, C _1-6 alkyl, or C _3-6 cycloalkyl);
Alternatively, NR ^1a R ^1b is a 3-6 membered alicyclic secondary amine, which optionally has 1 to 3 heteroatoms incorporated into the ring, and is halo, cyano, nitro, Optionally substituted 1-3 times by C _1-6 alkoxy, amide, or phenyl;
(b) R ^2a is up to 3 NR ^2c R ^2d , halo, cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 Alkenyl, C _1-6 alkoxy, hydroxy-C _1-6 alkyl, optionally substituted by up to 5 fluoro, optionally substituted by C _1-6 alkyl, or up to 5 fluoro C ₆ or C ₁₀ aryl optionally substituted by optionally substituted C _1-6 alkoxy;
R ^2c and R ^2d are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl, wherein the phenyl is a maximum of 3 halos. , Cyano, nitro, hydroxy, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, C _2-6 alkenyl, hydroxy-C _1-6 alkyl, optional up to 5 fluoro Optionally substituted by C _1-6 alkyl optionally substituted, or C _1-6 alkoxy optionally substituted by up to 5 fluoro; or R ^2c And R ^2d together with the nitrogen to which they are attached form indolinyl, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl;
Or R ^2a is a 5- or 6-membered unsaturated heteroaryl, or such defined heteroaryl fused to another ring, which may be a heterocycle or any other ring;
(c) R ⁵ is H, C (O) NR ⁶ R ⁷ , C (O) R ⁸ , or C (O) OR ⁸ ;
(d) R ⁶ and R ⁷ are each independently H, C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or phenyl;
(e) R ⁸ is C _1-6 alkyl, C _3-7 cycloalkyl, C _4-10 alkyl cycloalkyl, or 3-tetrahydrofuryl;
(f) The dashed line represents an optional double bond. ]