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US 2003/0125240 A1Published application
Cyclic peptide antifungal agents
AssigneeEli Lilly and Company
InventorsJames Andrew Jamison, Michael John Rodriguez, Venkatraghavan Vasudevan
Life of this patent
Estimating the term…
Abstract
The present invention relates to compounds of formula I: 1 where R5 is a sugar moiety. The compounds are useful in inhibiting fungal and parasitic activity and infections.
Claims18
A compound of formula I
- 78
- wherein:
- R is independently at each occurrence hydrogen, hydroxy, or O—Pg;
- R1 is hydrogen, methyl, CH2C(O)NH2, CH2C(O)NH—Pg;
- R2 and R3 are independently hydrogen or methyl;
- R4 is a moiety of the formula
- 79
- R5 is a moiety of the formula
- 80
- A is independently at each occurrence phen-di-yl, pyridin-di-yl, pyridazin-di-yl, pyrimidin-di-yl, pyrazin-di-yl, furan-di-yl, or thiophen-di-yl rings;
- X is independently at each occurrence a bond or C≡C;
- R6 is hydrogen, C1-C12 alkyl, C2-C12 alkynyl, C1-C12 alkoxy, C1-C12 alkylthio, halo, or —O—(CH2)m—[O—(CH2)n]p—O—(C1-C12 alkyl), or —O—(CH2)q—Z—R8;
- R7 is independently at each occurrence hydrogen, hydroxy, amino, azido, OR5, O—Pg, or NHp—Pg;
- R7′ is CHR7CH2R7, CHR7CH2OR9, ethyl, CHR7CO2H, CHR7CH2O—Pg, or CHR7C(O)—Pg;
- R7″ is hydrogen, CH2R7, CH2OR9, methyl, CO2H, CH2O—Pg, CH2NHp—Pg, or C(O)—Pg;
- m, n, and q are independently 2, 3 or 4;
- p is 0 or 1;
- Z is pyrrolidin-di-yl, piperidin-di-yl, or piperazin-di-yl;
- R8 is hydrogen, C1-C12 alkyl, benzyl, or substituted C3-C12 cycloalkylmethyl;
- R9 is SO3H or a moiety of the formula
- 81
- R10 is hydroxy, C1-C6 alkyl, C1-C6 alkoxy, phenyl, phenoxy, p-halophenyl, p-halophenoxy, p-nitrophenyl, p-nitrophenoxy, benzyl, benzyloxy, p-halobenzyl, p-halobenzyloxy, p-nitrobenzyl, or p-nitrobenzyloxy;
- and
- Pg is a hydroxy, amino, amido or carboxy protecting group;
- with the proviso that the total number of R7 substituents that are OR5 groups does not exceed two;
- or a pharmaceutical salt or solvate thereof.
23 more elements
A method of inhibiting fungal activity comprising administering to a host in need of such inhibition an effective amount of a compound of formula I
- 86
- wherein
- R is independently at each occurrence hydrogen, hydroxy, or O—Pg;
- R1 is hydrogen, methyl, CH2C(O)NH2, CH2C(O)NH—Pg;
- R2 and R3 are independently hydrogen or methyl;
- R4 is a moiety of the formula
- 87
- R5 is a moiety of the formula
- 88
- A is independently at each occurrence phen-di-yl, pyridin-di-yl, pyridazin-di-yl, pyrimidin-di-yl, pyrazin-di-yl, furan-di-yl, or thiophen-di-yl rings;
- X is independently at each occurrence a bond or C≡C;
- R6 is hydrogen, C1-C12 alkyl, C2-C12 alkynyl, C1-C12 alkoxy, C1-C12 alkylthio, halo, or —O—(CH2)m—[O—(CH2)n]p—O—(C1-C12 alkyl), or —O—(CH2)q—Z—R8;
- R7 is independently at each occurrence hydrogen, hydroxy, amino, azido, OR5, O—Pg, or NHp—Pg;
- R7′ is CHR7CH2R7, CHR7CH2OR9, ethyl, CHR7CO2H, CHR7CH2O—Pg, or CHR7C(O)—Pg;
- R7″ is hydrogen, CH2R7, CH2OR9, methyl, CO2H, CH2O—Pg, CH2NHp—Pg, or C(O)—Pg;
- m, n, and q are independently 2, 3 or 4;
- p is 0 or 1;
- Z is pyrrolidin-di-yl, piperidin-di-yl, or piperazin-di-yl;
- R8 is hydrogen, C1-C12 alkyl, benzyl, or substituted C3-C12 cycloalkylmethyl;
- R9 is SO3H or a moiety of the formula
- 89
- R10 is hydroxy, C1-C6 alkyl, C1-C6 alkoxy, phenyl, phenoxy, p-halophenyl, p-halophenoxy, p-nitrophenyl, p-nitrophenoxy, benzyl, benzyloxy, p-halobenzyl, p-halobenzyloxy, p-nitrobenzyl, or p-nitrobenzyloxy;
- and
- Pg is a hydroxy, amino, amido or carboxy protecting group;
- with the proviso that the total number of R7 substituents that are OR5 groups does not exceed two;
- or a pharmaceutical salt or solvate thereof.
23 more elements
A method of inhibiting parasitic activity comprising administering to a host in need of such inhibition an effective amount of a compound of formula I
- 94
- wherein
- R is independently at each occurrence hydrogen, hydroxy, or O—Pg;
- R1 is hydrogen, methyl, CH2C(O)NH2, CH2C(O)NH—Pg;
- R2 and R3 are independently hydrogen or methyl;
- R4 is a moiety of the formula
- 95
- R5 is a moiety of the formula
- 96
- A is independently at each occurrence phen-di-yl, pyridin-di-yl, pyridazin-di-yl, pyrimidin-di-yl, pyrazin-di-yl, furan-di-yl, or thiophen-di-yl rings;
- X is independently at each occurrence a bond or C≡C;
- R6 is hydrogen, C1-C12 alkyl, C2-C12 alkynyl, C1-C12 alkoxy, C1-C12 alkylthio, halo, or —O—(CH2)m—[O—(CH2)n]p—O—(C1-C12 alkyl), or —O—(CH2)q—Z—R8;
- R7 is independently at each occurrence hydrogen, hydroxy, amino, azido, OR5, O—Pg, or NHp—Pg;
- R7′ is CHR7CH2R7, CHR7CH2OR9, ethyl, CHR7CO2H, CHR7CH2O—Pg, or CHR7C(O)—Pg;
- R7″ is hydrogen, CH2R7, CH2OR9, methyl, CO2H, CH2O—Pg, CH2NHp—Pg, or C(O)—Pg;
- m, n, and q are independently 2, 3 or 4;
- p is 0 or 1;
- Z is pyrrolidin-di-yl, piperidin-di-yl, or piperazin-di-yl;
- R8 is hydrogen, C1-C12 alkyl, benzyl, or substituted C3-C12 cycloalkylmethyl;
- R9 is SO3H or a moiety of the formula
- 97
- R10 is hydroxy, C1-C6 alkyl, C1-C6 alkoxy, phenyl, phenoxy, p-halophenyl, p-halophenoxy, p-nitrophenyl, p-nitrophenoxy, benzyl, benzyloxy, p-halobenzyl, p-halobenzyloxy, p-nitrobenzyl, or p-nitrobenzyloxy;
- and
- Pg is a hydroxy, amino, amido or carboxy protecting group;
- with the proviso that the total number of R7 substituents that are OR5 groups does not exceed two;
- or a pharmaceutical salt or solvate thereof.
23 more elements
Dependencies are inferred from the claim text.