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US 2011/0237784 A1Published application
10a-azalide compound crosslinked at 10a- and 12-positions
AssigneesTaisho Pharmaceutical Co., Ltd., Meiji Seika Kaisha, Ltd.
InventorsTomohiro Sugimoto, Kanako Yamamoto, Jun Kurosaka, Naoki Sasamoto, Masato Kashimura, Tomoaki Miura, Kenichi Kanemoto, Tomohiro Ozawa, Ken Chikauchi, Eiki Shitara
Life of this patent
Estimating the term…
Abstract
A novel 10a-azalide compound crosslinked at the 10a- and 12-positions, which is represented by the following formula, and is effective on even Hemophilus influenzae, or erythromycin resistant bacteria (e.g., resistant pneumococci and streptococci).
Claims24
A 10a-azalide compound represented by the formula (I):
- {wherein, in the formula, R1 is:
- hydrogen atom, or
- a halogen atom,
- R2 and R3 combine together to represent oxo group, or
- one of them is hydrogen atom, and the other is:
- hydroxyl group,
- a protected hydroxyl group,
- a group represented by the formula —X031—R031, or a group represented by the formula (II):
- wherein X031 is:
- a group represented by the formula —O—,
- a group represented by the formula —OCO—, or
- a group represented by the formula) —OCON(R20)—,
- R031 is:
- a C1-6 alkyl group which may be substituted with 1 to 3 groups selected from the group consisting of “an aryl group, a heterocyclic group, and a biaryl group (the aryl group, the heterocyclic group, and the biaryl group may be substituted with 1 to 3 groups selected from the group A)”,
- a C2-6 alkenyl group which may be substituted with 1 to 3 groups selected from the group consisting of “an aryl group, a heterocyclic group, and a biaryl group (the aryl group, the heterocyclic group, and the biaryl group may be substituted with 1 to 3 groups selected from the group A)”,
- a C2-6 alkynyl group which may be substituted with 1 to 3 groups selected from the group consisting of “an aryl group, a heterocyclic group, and a biaryl group (the aryl group, the heterocyclic group, and the biaryl group may be substituted with 1 to 3 groups selected from the group A)”,
- an aryl group which may be substituted with 1 to 3 groups selected from the group A,
- a heterocyclic group which may be substituted with 1 to 3 groups selected from the group A, or
- a biaryl group which may be substituted with 1 to 3 groups selected from the group A,
- the group A is a group consisting of hydroxyl group, a halogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C1-6 alkoxy group, a C2-7 alkoxycarbonyl group, nitro group, a saturated heterocyclic group and a C1-11 acyl group,
- one of R32 and R33 is hydrogen atom, and the other is:
- hydrogen atom,
- hydroxyl group,
- a protected hydroxyl group,
- amino group,
- a protected amino group,
- a group represented by the formula —X331—R331,
- a group represented by the formula —X331-A331-X332—R331
- a group represented by the formula —X331-A331-X332-A332-X333—R331, or
- a group represented by the formula —X331-A331-X332-A332-X333-A333-X334—R331, wherein X331 is:
- a group represented by the formula —O—,
- a group represented by the formula —OCO—,
- a group represented by the formula) —OCON(R20)—,
- a group represented by the formula) —N(R20)—, or
- a group represented by the formula) —N(R20)CO—,
- R331 is:
- a C1-6 alkyl group which may be substituted with 1 to 3 groups selected from the group consisting of “an aryl group, a heterocyclic group, and a biaryl group (the aryl group, the heterocyclic group, and the biaryl group may be substituted with 1 to 3 groups selected from the group A)”,
- a C2-6 alkenyl group which may be substituted with 1 to 3 groups selected from the group consisting of “an aryl group, a heterocyclic group, and a biaryl group (the aryl group, the heterocyclic group, and the biaryl group may be substituted with 1 to 3 groups selected from the group A)”,
- a C2-6 alkynyl group which may be substituted with 1 to 3 groups selected from the group consisting of “an aryl group, a heterocyclic group, and a biaryl group (the aryl group, the heterocyclic group, and the biaryl group may be substituted with 1 to 3 groups selected from the group A)”,
- an aryl group which may be substituted with 1 to 3 groups selected from the group A,
- a heterocyclic group which may be substituted with 1 to 3 groups selected from the group A, or
- a biaryl group which may be substituted with 1 to 3 groups selected from the group A, or
- one of R32 and R33 is hydroxyl group, and the other is:
- a group represented by the formula —X335—R332,
- a group represented by the formula —X335-A334-X336—R332, or
- a group represented by the formula —X335-A334-X336-A335-X337—R332,
- wherein X335 is:
- a single bond,
- a group represented by the formula —CH2N(R20) —,
- a group represented by the formula —CH2N(R20)CO—,
- a group represented by the formula —CH2N(R20)CO2—,
- a group represented by the formula —CH2N(R20)CON(R21)—,
- a group represented by the formula —CH2O—, or
- a group represented by the formula —CH2S(O)p—
- R332 is:
- a C1-6 alkyl group which may be substituted with 1 to 3 groups selected from the group consisting of “amino group, hydroxyl group, an aryl group, a heterocyclic group, and a biaryl group (the aryl group, the heterocyclic group, and the biaryl group may be substituted with 1 to 3 substituents selected from the group A)”,
- a C2-6 alkenyl group which may be substituted with 1 to 3 groups selected from the group consisting of “an aryl group, a heterocyclic group, and a biaryl group (the aryl group, the heterocyclic group, and the biaryl group may be substituted with 1 to 3 groups selected from the group A)”,
- a C2-6 alkynyl group which may be substituted with 1 to 3 groups selected from the group consisting of “an aryl group, a heterocyclic group, and a biaryl group (the aryl group, the heterocyclic group, and the biaryl group may be substituted with 1 to 3 groups selected from the group A)”,
- an aryl group which may be substituted with 1 to 3 groups selected from the group A,
- a heterocyclic group which may be substituted with 1 to 3 groups selected from the group A, or
- a biaryl group which may be substituted with 1 to 3 groups selected from the group A,
- p is an integer of 0 to 2, or
- R32 and R33 combine together to represent oxo group,
- oxime group,
- a protected oxime group,
- a group represented by the formula (III)
- or
- a group represented by the formula (IV)
- wherein R334 is:
- a group represented by the formula —OH or
- a group represented by the formula —SH, or
- one of R2 and R3 is hydrogen atom, and the other may combine with R4 to represent a group represented by the formula (V):
- wherein R15 is a C1-6 alkyl group substituted with one biaryl group which may be substituted with 1 to 3 groups selected from the group A,
- R4 is:
- hydrogen atom,
- a group represented by the formula —R041,
- a group represented by the formula —CH2—CH(OH)—CH2—NHR041, or
- a group represented by the formula —CH2—CH(OH)—CH2—NH-A041-X042—R041,
- wherein A041 is:
- a divalent C1-10 aliphatic hydrocarbon group, or
- a divalent heterocyclic group, and
- R041 is:
- a C1-6 alkyl group which may be substituted with 1 to 3 groups selected from the group consisting of “an aryl group, a heterocyclic group, and a biaryl group (the aryl group, the heterocyclic group, and the biaryl group may be substituted with 1 to 3 groups selected from the group A)”,
- a C2-6 alkenyl group which may be substituted with 1 to 3 groups selected from the group consisting of “an aryl group, a heterocyclic group, and a biaryl group (the aryl group, the heterocyclic group, and the biaryl group may be substituted with 1 to 3 groups selected from the group A)”,
- a C2-6 alkynyl group which may be substituted with 1 to 3 groups selected from the group consisting of “an aryl group, a heterocyclic group, and a biaryl group (the aryl group, the heterocyclic group, and the biaryl group may be substituted with 1 to 3 groups selected from the group A)”,
- an aryl group which may be substituted with 1 to 3 groups selected from the group A,
- a heterocyclic group which may be substituted with 1 to 3 groups selected from the group A, or
- a biaryl group which may be substituted with 1 to 3 groups selected from the group A, or
- R4 may combine with R6 to form cyclic carbonate [—CO2—],
- one of R5 and R6 is hydrogen atom, and the other is:
- hydrogen atom,
- hydroxyl group,
- a protected hydroxyl group,
- amino group,
- a protected amino group,
- a group represented by the formula —X051—R051, or
- a group represented by the formula —X051-A051-X052—R051,
- wherein X051 is:
- a group represented by the formula —O—,
- a group represented by the formula —OCON(R22)—,
- a group represented by the formula —N(R22)—, or
- a group represented by the formula —N(R22)CO—, and
- R051 is:
- a C1-6 alkyl group which may be substituted with 1 to 3 groups selected from the group consisting of “an aryl group, a heterocyclic group, and a biaryl group (the aryl group, the heterocyclic group, and the biaryl group may be substituted with 1 to 3 groups selected from the group A)”,
- a C2-6 alkenyl group which may be substituted with 1 to 3 groups selected from the group consisting of “an aryl group, a heterocyclic group, and a biaryl group (the aryl group, the heterocyclic group, and the biaryl group may be substituted with 1 to 3 groups selected from the group A)”,
- a C2-6 alkynyl group which may be substituted with 1 to 3 groups selected from the group consisting of “an aryl group, a heterocyclic group, and a biaryl group (the aryl group, the heterocyclic group, and the biaryl group may be substituted with 1 to 3 groups selected from the group A)”,
- an aryl group which may be substituted with 1 to 3 groups selected from the group A,
- a heterocyclic group which may be substituted with 1 to 3 groups selected from the group A, or
- a biaryl group which may be substituted with 1 to 3 groups selected from the group A, or
- R5 and R6 combine together to represent
- oxo group,
- oxime group,
- a protected oxime group,
- a group represented by the formula ═N—X053—R052, or
- a group represented by the formula ═N—X053-A052-X054—R052,
- wherein X053 is:
- a group represented by the formula —O—, or
- a group represented by the formula —CO—, and
- R053 is:
- a C1-6 alkyl group which may be substituted with 1 to 3 groups selected from the group consisting of “an aryl group, a heterocyclic group, and a biaryl group (the aryl group, the heterocyclic group, and the biaryl group may be substituted with 1 to 3 groups selected from the group A)”,
- a C2-6 alkenyl group which may be substituted with 1 to 3 groups selected from the group consisting of “an aryl group, a heterocyclic group, and a biaryl group (the aryl group, the heterocyclic group, and the biaryl group may be substituted with 1 to 3 groups selected from the group A)”,
- a C2-6 alkynyl group which may be substituted with 1 to 3 groups selected from the group consisting of “an aryl group, a heterocyclic group, and a biaryl group (the aryl group, the heterocyclic group, and the biaryl group may be substituted with 1 to 3 groups selected from the group A)”,
- an aryl group which may be substituted with 1 to 3 groups selected from the group A,
- a heterocyclic group which may be substituted with 1 to 3 groups selected from the group A, or
- a biaryl group which may be substituted with 1 to 3 groups selected from the group A,
- the ring A is a group represented by the formula (VI)
- or
- a group represented by the formula (VII)
- wherein R7 and R8, which are the same or different, represent hydrogen atom, or
- a group represented by the formula —X071—R071,
- wherein X071 is:
- a single bond,
- a group represented by the formula -A072-N(R27)—,
- a group represented by the formula -A072-N(R27)CO—,
- a group represented by the formula -A072-N(R27)CO2—,
- a group represented by the formula -AO72-N(R27)CON(R28)—,
- a group represented by the formula -A072-OCON(R27)—,
- a group represented by the formula -A072-O—,
- a group represented by the formula -A072-CO2—,
- a group represented by the formula —CO2—,
- a group represented by the formula -A072-OCO—,
- a group represented by the formula -A072-OCO2—,
- a group represented by the formula -A072-S(O)t—,
- a group represented by the formula -A072-N(R27)SO2—,
- a group represented by the formula -A072-SO2N(R27)—,
- a group represented by the formula -A072-CON(R27)—, or,
- a group represented by the formula —CON(R27)—,
- A072 is:
- a divalent C1-10 aliphatic hydrocarbon group,
- t is an integer of 0 to 2,
- R071 is:
- a C1-6 alkyl group which may be substituted with 1 to 3 groups selected from the group consisting of “amino group, hydroxyl group, an aryl group, a heterocyclic group, and a biaryl group (the aryl group, the heterocyclic group, and the biaryl group may be substituted with 1 to 3 groups selected from the group A)”,
- a C2-6 alkenyl group which may be substituted with 1 to 3 groups selected from the group consisting of “amino group, hydroxyl group, an aryl group, a heterocyclic group, and a biaryl group (the aryl group, the heterocyclic group, and the biaryl group may be substituted with 1 to 3 groups selected from the group A)”,
- a C2-6 alkynyl group which may be substituted with 1 to 3 groups selected from the group consisting of “amino group, hydroxyl group, an aryl group, a heterocyclic group, and a biaryl group (the aryl group, the heterocyclic group, and the biaryl group may be substituted with 1 to 3 groups selected from the group A)”,
- an aryl group which may be substituted with 1 to 3 groups selected from the group A,
- a heterocyclic group which may be substituted with 1 to 3 groups selected from the group A, or
- a biaryl group which may be substituted with 1 to 3 groups selected from the group A, and
- R9 and R10, which are the same or different, represent
- hydrogen atom,
- hydroxyl group,
- a protected hydroxyl group,
- amino group,
- a protected amino group,
- azido group
- a halogen atom,
- a group represented by the formula —X091—R091,
- a group represented by the formula —X091-A091-X092—R091,
- a group represented by the formula —X091-A091-X092—X092—X093—R091, or
- a group represented by the formula —X091-A091-X092-A092-X093-A093-X094—R091,
- wherein X091 is:
- a single bond,
- a group represented by the formula -A094-N(R23)—,
- a group represented by the formula -A094-N(R23)CO—,
- a group represented by the formula -A094-N(R23)CO2—,
- a group represented by the formula -A094-N(R23)CON(R24)—,
- a group represented by the formula -A094-OCON(R23)—,
- a group represented by the formula -A094-O—,
- a group represented by the formula -A094-CO2—,
- a group represented by the formula -A094-OCO—,
- a group represented by the formula -A094-OCO2—,
- a group represented by the formula -A094-S(O)q—,
- a group represented by the formula -A094-N(R23)SO2—,
- a group represented by the formula -A094-SO2N(R23)—, or
- a group represented by the formula -A094-CON(R23)—,
- A094 is:
- a single bond,
- a divalent C1-10 aliphatic hydrocarbon group,
- an arylene group, or
- a divalent heterocyclic group,
- R091 is:
- a C1-6 alkyl group which may be substituted with 1 to 3 groups selected from the group consisting of “amino group, hydroxyl group, a C3-8 cycloalkyl group, a C3-8 cycloalkylidene group, a C1-6 alkoxy group, a C1-11 acyloxy group, a C2-7 alkoxycarbonyl group, a C1-11 acyl group, cyano group, an aryl group, a heterocyclic group, and a biaryl group (the aryl group, the heterocyclic group, and the biaryl group may be substituted with 1 to 3 groups selected from the group A)”,
- a C2-6 alkenyl group which may be substituted with 1 to 3 groups selected from the group consisting of “amino group, hydroxyl group, a C3-8 cycloalkyl group, a C1-6 alkoxy group, a C1-11 acyloxy group, a C2-7 alkoxycarbonyl group, cyano group, an aryl group, a heterocyclic group, and a biaryl group (the aryl group, the heterocyclic group, and the biaryl group may be substituted with 1 to 3 groups selected from the group A)”,
- a C2-6 alkynyl group which may be substituted with 1 to 3 groups selected from the group consisting of “amino group, hydroxyl group, a C3-8 cycloalkyl group, a C1-6 alkoxy group, a C1-11 acyloxy group, a C2-7 alkoxycarbonyl group, cyano group, an aryl group, a heterocyclic group, and a biaryl group (the aryl group, the heterocyclic group, and the biaryl group may be substituted with 1 to 3 groups selected from the group A)”,
- a C3-8 cycloalkyl group which may be substituted with a C1-6 alkyl group,
- an aryl group which may be substituted with 1 to 5 groups selected from the group B,
- a heterocyclic group which may be substituted with 1 to 5 groups selected from the group B, or
- a biaryl group which may be substituted with 1 to 5 groups selected from the group B,
- the group B is a group consisting of “hydroxyl group, a halogen atom, cyano group, a C1-6 alkyl group, a C1-6 hydroxyalkyl group, a C2-6 alkynyl group, a C3-8 cycloalkyl group, a C1-6 haloalkyl group, a C7-11 aralkyl group, a C1-10 alkoxy group, a C3-8 cycloalkoxy group, a C1-6 haloalkoxy group, a C7-11 aralkyloxy group, an aryloxy group, a C1-11 acyloxy group, a C1-6 alkylthio group, a C1-6 haloalkylthio group, adamantyl group, carboxy group, a C2-7 alkoxycarbonyl group, a C2-7 alkylaminocarbonyl group, an aryloxycarbonyl group, a C8-12 aralkyloxycarbonyl group, a C1-11 acyl group, a C1-11 haloacyl group, amino group, a C1-6 alkylamino group, nitro group, a saturated heterocyclic group and a C1-11 acylamino group”,
- q is an integer of 0 to 2, and
- the bond indicated with lines including a broken line is a single bond or a double bond,
- R11 is:
- hydrogen atom, or
- a protective group of hydroxyl group,
- R12 and R13, which are the same or different, represent
- hydrogen atom,
- a C1-6 alkyl group, or
- a protective group of amino group,
- X332, X333, X334, X336, X337, X042, X52, X054, X092, X093, and X094 mentioned above, which are the same or different, represent
- a single bond,
- a group represented by the formula —O—,
- a group represented by the formula —OCO—,
- a group represented by the formula —OCO2—,
- a group represented by the formula —OCON(R25)—,
- a group represented by the formula —S(O)r—,
- a group represented by the formula —SO2N(R25)—,
- a group represented by the formula —OCS—,
- a group represented by the formula —CO—,
- a group represented by the formula —CO2—,
- a group represented by the formula —CON(R25)—,
- a group represented by the formula —CH═N—,
- a group represented by the formula —CH═N—O—,
- a group represented by the formula —C(R25)═N—,
- a group represented by the formula —C(R25)═N—O—,
- a group represented by the formula —C(R25)═N—N(R26)—,
- a group represented by the formula —CH═N—N(R25)—,
- a group represented by the formula —CS—,
- a group represented by the formula —C(S)O—,
- a group represented by the formula —CSN(R25)—,
- a group represented by the formula —O—N═C(R25)—,
- a group represented by the formula —N═CH—,
- a group represented by the formula —N(R25)—,
- a group represented by the formula —N(R25)CO—,
- a group represented by the formula —N(R25)CS—,
- a group represented by the formula —N(R25)SO2—,
- a group represented by the formula —N(R25)CO2—, or
- a group represented by the formula —N(R25)CON(R26)—,
- r is an integer of 0 to 2,
- A331, A332, A333, A334, A335, A051, A052, A091, A092 and A093 mentioned above, which are the same or different, represent
- a divalent C1-10 aliphatic hydrocarbon group which may be substituted with hydroxyl group or a C1-6 alkoxy group,
- an arylene group which may be substituted with hydroxyl group or a C1-6 alkoxy group, or a divalent heterocyclic group which may be substituted with hydroxyl group or a C1-6 alkoxy group, and
- R20, R21, R22, R23, R24, R25, R26, R27 and R28 mentioned above, which are the same or different, represent
- hydrogen atom, or
- a C1-6 alkyl group}, or a salt thereof, or a hydrate or solvate thereof.
240 more elements
Dependencies are inferred from the claim text.