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US 8,299,035 B2Granted
10a-azalide compound having 4-membered ring structure
AssigneesTaisho Pharmaceutucal Co., Ltd., Meiji Seika Pharma Co., Ltd.
InventorsTomohiro Sugimoto, Kanako Yamamoto, Jun Kurosaka, Naoki Sasamoto, Masato Kashimura, Tomoaki Miura, Kenichi Kanemoto, Satoshi Yoshida, Kou Kumura, Keiichi Ajito
Life of this patent
Estimating the term…
Abstract
A 10a-azalide compound having a 4-membered ring structure crosslinked at the 10a- and 12-positions, which is represented by the formula (I), and is effective on even Haemophilus influenzae, or erythromycin resistant bacteria (e.g., resistant pneunococci and streptococci).
Claims30
A 10a-azalide compound represented by the formula (I):
- wherein, in the formula, R2 and R3 combine together to represent an oxo group, or one of them is a hydrogen atom, and the other is:
- a 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 a hydroxyl group, a halogen atom, an amino group, a carboxyl group, a cyano group, a C1-6 alkyl group (this C1-6 alkyl group may be substituted with amino group, or a C1-6 alkylamino group), a C1-6 alkylamino group, a C1-6 haloalkyl group, a C1-6 alkoxy group, a C1-6 alkylthio group, a C2-7 alkoxycarbonyl group, nitro group, a saturated heterocyclic group, a C7-12 aralkyloxy group, and a C1-11 acyl group,
- one of R32 and R33 is a hydrogen atom, and the other is:
- a hydrogen atom,
- a hydroxyl group,
- a protected hydroxyl group,
- an 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)—,
- a group represented by the formula —N(R20)CO—, or
- a group represented by the formula —OCSN(R20)—, and
- 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 a 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 —CH2—A336—,
- a group represented by the formula —CH2O—, or
- a group represented by the formula —CH2S(O)p—,
- A336 is:
- a divalent nitrogen-containing heterocyclic group which may be substituted with a hydroxyl group or a C1-6 alkoxy group,
- R332 is:
- a C1-6 alkyl group which may be substituted with 1 to 3 groups selected from the group consisting of “an amino group, a 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 “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, and
- p is an integer of 0 to 2, or
- R32 and R33 combine together to represent oxo group,
- an oxime group,
- a protected oxime group,
- a group represented by the formula 3:
- a group represented by the formula 4:
- or
- a group represented by the formula 5:
- wherein R334 is:
- a group represented by the formula —OH, or
- by the formula —SH,
- R335 is a hydrogen atom, or a C1-6 alkyl group,
- R34 is:
- a group represented by the formula —R336,
- a group represented by the formula —A337—X338—R336, or
- a group represented by the formula —A337—X338—A338—X339—R336, and
- R336 is:
- a C1-6 alkyl group which may be substituted with 1 to 3 groups selected from the group consisting of “an 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 “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,
- R4 is:
- a 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 a cyclic carbonate [—CON(R22)—],
- one of R5 and R6 is hydrogen atom, and the other is:
- a hydrogen atom,
- a hydroxyl group,
- a protected hydroxyl group,
- an 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
- an oxo group,
- an 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
- R052 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,
- R7 is:
- a hydrogen atom, or
- a protective group of hydroxyl group,
- R8 and R9, which are the same or different, represent
- a hydrogen atom,
- a C1-6 alkyl group, or
- a protective group of an amino group,
- X332, X333, X334, X336, X337, X338, X339, X042, X052, and X054 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, A337, A338, A051, and A052 mentioned above, which are the same or different, represent
- a divalent C1-6 aliphatic hydrocarbon group which may be substituted with a hydroxyl group, a C1-6 alkoxy group, an amino group, a C1-6 alkylamino group, or a heterocyclic group,
- an arylene group which may be substituted with a hydroxyl group or a C1-6 alkoxy group, or
- a divalent heterocyclic group which may be substituted with a hydroxyl group or a C1-6 alkoxy group, and
- R20, R21, R22, R25, and R26 mentioned above, which are the same or different, represent
- a hydrogen atom, or a C1-6 alkyl group which may be substituted with 1 to 3 groups selected from the group A, or a salt thereof.
177 more elements
Dependencies are inferred from the claim text.