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US 7,351,696 B2Granted
Compounds
AssigneeGlaxo Group Limited
InventorsJohn Michael Berge, Catherine Simone Victoire Frydrych, Richard Lewis Jarvest
Life of this patent
Estimating the term…
Abstract
The present invention relates to compounds of formula (I) and pharmaceutically acceptable derivatives thereof, to processes for their preparation and their use in therapy or prophylaxis of systemic or topical microbial infections in a human or animal body.
Claims12
A compound of formula (I)
- wherein
- R1 is OC(O)(CH2)mXR7;
- R2 is hydrogen or a hydroxyl protecting group;
- R3 is hydrogen, C1-4alkyl or C3-6alkenyl optionally substituted by 9 to 10 membered fused bicyclic heteroaryl;
- R4 is hydrogen, C1-4alkyl, C3-7cycloalkyl, C3-6alkenyl or a 5 or 6 membered heterocyclic group, wherein the alkyl, cycloalkyl, alkenyl and heterocyclic groups are optionally substituted by up to three substituents independently selected from optionally substituted 5 or 6 membered heterocyclic group, optionally substituted 5 or 6 membered heteroaryl, OR8,
- S(O)nR8, NR8R9, CONR8R9, halogen and cyano;
- R5 is hydroxy, C3-6alkenyloxy optionally substituted by 9 to 10 membered fused bicyclic heteroaryl, or O(CH2)pO(CH2)qR10,
- R6 is hydroxy, or
- R5 and R6 taken together with the intervening atoms form a cyclic group having the following structure:
- wherein Y is a bivalent radical selected from —CH2—, —CH(CN)—, —O—, —N(R11)— and —CH(SR11)—;
- R7 is a heterocyclic group having the following structure:
- R8 and R9 are each independently selected from hydrogen and C1-4alkyl;
- R10 is hydrogen or NR8R9;
- R11 is hydrogen or C1-4alkyl substituted by a group selected from optionally substituted phenyl, optionally substituted 5 or 6 membered heteroaryl and optionally substituted 9 to 10 membered fused bicyclic heteroaryl;
- R12 is hydrogen, C(O)OR15, C(O)NHR15 or C(O)CH2NO2;
- R13 is C1-4alkyl optionally substituted by hydroxy or C1-4alkoxy,
- C3-7cycloalkyl, or optionally substituted phenyl or benzyl;
- R14 is halogen, C1-4alkyl, C1-4thioalkyl, C1-4alkoxy, NH2, NH(C1-4alkyl) or N(C1-4alkyl)2;
- R15 is hydrogen or C1-4alkyl optionally substituted by up to three groups independently selected from halogen, C1-4alkoxy, OC(O)C1-4alkyl and OC(O)OC14alkyl;
- R16 is hydrogen, C1-4alkyl, C3-7cycloalkyl, optionally substituted phenyl or benzyl, acetyl or benzoyl;
- R17 is hydrogen or R14, or R17 and R13 are linked to form the bivalent radical —O(CH2)2— or —(CH2)v—;
- X is —U(CH2)sZ- or X is a group selected from:
- U and Z independently are a divalent radical selected from —N(R16)—, —O—, —S(O)t—, —N(R16)C(O)—, —C(O)N(R16)— and —N[C(O)R16]—;
- W is CR17 or a nitrogen atom;
- m is 0 or an integer from 1 to 5;
- n, r and t are each independently selected from 0, 1 and 2;
- p and q are each independently selected from 1 to 6;
- s is an integer from 2 to 8;
- and
- v is 2 or 3;
- or a pharmaceutically acceptable salt thereof.
28 more elements
A compound selected from:
- 4′-O-[3-[[2-[(3-carboxy-7-chloro-1-cyclopropyl-1,4-dihydro-4-oxo-6-quinolinyl) amino]ethyl]amino]propionyl]-11-O-(2-dimethylaminoethoxymethyl)-(9E)-methoximino erythromycin A,
- 4′-O-[3-[[2-[(3-carboxy-7-chloro-1-cyclopropyl-1,4-dihydro-4-oxo-6-quinolinyl) amino]ethyl]amino]propionyl]-11,12-carbonate-(9E)-O-(2-propyl)oximino erythromycin A,
- 4′-O-[3-[[2-[(3-carboxy-7-chloro-1-cyclopropyl-1,4-dihydro-4-oxo-6-quinolinyl) amino]ethyl]amino]propionyl]-11,12-carbonate-(9E)-methoximino erythromycin A, and
- 4′-O-[3-[[2-[(3-carboxy-7-chloro-1-cyclopropyl-1,4-dihydro-4-oxo-6-quinolinyl) amino]ethyl]amino]propionyl]-11,12-carbonate-(9E)-O-(ethoxymethyl)oximino erythromycin A,
- or a pharmaceutically acceptable salt thereof.
2 more elements
A compound of gene*al formula (IA)
- wherein
- R1 is OC(O)(CH2)mXR7;
- R2 is hydrogen or a hydroxyl protecting group;
- R3 is hydrogen, C1-4alkyl or C3-6alkenyl optionally substituted by 9 to 10 membered fused bicyclic heteroaryl;
- R4 is hydrogen, C1-4alkyl, C3-7cycloalkyl, C3-6alkenyl or a 5 or 6 membered heterocyclic group, wherein the alkyl, cycloalkyl, alkenyl and heterocyclic groups are optionally substituted by up to three substituents independently selected from optionally substituted 5 or 6 membered heterocyclic group, optionally substituted 5 or 6 membered heteroaryl, OR8, S(O)nR8, NR8R9, CONR8R9, halogen and cyano;
- R5 is hydroxy, C3-6alkenyloxy optionally substituted by 9 to 10 membered fused bicyclic heteroaryl or O(CH2)pO(CH2)qR10,
- R6 is hydroxy, or
- R5 and R6 taken together with the intervening atoms form a cyclic group having the following structure:
- wherein Y is a bivalent radical selected from —CH2—, —CH(CN)—, —O—, —N(R11)— and —CH(SR8)—;
- R7 is a heterocyclic group having the following structure:
- R8 and R9 are each independently selected from hydrogen and C1-4alkyl;
- R10 is hydrogen or NR8R9;
- R11 is hydrogen or C1-4alkyl substituted by a group selected from optionally substituted phenyl, optionally substituted 5 or 6 membered heteroaryl and optionally substituted 9 to 10 membered fused bicyclic heteroaryl;
- R12 is hydrogen, C(O)OR15, C(O)NHR15 or C(O)CH2NO2;
- R13 is hydrogen C1-4alkyl, C3-7cycloalkyl, or optionally substituted phenyl or benzyl;
- R14 is halogen, C1-4alkyl, C1-4thioalkyl, C1-4alkoxy, NH2, NH(C1-4alkyl) or N(C1-4alkyl)2;
- R15 is hydrogen or C1-4alkyl;
- R16 is hydrogen, C1-4alkyl, C3-7cycloalkyl, optionally substituted phenyl or benzyl, acetyl or benzoyl;
- X is —U(CH2)sZ- or X is a group selected from:
- U and Z independently are a divalent radical selected from —N(R16)—, —O—, —S(O)t—, —N(R16)C(O)—, —C(O)N(R16)— and —N[C(O)R16]—;
- W is a carbon or a nitrogen atom;
- m is O or an integer from 1 to 5;
- n, r and t are each independently selected from 0, 1 and 2;
- p and q are each independently selected from 1 and 2;
- and
- s is an integer from 2 to 8;
- or a pharmaceutically acceptable salt thereof.
24 more elements
Dependencies are inferred from the claim text.