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US 2006/0041123 A1Published application
Antibacterial agents
OwnerJeffrey Axten, Gerald Brooks +7inventors
InventorsJeffrey Axten, Gerald Brooks, Pamela Brown, David Davies, Timothy Gallagher, Roger Markwell, William Miller, Neil Pearson, Mark Seefeld
Life of this patent
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Abstract
Quinoline and naphthyridine derivatives useful in the treatment of bacterial infections in mammals, particularly humans.
Claims13
A compound according to formula (I):
- wherein:
- Z1 is Nor CR1a;
- R1 and R1a are independently selected from H, nitro, halogen, (C1-3)alkylthio, (C1-3)alkyl, and (C1-3)alkoxy optionally substituted by (C1-3)alkoxy;
- or R1 and R1a are joined together to form ethylenedioxy;
- R1b is H or halogen;
- with the proviso that when Z1 is N, then R1b is H and when Z1 is CR1a then R1 is not H;
- R1c is halogen;
- AB is CHR6—CO or CHR6—CH2;
- R6 is H, NH2, —CH2OH, or hydroxy;
- R3 is up to two substituents selected from H, halogen, (C1-3)alkyl, hydroxy(C1-3)alkyl, CONH2, COOH, —CH2CONH2, —CH2COOH, —CONHCH3, and hydroxy in the 3-position optionally substituted by (C1-3)alkyl;
- R4 is a group —U—R5 where R5 is a substituted or unsubstituted bicyclic carbocyclic or heterocyclic ring system (A):
- containing up to four heteroatoms in each ring in which
- at least one of rings (a) and (b) is aromatic;
- X1 is C or N when part of an aromatic ring or CR14 when part of a non aromatic ring;
- X2 is N, NR13, O, S(O)x, CO or CR14 when part of an aromatic or non-aromatic ring or may in addition be CR14R15 when part of a non aromatic ring;
- X3 and X5 are independently N or C;
- Y1 is a 0 to 4 atom linker group each atom of which is independently selected from N, NR13, O, S(O)x, CO and CR14 when part of an aromatic or non-aromatic ring or may additionally be CR14R15 when part of a non aromatic ring,
- Y2 is a 2 to 6 atom linker group, each atom of Y2 being independently selected from N, NR13, O, S(O)x, CO and CR14 when part of an aromatic or non-aromatic ring or may additionally be CR14R15 when part of a non aromatic ring;
- each of R14 and R15 is independently selected from H;
- (C1-4)alkylthio;
- halo;
- (C1-4)alkyl;
- (C2-4)alkenyl;
- hydroxy;
- hydroxy(C1-4)alkyl;
- mercapto(C1-4)alkyl;
- (C1-4)alkoxy;
- trifluoromethoxy;
- nitro;
- cyano;
- carboxy;
- amino or aminocarbonyl optionally substituted by (C1-4)alkyl;
- each R13 is independently H;
- trifluoromethyl;
- (C1-4)alkyl optionally substituted by hydroxy, carboxy, (C1-4)alkoxy, (C1-6)alkylthio, halo or trifluoromethyl;
- (C2-4)alkenyl;
- or aminocarbonyl wherein the amino group is optionally substituted (C1-4)alkyl;
- each x is independently 0, 1 or 2;
- and
- U is CO, SO2 or CH2;
- or a pharmaceutically acceptable salt thereof.
38 more elements
A process for preparing compounds of formula (I), and pharmaceutically acceptable derivatives thereof, which process comprises reacting a compound of formula (IV) with a compound of formula (V):
- wherein Z1′, R1′, R1b′, R1c′ and R3′ are Z1, R1, R1b, R1c and R3 as defined in formula (I) or groups convertible thereto;
- Q1 is NHR4′ or a group convertible thereto wherein R4′ is R4 as defined in formula (I) or groups convertible thereto and Q2 is H or R3′ or Q1 and Q2 together form an optionally protected oxo group;
- (i) X is A′-COW, Y is H;
- (ii) X is CH═CH2, Y is H;
- (iii) X is oxirane, Y is H;
- (iv) one of X and Y is CO2Ry and the other is CH2CO2Rx;
- in which W is a leaving group, e.g. halo or imidazolyl;
- Rx and Ry are (C1-4)alkyl;
- A′ is A as defined in formula (I), or groups convertible thereto;
- and oxirane is:
- and thereafter optionally or as necessary converting Q1 and Q2 to NHR4′;
- converting A′, Z1′R1′, R1b′, R1c′, R3′, and R4′ to A, Z1, R1, R1b, R1c, R3, and R4;
- converting A-B to other A-B, interconverting R1, R1b, R1c, R3, and/or R4, and/or
- forming a pharmaceutically acceptable derivative thereof.
11 more elements
Dependencies are inferred from the claim text.