US 7,732,461 B2Granted

Tryclic nitrogen containing compounds and their use as antibacterials

AssigneeGlaxo Group Limited

InventorsGerald Brooks, Ilaria Giordano, Alan Joseph Hennessy, Neil David Pearson

Life of this patent

Estimating the term…

Abstract

Tricyclic nitrogen containing compounds of formula (I) and their use as antibacterials.

Drawings

Claims15

Dependent claims

A compound of formula (I) or a pharmaceutically acceptable salt;

N-oxide thereof:
wherein:
R1a and R1b are independently selected from hydrogen;
halogen;
cyano;
(C1-6)alkyl;
(C1-6)alkylthio;
trifluoromethyl;
trifluoromethoxy;
carboxy;
hydroxy optionally substituted with (C1-6)alkyl or (C1-6)alkoxy-substituted(C1-6)alkyl;
(C1-6)alkoxy-substituted(C1-6)alkyl;
hydroxy (C1-6)alkyl;
an amino group optionally N-substituted by one or two (C1-6)alkyl, formyl, (C1-6)alkylcarbonyl or (C1-6)alkylsulphonyl groups;
and aminocarbonyl wherein the amino group is optionally substituted by (C1-4)alkyl;
R2 is hydrogen, or (C1-4)alkyl, or together with R6 forms Y as defined below;
A is a group (i):
in which:
R3 is as defined for R1a or R1b or is oxo and n is 1 or 2;
or A is a group (ii):
in which:
W1, W2 and W3 are CR4R8;
or W2 and W3 are CR4R8 and W1 represents a bond between W3 and N;
X is O, CR4R8, or NR6;
one R4 is as defined for R1a and R1b and the remainder and R8 are hydrogen, or one R4 and R8 are together oxo and the remainder are hydrogen;
R6 is hydrogen or (C1-6)alkyl;
or together with R2 forms Y;
R7 is hydrogen;
halogen;
hydroxy optionally substituted with (C1-6)alkyl;
or (C1-6)alkyl;
Y is CR4R8CH2;
CH2CR4R8;
(C═O);
CR4R8;
CR4R8(C═O);
or (C═O)CR4R8;
or when X is CR4R8, R8 and R7 together represent a bond;
U is selected from CO and CH2 and
R5 is an optionally substituted bicyclic carbocyclic or heterocyclic ring system (B):
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;
carboxy(C1-4)alkyl;
(C1-4)alkyl;
(C1-4)alkoxycarbonyl;
(C1-4)alkylcarbonyl;
(C1-4)alkoxy (C1-4)alkyl;
hydroxy;
hydroxy(C1-4)alkyl;
(C1-4)alkoxy;
nitro;
cyano;
carboxy;
amino and aminocarbonyl, wherein the amino or aminocarbonyl are optionally mono- or di-substituted by (C1-4)alkyl;
or
R14 and R15 may together represent oxo;
each R13 is independently H;
trifluoromethyl;
(C1-4)alkyl optionally substituted by hydroxy, (C1-6)alkoxy, (C1-6)alkylthio, halo or trifluoromethyl;
(C2-4)alkenyl;
(C1-4)alkoxycarbonyl;
(C1-4)alkylcarbonyl;
(C1-6)alkylsulphonyl;
or aminocarbonyl wherein the amino group is optionally mono or disubstituted by (C1-4)alkyl;
and
each x is independently 0, 1 or 2.

72 more elements

A compound selected from the group consisting of:

4-[(4-{[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)methyl]amino]-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-chloro-4-({4-[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-chloro-4-[(4-{[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or an enantiomer thereof;
3-chloro-4-[(4-{[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)methyl]amino-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-chloro-4-[(4-{[(7-chloro-3-oxo-3,4-dihydro-2,1-pyrido[3,2-b][1,4]oxazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-chloro-4-[(4-{[(8-fluoro-2,3-dihydro-1,4-benzodioxin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
N-{1-[(3-chloro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl)methyl]-4-piperidinyl)-3-oxo-3,4-dihydro-2H-pyrido[(3,2-b][1,4]thiazine-6-carboxamide;
4-({4-[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-fluoro-4-[(4-{[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
N-{1-[(3-fluoro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl)methyl]-4-piperidinyl}-3-oxo-3,4-dihydro-2H-pyrido[3,2-b]4]oxazine-6-carboxamide;
3-chloro-4-[((3R,4S)-4-{[(7-fluoro-2,3-dihydro-1,4-benzodioxin-6-yl)methyl]amino}-3-hydroxy-1-piperidinyl)methyl)-4,5-dihydro-7H-1-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or a diastereomer thereof;
4-({(3R,4S)-4-((2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino)-3-hydroxy-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
4-({(3R,4S)-4-[(2,3-dihydro-1-benzofuran-5-ylmethyl)amino]-3-hydroxy-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
4-({(3R,4S)-4-[(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino]-3-hydroxy-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-chloro-4-[((3R,4S)-4-{[(7-fluoro-3-oxo-3,4-dihydro-2H-1,4-benzothiazin-6-yl)methyl]amino}-3-hydroxy-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or a diastereomer thereof;
3-chloro-4-[((3R,4S)-3-hydroxy-4-{[(3-oxo-3,4-dihydro-2H-pyrido-3,2-b][1,4]thiazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
N-{(3R,4S)-1-[(3-chloro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl)methyl]-3-hydroxy-4-piperidinyl}-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carboxamide;
3-chloro-4-({(3R,4S)-4-[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino)-3-hydroxy-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-chloro-4-[(4-{[(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-chloro-4-({4-[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or an enantiomer thereof;
3-chloro-4-[(4-{[(3-oxo-3,4-dihydro-2H-1,4-benzothiazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or an enantiomer thereof;
3-chloro-4-[(4-{[(2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazin-7-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or an enantiomer thereof;
3-chloro-4-({(3R,4S)-3-hydroxy-4-[([1,3]oxathiolo[5,4-c]pyridin-6-ylmethyl)amino]-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or a diastereomer thereof;
3-chloro-4 ({(3R,4S)-4-[(3,4-dihydro-2H-pyrano[2,3-c]pyridin-6-ylmethyl)amino]-3-hydroxy-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-chloro-4-({4-[(2,3-dihydro[1,4]oxathiino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or an enantiomer thereof;
3-chloro-4-({4-[(2,3-dihydrofuro[2,3-c]pyridin-5-ylmethyl)amino]-1-piperidinyl}methyl)4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-4-({4-[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-4-({4-[(3,4-Dihydro-2H-pyrano[2,3-c]pyridin-6-ylmethyl)amino]-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-3-fluoro-4-({4-[([1,3]oxathiolo[5,4-c]pyridin-6-ylmethyl)amino]-1-piperidinyl methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-3-fluoro-4-[(4-{[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-3-fluoro-4-[(4-{[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4S)-4-({4-[2,3-dihydro[1,4]-dioxino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-[1,5-naphthyridin-7-one;
(4R)-4-({4-[(2,3-dihydro[1,4]oxathiino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-4-({4-[(2,3-dihydrofuro[2,3c]-pyridin-5-ylmethyl)amino]-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
4-({cis-4-[(2,3-dihydro[1,4]dioxino[2,3c]pyridin-7-ylmethyl)amino]-3-fluoro-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5-naphthyridin-7-one;
3-fluoro-4-[(cis-3-fluoro-4-{[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-fluoro-4-[(cis-3-fluoro-4-{[3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
4-[{(cis-4-[(2,3-dihydro[1,4-benzodioxin-6-ylmethyl)amino]-3-fluoro-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-fluoro-4-{cis-4-hydroxy-3-({[(3-oxo-3,4-dihydro-2H-pyrido-[3,2-b][1,4]thiazin-6-yl)methyl]amino}methyl)-1-piperidinyl]methyl}-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
4-[(cis-3-{[2,3-dihydro1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]methyl}4-hydroxy-1-piperidinyl)methyl]-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
4-[((2S)-2-{[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]methyl-4-morpholinyl)methyl]-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-fluoro-4-[((2S)-2-{[([1,3]oxathiolo[5,4-c]pyridin-6-ylmethyl)amino]methyl}-4-morpholinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-fluoro-4-{[(2S)-2-({[(3-oxo-3,4-dihydro-2H-pyrido[32-b][1,4]thiazin-6-yl)methyl]amino}methyl)-4-morpholinyl]methyl-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-chloro-4-({4-[([1,3]oxathiolo[5,4-c]pyridin-6-ylmethyl)amino]-1-piperidinyl]methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or an enantiomer thereof;
3-chloro-4-({4-[(3,4-dihydro-2H-pyrano[2,3-c]pyridin-6-ylmethyl)amino]-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or an enantiomer thereof;
3-chloro-4-[(4-{[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-1-7-one;
or an enantiomer thereof;
3-chloro-4-({(3R,4S)-3-hydroxy-4-[([1,3]oxathiolo[5,4-c]pyridin-6-ylmethyl)amino]-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or a diastereomer thereof;
3-fluoro-4-((3R,4S)-3-hydroxy-4-[([1,3]oxathiolo[5,4-c]pyridin-6-ylmethyl)amino]-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or a diastereomer thereof;
7-[({3R,4S)-1-[(3-chloro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl)methyl]-3-hydroxy-4-piperidinyl}amino)methyl]-2,3-dihydro-1,4-benzodioxin-5-carbonitrile or a diastereomer thereof;
4-({4-[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
4-({4-[([1,3]oxathiolo[5,4-c]pyridin-6-ylmethyl)amino]-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
7-{[(1-{[(4R)-3-fluoro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de)-1,5-naphthyridin-4-yl]methyl}-4-piperidinyl)amino]methyl}-2,3-dihydro-1,4-benzodioxin-5-carbonitrile;
(4R)-3-fluoro-4-[(4-{[(2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazin-7-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-chloro-4-{(4-{[(5-oxo-1,2,3,5-tetrahydro-7-indolizinyl)methyl]amino}-1-piperidinyl)methyl-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-chloro-4-[(4-{((2-methyl-1-oxo-1,2,3,4-tetrahydro-7-isoquinolinyl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-3-fluoro-4-[(4-{((3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-4-[(4-{[(7-chloro-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-3-fluoro-4-[(4-{[(8-fluoro-2,3-dihydro-1,4-benzodioxin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-4-[(4-{[(7-bromo-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
4-({(3S,4R)-4-[([1,3]oxathiolo[5,4-c]pyridin-6-ylmethyl)amino]-3-hydroxy-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or a diastereomer thereof;
4-({(3R,4S)-4-[([1,3]oxathiolo[5,4-c]pyridin-6-ylmethyl)amino]-3-hydroxy-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or a diastereomer thereof;
4-({(3R,4S)-4-[2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-3-hydroxy-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or a diastereomer thereof;
4-(3R,4S)-4-[(2,3-dihydro[1,4]oxathiino[2,3-c]pyridin-7-ylmethyl)amino]-3-hydroxy-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or a diastereomer thereof;
3-fluoro-4-({(3R,4S)-4-[(3,4-dihydro-2H-pyrano[2,3-c]pyridin-6-ylmethyl)amino]-3-hydroxy-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-3-fluoro-4-[(4-{[(3-oxo-3,4-dihydro-2H-1,4-benzothiazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
5-{[(1-{[(4R)-3-fluoro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl]methyl}-4-piperidinyl)amino]methyl}-2,3-dihydro-1-benzofuran-7-carbonitrile;
4-{[(3R,4S)-4-[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-3-(methyloxy)-1-piperidinyl]methyl}-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
4-{[(3R,4S)-4-[(3,4-dihydro-2H-pyrano[2,3-c]pyridin-6-ylmethyl)amino]-3-(methyloxy)-1-piperidinyl]methyl}1-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-fluoro-4-((3R,4S)-3-(methyloxy)-4-[([1,3]oxathiolo[5,4-c]pyridin-6-ylmethyl)amino]-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
5-({[(3R,4S)-1-[(3-fluoro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl)methyl]-3-(methyloxy)-4-piperidinyl]amino}methyl)-2,3-dihydro-1-benzofuran-7-carbonitrile;
4-[((3R,4S)-4-{[(7-bromo-2,3-dihydro-1,4-benzodioxin-6-yl)methyl]amino}-3-hydroxy-1-piperidinyl)methyl]-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or a diastereomer thereof;
4-({(3R,4S)-4-[(5,6-dihydro-4H-cyclopenta[b]thien-2-ylmethyl)amino]-3-hydroxy-1-piperidinyl)methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or a diastereomer thereof;
(4R)-3-fluoro-4-[(4-{[(7-fluoro-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-3-fluoro-4-[(4-{[(7-fluoro-3-oxo-3,4-dihydro-2H-1,4-benzothiazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-3-fluoro-4-{[(4-{[(8-fluoro-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7one;
(4R)-4-({4-[(2,3-dihydro(1,4]dioxino[2,3-b]pyridin-7-ylmethyl)amino]-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-4-({4-[(5,6-dihydro-4H-cyclopenta[b]thien-2-ylmethyl)amino]-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-4-({4-[(6,7-dihydro-5H-thieno[3,2-b]pyran-2-ylmethyl)amino]-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-4-({4-[(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino]-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
and
(4R)-3-fluoro-4-({4-[([1,2,3]thiadiazolo[5,4-b]pyridin-6-ylmethyl)amino]-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
or a pharmaceutically acceptable salt thereof.

80 more elements

Dependencies are inferred from the claim text.

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US 7,732,461 B2Granted

Tryclic nitrogen containing compounds and their use as antibacterials

AssigneeGlaxo Group Limited

InventorsGerald Brooks, Ilaria Giordano, Alan Joseph Hennessy, Neil David Pearson

Life of this patent

About 6 months of term left · ends 25 Apr 2027 (estimated)

Priority, United Kingdom26 Apr 2006

Filed25 Apr 2007

Granted8 Jun 2010

Today12 Oct 2026

Term ends25 Apr 2027

Priority, United Kingdom26 Apr 2006

Granted8 Jun 2010

Term ends25 Apr 2027

Life of this patent

Estimating the term…

Abstract

Tricyclic nitrogen containing compounds of formula (I) and their use as antibacterials.

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Claims15

Dependent claims

A compound of formula (I) or a pharmaceutically acceptable salt;

N-oxide thereof:
wherein:
R1a and R1b are independently selected from hydrogen;
halogen;
cyano;
(C1-6)alkyl;
(C1-6)alkylthio;
trifluoromethyl;
trifluoromethoxy;
carboxy;
hydroxy optionally substituted with (C1-6)alkyl or (C1-6)alkoxy-substituted(C1-6)alkyl;
(C1-6)alkoxy-substituted(C1-6)alkyl;
hydroxy (C1-6)alkyl;
an amino group optionally N-substituted by one or two (C1-6)alkyl, formyl, (C1-6)alkylcarbonyl or (C1-6)alkylsulphonyl groups;
and aminocarbonyl wherein the amino group is optionally substituted by (C1-4)alkyl;
R2 is hydrogen, or (C1-4)alkyl, or together with R6 forms Y as defined below;
A is a group (i):
in which:
R3 is as defined for R1a or R1b or is oxo and n is 1 or 2;
or A is a group (ii):
in which:
W1, W2 and W3 are CR4R8;
or W2 and W3 are CR4R8 and W1 represents a bond between W3 and N;
X is O, CR4R8, or NR6;
one R4 is as defined for R1a and R1b and the remainder and R8 are hydrogen, or one R4 and R8 are together oxo and the remainder are hydrogen;
R6 is hydrogen or (C1-6)alkyl;
or together with R2 forms Y;
R7 is hydrogen;
halogen;
hydroxy optionally substituted with (C1-6)alkyl;
or (C1-6)alkyl;
Y is CR4R8CH2;
CH2CR4R8;
(C═O);
CR4R8;
CR4R8(C═O);
or (C═O)CR4R8;
or when X is CR4R8, R8 and R7 together represent a bond;
U is selected from CO and CH2 and
R5 is an optionally substituted bicyclic carbocyclic or heterocyclic ring system (B):
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;
carboxy(C1-4)alkyl;
(C1-4)alkyl;
(C1-4)alkoxycarbonyl;
(C1-4)alkylcarbonyl;
(C1-4)alkoxy (C1-4)alkyl;
hydroxy;
hydroxy(C1-4)alkyl;
(C1-4)alkoxy;
nitro;
cyano;
carboxy;
amino and aminocarbonyl, wherein the amino or aminocarbonyl are optionally mono- or di-substituted by (C1-4)alkyl;
or
R14 and R15 may together represent oxo;
each R13 is independently H;
trifluoromethyl;
(C1-4)alkyl optionally substituted by hydroxy, (C1-6)alkoxy, (C1-6)alkylthio, halo or trifluoromethyl;
(C2-4)alkenyl;
(C1-4)alkoxycarbonyl;
(C1-4)alkylcarbonyl;
(C1-6)alkylsulphonyl;
or aminocarbonyl wherein the amino group is optionally mono or disubstituted by (C1-4)alkyl;
and
each x is independently 0, 1 or 2.

72 more elements

A compound selected from the group consisting of:

4-[(4-{[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)methyl]amino]-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-chloro-4-({4-[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-chloro-4-[(4-{[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or an enantiomer thereof;
3-chloro-4-[(4-{[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)methyl]amino-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-chloro-4-[(4-{[(7-chloro-3-oxo-3,4-dihydro-2,1-pyrido[3,2-b][1,4]oxazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-chloro-4-[(4-{[(8-fluoro-2,3-dihydro-1,4-benzodioxin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
N-{1-[(3-chloro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl)methyl]-4-piperidinyl)-3-oxo-3,4-dihydro-2H-pyrido[(3,2-b][1,4]thiazine-6-carboxamide;
4-({4-[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-fluoro-4-[(4-{[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
N-{1-[(3-fluoro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl)methyl]-4-piperidinyl}-3-oxo-3,4-dihydro-2H-pyrido[3,2-b]4]oxazine-6-carboxamide;
3-chloro-4-[((3R,4S)-4-{[(7-fluoro-2,3-dihydro-1,4-benzodioxin-6-yl)methyl]amino}-3-hydroxy-1-piperidinyl)methyl)-4,5-dihydro-7H-1-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or a diastereomer thereof;
4-({(3R,4S)-4-((2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino)-3-hydroxy-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
4-({(3R,4S)-4-[(2,3-dihydro-1-benzofuran-5-ylmethyl)amino]-3-hydroxy-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
4-({(3R,4S)-4-[(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino]-3-hydroxy-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-chloro-4-[((3R,4S)-4-{[(7-fluoro-3-oxo-3,4-dihydro-2H-1,4-benzothiazin-6-yl)methyl]amino}-3-hydroxy-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or a diastereomer thereof;
3-chloro-4-[((3R,4S)-3-hydroxy-4-{[(3-oxo-3,4-dihydro-2H-pyrido-3,2-b][1,4]thiazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
N-{(3R,4S)-1-[(3-chloro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl)methyl]-3-hydroxy-4-piperidinyl}-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carboxamide;
3-chloro-4-({(3R,4S)-4-[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino)-3-hydroxy-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-chloro-4-[(4-{[(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-chloro-4-({4-[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or an enantiomer thereof;
3-chloro-4-[(4-{[(3-oxo-3,4-dihydro-2H-1,4-benzothiazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or an enantiomer thereof;
3-chloro-4-[(4-{[(2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazin-7-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or an enantiomer thereof;
3-chloro-4-({(3R,4S)-3-hydroxy-4-[([1,3]oxathiolo[5,4-c]pyridin-6-ylmethyl)amino]-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or a diastereomer thereof;
3-chloro-4 ({(3R,4S)-4-[(3,4-dihydro-2H-pyrano[2,3-c]pyridin-6-ylmethyl)amino]-3-hydroxy-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-chloro-4-({4-[(2,3-dihydro[1,4]oxathiino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or an enantiomer thereof;
3-chloro-4-({4-[(2,3-dihydrofuro[2,3-c]pyridin-5-ylmethyl)amino]-1-piperidinyl}methyl)4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-4-({4-[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-4-({4-[(3,4-Dihydro-2H-pyrano[2,3-c]pyridin-6-ylmethyl)amino]-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-3-fluoro-4-({4-[([1,3]oxathiolo[5,4-c]pyridin-6-ylmethyl)amino]-1-piperidinyl methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-3-fluoro-4-[(4-{[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-3-fluoro-4-[(4-{[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4S)-4-({4-[2,3-dihydro[1,4]-dioxino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-[1,5-naphthyridin-7-one;
(4R)-4-({4-[(2,3-dihydro[1,4]oxathiino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-4-({4-[(2,3-dihydrofuro[2,3c]-pyridin-5-ylmethyl)amino]-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
4-({cis-4-[(2,3-dihydro[1,4]dioxino[2,3c]pyridin-7-ylmethyl)amino]-3-fluoro-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de][1,5-naphthyridin-7-one;
3-fluoro-4-[(cis-3-fluoro-4-{[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-fluoro-4-[(cis-3-fluoro-4-{[3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
4-[{(cis-4-[(2,3-dihydro[1,4-benzodioxin-6-ylmethyl)amino]-3-fluoro-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-fluoro-4-{cis-4-hydroxy-3-({[(3-oxo-3,4-dihydro-2H-pyrido-[3,2-b][1,4]thiazin-6-yl)methyl]amino}methyl)-1-piperidinyl]methyl}-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
4-[(cis-3-{[2,3-dihydro1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]methyl}4-hydroxy-1-piperidinyl)methyl]-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
4-[((2S)-2-{[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]methyl-4-morpholinyl)methyl]-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-fluoro-4-[((2S)-2-{[([1,3]oxathiolo[5,4-c]pyridin-6-ylmethyl)amino]methyl}-4-morpholinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-fluoro-4-{[(2S)-2-({[(3-oxo-3,4-dihydro-2H-pyrido[32-b][1,4]thiazin-6-yl)methyl]amino}methyl)-4-morpholinyl]methyl-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-chloro-4-({4-[([1,3]oxathiolo[5,4-c]pyridin-6-ylmethyl)amino]-1-piperidinyl]methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or an enantiomer thereof;
3-chloro-4-({4-[(3,4-dihydro-2H-pyrano[2,3-c]pyridin-6-ylmethyl)amino]-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or an enantiomer thereof;
3-chloro-4-[(4-{[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-1-7-one;
or an enantiomer thereof;
3-chloro-4-({(3R,4S)-3-hydroxy-4-[([1,3]oxathiolo[5,4-c]pyridin-6-ylmethyl)amino]-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or a diastereomer thereof;
3-fluoro-4-((3R,4S)-3-hydroxy-4-[([1,3]oxathiolo[5,4-c]pyridin-6-ylmethyl)amino]-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or a diastereomer thereof;
7-[({3R,4S)-1-[(3-chloro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl)methyl]-3-hydroxy-4-piperidinyl}amino)methyl]-2,3-dihydro-1,4-benzodioxin-5-carbonitrile or a diastereomer thereof;
4-({4-[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
4-({4-[([1,3]oxathiolo[5,4-c]pyridin-6-ylmethyl)amino]-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
7-{[(1-{[(4R)-3-fluoro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de)-1,5-naphthyridin-4-yl]methyl}-4-piperidinyl)amino]methyl}-2,3-dihydro-1,4-benzodioxin-5-carbonitrile;
(4R)-3-fluoro-4-[(4-{[(2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazin-7-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-chloro-4-{(4-{[(5-oxo-1,2,3,5-tetrahydro-7-indolizinyl)methyl]amino}-1-piperidinyl)methyl-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-chloro-4-[(4-{((2-methyl-1-oxo-1,2,3,4-tetrahydro-7-isoquinolinyl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-3-fluoro-4-[(4-{((3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-4-[(4-{[(7-chloro-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-3-fluoro-4-[(4-{[(8-fluoro-2,3-dihydro-1,4-benzodioxin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-4-[(4-{[(7-bromo-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
4-({(3S,4R)-4-[([1,3]oxathiolo[5,4-c]pyridin-6-ylmethyl)amino]-3-hydroxy-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or a diastereomer thereof;
4-({(3R,4S)-4-[([1,3]oxathiolo[5,4-c]pyridin-6-ylmethyl)amino]-3-hydroxy-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or a diastereomer thereof;
4-({(3R,4S)-4-[2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-3-hydroxy-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or a diastereomer thereof;
4-(3R,4S)-4-[(2,3-dihydro[1,4]oxathiino[2,3-c]pyridin-7-ylmethyl)amino]-3-hydroxy-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or a diastereomer thereof;
3-fluoro-4-({(3R,4S)-4-[(3,4-dihydro-2H-pyrano[2,3-c]pyridin-6-ylmethyl)amino]-3-hydroxy-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-3-fluoro-4-[(4-{[(3-oxo-3,4-dihydro-2H-1,4-benzothiazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
5-{[(1-{[(4R)-3-fluoro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl]methyl}-4-piperidinyl)amino]methyl}-2,3-dihydro-1-benzofuran-7-carbonitrile;
4-{[(3R,4S)-4-[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-3-(methyloxy)-1-piperidinyl]methyl}-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
4-{[(3R,4S)-4-[(3,4-dihydro-2H-pyrano[2,3-c]pyridin-6-ylmethyl)amino]-3-(methyloxy)-1-piperidinyl]methyl}1-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
3-fluoro-4-((3R,4S)-3-(methyloxy)-4-[([1,3]oxathiolo[5,4-c]pyridin-6-ylmethyl)amino]-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
5-({[(3R,4S)-1-[(3-fluoro-7-oxo-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-4-yl)methyl]-3-(methyloxy)-4-piperidinyl]amino}methyl)-2,3-dihydro-1-benzofuran-7-carbonitrile;
4-[((3R,4S)-4-{[(7-bromo-2,3-dihydro-1,4-benzodioxin-6-yl)methyl]amino}-3-hydroxy-1-piperidinyl)methyl]-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or a diastereomer thereof;
4-({(3R,4S)-4-[(5,6-dihydro-4H-cyclopenta[b]thien-2-ylmethyl)amino]-3-hydroxy-1-piperidinyl)methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one or a diastereomer thereof;
(4R)-3-fluoro-4-[(4-{[(7-fluoro-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-3-fluoro-4-[(4-{[(7-fluoro-3-oxo-3,4-dihydro-2H-1,4-benzothiazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-3-fluoro-4-{[(4-{[(8-fluoro-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)methyl]amino}-1-piperidinyl)methyl]-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7one;
(4R)-4-({4-[(2,3-dihydro(1,4]dioxino[2,3-b]pyridin-7-ylmethyl)amino]-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-4-({4-[(5,6-dihydro-4H-cyclopenta[b]thien-2-ylmethyl)amino]-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-4-({4-[(6,7-dihydro-5H-thieno[3,2-b]pyran-2-ylmethyl)amino]-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
(4R)-4-({4-[(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino]-1-piperidinyl}methyl)-3-fluoro-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
and
(4R)-3-fluoro-4-({4-[([1,2,3]thiadiazolo[5,4-b]pyridin-6-ylmethyl)amino]-1-piperidinyl}methyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one;
or a pharmaceutically acceptable salt thereof.

80 more elements

Dependencies are inferred from the claim text.

Description24,762 words

Summary3,926 words

#This application is a 371 of International Application No. PCT/EP2007/054079 filed 25 Apr. 2007, and claims the priority of GB 0608263.0 filed 26 Apr. 2006, which applications are incorporated herein in their entirety.

#This invention relates to novel compounds, compositions containing them and their use as antibacterials.

#WO02/08224, WO02/50061, WO02/56882, WO02/96907, WO2003087098, WO2003010138, WO2003064421, WO2003064431, WO2004002992, WO2004002490, WO2004014361, WO2004041210, WO2004096982, WO2002050036, WO2004058144, WO2004087145, WO06002047, WO06014580, WO06010040, WO06017326, WO06012396, WO06017468, WO06020561, WO01/25227, WO02/40474, WO02/07572, WO2004035569, WO2004089947, WO04024712, WO04024713, WO04087647, WO2005016916, WO2005097781, WO06010831, WO04035569, WO04089947, WO06021448, WO06032466 and WO06038172 disclose quinoline, naphthyridine, morpholine, cyclohexane, piperidine and piperazine derivatives having antibacterial activity. WO2004104000 discloses tricyclic condensed ring compounds capable of selectively acting on cannabinoid receptors.

Detailed description20,836 words

#Abbreviations in the Examples:

#RT=room temperature

#ES=Electrospray mass spec.

Facts

Application: 12/298,326Filed 25 Apr 2007
Priority: GB 0608263.026 Apr 2006
Published: US 2009/0137568 A128 May 2009
Granted: 8 Jun 2010
Term ends: 25 Apr 2027
Estimated · howhide
20 years from earliest known nonprovisional domestic filing plus recorded patent term adjustment. Maintenance-fee lapses, terminal disclaimers and statutory extensions have not been checked. The continuity chain may be incomplete; this is not an enforceability determination.

Classification6 codes

C07D 471/16
In which the condensed system contains three hetero rings: peri-condensed systems
A61P 31/00
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
A61P 31/04
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics: antibacterial agents
C07D 519/00
Heterocyclic compounds containing more than one system of two or more relevant

Family

US 2009/0137568 A1Pre-grant publication · published 28 May 2009
US 7,732,461 B2This patent

From the US filing history. Foreign family members aren’t listed.

Timeline

26 Apr 2006Priority claimedGB 0608263.0
25 Apr 2007Application filedUS 12/298,326
24 Oct 2008Assigned to Glaxo Group Limitedassignment of assignor's interest
28 May 2009PublishedUS 2009/0137568 A1
8 Jun 2010GrantedUS 7,732,461 B2
12 Oct 2026TodayWithin its term
25 Apr 2027Term endsEstimated

Citations

No references of this kind are recorded.