US 2006/0223810 A1Published application

Bicyclic pyrazole compounds as antibacterial agents

AssigneeJanssen Pharmaceutica NV

InventorsBrett Allison, Laurent Gomez, Cheryl Grice, Michael Hack, Brian Morrow, S. Motley, Alejandro Santillan, Karen Shaw, Kimberly Schwarz, Liu Tang, Hariharan Venkatesan, John Wiener

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Abstract

Antibacterial compounds, compositions containing them, and methods of use for the inhibition of bacterial activity and the treatment, prevention or inhibition of bacterial infection.

Claims42

Dependent claims

A compound of formula (I):

where said formula (I) has a B-containing bicyclic ring system
and a fused pyrazole moiety
wherein
each of B1, B5, and B8 is independently CRa or N, wherein not all three B1, B5, and B8are N;
each of Ra, R2, R3, R6 and R7 is independently selected from the group consisting of —H, —C1-4alkyl, —C2-4alkenyl, —C2-4alkynyl, —C3-6cycloalkyl, —ORb, —NRcRd, —O(CH2)2-3NRcRd, —SRb, —S(O)Rb, —SO2Rb, cyano, —CF3, halo, —NO2, —OCF3, —C(O)Rb, —OC(O)Rb, —C(O)NRcRd, and —CO2Rb;
wherein each of Rb, Rc and Rd is independently selected from the group consisting of —H, —C1-4alkyl, —C3-6cycloalkyl, and —C1-2alkyl(C3-6cycloalkyl)-;
and wherein each alkyl or cycloalkyl moiety in any of Ra, R2, R3, R6, R7, Rb, Rc, and Rd is optionally and independently substituted with one, two or three substituents selected from —C1-3alkyl, halo, hydroxy, amino, and —C1-3alkoxy;
the B-containing bicyclic ring system is attached at the 1- or 2-position of the fused pyrazole moiety;
m is 0 or 1;
n is 1 or 2,wherein m+n is 2 or 3;
X is CH or N;
provided that when X is N, then Y is —C(O)—, —CH2C(O)—, or —(CH2)2-3O— optionally substituted with -C1-3alkyl;
and when X is CH, then Y is —N(Re)Z-;
Z is selected from the group consisting of:
C1-3alkylene optionally substituted with —C1-3alkyl;
C3alkenylene optionally substituted with —C1-3alkyl;
—C(O)C2alkenyl-optionally substituted with —C1-3alkyl;
—(CH2)0-1C(O)—;
—CH2C(O)N(Rf)(CH2)0-1—;
—(CH2)2-3O—;
and —C(O)C(Rg1)(Rg2)—;
where Re is —H, —C1-4alkyl, benzyl, —C(O)C1-6alkyl, —C(O)phenyl, —C(O)benzyl, —C1-6alkylCO2C1-6alkyl, or —C1-6alkylCO2H;
Rf is —H or —C1-4alkyl;
and
each of Rg1 and Rg2 is independently —H or methyl, or Rg1 and Rg2 are taken together with their carbon of attachment to form a C3-7cycloalkyl, or the group C(Rg1)(Rg2) is the group C═O;
A is an aryl or heteroaryl ring selected from the group consisting of:
a) unsubstituted phenyl, unsubstituted pyridyl, substituted phenyl, and substituted pyridyl, wherein said substituted phenyl is moiety (M1) or moiety (M2)
and said substituted pyridyl is moiety (M3) or moiety (M4)
wherein Rr(p-q) stands for a number of Rr substituents that is at least p and does not exceed q, and
is a disubstituent at two adjacent carbon members, said disubstituent being selected from the group consisting of —O—C14AL-O—, —N(Rh)(CH2)2-3S—, —N(Rh)C(O)(CH2)1-2S—, —N(Rh)C(O)C(CH3)2S—, —N(Rh)(CH2)2-3—, —N(Rh)C(O)(CH2)1-2O—, —N(Rh)(CH2)2-3NH—, and —N(Rh)C(O)(CH2)1-2NH—, wherein said C14AL is a C1-4alkylene optionally mono- or di-substituted with F,
where each —Rr is independently selected from the group consisting of —OH, —C1-6alkyl, —OC1-6alkyl, —C2-6alkenyl, —OC3-6alkenyl, —C2-6alkynyl, —OC3-6alkynyl, —CN, —NO2, —N(Ry)Rz, —C(O)N(Ry)Rz, —N(Rt)C(O)Rt, —N(Rt)SO2C1-6alkyl, —C(O)C1-6alkyl, —SC1-6alkyl, —SO2C1-6alkyl, —SO2N(Ry)Rz, halo, —CF3, —OCF3, —CO2H and —CO2C1-6alkyl;
wherein Rt is —H or —C1-6alkyl;
Ry and Rz are independently selected from —H and —C1-6alkyl, or Ry and Rz are taken together with their nitrogen of attachment to form pyrrolidinyl or piperidinyl;
and
Rh is selected from the group consisting of —H, —C1-6alkyl, —C1-6alkylCO2H, —C1-6alkylCO2C1-6alkyl, and benzyl;
b) a five-membered monocyclic heteroaromatic group having a carbon member which is the point of attachment, having one hetero-member that is >O, >S, >NH or >N(C1-4alkyl), having up to one additional hetero-member that is —N═, said five-membered monocyclic heteroaromatic group being optionally mono- or di-substituted with Rr and optionally benzofused or pyridofused, where the benzofused or pyridofused moiety is optionally mono-, di-, or tri-substituted with Rr;
and
c) a six-membered monocyclic heteroaromatic group having a carbon member which is the point of attachment, having two hetero-members each being —N═, said six-membered monocyclic heteroaromatic group being optionally mono- or di-substituted with Rr and optionally benzofused or pyridofused, where the benzofused or
pyridofused moiety is optionally mono- or di-substituted with Rr;
an isomer, racemate, tautomer, hydrate, solvate, pharmaceutically acceptable salt, ester, or amide thereof.

37 more elements

A compound of formula (I):

where said formula (I) has a B-containing bicyclic ring system
and a fused pyrazole moiety
wherein
each of B1, B5, and B8 is independently CRa or N, wherein not all three B1, B5, and B8 are N;
each of Ra, R2, R3, R6 and R7 is independently selected from the group consisting of —H, —C1-4alkyl, —C2-4alkenyl, —C2-4alkynyl, —C3-6cycloalkyl, —ORb, —NRcRd, —O(CH2)2-3NRcRd, —SRb, —S(O)Rb, —SO2Rb, cyano, —CF3, halo, —NO2, —OCF3, —C(O)Rb, —OC(O)Rb, —C(O)NRcRd, and —CO2Rb;
wherein each of Rb, Rc and Rd is independently selected from the group consisting of —H, —C1-4alkyl, —C3-6cycloalkyl, and —C1-2alkyl(C3-6cycloalkyl)-;
and wherein each alkyl or cycloalkyl moiety in any of Ra, R2, R3, R6, R7, Rb, Rc, and Rd is optionally and independently substituted with one, two or three substituents selected from —C1-3alkyl, halo, hydroxy, amino, and —C1-3alkoxy;
the B-containing bicyclic ring system is attached at the 1- or 2-position of the fused pyrazole moiety;
m is 0 or 1;
n is 1 or 2, wherein m+n is 2 or 3;
X is CH or N;
provided that when X is N, then Y is —C(O)—, —CH2C(O)—, or —(CH2)2-3O— optionally substituted with —C1-3alkyl;
and when X is CH, then Y is —N(Re)Z-;
Z is selected from the group consisting of:
C1-3alkylene optionally substituted with —C1-3alkyl;
C3alkenylene optionally substituted with —C1-3alkyl;
—C(O)C2alkenyl-optionally substituted with —C1-3alkyl;
—(CH2)0-1C(O)—;
—CH2C(O)N(Rf)(CH2)0-1—;
—(CH2)2-3O—;
and —C(O)C(Rg1)(Rg2)—;
where Re is —H, —C1-4alkyl, benzyl, —C(O)C1-6alkyl, —C(O)phenyl, —C(O)benzyl, —C1-6alkylCO2C1-6alkyl, or —C1-6alkylCO2H;
Rf is —H or —C1-4alkyl;
and
each of Rg1 and Rg2 is independently —H or methyl, or Rg1 and Rg2 are taken together with their carbon of attachment to form a C3-7cycloalkyl, or the group C(Rg1)(Rg2) is the group C═O;
A is an aryl or heteroaryl ring selected from the group consisting of:
a) unsubstituted phenyl, unsubstituted pyridyl, substituted phenyl, and substituted pyridyl, wherein said substituted phenyl is moiety (M1) or moiety (M2)
and said substituted pyridyl is moiety (M3) or moiety (M4)
wherein Rr(p-q) stands for a number of Rr substituents that is at least p and does not exceed q, and
is a disubstituent at two adjacent carbon members, said disubstituent being selected from the group consisting of —O—C14AL-O—, —N(Rh)(CH2)2-3S—, —N(Rh)C(O)(CH2)1-2S—, —N(Rh)(CH2)2-3—, —N(Rh)C(O)(CH2)1-2—, —N(Rh)(CH2)2-3NH—, and —N(Rh)C(O)(CH2)1-2NH—, wherein said C14AL is a C1-4alkylene optionally mono- or di-substituted with F,
where each —Rr is independently selected from the group consisting of —OH, —C1-6alkyl, —OC1-6alkyl, —C2-6alkenyl, —OC3-6alkenyl, —C2-6alkynyl, —OC3-6alkynyl, —CN, —NO2, —N(Ry)Rz, —C(O)N(Ry)Rz, —N(Rt)C(O)Rt, —N(Rt)SO2C1-6alkyl, —C(O)C1-6alkyl, —SC1-6alkyl, —SO2C1-6alkyl, —SO2N(Ry)Rz, halo, —CF3, —OCF3, —CO2H and —CO2C1-6alkyl;
wherein Rt is —H or —C1-6alkyl;
Ry and Rz are independently selected from —H and —C1-6alkyl, or Ry and Rz are taken together with their nitrogen of attachment to form pyrrolidinyl or piperidinyl;
and
Rh is selected from the group consisting of —H, —C1-6alkyl, —C1-6alkylCO2H, —C1-6alkylCO2C1-6alkyl, and benzyl;
b) a five-membered monocyclic heteroaromatic group having a carbon member which is the point of attachment, having one hetero-member that is >O, >S, >NH or >N(C1-4alkyl), having up to one additional hetero-member that is —N═, said five-membered monocyclic heteroaromatic group being optionally mono- or di-substituted with Rr and optionally benzofused or pyridofused, where the benzofused or pyridofused moiety is optionally mono-, di-, or tri-substituted with Rr;
and
c) a six-membered monocyclic heteroaromatic group having a carbon member which is the point of attachment, having two hetero-members each being —N═, said six-membered monocyclic heteroaromatic group being optionally mono- or di-substituted with Rr and optionally benzofused or pyridofused, where the benzofused or
pyridofused moiety is optionally mono- or di-substituted with Rr;
an isomer, racemate, tautomer, hydrate, solvate, pharmaceutically acceptable salt, ester, or amide thereof.

37 more elements

A compound selected from:

2,3-Dihydro-benzo[1,4]dioxine-6-carboxylic acid [2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
7-Fluoro-2,3-dihydro-benzo[1,4]dioxine-6-carboxylic acid [2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
3,4-Dihydro-2H-benzo[b][1,4]dioxepine-7-carboxylic acid [2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
3-Oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
7-Fluoro-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
7-Chloro-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
4,6-Difluoro-1H-indole-2-carboxylic acid [2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
1H-Benzoimidazole-2-carboxylic acid [2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
2-(1H-Indol-2-yl)-N-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-2-oxo-acetamide;
N-[2-(6-Methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-3-phenyl-acrylamide;
3-(3,5-Difluoro-phenyl)-N-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-acrylamide;
3-(3-Chloro-phenyl)-N-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-acrylamide;
3-(4-Fluoro-phenyl)-N-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-acrylamide;
N-[2-(6-Methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-3-(3-nitro-phenyl)-acrylamide;
6-[2-(6-Methoxy-[1,5]naphthyridin-4-yl)-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6-carbonyl]-4H-benzo[1,4]thiazin-3-one;
2,3-Dihydro-benzo[1,4]dioxine-6-carboxylic acid [2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
3-Oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
7-Fluoro-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
7-Fluoro-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [1-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-1H-indazol-5-yl]-amide;
7-Chloro-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
1H-Indole-2-carboxylic acid [2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
4,6-Difluoro-1H-indole-2-carboxylic acid [2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
Benzo[b]thiophene-2-carboxylic acid [2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
4-Fluoro-benzo[b]thiophene-2-carboxylic acid [2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
Benzofuran-2-carboxylic acid (2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
2-(1H-Indol-2-yl)-N-[2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-2-oxo-acetamide;
3-Oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-6-yl]-amide;
7-Fluoro-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-6-yl]-amide;
N-[2-(6-Methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-3-phenyl-acrylamide;
N-[2-(6-Methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-3-thiophen-2-yl-acrylamide;
3-Oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid (2-quinolin-8-yl-4,5,6,7-tetrahydro-2H-indazol-5-yl)-amide;
7-Fluoro-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid (2-quinolin-8-yl-4,5,6,7-tetrahydro-2H-indazol-5-yl)-amide;
7-Fluoro-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid (2-naphthalen-1-yl-4,5,6,7-tetrahydro-2H-indazol-5-yl)-amide;
3-Oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid (2-naphthalen-1-yl-4,5,6,7-tetrahydro-2H-indazol-5-yl)-amide;
6-Dimethylamino-2-fluoro-3-{[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-ylamino]-methyl}-benzonitrile;
(3,4-Dihydro-2H-benzo[1,4]thiazin-6-ylmethyl)-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amine;
Benzo[1,3]dioxol-5-ylmethyl-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amine;
(2,2-Difluoro-benzo[1,3]dioxol-5-ylmethyl)-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amine;
(4-Dimethylamino-benzyl)-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amine;
7-Fluoro-6-{[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-ylamino]-methyl}-4H-benzo[1,4]thiazin-3-one;
6-{[2-(6-Methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-ylamino]-methyl}-4H-benzo[1,4]thiazin-3-one;
(2,3-Dihydro-benzo[1,4]dioxin-6-ylmethyl)-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amine;
(7-Fluoro-2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amine;
6-{[2-(6-Methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-ylamino]-methyl}-4H-pyrido[3,2-b][1,4]oxazin-3-one;
[2-(6-Methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-(3-phenyl-propyl)-amine;
[2-(6-Methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-(3-phenyl-allyl)-amine;
[2-(6-Methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-(3-pyridin-3-yl-allyl)-amine;
[3-(3,4-Dichloro-phenyl)-propyl]-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amine;
[2-(6-Methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-(3-p-tolyl-propyl)-amine;
(2,3-Dihydro-benzo[1,4]dioxin-6-ylmethyl)-[2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amine;
(7-Fluoro-2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-[2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amine;
6-{[2-(6-Methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-ylamino]-methyl}-4H-benzo[1,4]thiazin-3-one;
7-Fluoro-6-{[2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-ylamino]-methyl}-4H-benzo[1,4]thiazin-3-one;
6-{[2-(6-Methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-ylamino]-methyl}-4H-pyrido[3,2-b][1,4]oxazin-3-one;
[2-(6-Methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-(3-phenyl-allyl)-amine;
[2-(6-Methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-(2-methyl-3-phenyl-allyl)-amine;
[3-(4-Fluoro-phenyl)-allyl]-[2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amine;
N-(3,5-Difluoro-phenyl)-2-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-ylamino]-acetamide;
2-[2-(6-Methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-ylamino]-N-phenyl-acetamide;
2-[2-(6-Methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-ylamino]-N-p-tolyl-acetamide;
N-(3,5-Difluoro-phenyl)-2-[2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-ylamino]-acetamide;
N-(3,4-Dichloro-phenyl)-2-[2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-ylamino]-acetamide
6-{2-[2-(6-Methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-ylamino]-acetyl}-4H-benzo[1,4]oxazin-3-one;
6-{2-[2-(6-Methoxy-quinolin-4-yl)-2,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-acetyl)-4H-benzo[1,4]oxazin-3-one;
[2-(6-Methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-(2-phenoxy-ethyl)-amine;
6-({Benzyl-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amino}-methyl)-4H-benzo[1,4]thiazin-3-one;
[[2-(6-Methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-ylmethyl)-amino]-acetic acid tert-butyl ester;
[[2-(6-Methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-ylmethyl)-amino]-acetic acid;
4-Methyl-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
Quinoxaline-2-carboxylic acid [2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
1H-Benzoimidazole-2-carboxylic acid [2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
5-Bromo-thiophene-2-carboxylic acid [2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
5-Acetyl-thiophene-2-carboxylic acid [2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
5,6-Difluoro-1H-indole-2-carboxylic acid [2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
5-Methyl-1H-indole-2-carboxylic acid [2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
5-Bromo-1H-indole-2-carboxylic acid [2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
5-Chloro-1H-indole-2-carboxylic acid [2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
2-Chloro-N-[2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-nicotinamide;
4-Methyl-3,4-dihydro-2H-benzo[1,4]oxazine-7-carboxylic acid [2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
1-(4-Chloro-phenyl)-cyclopentanecarboxylic acid [2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
3-Oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [2-(7-chloro-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
3-Oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [2-(6-fluoro-2-methyl-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
2-[2-(6-Methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-ylamino]-N-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-acetamide;
N-Benzyl-2-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-ylamino]-acetamide;
(4-Diethylamino-benzyl)-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amine;
[2-(6-Methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-(4-piperidin-1-yl-benzyl)-amine;
[2-(6-Methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-(4-pyrrolidin-1-yl-benzyl)-amine;
(2-Fluoro-4,5-dimethoxy-benzyl)-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amine;
[2-(6-Methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-[3-(2-nitro-phenyl)-allyl]-amine;
3-(4-Chloro-phenyl)-N-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-acrylamide;
[3-(5-Fluoro-2-trifluoromethyl-phenyl)-allyl]-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amine;
3-(3,4-Dichloro-phenyl)-N-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-acrylamide;
3-(3,4-Difluoro-phenyl)-N-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-acrylamide;
3-(2-Chloro-5-nitro-phenyl)-N-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-acrylamide;
N-[2-(6-Methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-3-pyridin-2-yl-acrylamide;
3-Oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [1-(2,8-bis-trifluoromethyl-quinolin-4-yl)-4,5,6,7-tetrahydro-1H-indazol-5-yl]-amide;
3-Oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [1-(2-trifluoromethyl-quinolin-4-yl)-4,5,6,7-tetrahydro-1H-indazol-5-yl]-amide;
7-Bromo-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [1-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-1H-indazol-5-yl]-amide;
and
3-Oxo-7-trifluoromethyl-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [1-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-1H-indazol-5-yl]-amide.

97 more elements

A compound selected from:

(8-Fluoro-2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-[2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amine;
(8-Fluoro-2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amine;
3,4-Dihydro-2H-benzo[1,4]thiazin-6-ylmethyl)-[2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amine;
(7-Chloro-2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-[2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amine;
(7-Chloro-2, 3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amine;
[2-(3-Amino-pyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-amine;
(7-Fluoro-3,4-dihydro-2H-benzo[1,4]thiazin-6-ylmethyl)-[2-(6-methoxy-quinolin-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amine;
(7-Fluoro-3,4-dihydro-2H-benzo[1,4]thiazin-6-ylmethyl)-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amine;
5,7-Difluoro-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
5,7-Difluoro-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
N-[2-(6-Methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-4-methyl-3-nitro-benzamide;
N-[2-(6-Methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-4-methyl-3-nitro-benzamide;
3-Oxo-7-trifluoromethyl-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
7-Bromo-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
7-Bromo-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
3-Oxo-7-trifluoromethyl-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
3-Oxo-3,4-dihydro-2H-benzo[1,4]oxazine-6-carboxylic acid [2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
3-Oxo-3,4-dihydro-2H-benzo[1,4]oxazine-6-carboxylic acid [2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
2-Fluoro-N-[2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-4-nitro-benzamide;
4-Methoxy-N-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-3-nitro-benzamide;
3-(2,4-Difluoro-phenyl)-N-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-acrylamide;
[2-(3,5-Difluoro-phenoxy)-ethyl]-{2-[1-(6-methoxy-quinolin-4-yl)-1H-pyrazol-4-yl]-1-methyl-ethyl}-amine;
2-[2-(6-Methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-ylamino]-N-(3-trifluoromethyl-phenyl)-acetamide;
N-(3-Chloro-phenyl)-2-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-ylamino]-acetamide;
5-Acetylamino-2-bromo-N-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-benzamide;
2,4-Dichloro-5-fluoro-N-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-benzamide;
6-Dimethylamino-2-fluoro-3-{[2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-ylamino]-methyl}-benzonitrile;
8-Fluoro-2,3-dihydro-benzo[1,4]dioxine-6-carboxylic acid [2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
8-Fluoro-2,3-dihydro-benzo[1,4]dioxine-6-carboxylic acid [2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
2,2-Dimethyl-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
7-Methoxy-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
7-Methyl-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [2-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
7-Methyl-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [1-(6-methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-1H-indazol-5-yl]-amide;
7-Methyl-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid [2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amide;
[2-(3,5-Difluoro-phenoxy)-ethyl]-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-yl]-amine;
6-[2-(6-Methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-ylcarbamoyl]-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-7-carboxylic acid ethyl ester;
6-[2-(6-Methoxy-quinolin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-ylcarbamoyl]-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-7-carboxylic acid, potassium salt;
6-[2-(6-Methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-ylcarbamoyl]-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-7-carboxylic acid ethyl ester;
6-[2-(6-Methoxy-[1,5]naphthyridin-4-yl)-4,5,6,7-tetrahydro-2H-indazol-5-ylcarbamoyl]-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-7-carboxylic acid;
and
6-{(1-(2-Trifluoromethyl-quinolin-4-yl)-4,5,6,7-tetrahydro-1H-indazol-5-ylamino]-methyl}-4H-benzo[1,4]thiazin-3-one.

38 more elements

Dependencies are inferred from the claim text.

Facts

Application: 11/393,558Filed 30 Mar 2006
Priority: 31 Mar 2005
Published: 5 Oct 2006
Term ends: Not estimatedThe source records don’t support an estimate.

Classification21 codes

A61K 31/4375
Ortho- or peri-condensed with heterocyclic ring systems: the heterocyclic ring system containing a six-membered ring having nitrogen as a ring…
A61K 31/444
Containing further heterocyclic ring systems: containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
A61K 31/4453
Non condensed piperidines, e.g. piperocaine: only substituted in position 1, e.g. propipocaine, diperodon
A61K 31/4709
Quinolines; Isoquinolines: non-condensed quinolines and containing further heterocyclic rings

Family

Application60/667,198Us provisional application · filed 31 Mar 2005
US 7,842,810 B2Related patent
US 2006/0223810 A1This patent

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

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Abstract

Antibacterial compounds, compositions containing them, and methods of use for the inhibition of bacterial activity and the treatment, prevention or inhibition of bacterial infection.

A compound of formula (I):

where said formula (I) has a B-containing bicyclic ring system
and a fused pyrazole moiety
wherein
each of B1, B5, and B8 is independently CRa or N, wherein not all three B1, B5, and B8are N;
each of Ra, R2, R3, R6 and R7 is independently selected from the group consisting of —H, —C1-4alkyl, —C2-4alkenyl, —C2-4alkynyl, —C3-6cycloalkyl, —ORb, —NRcRd, —O(CH2)2-3NRcRd, —SRb, —S(O)Rb, —SO2Rb, cyano, —CF3, halo, —NO2, —OCF3, —C(O)Rb, —OC(O)Rb, —C(O)NRcRd, and —CO2Rb;
wherein each of Rb, Rc and Rd is independently selected from the group consisting of —H, —C1-4alkyl, —C3-6cycloalkyl, and —C1-2alkyl(C3-6cycloalkyl)-;
and wherein each alkyl or cycloalkyl moiety in any of Ra, R2, R3, R6, R7, Rb, Rc, and Rd is optionally and independently substituted with one, two or three substituents selected from —C1-3alkyl, halo, hydroxy, amino, and —C1-3alkoxy;
the B-containing bicyclic ring system is attached at the 1- or 2-position of the fused pyrazole moiety;
m is 0 or 1;
n is 1 or 2,wherein m+n is 2 or 3;
X is CH or N;
provided that when X is N, then Y is —C(O)—, —CH2C(O)—, or —(CH2)2-3O— optionally substituted with -C1-3alkyl;
and when X is CH, then Y is —N(Re)Z-;
Z is selected from the group consisting of:
C1-3alkylene optionally substituted with —C1-3alkyl;
C3alkenylene optionally substituted with —C1-3alkyl;
—C(O)C2alkenyl-optionally substituted with —C1-3alkyl;
—(CH2)0-1C(O)—;
—CH2C(O)N(Rf)(CH2)0-1—;
—(CH2)2-3O—;
and —C(O)C(Rg1)(Rg2)—;
where Re is —H, —C1-4alkyl, benzyl, —C(O)C1-6alkyl, —C(O)phenyl, —C(O)benzyl, —C1-6alkylCO2C1-6alkyl, or —C1-6alkylCO2H;
Rf is —H or —C1-4alkyl;
and
each of Rg1 and Rg2 is independently —H or methyl, or Rg1 and Rg2 are taken together with their carbon of attachment to form a C3-7cycloalkyl, or the group C(Rg1)(Rg2) is the group C═O;
A is an aryl or heteroaryl ring selected from the group consisting of:
a) unsubstituted phenyl, unsubstituted pyridyl, substituted phenyl, and substituted pyridyl, wherein said substituted phenyl is moiety (M1) or moiety (M2)
and said substituted pyridyl is moiety (M3) or moiety (M4)
wherein Rr(p-q) stands for a number of Rr substituents that is at least p and does not exceed q, and
is a disubstituent at two adjacent carbon members, said disubstituent being selected from the group consisting of —O—C14AL-O—, —N(Rh)(CH2)2-3S—, —N(Rh)C(O)(CH2)1-2S—, —N(Rh)C(O)C(CH3)2S—, —N(Rh)(CH2)2-3—, —N(Rh)C(O)(CH2)1-2O—, —N(Rh)(CH2)2-3NH—, and —N(Rh)C(O)(CH2)1-2NH—, wherein said C14AL is a C1-4alkylene optionally mono- or di-substituted with F,
where each —Rr is independently selected from the group consisting of —OH, —C1-6alkyl, —OC1-6alkyl, —C2-6alkenyl, —OC3-6alkenyl, —C2-6alkynyl, —OC3-6alkynyl, —CN, —NO2, —N(Ry)Rz, —C(O)N(Ry)Rz, —N(Rt)C(O)Rt, —N(Rt)SO2C1-6alkyl, —C(O)C1-6alkyl, —SC1-6alkyl, —SO2C1-6alkyl, —SO2N(Ry)Rz, halo, —CF3, —OCF3, —CO2H and —CO2C1-6alkyl;
wherein Rt is —H or —C1-6alkyl;
Ry and Rz are independently selected from —H and —C1-6alkyl, or Ry and Rz are taken together with their nitrogen of attachment to form pyrrolidinyl or piperidinyl;
and
Rh is selected from the group consisting of —H, —C1-6alkyl, —C1-6alkylCO2H, —C1-6alkylCO2C1-6alkyl, and benzyl;
b) a five-membered monocyclic heteroaromatic group having a carbon member which is the point of attachment, having one hetero-member that is >O, >S, >NH or >N(C1-4alkyl), having up to one additional hetero-member that is —N═, said five-membered monocyclic heteroaromatic group being optionally mono- or di-substituted with Rr and optionally benzofused or pyridofused, where the benzofused or pyridofused moiety is optionally mono-, di-, or tri-substituted with Rr;
and
c) a six-membered monocyclic heteroaromatic group having a carbon member which is the point of attachment, having two hetero-members each being —N═, said six-membered monocyclic heteroaromatic group being optionally mono- or di-substituted with Rr and optionally benzofused or pyridofused, where the benzofused or
pyridofused moiety is optionally mono- or di-substituted with Rr;
an isomer, racemate, tautomer, hydrate, solvate, pharmaceutically acceptable salt, ester, or amide thereof.

37 more elements

Facts

Application

11/393,558Filed 30 Mar 2006

Priority

31 Mar 2005

Published

5 Oct 2006

Term ends

Not estimatedThe source records don’t support an estimate.

Classification21 codes

A61K 31/4375
Ortho- or peri-condensed with heterocyclic ring systems: the heterocyclic ring system containing a six-membered ring having nitrogen as a ring…
A61K 31/444
Containing further heterocyclic ring systems: containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
A61K 31/4453
Non condensed piperidines, e.g. piperocaine: only substituted in position 1, e.g. propipocaine, diperodon
A61K 31/4709
Quinolines; Isoquinolines: non-condensed quinolines and containing further heterocyclic rings