3-aminoquinazolin-2,4-dione antibacterial agents
Antibacterial 3-aminoquinazolin-2,4-diones have formula (I) wherein: R 1 and R 3 include alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclic, and heteroaryl; R 5 , R 6 , and R 8 include H, alkyl, alkoxy, halo, NO 2 , CN, NH 2 , alkyl and dialkylamino; R 7 includes hydrogen, alkyl, cycloalkyl, heterocyclic, fused heterocyclic, aryl and fused aryl; J and K are C or N; and pharmaceutically acceptable salts thereof.
1. A compound of Formula VII
or pharmaceutically acceptable salt thereof,
wherein:
R 1 and R 3 independently are H,
C 1 -C 12 alkyl and substituted alkyl,
C 2 -C 12 alkenyl and substituted alkenyl,
C 2 -C 12 alkynyl and substituted alkynyl,
C 3 -C 12 cycloalkyl and substituted cycloalkyl,
aryl and substituted aryl,
heterocyclic and substituted heterocyclic,
or heteroaryl and substituted heteroaryl;
R 7 is hydrogen,
C 1 -C 12 alkyl and substituted alkyl,
C 2 -C 12 alkenyl and substituted alkenyl,
C 2 -C 12 alkynyl and substituted alkynyl,
halo,
NO 2 ,
CN,
NR′R″,
COOR′
aryl,
fused aryl,
heterocyclic,
fused heterocyclic,
bicyclic heterocyclic, or
spiro heterocyclic,
wherein all ring groups can be substituted; and
R 8 is H,
(O) n C 1 -C 12 alkyl and substituted alkyl,
(O) n C 2 -C 12 alkenyl and substituted alkenyl,
(O) n C 2 -C 12 alkynyl and substituted alkynyl,
wherein n is 0 or 1,
halo,
NO 2 ,
CN,
NR′R″;
wherein R′ and R″ independently are H,
C 1 -C 12 alkyl and substituted alkyl,
C 2 -C 12 alkenyl and substituted alkenyl,
C 2 -C 12 alkynyl and substituted alkynyl,
CO—C 1 -C 12 alkyl and substituted alkyl,
or R′ and R″ taken together with the nitrogen to which they are attached form a 3- to 7-membered ring containing from 1 to 3 heteroatoms selected from N, O, and S, said ring being unsubstituted or substituted with up to 4 substituent groups,
R 7 is hydrogen,
C 1 -C 12 alkyl and substituted alkyl,
C 2 -C 12 alkenyl and substituted alkenyl,
C 2 -C 12 alkynyl and substituted alkynyl,
halo,
NO 2 ,
CN,
NR′R″,
COOR′
aryl,
fused aryl,
heterocyclic,
fused heterocyclic,
bicyclic heterocyclic, or
spiro heterocyclic,
wherein all ring groups can be substituted.
2. A compound, or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
3-Amino-7-[3-(1-aminoethyl)-4-fluoropyrrolidin-1-yl]-1-cyclopropyl-8-methyl-1H-pyrido[4,3-d]pyrimidine-2,4-dione;
3-Amino-7-[3-(1-amino-1-methylethyl)-4-fluoropyrrolidin-1-yl]-1-cyclopropyl-8-methyl-1H-pyrido[4,3-d]pyrimidine-2,4-dione;
3-Amino-7-[3-(1-amino-2-methoxyethyl)-4-fluoropyrrolidin-1-yl]-1-cyclopropyl-8-methyl-1H-pyrido[4,3-d]pyrimidine-2,4-dione;
3-Amino-7-[4-(1-amino-2-methoxyethyl)-3,3-dimethylpyrrolidin-1-yl]-1-cyclopropyl-8-methyl-1H-pyrido[4,3-d]pyrimidine-2,4-dione;
3-Amino-7-[3-(1-amino-2-phenoxyethyl)-pyrrolidin-1-yl]-1-cyclopropyl-8-methyl-1H-pyrido[4,3-d]pyrimidine-2,4-dione;
3-Amino-7-[3-(1-amino-2-phenoxyethyl)-4-methylpyrrolidin-1-yl]-1-cyclopropyl-8-methyl-1H-pyrido[4,3-d]pyrimidine-2,4-dione;
3-Amino-7-[3-(1-amino-2-phenoxyethyl)-4-fluoropyrrolidin-1-yl]-1-cyclopropyl-8-methyl-1H-pyrido[4,3-d]pyrimidine-2,4-dione;
3-Amino-7-[3-(1-amino-2-methoxyethyl)-4-fluoropyrrolidin-1-yl]-1-cyclopropyl-8-methyl-1H-pyrido[4,3-d]pyrimidine-2,4-dione;
3-Amino-7-[4-(1-amino-2-phenoxyethyl)-3,3-dimethylpyrrolidin-1-yl]-1-cyclopropyl-8-methyl-1H-pyrido[4,3-d]pyrimidine-2,4-dione;
3-Amino-7-[3-(1-amino-2-ethoxyethyl)pyrrolidin-1-yl]-1-cyclopropyl-8-methyl-1H-pyrido[4,3-d]pyrimidine-2,4-dione;
3-Amino-7-[3-(1-amino-2-ethoxyethyl)-4-methylpyrrolidin-1-yl]-1-cyclopropyl-8-methyl-1H-pyrido[4,3-d]pyrimidine-2,4-dione;
3-Amino-7-[3-(1-amino-2-ethoxyethyl)-4-fluoropyrrolidin-1-yl]-1-cyclopropyl-8-methyl-1H-pyrido[4,3-d]pyrimidine-2,4-dione;
3-Amino-7-[3-(1-amino-2-phenoxyethyl)-4,4-dimethylpyrrolidin-1-yl]-1-cyclopropyl-8-methyl-1H-pyrido[4,3-d]pyrimidine-2,4-dione;
3-Amino-7-[3-(1-amino-2-methoxypropyl)pyrrolidin-1-yl]-1-cyclopropyl-8-methyl-1H-pyrido[4,3-d]pyrimidine-2,4-dione;
3-Amino-7-[3-(1-amino-2-methoxyethyl)-4-methylpyrrolidin-1-yl]-1-cyclopropyl-8-methyl-1H-pyrido[4,3-d]pyrimidine-2,4-dione;
3-Amino-7-[3-(1-amino-2-methoxypropyl)-4-fluoropyrrolidin-1-yl]-1-cyclopropyl-8-methyl-1H-pyrido[4,3-d]pyrimidine-2,4-dione;
{2-Amino-2-[1-(3-amino-1-cyclopropyl-8-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[4,3-d]pyrimidin-7-yl)pyrrolidin-3-yl]ethylurea;
{2-Amino-2-[1-(3-amino-1-cyclopropyl-8-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[4,3-d]pyrimidin-7-yl)pyrrolidin-3-yl]ethylurea;
{2-Amino-2-[1-(3-amino-1-cyclopropyl-8-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[4,3-d]pyrimidin-7-yl)-4-methylpyrrolidin-3-yl]ethylurea;
{2-Amino-2-[1-(3-amino-1-cyclopropyl-8-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[4,3-d]pyrimidin-7-yl)-4-fluoropyrrolidin-3-yl]ethylurea; and
{2-Amino-2-[1-(3-amino-1-cyclopropyl-8-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[4,3-d]pyrimidin-7-yl)-4,4-dimethylpyrrolidin-3-yl]ethylurea.