US 11,571,423 B2Granted

Small molecule modulators of human sting

AssigneeCuradev Pharma Limited

InventorsMonali Banerjee, Sandip Middya, Sourav Basu, Rajib Ghosh, David Pryde, Dharmendra Yadav, Ritesh Shrivastava, Arjun Surya

Life of this patent

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Abstract

The present invention relates to compounds of formula (I). The compounds maybe used to modulate the Stimulator of Interferon Genes (STING) protein and thereby treat diseases such as cancer and microbial infections.

Claims35

Dependent claims

A compound of formula (I):

wherein X1 is CR1 or N;
X2 is CR2 or N;
X3 is CR3 or N;
Q is C═O or;
L is optionally substituted C1-C6 alkyl, C═O, S═O, SO2, or —CH2C(O)—;
R1, R2 and R3 are each independently selected from the group consisting of H, halogen, CN, hydroxyl, CONR1R2, NR1R2, NHCOR1, optionally substituted C1-C6 alkyl, optionally substituted mono or bicyclic C3-C6 cycloalkyl, and optionally substituted C1-C6 alkoxy
R6 is a ring optionally substituted with one or more R12 groups, wherein the ring is selected from the group consisting of phenyl, pyridyl, thiazole, isoxazole, oxazole, pyrazole, and pyridone;
Y is an optionally substituted C1-C6 alkyl;
R7 is H, or optionally substituted C1-C6 alkyl;
R8 is an optionally substituted ring selected from phenyl, furan, benzofuran and cyclohexyl;
R9 and R10 are each independently selected from the group consisting of optionally substituted C1-C6 alkyl, H, halogen, optionally substituted C3-C6 cycloalkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, mono or bicyclic optionally substituted
C5-C10 aryl, and mono or bicyclic optionally substituted 5 to 10 membered heteroaryl, or R9 and R10 together with the C atom to which they are attached can combine to form an optionally substituted spirocyclic ring;
R11 is selected from the group consisting of optionally substituted C1-C6 alkyl, H, optionally substituted C3-C6 cycloalkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C1-C6 alkoxy, mono and bicyclic optionally substituted 5 to 10 membered heteroaryl;
each R12 group is independently selected from the group consisting of halogen, OH, OP(O)(OH)2, NR13R14, CONR13R14, CN, COOR13, NO2, azido, SO2R13, OSO2R13, NR13SO2R14, NR13C(O)R14, O(CH2)nOC(O)R13, NR13(CH2)nOC(O)R14, OC(O)R13, OC(O)OR13, OC(O)NR13R14, OC(O)O(CH2)nCOOR14, OC(O)NR13(CH2)nCOOR14, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, an optionally substituted mono or bicyclic C5-C10 aryl, an optionally substituted mono or bicyclic 5 to 10 membered heteroaryl, an optionally substituted C3-C6 cycloalkyl and an optionally substituted mono or bicyclic 3 to 8 membered heterocycle;
R13 and R14 are each independently selected from the group consisting of H, optionally substituted C1-C6 alkyl, optionally substituted mono or bicyclic C3-C6 cycloalkyl, mono or bicyclic optionally substituted C5-C10 aryl, mono or bicyclic optionally substituted 5 to 10 membered heteroaryl, and optionally substituted mono or bicyclic 3 to 8 membered heterocycle;
and
n is an integer between 0 and 6;
or a pharmaceutically acceptable salt thereof.

15 more elements

A compound, wherein the compound is:

1-(3,5-difluorobenzyl)-3-methyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(3,5-difluorobenzyl)-3-methyl-N-((5-methylfuran-2-yl)methyl)-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
3-cyclopropyl-1-(3,5-difluorobenzyl)-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
N-(2,4-difluorobenzyl)-1-(3,5-difluorobenzyl)-3-methyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-chloro-6-fluorobenzyl)-3-methyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(4-fluorobenzyl)-3-methyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(3,5-difluorobenzyl)-3-ethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2,4-difluorobenzyl)-3-methyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-fluoro-6-methylbenzyl)-3-methyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-fluoro-6-methoxybenzyl)-3-methyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-bromo-6-fluorobenzyl)-3-methyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-fluorobenzyl)-3-methyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-fluoro-3-methylbenzyl)-3-methyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(3-carbamoylbenzyl)-3-methyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(3,5-difluorobenzyl)-3-isopropyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
N-(benzofuran-2-ylmethyl)-1-(3,5-difluorobenzyl)-3-methyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-chloro-4-fluorobenzyl)-3-methyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(3,5-difluorobenzyl)-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-chlorobenzyl)-3-methyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
3-methyl-1-((2-methylthiazol-5-yl)methyl)-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-chloro-6-fluorobenzyl)-2-oxo-3-(pyrimidin-2-yl)-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-chloro-6-fluorobenzyl)-N-((6-methoxybenzofuran-2-yl)methyl)-3-methyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-chloro-6-fluorobenzyl)-N-((6-fluorobenzofuran-2-yl)methyl)-3-methyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-chloro-6-fluorobenzyl)-N-((5-fluorobenzofuran-2-yl)methyl)-3-methyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-chloro-6-fluorobenzyl)-3-methyl-N-(3-(oxazol-2-yl)benzyl)-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
N-(2-(1H-1,2,4-triazol-1-yl)ethyl)-1-(2-chloro-6-fluorobenzyl)-3-methyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-chloro-6-fluorobenzyl)-N-((5-hydroxybenzofuran-2-yl)methyl)-3-methyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-chloro-6-fluorobenzyl)-3-methyl-N-(3-(1-methyl-1H-pyrazol-3-yl)benzyl)-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-chloro-6-fluorobenzyl)-3-methyl-N-(3-(1-methyl-1H-pyrazol-5-yl)benzyl)-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-chloro-6-fluorobenzyl)-N-(2-fluorobenzyl)-3-methyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-chloro-6-fluorobenzyl)-3-methyl-N-(3-(4-methylpiperazin-1-yl)benzyl)-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
N-(benzofuran-5-ylmethyl)-1-(2-chloro-6-fluorobenzyl)-3-methyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
3-methyl-1-((5-methylisoxazol-3-yl)methyl)-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-chloro-6-fluorobenzyl)-3-(1-methyl-1H-imidazol-4-yl)-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-((1,2,5-thiadiazol-3-yl)methyl)-3-methyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
3-methyl-1-((2-methyloxazol-4-yl)methyl)-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
3-methyl-1-((1-methyl-1H-imidazol-4-yl)methyl)-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
3-methyl-1-((5-methyl-2-(m-tolyl)oxazol-4-yl)methyl)-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-cyano-6-fluorobenzyl)-3-methyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
3-methyl-1-((5-methyl-2-(p-tolyl)oxazol-4-yl)methyl)-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-chloro-6-fluorobenzyl)-N-(2-fluoro-6-methoxybenzyl)-3-methyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-((2-(4-fluorophenyl)-5-methyloxazol-4-yl)methyl)-3-methyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
N-(benzo[d][1,3]dioxol-4-ylmethyl)-1-(2-chloro-6-fluorobenzyl)-3-methyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-chloro-6-fluorobenzyl)-N-((2,3-dihydrobenzo[b][1,4]dioxin-5-yl)methyl)-3-methyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-((6-fluoroimidazo[1,2-a]pyridin-2-yl)methyl)-3-methyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(4-fluoro-2-methoxybenzyl)-3-methyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-chloro-6-fluorobenzyl)-N-((7-methoxybenzofuran-2-yl)methyl)-3-methyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-chloro-6-fluorobenzyl)-3-methyl-N-((5-nitrobenzofuran-2-yl)methyl)-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-chloro-6-fluorobenzyl)-3-methoxy-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
N-(benzofuran-4-ylmethyl)-1-(2-chloro-6-fluorobenzyl)-3-methyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-chloro-6-fluorobenzyl)-3-methyl-N-((1-methyl-1H-indazol-6-yl)methyl)-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
N-(benzofuran-6-ylmethyl)-1-(2-chloro-6-fluorobenzyl)-3-methyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
3-methyl-1-((1-methyl-1H-pyrazol-5-yl)methyl)-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
3-methyl-1-((3-methylisoxazol-5-yl)methyl)-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
3-methyl-1-((1-methyl-1H-1,2,3-triazol-4-yl)methyl)-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-fluoro-6-(trifluoromethyl)benzyl)-3-methyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-((1,5-dimethyl-1H-pyrazol-3-yl)methyl)-3-methyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
N-((5-aminobenzofuran-2-yl)methyl)-1-(2-chloro-6-fluorobenzyl)-3-methyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-chloro-6-fluorobenzyl)-3-methyl-2-oxo-N-((2-oxoindolin-5-yl)methyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-chloro-6-fluorobenzyl)-N-(2,6-difluoro-4-methoxybenzyl)-3-methyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-chloro-6-fluorobenzyl)-N-(4-fluoro-2-methoxybenzyl)-3-methyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2,6-dichlorobenzyl)-3-methyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-fluoro-3-methoxybenzyl)-3-methyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-((3-cyclopropylisoxazol-5-yl)methyl)-3-methyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(imidazo[1,2-a]pyridin-2-ylmethyl)-3-methyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(6-chloro-2-fluoro-3-methylbenzyl)-3-methyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-((4-bromo-1,3-dimethyl-1H-pyrazol-5-yl)methyl)-3-methyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
3-(benzyloxy)-1-(2-chloro-6-fluorobenzyl)-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-chloro-6-fluorobenzyl)-3-hydroxy-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(3,5-difluorobenzyl)-3-methyl-N-(2,4,6-trifluorobenzyl)-3,4-dihydro-1H-benzo[c][1,2,6]thiadiazine-7-carboxamide 2,2-dioxide;
1-(2-chloro-6-fluorobenzyl)-3-methyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydropyrido[3,2-d]pyrimidine-7-carboxamide;
1-(3,5-difluorobenzyl)-3-methyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydropyrido[3,2-d]pyrimidine-7-carboxamide;
N-(benzofuran-2-ylmethyl)-1-(2-chloro-6-fluorobenzyl)-3-methyl-2-oxo-1,2,3,4-tetrahydropyrido[3,2-d]pyrimidine-7-carboxamide;
1-(2-chloro-6-fluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2-Chloro-6-fluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(R)-1-(2-chloro-6-fluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-((5-chloro-3-fluoro-2-methylpyridin-4-yl)methyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2,6-difluoro-4-hydroxybenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2,6-Difluoro-4-methoxybenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2,6-difluoro-4-(2-hydroxyethoxy)benzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2,6-difluoro-4-(3-hydroxypropoxy)benzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-3-(4-((3,4-dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-3,5-difluorophenoxy)propyl dihydrogen phosphate;
(S)-(4-((3,4-dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-3,5-difluorophenoxy)methyl dihydrogen phosphate;
(S)-4-((3,4-dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-3,5-difluorophenyl dihydrogen phosphate;
(S)-4-Acetamidobenzyl-(4-((3,4-dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-3,5-difluorophenyl) carbonate;
(S)-Benzyl-3-(((4-((3,4-dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-3,5-difluorophenoxy)carbonyl)(methyl)amino)propanoate;
(S)-1-(2-Chloro-6-fluoro-3-hydroxybenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2-Chloro-6-fluoro-3-methoxybenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-2-chloro-3-((3,4-dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-4-fluorophenyl dihydrogen phosphate;
(S)-(2-Chloro-3-((3,4-dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-4-fluorophenoxy)methyl dihydrogen phosphate;
(S)-2-(2-((3,4-dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-3,4-difluorophenoxy)ethyl dihydrogen phosphate;
(S)-4-((3,4-dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-3-fluorophenyl dihydrogen phosphate;
(S)-2-((1-(2-chloro-6-fluorobenzyl)-3,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamido)methyl)-5-fluorophenyl dihydrogen phosphate;
(S)-3-(2-((3,4-dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-3,5-difluorophenoxy)propyl dihydrogen phosphate;
(S)-2-(2-chloro-3-((3,4-dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-4-fluorophenoxy)ethyl dihydrogen phosphate;
(S)-3-(2-chloro-3-((3,4-dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-4-fluorophenoxy)propyl dihydrogen phosphate;
(S)-2-(4-((3,4-dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-3,5-difluorophenoxy)ethyl dihydrogen phosphate;
(S)-3-chloro-4-((3,4-dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-5-fluorophenyl dihydrogen phosphate;
(S)-2-((3,4-dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-3,4-difluorophenyl dihydrogen phosphate;
(S)-2-((1-(2-chloro-6-fluorobenzyl)-3,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamido)methyl)-3-fluorophenyl dihydrogen phosphate;
(S)-4-((1-(2-chloro-6-fluorobenzyl)-3,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamido)methyl)-3,5-difluorophenyl dihydrogen phosphate;
(S)-3-((3,4-dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-2,4-difluorophenyl dihydrogen phosphate;
(S)-2-(3-((3,4-dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-2,4-difluorophenoxy)ethyl dihydrogen phosphate;
(S)-3-(3-((3,4-dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-2,4-difluorophenoxy)propyl dihydrogen phosphate;
(S)-2-((3,4-dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-3,5-difluorophenyl dihydrogen phosphate;
(S)-1-(2-Chloro-6-fluoro-3-(2-hydroxyethoxy)benzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2-Chloro-6-fluoro-3-(3-hydroxypropoxy)benzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-4-Acetamidobenzyl-(2-chloro-3-((3,4-dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-4-fluorophenyl) carbonate;
(S)-Benzyl 3-(((2-chloro-3-((3,4-dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-4-fluorophenoxy)carbonyl)(methyl)amino)propanoate;
(S)-1-(3-Carbamoyl-2,6-difluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-3-((3,4-Dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-2,4-difluorobenzoic acid;
(S)-1-(2,6-Difluoro-3-((2-hydroxyethyl)carbamoyl)benzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(4-(Allyloxy)-2,6-difluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(4S)-1-(4-(2,3-Dihydroxypropoxy)-2,6-difluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(4-((R)-2,3-Dihydroxypropoxy)-2,6-difluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(4-((S)-2,3-Dihydroxypropoxy)-2,6-difluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-Chloro-6-fluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydropyrido[3,2-d]pyrimidine-7-carboxamide;
(S)—N,1-bis(2,6-difluoro-4-methoxybenzyl)-3,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)—N,1-bis(2,6-Difluoro-4-hydroxybenzyl)-3,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2-Chloro-6-fluorobenzyl)-N-(2-hydroxyethyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(3,5-difluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-fluoro-6-methoxybenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-bromo-6-fluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-fluoro-6-hydroxybenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-fluoro-6-methylbenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(6-chloro-2-fluoro-3-methylbenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-fluoro-3-methylbenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2,6-difluoro-4-methoxybenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-fluoro-5-methoxybenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(5-carbamoyl-2-fluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2-fluoro-3-methylbenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(6-chloro-2-fluoro-3-methylbenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2-fluoro-4-methylbenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-amino-6-fluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-fluoro-6-(methylamino)benzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-(dimethylamino)-6-fluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-((5-chloro-3-fluoro-2-methylpyridin-4-yl)methyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(6-chloro-2,3-difluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2,3-difluoro-6-methoxybenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2-chloro-3,6-difluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-((3-fluoro-2-methylpyridin-4-yl)methyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-fluoro-4-hydroxybenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2-amino-6-fluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2-fluoro-5-methoxybenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-((5-chloro-3-fluoro-2-methoxypyridin-4-yl)methyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-methyl 2-chloro-3-((3,4-dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-4-fluorobenzoate;
(S)-1-(3-carbamoyl-2-chloro-6-fluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-2-(4-((3,4-dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-3,5-difluorophenoxy)ethyl 2-aminoacetate;
(S)-1-(3-amino-2-chloro-6-fluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-chloro-6-fluorobenzyl)-4-methyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-benzyl-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-fluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2,6-difluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-fluoro-6-(trifluoromethyl)benzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
N-(2,4-difluorobenzyl)-1-(2-fluorobenzyl)-3,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
3,4-dimethyl-1-((2-methylpyridin-4-yl)methyl)-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
3,4-dimethyl-1-((3-methylisoxazol-5-yl)methyl)-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
3,4-dimethyl-1-((5-methylisoxazol-3-yl)methyl)-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
2-((3,4-dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-3-fluorophenyl methanesulfonate;
1-(2,4-difluoro-6-(trifluoromethoxy)benzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-((3-fluoropyridin-4-yl)methyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-chloro-6-fluorobenzyl)-3,4-dimethyl-N-((5-methylfuran-2-yl)methyl)-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
N-(benzofuran-2-ylmethyl)-1-(2-chloro-6-fluorobenzyl)-3,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
N,1-dibenzyl-3,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2,6-dimethylbenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-(difluoromethoxy)-6-fluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-fluoro-4-methoxybenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(4-fluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(4-chloro-2-fluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-bromo-6-fluoro-3-methylbenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-chloro-4-fluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(4-chloro-2,6-difluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-((1,3-dimethyl-1H-pyrazol-5-yl)methyl)-N-((5-fluorobenzofuran-2-yl)methyl)-3,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-((4-fluoro-1,3-dimethyl-1H-pyrazol-5-yl)methyl)-N-((5-fluorobenzofuran-2-yl)methyl)-3,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-fluoro-6-(methylsulfonamido)benzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide
1-(2-acetamido-6-fluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-((3-fluoropyridin-2-yl)methyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
2-(4-((3,4-dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-3-fluorophenoxy)acetic acid;
2-(3-((3,4-dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-4-fluorophenoxy)acetic acid;
1-(2-fluoro-4-(2-hydroxyethoxy)benzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-fluoro-5-hydroxybenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-((3-bromo-5-fluoropyridin-4-yl)methyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-fluoro-5-(2-hydroxyethoxy)benzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
2-(2-((3,4-dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-3-fluorophenoxy)acetic acid;
1-(2-chloro-6-fluorobenzyl)-N-(4-hydroxybenzyl)-3,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-(2-fluoro-6-(2-hydroxyethoxy)benzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-((5-fluoro-2-methylpyridin-4-yl)methyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
1-((3-fluoro-6-methylpyridin-2-yl)methyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(4-azidobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
2-(4-((1-(2-chloro-6-fluorobenzyl)-3,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamido)methyl)phenoxy)acetic acid;
(S)-1-(2,3-difluoro-6-methoxybenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2,3-difluoro-6-hydroxybenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(4-aminobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-2-(2-((3,4-dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-3,4-difluorophenoxy)acetic acid;
(S)-1-(2-chloro-6-fluorobenzyl)-N-(2-fluoro-6-methoxybenzyl)-3,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2-chloro-6-fluorobenzyl)-N-(2,6-difluoro-4-methoxybenzyl)-3,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2-chloro-6-fluorobenzyl)-N-(4-fluoro-2-methoxybenzyl)-3,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2-chloro-6-fluorobenzyl)-N-(3-fluoro-5-methoxybenzyl)-3,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2-chloro-6-fluorobenzyl)-N-(2-fluoro-3-methoxybenzyl)-3,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2-chloro-6-fluorobenzyl)-N-(3-fluoro-5-hydroxybenzyl)-3,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2-chloro-6-fluorobenzyl)-N-(2-fluoro-6-hydroxybenzyl)-3,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2-chloro-6-fluorobenzyl)-N-(2,6-difluoro-4-hydroxybenzyl)-3,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2-chloro-6-fluorobenzyl)-N-(4-fluoro-2-hydroxybenzyl)-3,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2,3-difluoro-6-(2-hydroxyethoxy)benzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2,6-difluoro-3-hydroxybenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2,6-difluoro-3-(2-hydroxyethoxy)benzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2,6-difluoro-3-(3-hydroxypropoxy)benzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2,6-difluoro-3-methoxybenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2,4-difluoro-6-methoxybenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2,4-difluoro-6-hydroxybenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-((3-fluoro-2-methylpyridin-4-yl)methyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2-fluoro-5-hydroxybenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2-fluoro-5-(2-hydroxyethoxy)benzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2-fluoro-6-((2-hydroxyethyl)amino)benzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide hydrochloride;
(S)-1-(2-fluoro-4,5-dimethoxybenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2-chloro-6-fluorobenzyl)-N-(3-fluoro-5-(2-hydroxyethoxy)benzyl)-3,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2-chloro-6-fluorobenzyl)-N-(2-fluoro-3-hydroxybenzyl)-3,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
-(2-fluoro-5-(hydroxymethyl)benzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2,6-difluoro-3-(hydroxymethyl)benzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2,3-difluoro-5-methoxybenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2-fluoro-5-(3-hydroxypropoxy)benzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2-(2-aminoacetamido)-6-fluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide dihydrochloride;
(S)-1-(5-amino-2-fluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2-fluoro-4,5-dihydroxybenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2,4-difluoro-6-(3-hydroxypropoxy)benzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2-chloro-6-fluorobenzyl)-N-(2-fluoro-3-(2-hydroxyethoxy)benzyl)-3,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide
(S)-2-(4-((3,4-dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-3,5-difluorophenoxy)acetic acid;
(S)-1-(2-fluoro-6-((3-hydroxypropyl)amino)benzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2-fluoro-3-methoxybenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(4-(3-aminopropoxy)-2,6-difluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2,3-difluoro-5-hydroxybenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2,3-difluoro-5-(2-hydroxyethoxy)benzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2,3-difluoro-5-(3-hydroxypropoxy)benzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2-chloro-6-fluorobenzyl)-N-(4-fluoro-2-(2-hydroxyethoxy)benzyl)-3,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(6-amino-2,3-difluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(4-amino-2,6-difluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-((5-chloro-3-fluoro-2-oxo-1,2-dihydropyridin-4-yl)methyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-((5-chloro-3-fluoro-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)methyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(4S)-1-(2,6-difluoro-3-(1-hydroxyethyl)benzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2,6-difluoro-4-(2-(methylsulfonamido)ethoxy)benzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2,6-difluoro-4-(2-morpholinoethoxy)benzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(4-(2-aminoethoxy)-2,6-difluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide hydrochloride;
(S)-1-(2-chloro-6-fluoro-4-methoxybenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-4-(4-((3,4-dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-3,5-difluorophenoxy)butanoic acid;
(S)-1-((3,5-difluoropyridin-4-yl)methyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-((3-fluoro-5-methoxy-2-methylpyridin-4-yl)methyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-((5-chloro-3-fluoro-1-(2-hydroxyethyl)-2-oxo-1,2-dihydropyridin-4-yl)methyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(2-chloro-6-fluoro-4-hydroxybenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide;
(S)-1-(4-(2-aminoethoxy)-2-chloro-6-fluorobenzyl)-3,4-dimethyl-2-oxo-N-(2,4,6-trifluorobenzyl)-1,2,3,4-tetrahydroquinazoline-7-carboxamide hydrochloride;
or
(S)-2-chloro-3-((3,4-dimethyl-2-oxo-7-((2,4,6-trifluorobenzyl)carbamoyl)-3,4-dihydroquinazolin-1(2H)-yl)methyl)-4-fluorophenyl methyl(2-(methylamino)ethyl)carbamate hydrochloride.

248 more elements

Dependencies are inferred from the claim text.

Facts

Application: 16/625,047Filed 21 Jun 2018
Priority: GB 170995922 Jun 2017
Published: US 2020/0147083 A114 May 2020
Granted: 7 Feb 2023
Term ends: Not estimatedThe source records don’t support an estimate.

Classification24 codes

A61K 31/517
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/519
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: ortho- or peri-condensed with heterocyclic rings
A61K 31/549
Having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame: having two or more nitrogen atoms in…
A61K 45/06
Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00: mixtures of active ingredients without…

Family

US 2020/0147083 A1Pre-grant publication · published 14 May 2020
US 11,571,423 B2This patent

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

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Abstract

A compound of formula (I):

wherein X1 is CR1 or N;
X2 is CR2 or N;
X3 is CR3 or N;
Q is C═O or;
L is optionally substituted C1-C6 alkyl, C═O, S═O, SO2, or —CH2C(O)—;
R1, R2 and R3 are each independently selected from the group consisting of H, halogen, CN, hydroxyl, CONR1R2, NR1R2, NHCOR1, optionally substituted C1-C6 alkyl, optionally substituted mono or bicyclic C3-C6 cycloalkyl, and optionally substituted C1-C6 alkoxy
R6 is a ring optionally substituted with one or more R12 groups, wherein the ring is selected from the group consisting of phenyl, pyridyl, thiazole, isoxazole, oxazole, pyrazole, and pyridone;
Y is an optionally substituted C1-C6 alkyl;
R7 is H, or optionally substituted C1-C6 alkyl;
R8 is an optionally substituted ring selected from phenyl, furan, benzofuran and cyclohexyl;
R9 and R10 are each independently selected from the group consisting of optionally substituted C1-C6 alkyl, H, halogen, optionally substituted C3-C6 cycloalkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, mono or bicyclic optionally substituted
C5-C10 aryl, and mono or bicyclic optionally substituted 5 to 10 membered heteroaryl, or R9 and R10 together with the C atom to which they are attached can combine to form an optionally substituted spirocyclic ring;
R11 is selected from the group consisting of optionally substituted C1-C6 alkyl, H, optionally substituted C3-C6 cycloalkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C1-C6 alkoxy, mono and bicyclic optionally substituted 5 to 10 membered heteroaryl;
each R12 group is independently selected from the group consisting of halogen, OH, OP(O)(OH)2, NR13R14, CONR13R14, CN, COOR13, NO2, azido, SO2R13, OSO2R13, NR13SO2R14, NR13C(O)R14, O(CH2)nOC(O)R13, NR13(CH2)nOC(O)R14, OC(O)R13, OC(O)OR13, OC(O)NR13R14, OC(O)O(CH2)nCOOR14, OC(O)NR13(CH2)nCOOR14, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, an optionally substituted mono or bicyclic C5-C10 aryl, an optionally substituted mono or bicyclic 5 to 10 membered heteroaryl, an optionally substituted C3-C6 cycloalkyl and an optionally substituted mono or bicyclic 3 to 8 membered heterocycle;
R13 and R14 are each independently selected from the group consisting of H, optionally substituted C1-C6 alkyl, optionally substituted mono or bicyclic C3-C6 cycloalkyl, mono or bicyclic optionally substituted C5-C10 aryl, mono or bicyclic optionally substituted 5 to 10 membered heteroaryl, and optionally substituted mono or bicyclic 3 to 8 membered heterocycle;
and
n is an integer between 0 and 6;
or a pharmaceutically acceptable salt thereof.

15 more elements

Facts

Application

16/625,047Filed 21 Jun 2018

Priority

GB 170995922 Jun 2017

Published

US 2020/0147083 A114 May 2020

Granted

7 Feb 2023

Term ends

Not estimatedThe source records don’t support an estimate.

Classification24 codes

A61K 31/517
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/519
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: ortho- or peri-condensed with heterocyclic rings
A61K 31/549
Having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame: having two or more nitrogen atoms in…
A61K 45/06
Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00: mixtures of active ingredients without…