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US 10,640,494 B2Granted
N-acylethanolamine hydrolyzing acid amidase (NAAA) inhibitors and their use thereof
AssigneeNortheastern University
InventorsMichael Malamas, Alexandros Makriyannis, Kumara Vadivel Subramanian, Kyle M. Whitten, Nikolai M. Zvonok, Jay Matthew West, Michael McCormack, Spiro Pavlopoulos
Life of this patent
Estimating the term…
Abstract
A compound is represented as Formula I, a tautomer thereof, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof: Compounds of Formula I are inhibitors of N-acylethanolamine hydrolyzing acid amidase (NAAA).
Claims13
A compound of Formula I, a tautomer thereof, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof:
- wherein:
- M is CR, wherein R is H or alkyl;
- Z is NCS;
- W is (CH2)n, and n is 0, 1, 2, or 3;
- D is a substituted or unsubstituted cycloalkyl;
- Y is (CH2)n, O(CH2)n, NR3(CH2)n, (CH2)nO, (CH2)nNR3, where n is 0, 1, or 2, and R3 is H or C1-C4 alkyl;
- X is (CH2)n, where n is 0, 1, or 2;
- V is absent or O;
- B is a substituted or unsubstituted aryl or heteroaryl;
- and
- A is substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl, wherein
- A, B and D, when substituted, are each independently substituted with one or more substituent groups selected from halogen, hydroxyl, alkoxy, alkenoxy, aryloxy, aralkyloxy, heterocyclyl, heterocyclylalkyl, heterocyclyloxy, heterocyclylalkoxy, carbonyl, carboxylate, ester, urethane, oxime, hydroxylamine, alkoxyamine, aralkoxyamine, thiol, sulfide, sulfoxide, sulfone, sulfonyl, pentafluorosulfanyl, sulfonamide, amine, N-oxide, hydrazine, hydrazide, hydrazone, azide, amide, urea, amidine, guanidine, enamine, imide, isocyanate, isothiocyanate, cyanate, thiocyanate, imine, nitro, nitrile or alkyl optionally substituted one or more times with halo, hydroxy, thio, amino, alkylamino, dialkylamino, alkoxy or carboxy.
9 more elements
A compound selected from the group consisting of:
- 4-(((1R,3R)-3-isothiocyanatocyclobutoxy)methyl)-4′-methyl-1,1′-biphenyl;
- 4-(((1S,3S)-3-isothiocyanatocyclobutoxy)methyl)-4′-methyl-1,1′-biphenyl;
- 4-(((1R,3R)-3-isothiocyanatocyclobutoxy)methyl)-1,1′-biphenyl;
- 4-(((1S,3S)-3-isothiocyanatocyclobutoxy)methyl)-1,1′-biphenyl;
- 3,4′-difluoro-4-(((1 S, 3S)-3-isothiocyanatocyclobutoxy)methyl)-1,1′-biphenyl;
- 3,3′-difluoro-4-(((1 S, 3S)-3-isothiocyanatocyclobutoxy)methyl)-4′-methoxy-1,1′-biphenyl;
- 4′-(((1R,3R)-3-isothiocyanatocyclobutoxy)methyl)-3-methoxy-1,1′-biphenyl;
- 4′-(((1S,3S)-3-isothiocyanatocyclobutoxy)methyl)-3-methoxy-1,1′-biphenyl;
- 4-ethoxy-3,3′-difluoro-4′-(((1S,3S)-3-isothiocyanatocyclobutoxy)methyl)-1,1′-biphenyl;
- 3,3′-difluoro-4-isopropoxy-4′-(((1S,3S)-3-isothiocyanatocyclobutoxy)methyl)-1,1′-biphenyl;
- 6-(3-fluoro-4-(((1S,3S)-3-isothiocyanatocyclobutoxy)methyl)phenyl)-2,3-dihydrobenzo[b][1,4]dioxine;
- 5-(3-fluoro-4-(((1S,3S)-3-isothiocyanatocyclobutoxy)methyl)phenyl)benzo[d][1,3]dioxole;
- 3-fluoro-4-(((1S,3S)-3-isothiocyanatocyclobutoxy)methyl)-3′,4′-dimethoxy-1,1′-biphenyl;
- 3-(3-fluoro-4-(((1R,3R)-3-isothiocyanatocyclobutoxy)methyl)phenyl)-2-methoxypyridine;
- 5-(3-fluoro-4-methoxyphenyl)-2-(((1R,3R)-3-isothiocyanatocyclobutoxy)methyl)pyridine;
- 3,4′-difluoro-3′-(((1 S, 3S)-3-isothiocyanatocyclobutoxy)methyl)-4-methoxy-1,1′-biphenyl;
- 4-(3-fluoro-4-(((1R,3R)-3-isothiocyanatocyclobutoxy)methyl)phenyl)-3,5-dimethylisoxazole;
- 4-(3-fluoro-4-(((1R,3R)-3-isothiocyanatocyclobutoxy)methyl)phenyl)-1-methyl-1h-pyrazole;
- 3-fluoro-4-(((1R,3R)-3-isothiocyanatocyclobutoxy)methyl)-3′-(trifluoromethyl)-1,1′-biphenyl;
- 3′-(benzyloxy)-3-fluoro-4-(((1R,3R)-3-isothiocyanatocyclobutoxy)methyl)-1,1′-biphenyl;
- 3-fluoro-4′-((1R,3R)-3-isothiocyanatocyclobutoxy)-4-methoxy-1,1′-biphenyl;
- and
- 3-fluoro-4′-((1S,3S)-3-isothiocyanatocyclobutoxy)-4-methoxy-1,1′-biphenyl;
- or
- a tautomer thereof;
- a stereoisomer thereof;
- or
- a pharmaceutically acceptable salt thereof.
25 more elements
A compound of the following structural formula:
- or an N-oxide thereof, or a pharmaceutically acceptable salt of either of the foregoing.
Dependencies are inferred from the claim text.