Compounds and therapeutic uses thereof

A compound having a structure according to Formula I

• J-K-L-E-Q-P Formula I
• and pharmaceutically-acceptable salts and solvates thereof;
• wherein:
• J is selected from:
• alkyl, nitro, cyano, alkoxy, C-amido, N-amido, haloalkyl, C-carboxy, O-carboxy, sulfonamide, amino, hydroxyl, mercapto, alkylthio, sulfonyl, sulfinyl, carbocycle, spiro-linked (i.e., two adjacent atoms of J are linked to one atom of K) carbocycle, cycloalkyl, spiro-linked cycloalkyl, cycloalkenyl, spiro-linked cycloalkenyl, heterocycle, spiro-linked heterocycle, heterocyclonoyl, aryl, spiro-linked aryl, heteroaryl, spiro-linked heteroaryl, carbocycloalkyl, heterocyclylalkyl, arylalkyl, arylalkenyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, or arylalkynyl, wherein any of the foregoing groups are optionally substituted at least once with alkyl, alkylene, alkenyl, alkenylene, alkynyl, alkynylene, carbocycle, cycloalkyl, cycloalkenyl, heterocycle, aryl, heteroaryl, halo, hydro, hydroxyl, alkoxy, alkynyloxy, cycloalkyloxy, heterocycloxy, aryloxy, heteroaryloxy, arylalkoxy, heteroarylalkoxy, mercapto, alkylthio, arylthio, arylalkyl, heteroarylalkyl, heteroarylalkenyl, arylalkynyl, haloalkyl, aldehyde, thiocarbonyl, heterocyclonoyl, O-carboxy, C-carboxy, carboxylic acid, ester, C-carboxy salt, carboxyalkyl, carboxyalkenylene, carboxyalkyl salt, carboxyalkoxy, carboxyalkoxyalkanoyl, amino, aminoalkyl, nitro, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, aminothiocarbonyl, hydroxyamino carbonyl, alkoxyaminocarbonyl, cyano, nitrile, cyanato, isocyanato, thiocyanato, isothiocyanato, sulfinyl, sulfonyl, sulfonamide, aminosulfonyl, aminosulfonyloxy, sulfonamidecarbonyl, alkanoylaminosulfonyl, trihalomethylsulfonyl, or trihalomethylsulfonamide, wherein any of the foregoing optional substituents are themselves optionally substituted;
• K is an optionally further substituted 5-membered heteroaryl or heterocyclic ring;
• L is either (i) an optionally-substituted phenyl or an optionally-substituted 5- or 6-membered heteroaryl ring, (ii) optionally-substituted 5- or 6-membered cycloalkyl, (iii) optionally-substituted alkyl, (iv) optionally-substituted alkenyl, or (v) optionally-substituted alkynyl;
• E is either (i) —C0-2 alkylene-N(H)—C(═X)—N(H)— or (ii) -M-C(═X′)—N(H)—, wherein X is O, S, or N—C≡N, wherein M is optionally-substituted ethenylene or optionally-substituted ethylene, and wherein X′ is O or S;
• Q is optionally present and if present is optionally-substituted ethylene or optionally-substituted methylene;
• P is an optionally-substituted pyridinyl ring;
• with the proviso that when L is optionally-substituted alkyl, then K is an optionally-substituted 5-membered bicyclic heteroaryl or bicyclic heterocyclic ring (i.e., K comprises a 5-membered heteroaryl or heterocyclic ring fused to a second ring, wherein attachment to J and L is via the 5-membered heteroaryl or heterocyclic ring);
• and
• with the proviso that when E is -M-C(═X′)—N(H)—, then K is not xanthine;
• and also with the proviso that when E is —C0-2 alkylene-N(H)—C(═X)—N(H)—, then either K is an optionally-substituted 5-membered bicyclic heteroaryl or bicyclic heterocyclic ring (i.e., K comprises a 5-membered heteroaryl or heterocyclic ring fused to a second ring, wherein attachment to J and L is via the 5-membered heteroaryl or heterocyclic ring) or J is a spiro-linked moiety (i.e., two adjacent atoms of J are linked to one atom of K), such as, for example, spiro-linked carbocycle, spiro-linked cycloalkyl, spiro-linked cycloalkenyl, spiro-linked heterocycle, spiro-linked aryl, and spiro-linked heteroaryl;
• and
• with the proviso that the compound is not:
• Urea, N-(6-chloro-3-pyridinyl)-N′-[2-[4-(5-methyl-3-oxo-1H-imidazo[1,5-c]imidazol-2(3H)-yl)-1-piperidinyl]-2-oxo-1-phenylethyl]-;
• Urea, N-[2-(3′-chloro[1,1′-biphenyl]-4-yl)-2-(1-cyclopentyl-4-piperidinyl)ethyl]-N′-3-pyridinyl-;
• Urea, N-[2-(3′-cyano[1,1′-biphenyl]-4-yl)-2-(1-cyclopentyl-4-piperidinyl)ethyl]-N′-3-pyridinyl-;
• 2H-Pyrazino[2,1-c][1,2,4]triazine-1(6H)-carboxamide,hexahydro-6-[(4-hydroxyphenyl)methyl]-8-[[1-methyl-3-[4-[[[[6-(4-methyl-1-piperazinyl)-3-pyridinyl]amino]carbonyl]amino]phenyl]-1H-indol-7-yl]methyl]-4,7-dioxo-N-(phenylmethyl)-2-(2-propen-1-yl)-,(6S,9aS)-;
• or
• 2H-Pyrazino[2,1-c][1,2,4]triazine-1(6H)-carboxamide,hexahydro-6-[(4-hydroxyphenyl)methyl]-8-[[3-[4-[[[(6-methoxy-3-pyridinyl)amino]carbonyl]amino]phenyl]-1-methyl-1H-indol-7-yl]methyl]-4,7-dioxo-N-(phenylmethyl)-2-(2-propen-1-yl)-(6S,9aS)-.