SUBSTITUTED BENZALDEHYDE COMPOUNDS AND METHODS FOR THEIR USE IN INCREASING TISSUE OXYGENATION

1 . A compound of Formula (I):

or a tautomer or pharmaceutically acceptable salt thereof,

wherein Q is selected from the group consisting of aryl, heteroaryl, and heterocycloalkyl, each optionally substituted with one to three R a ;

Y is O or CR 1a R 1b , where R 1a is H or halo and R 1b is selected from the group consisting of H, halo, and OH;

X is selected from the group consisting of O, >CH(CH 2 ) n R 8 , and C(R 9 ) 2 where n is 0 or 1, R 8 is OH, and R 9 is independently H or halo; or Y—X taken together is —NHC(O)— or —C(O)NH—;

R 2 , R 3 , R 4 , and R 5 are independently selected from the group consisting of hydrogen, halo, R b , OR d , —O(CH 2 ) z OR d , —O(CH 2 ) z NR d R d , OC(O)R e , SR d , CN, NO 2 , CO 2 R d , CONR d R d , C(O)R d , OC(O)NR d R d , NR d R d , NR d C(O)R e , NR d C(O) 2 R e , NR d C(O)NR d R d , S(O)R e , S(O) 2 R e , NR d S(O) 2 R e , S(O) 2 NR d R d , and N 3 , where z is 0, 1, 2, 3, 4, 5, or 6; or R 5 is —(CH 2 ) p R 5a where p is 0 or 1 and R 5a is OH;

R 6 and R 7 together form oxo or an aldehyde protecting group, or R 6 together with R 1b , R 8 , or R 5 forms a cyclic ether where one of R 1b , R 8 , or R 5a is O, R 6 is a bond, and R 7 is selected from the group consisting of OH, C 1-8 alkoxy, and haloC 1-8 alkoxy;

each R a is independently selected from the group consisting of halo, oxo, R b , OR d , O(CH 2 ) u OR d , O(CH 2 ) u NR d R d , O(CH 2 ) u NR d C(O)R e , O(CH 2 ) u NR d C(O) 2 R e , O(CH 2 ) u NR d S(O) 2 R e , NH 2 , —(CH 2 ) k OC(O)R e , —(CH 2 ) k SR d , CN, NO 2 , —(CH 2 ) k CO 2 (C 1-8 alkyl)OH, —(CH 2 ) k CO 2 (C 1-8 alkyl)(heteroaryl)C(O)(C 1-8 alkyl), —(CH 2 ) k CO 2 R d , —(CH 2 ) k CONR d R d , —(CH 2 ) k NR d C(O)R e , —(CH 2 ) k NR d C(O) 2 R e , —(CH 2 ) k C(O)R d , —(CH 2 ) k OC(O)NR d R d , —NR d (CH 2 ) u OR d , —NR d (CH 2 ) u NR d R d , —NR d (CH 2 ) u NR d C(O)R e , —NR d (CH 2 ) u NR d C(O) 2 R e , —NR d (CH 2 ) u NR d S(O) 2 R e , —(CH 2 ) k NR d C(O)R e , —(CH 2 ) k NR d C(O) 2 R d , —(CH 2 ) k NR d C(O)NR d R d , —(CH 2 ) k S(O)R e , —(CH 2 ) k S(O) 2 R e , —(CH 2 ) k NR d S(O) 2 R e , —(CH 2 ) k S(O) 2 NR d R d , N 3 , —(CH 2 ) k aryl optionally substituted with one to three R e , —NR d (CH 2 ) k aryl optionally substituted with one to three R c , —(CH 2 ) k heteroaryl optionally substituted with one to three R c , —NR d (CH 2 ) k heteroaryl optionally substituted with one to three R e , —(CH 2 ) k heterocycloalkyl optionally substituted with one to three R e , and —NR d (CH 2 ) k heterocycloalkyl optionally substituted with one to three R c where k is 0, 1, 2, 3, 4, 5, or 6 and u is 1, 2, 3, 4, 5, or 6;

each R b is independently selected from the group consisting of C 1-8 alkyl, C 2-8 alkenyl, and C 2-8 alkynyl, each optionally independently substituted with one to three halo, OR d , or NR d R d ;

each R e is independently selected from the group consisting of halo, C 1-8 alkyl, haloC 1-8 alkyl, C 2-8 alkenyl, haloC 2-8 alkenyl, C 2-8 alkynyl, haloC 2-8 alkynyl, (CH 2 ) m OR f , OC(O)R g , SR f , CN, NO 2 , CO 2 R f , CONR f R f , C(O)R f , OC(O)NR f R f , (CH 2 ) m NR f R f , NR f C(O)R g , NR f C(O) 2 R g , NR f C(O)NR f R f , S(O)R g , S(O) 2 R g , NR f S(O) 2 R g , S(O) 2 NR f R f , N 3 , heteroaryl optionally substituted with one to three R h , and heterocycloalkyl optionally substituted with one to three R h where m is selected from the group consisting of 0, 1, 2, 3, 4, 5, and 6;

each R h is independently selected from the group consisting of halo, C 1-8 alkyl, haloC 1-8 alkyl, OR j , OC(O)R, SR j , NO 2 , CO 2 R j , CONR j R j , C(O)R j , OC(O)NR j R j , NR j R j , NR j C(O)R t , NR j C(O) 2 R t , NR j C(O)NR j R j , S(O)R t , S(O) 2 R t , NR j S(O) 2 R t , and S(O) 2 NR j R j ;

R d , R f , and R j are each independently selected from the group consisting of hydrogen, C 1-8 alkyl, haloC 1-8 alkyl, C 2-8 alkenyl, haloC 2-8 alkenyl, C 2-8 alkynyl, and haloC 2-8 alkynyl; and

R e , R g , and R t are each independently selected from the group consisting of C 1-8 alkyl, haloC 1-8 alkyl, C 2-8 alkenyl, haloC 2-8 alkenyl, C 2-8 alkynyl, and haloC 2-8 alkynyl;

provided that X and Y are not both O;

provided that when X is O, R 1b is not OH;

provided that when Y is O, and n is O, R 8 is not OH; and

provided that when R 6 and R 7 together are oxo, Y is CH 2 , X is O or CH 2 , and R 5 is H, halo, OH, CHO, or OCH 3 , then Q is V or W;

V is selected from the group consisting of

and naphthalene containing three to four ring nitrogen atoms; wherein V is optionally substituted with one to three R a ; and

W is selected from the group consisting of pyridin-2-yl, pyridin-3-yl, and pyridine-4-yl,

wherein W is optionally substituted with one to three R a or is substituted with one to three R a when W is pyridin-2-yl, pyridin-3-yl, or pyridine-4-yl, and wherein the wavy line signifies the point of attachment to Y, provided that when V is

optionally substituted with one R a , then at least one of R 2 , R 3 , R 4 , and R 5 is OR d ; and provided that when V is

then V is substituted with one to three R a .

2 . A compound according to claim 1 , wherein:

Y is O or CH 2 ;

X is O or CH 2 ;

Q is selected from the group consisting of:

iii) imidazopyridinyl, methylimidazopyridinyl, indazolyl, pyrrolopyridinyl, pyrrolopyrazinyl, pyrazolopyridinyl, pyrazolopyrazinyl, and quinolinyl, each of which is optionally substituted with one to three R a ; wherein

R 2 , R 3 , R 4 , and R 5 , are independently selected from the group consisting of hydrogen, halo, R b , OR d , O(CH 2 ) z OR d , O(CH 2 ) z NR d R d , OC(O)R e , SR d , CN, NO 2 , CO 2 R d , CONR d R d , C(O)R d , OC(O)NR d R d , NR d R d , NR d C(O)R e , NR d C(O) 2 R e , NR d C(O)NR d R d , S(O)R e , S(O) 2 R e , NR d S(O) 2 R e , S(O) 2 NR d R d , and N 3 where z is 1, 2, or 3; and

iv) pyridinyl and piperidinyl, each of which is optionally substituted with one to three R a ; wherein

R 2 , R 3 , and R 4 are independently selected from the group consisting of hydrogen, halo, R b , OR d , O(CH 2 ) z OR d , O(CH 2 ) z NR d R d , OC(O)R e , SR d , CN, NO 2 , CO 2 R d , CONR d R d , C(O)R d , OC(O)NR d R d , NR d R d , NR d C(O)R e , NR d C(O) 2 R e , NR d C(O)NR d R d , S(O)R e , S(O) 2 R e , NR d S(O) 2 R e , S(O) 2 NR d R d , and N 3 where z is 1, 2, or 3; and

R 5 is selected from the group consisting of halo and OR d ;

R 6 and R 7 together form oxo or an aldehyde protecting group;

each R a is independently selected from the group consisting of halo, oxo, R b , OR d , O(CH 2 ) u OR d , O(CH 2 ) u NR d R d , O(CH 2 ) u NR d C(O)R e , O(CH 2 ) u NR d C(O) 2 R e , O(CH 2 ) u NR d S(O) 2 R e , NH 2 , —(CH 2 ) k OC(O)R e , —(CH 2 ) k SR d , CN, NO 2 , —(CH 2 ) k CO 2 (C 1-8 alkyl)OH, —(CH 2 ) k CO 2 (C 1-8 alkyl)(heteroaryl)C(O)(C 1-8 alkyl), —(CH 2 ) k CO 2 R d , —(CH 2 ) k CONR d R d , —(CH 2 ) k NR d C(O)R e , —(CH 2 ) k NR d C(O) 2 R e , —(CH 2 ) k C(O)R d , —(CH 2 ) k OC(O)NR d R d , —NR d (CH 2 ) u OR d , —NR d (CH 2 ) u NR d R d , —NR d (CH 2 ) u NR d C(O)R e , —NR d (CH 2 ) u NR d C(O) 2 R e , —NR d (CH 2 ) u NR d S(O) 2 R e , —(CH 2 ) k NR d C(O)R e , —(CH 2 ) k NR d C(O) 2 R d , —(CH 2 ) k NR d C(O)NR d R d , —(CH 2 ) k S(O)R e , —(CH 2 ) k S(O) 2 R e , —(CH 2 ) k NR d S(O) 2 R e , —C(O)(CH 2 ) k NR d S(O) 2 R e , —(CH 2 ) k C(O)NR d S(O) 2 R e , —(CH 2 ) k S(O) 2 NR d R d , N 3 , —(CH 2 ) k aryl optionally substituted with one to three R c , —NR d (CH 2 ) k aryl optionally substituted with one to three R c , —(CH 2 ) k heteroaryl optionally substituted with one to three R c , —NR d (CH 2 ) k heteroaryl optionally substituted with one to three R c , —(CH 2 ) k heterocycloalkyl optionally substituted with one to three R c , and —NR d (CH 2 ) k heterocycloalkyl optionally substituted with one to three R c where k is 0, 1, 2, 3, 4, 5, or 6 and u is 1, 2, 3, 4, 5, or 6;

each R b is independently selected from the group consisting of C 1-8 alkyl, C 2-8 alkenyl, and C 2-8 alkynyl, each optionally independently substituted with one to three halo, OR d , or NR d R d ;

each R c is independently selected from the group consisting of halo, C 1-8 alkyl, haloC 1-8 alkyl, C 2-8 alkenyl, haloC 2-8 alkenyl, C 2-8 alkynyl, haloC 2-8 alkynyl, (CH 2 ) m OR f , OC(O)R g , SR f , CN, NO 2 , (CH 2 ) m CO 2 R f , CONR f R f , C(O)R f , OC(O)NR f R f , (CH 2 ) m NR f R f , NR f C(O)R g , NR f C(O) 2 R g , NR f C(O)NR f R f , S(O)R g , S(O) 2 R g , NR f S(O) 2 R g , S(O) 2 NR f R f , N 3 , (R f ) m SiC 1-8 alkyl, heteroaryl optionally substituted with one to three R h , cycloalkyl optionally substituted with one to three R h , and heterocycloalkyl optionally substituted with one to three R h where m is selected from the group consisting of 0, 1, 2, 3, 4, 5, and 6;

each R h is independently selected from the group consisting of halo, C 1-8 alkyl, haloC 1-8 alkyl, OR j , OC(O)R, SR j , NO 2 , CO 2 R j , CONR j R j , C(O)R j , OC(O)NR j R j , NR j R j , NR j C(O)R t , NR j C(O) 2 R t , NR j C(O)NR j R j , S(O)R t , S(O) 2 R t , NR j S(O) 2 R t , and S(O) 2 NR j R j ;

R d , R f , and R j are each independently selected from the group consisting of hydrogen, C 1-8 alkyl, haloC 1-8 alkyl, C 2-8 alkenyl, haloC 2-8 alkenyl, C 2-8 alkynyl, and haloC 2-8 alkynyl; and

R e , R g , and R t are each independently selected from the group consisting of C 1-8 alkyl, haloC 1-8 alkyl, C 2-8 alkenyl, haloC 2-8 alkenyl, C 2-8 alkynyl, and haloC 2-8 alkynyl.

3 . A compound according to claim 1 , wherein:

Y is CH 2 ; and X is CH 2 .

4 . A compound according to claim 2 , or a tautomer or pharmaceutically acceptable salt thereof, wherein Q is selected from the group consisting of imidazo[1,5-a]pyridin-8-yl, imidazo[1,5-a]pyridin-6-yl, imidazo[1,5-a]pyridin-5-yl, imidazo[1,2-a]pyridin-8-yl, imidazo[1,2-a]pyridin-7-yl, imidazo[1,2-a]pyridin-6-yl, imidazo[1,2-a]pyridin-5-yl, imidazo[1,2-a]pyridin-3-yl, 8-methylimidazo[1,2-a]pyridin-2-yl, indazol-4-yl, pyrrolo[2,3-b]pyridin-4-yl, pyrrolo[1,2-a]pyrazin-6-yl, pyrrolo[1,2-a]pyrazin-4-yl, pyrazolo[3,4-b]pyridin-4-yl, pyrazolo[1,5-a]pyrazin-3-yl, and quinolin-5-yl, each of which is optionally substituted with one to three R a .

5 . A compound according to claim 4 , or a tautomer or pharmaceutically acceptable salt thereof, wherein R 2 is selected from the group consisting of H and OR d ;

R 3 is selected from the group consisting of H, CN, halo, and OR d ;

R 4 is selected from the group consisting of H, CN, and OR d : and

R 5 is H.

6 . A compound according to claim 5 , or a tautomer or pharmaceutically acceptable salt thereof, wherein R 4 is methoxy.

7 . A compound according to claim 3 , or a tautomer or pharmaceutically acceptable salt thereof, wherein Q is selected from the group consisting of pyridine-3-yl and piperidin-1-yl.

8 . A compound according to claim 7 , or a tautomer or pharmaceutically acceptable salt thereof, wherein R 5 is selected from the group consisting of hydroxy and fluoro.

9 . A compound according to any of the preceeding claims, or a tautomer or pharmaceutically acceptable salt thereof, wherein R 6 and R 7 together form oxo.

10 . A compound according to claim 1 selected from the group consisting of:

2-(imidazo[1,2-a]pyridin-8-ylmethoxy)-5-methoxybenzaldehyde,

4-formyl-3-(imidazo[1,2-a]pyridin-8-ylmethoxy)benzonitrile,

2-(imidazo[1,2-a]pyridin-8-ylmethoxy)-4-methoxybenzaldehyde,

2-(imidazo[1,2-a]pyridin-6-ylmethoxy)-5-methoxybenzaldehyde,

2-(imidazo[1,5-a]pyridin-8-ylmethoxy)-4-methoxybenzaldehyde,

2-(imidazo[1,5-a]pyridin-8-ylmethoxy)-5-methoxybenzaldehyde,

2-(imidazo[1,2-a]pyridin-7-ylmethoxy)-5-methoxybenzaldehyde,

2-(imidazo[1,2-a]pyridin-3-ylmethoxy)-5-methoxybenzaldehyde,

5-methoxy-2-(quinolin-5-ylmethoxy)benzaldehyde,

5-bromo-2-(imidazo[1,2-a]pyridin-8-ylmethoxy)benzaldehyde,

4-chloro-2-(imidazo[1,2-a]pyridin-8-ylmethoxy)benzaldehyde,

2-(imidazo[1,2-a]pyridin-8-ylmethoxy)benzaldehyde,

4-fluoro-2-(imidazo[1,2-a]pyridin-8-ylmethoxy)benzaldehyde,

2-(imidazo[1,2-a]pyridin-8-ylmethoxy)-3-methoxybenzaldehyde,

2-(imidazo[1,2-a]pyridin-8-ylmethoxy)-5-methylbenzaldehyde,

5-methoxy-2-(pyrrolo[1,2-a]pyrazin-4-ylmethoxy)benzaldehyde,

2-(imidazo[1,5-a]pyridin-6-ylmethoxy)-4-methoxybenzaldehyde,

2-(imidazo[1,5-a]pyridin-5-ylmethoxy)-5-methoxybenzaldehyde,

3-formyl-4-(imidazo[1,5-a]pyridin-5-ylmethoxy)benzonitrile,

2-((1H-pyrrolo[2,3-b]pyridin-4-yl)methoxy)-5-methoxybenzaldehyde,

5-ethyl-2-(imidazo[1,2-a]pyridin-8-ylmethoxy)benzaldehyde,

5-methoxy-2-((1-methyl-1H-indazol-4-yl)methoxy)benzaldehyde,

5-methoxy-2-((8-methylimidazo[1,2-a]pyridin-2-yl)methoxy)benzaldehyde,

2-((1H-indazol-4-yl)methoxy)-5-methoxybenzaldehyde,

2-((1H-pyrrolo[2,3-b]pyridin-4-yl)methoxy)-5-methoxybenzaldehyde,

3-formyl-4-(imidazo[1,2-a]pyridin-8-ylmethoxy)benzonitrile,

5-methoxy-2-(pyrrolo[1,2-a]pyrazin-6-ylmethoxy)benzaldehyde,

6-((2-formyl-4-methoxyphenoxy)methyl)pyrrolo[1,2-a]pyrazine-7-carbonitrile,

6-((2-formyl-4-methoxyphenoxy)methyl)pyrrolo[1,2-a]pyrazine-7-carboxamide,

2-((1H-pyrazolo[3,4-b]pyridin-4-yl)methoxy)-5-methoxybenzaldehyde,

5-methoxy-2-(pyrazolo[1,5-a]pyrazin-3-ylmethoxy)benzaldehyde,

5-methoxy-2-(pyrrolo[1,2-a]pyrazin-6-ylmethoxy)benzaldehyde,

2-(imidazo[1,5-a]pyridin-6-ylmethoxy)-5-methoxybenzaldehyde,

3-formyl-4-(imidazo[1,2-a]pyridin-8-ylmethoxy)benzonitrile,

3-(imidazo[1,2-a]pyridin-8-ylmethyl)-1,3-dihydroisobenzofuran-1-ol,

2-(imidazo[1,2-a]pyridin-5-ylmethoxy)-5-methoxybenzaldehyde,

N-(2-formyl-4-methoxyphenyl)imidazo[1,2-a]pyridine-8-carboxamide,

N-(2-formylphenyl)imidazo[1,2-a]pyridine-8-carboxamide,

2-formyl-N-(imidazo[1,2-a]pyridin-8-yl)benzamide,

2-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)-5-methoxybenzaldehyde,

2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde

2-((3-(2H-tetrazol-5-yl)benzyl)oxy)-6-hydroxybenzaldehyde,

2-((4-(2H-tetrazol-5-yl)benzyl)oxy)-6-hydroxybenzaldehyde,

2-hydroxy-6-((2-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde,

2-hydroxy-6-((2-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde,

2-fluoro-6-((2-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde,

2-fluoro-6-((2-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde,

2-fluoro-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde, and

1-(2-formyl-3-hydroxyphenethyl)piperidine-4-carboxylic acid

or a tautomer or pharmaceutically acceptable salt thereof.

11 . A compound according to claim 1 selected from the group consisting of:

2-(imidazo[1,2-a]pyridin-8-ylmethoxy)-5-methoxybenzaldehyde,

2-(imidazo[1,5-a]pyridin-8-ylmethoxy)-5-methoxybenzaldehyde,

5-methoxy-2-(quinolin-5-ylmethoxy)benzaldehyde,

5-methoxy-2-((1-methyl-1H-indazol-4-yl)methoxy)benzaldehyde,

5-methoxy-2-((8-methylimidazo[1,2-a]pyridin-2-yl)methoxy)benzaldehyde,

2-((1H-indazol-4-yl)methoxy)-5-methoxybenzaldehyde,

2-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)-5-methoxybenzaldehyde,

2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde,

2-((3-(2H-tetrazol-5-yl)benzyl)oxy)-6-hydroxybenzaldehyde,

2-((4-(2H-tetrazol-5-yl)benzyl)oxy)-6-hydroxybenzaldehyde,

2-hydroxy-6-((2-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde,

2-hydroxy-6-((2-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde,

2-fluoro-6-((2-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde,

2-fluoro-6-((2-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde,

2-fluoro-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde, and

1-(2-formyl-3-hydroxyphenethyl)piperidine-4-carboxylic acid,

or a tautomer or pharmaceutically acceptable salt thereof.

12 . A pharmaceutical composition comprising a compound of any of the preceding claims or a tautomer or pharmaceutically acceptable salt thereof.

13 . A method for increasing tissue oxygenation, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of any of the preceding claims or a tautomer or pharmaceutically acceptable salt thereof.

14 . A method for treating a condition associated with oxygen deficiency, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of any of the preceding claims or a tautomer or pharmaceutically acceptable salt thereof.

15 . The method of claim 14 , wherein the condition is selected from the group consisting of sickle cell disease, cancer, a pulmonary disorder, stroke, high altitude sickness, an ulcer, a pressure sore, Alzheimer's disease, acute respiratory disease syndrome, and a wound

16 . The method of any of claims 13 - 15 , wherein the compound is selected from the group consisting of:

2-(imidazo[1,2-a]pyridin-8-ylmethoxy)-5-methoxybenzaldehyde,

4-formyl-3-(imidazo[1,2-a]pyridin-8-ylmethoxy)benzonitrile,

2-(imidazo[1,2-a]pyridin-8-ylmethoxy)-4-methoxybenzaldehyde,

2-(imidazo[1,2-a]pyridin-6-ylmethoxy)-5-methoxybenzaldehyde,

2-(imidazo[1,2-a]pyridin-2-ylmethoxy)-5-methoxybenzaldehyde,

2-(imidazo[1,5-a]pyridin-8-ylmethoxy)-4-methoxybenzaldehyde,

2-(imidazo[1,5-a]pyridin-8-ylmethoxy)-5-methoxybenzaldehyde,

2-(imidazo[1,2-a]pyridin-7-ylmethoxy)-5-methoxybenzaldehyde,

2-(imidazo[1,2-a]pyridin-3-ylmethoxy)-5-methoxybenzaldehyde,

5-methoxy-2-(quinolin-5-ylmethoxy)benzaldehyde,

5-bromo-2-(imidazo[1,2-a]pyridin-8-ylmethoxy)benzaldehyde,

4-chloro-2-(imidazo[1,2-a]pyridin-8-ylmethoxy)benzaldehyde,

2-(imidazo[1,2-a]pyridin-8-ylmethoxy)benzaldehyde,

4-fluoro-2-(imidazo[1,2-a]pyridin-8-ylmethoxy)benzaldehyde,

2-(imidazo[1,2-a]pyridin-8-ylmethoxy)-3-methoxybenzaldehyde,

2-(imidazo[1,2-a]pyridin-8-ylmethoxy)-5-methylbenzaldehyde,

5-methoxy-2-(pyrrolo[1,2-a]pyrazin-4-ylmethoxy)benzaldehyde,

2-(imidazo[1,5-a]pyridin-6-ylmethoxy)-4-methoxybenzaldehyde,

2-(imidazo[1,5-a]pyridin-5-ylmethoxy)-5-methoxybenzaldehyde,

3-formyl-4-(imidazo[1,5-a]pyridin-5-ylmethoxy)benzonitrile,

2-((1H-pyrrolo[2,3-b]pyridin-4-yl)methoxy)-5-methoxybenzaldehyde,

5-ethyl-2-(imidazo[1,2-a]pyridin-8-ylmethoxy)benzaldehyde,

5-methoxy-2-((1-methyl-1H-indazol-4-yl)methoxy)benzaldehyde,

5-methoxy-2-((8-methylimidazo[1,2-a]pyridin-2-yl)methoxy)benzaldehyde,

2-((1H-indazol-4-yl)methoxy)-5-methoxybenzaldehyde,

2-((1H-pyrrolo[2,3-b]pyridin-4-yl)methoxy)-5-methoxybenzaldehyde,

3-formyl-4-(imidazo[1,2-a]pyridin-8-ylmethoxy)benzonitrile,

5-methoxy-2-(pyrrolo[1,2-a]pyrazin-6-ylmethoxy)benzaldehyde,

6-((2-formyl-4-methoxyphenoxy)methyl)pyrrolo[1,2-a]pyrazine-7-carbonitrile,

6-((2-formyl-4-methoxyphenoxy)methyl)pyrrolo[1,2-a]pyrazine-7-carboxamide,

2-((1H-pyrazolo[3,4-b]pyridin-4-yl)methoxy)-5-methoxybenzaldehyde,

5-methoxy-2-(pyrazolo[1,5-a]pyrazin-3-ylmethoxy)benzaldehyde,

5-methoxy-2-(pyrrolo[1,2-a]pyrazin-6-ylmethoxy)benzaldehyde,

2-(imidazo[1,5-a]pyridin-6-ylmethoxy)-5-methoxybenzaldehyde,

3-formyl-4-(imidazo[1,2-a]pyridin-8-ylmethoxy)benzonitrile,

3-(imidazo[1,2-a]pyridin-8-ylmethyl)-1,3-dihydroisobenzofuran-1-ol,

2-(imidazo[1,2-a]pyridin-5-ylmethoxy)-5-methoxybenzaldehyde,

N-(2-formyl-4-methoxyphenyl)imidazo[1,2-a]pyridine-8-carboxamide,

N-(2-formylphenyl)imidazo[1,2-a]pyridine-8-carboxamide,

2-formyl-N-(imidazo[1,2-a]pyridin-8-yl)benzamide,

5-methoxy-2-(pyridin-3-ylmethoxy)benzaldehyde,

4-((2-formyl-3-hydroxyphenoxy)methyl)benzoic acid,

2-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)-5-methoxybenzaldehyde,

2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde,

2-((3-(2H-tetrazol-5-yl)benzyl)oxy)-6-hydroxybenzaldehyde,

2-((4-(2H-tetrazol-5-yl)benzyl)oxy)-6-hydroxybenzaldehyde,

methyl 4-((2-formylphenoxy)methyl)benzoate,

4-((2-formylphenoxy)methyl)benzoic acid,

methyl 3-((2-formylphenoxy)methyl)benzoate,

2-hydroxy-6-((2-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde,

2-hydroxy-6-((2-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde,

2-fluoro-6-((2-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde,

2-fluoro-6-((2-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde,

2-fluoro-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde, and

1-(2-formyl-3-hydroxyphenethyl)piperidine-4-carboxylic acid

or a tautomer or pharmaceutically acceptable salt thereof.

17 . The method of any of claims 13 - 15 , wherein the compound is selected from the group consisting of:

2-(imidazo[1,2-a]pyridin-8-ylmethoxy)-5-methoxybenzaldehyde,

4-formyl-3-(imidazo[1,2-a]pyridin-8-ylmethoxy)benzonitrile,

2-(imidazo[1,2-a]pyridin-8-ylmethoxy)-4-methoxybenzaldehyde,

2-(imidazo[1,2-a]pyridin-6-ylmethoxy)-5-methoxybenzaldehyde,

2-(imidazo[1,2-a]pyridin-2-ylmethoxy)-5-methoxybenzaldehyde,

2-(imidazo[1,5-a]pyridin-8-ylmethoxy)-4-methoxybenzaldehyde,

2-(imidazo[1,5-a]pyridin-8-ylmethoxy)-5-methoxybenzaldehyde,

2-(imidazo[1,2-a]pyridin-7-ylmethoxy)-5-methoxybenzaldehyde,

2-(imidazo[1,2-a]pyridin-3-ylmethoxy)-5-methoxybenzaldehyde,

5-methoxy-2-(quinolin-5-ylmethoxy)benzaldehyde,

5-bromo-2-(imidazo[1,2-a]pyridin-8-ylmethoxy)benzaldehyde,

4-chloro-2-(imidazo[1,2-a]pyridin-8-ylmethoxy)benzaldehyde,

2-(imidazo[1,2-a]pyridin-8-ylmethoxy)benzaldehyde,

4-fluoro-2-(imidazo[1,2-a]pyridin-8-ylmethoxy)benzaldehyde,

2-(imidazo[1,2-a]pyridin-8-ylmethoxy)-3-methoxybenzaldehyde,

2-(imidazo[1,2-a]pyridin-8-ylmethoxy)-5-methylbenzaldehyde,

5-methoxy-2-(pyrrolo[1,2-a]pyrazin-4-ylmethoxy)benzaldehyde,

2-(imidazo[1,5-a]pyridin-6-ylmethoxy)-4-methoxybenzaldehyde,

2-(imidazo[1,5-a]pyridin-5-ylmethoxy)-5-methoxybenzaldehyde,

3-formyl-4-(imidazo[1,5-a]pyridin-5-ylmethoxy)benzonitrile,

2-((1H-pyrrolo[2,3-b]pyridin-4-yl)methoxy)-5-methoxybenzaldehyde,

5-ethyl-2-(imidazo[1,2-a]pyridin-8-ylmethoxy)benzaldehyde,

5-methoxy-2-((1-methyl-1H-indazol-4-yl)methoxy)benzaldehyde,

5-methoxy-2-((8-methylimidazo[1,2-a]pyridin-2-yl)methoxy)benzaldehyde,

2-((1H-indazol-4-yl)methoxy)-5-methoxybenzaldehyde,

2-((1H-pyrrolo[2,3-b]pyridin-4-yl)methoxy)-5-methoxybenzaldehyde,

3-formyl-4-(imidazo[1,2-a]pyridin-8-ylmethoxy)benzonitrile,

5-methoxy-2-(pyrrolo[1,2-a]pyrazin-6-ylmethoxy)benzaldehyde,

6-((2-formyl-4-methoxyphenoxy)methyl)pyrrolo[1,2-a]pyrazine-7-carbonitrile,

6-((2-formyl-4-methoxyphenoxy)methyl)pyrrolo[1,2-a]pyrazine-7-carboxamide,

2-((1H-pyrazolo[3,4-b]pyridin-4-yl)methoxy)-5-methoxybenzaldehyde,

5-methoxy-2-(pyrazolo[1,5-a]pyrazin-3-ylmethoxy)benzaldehyde,

5-methoxy-2-(pyrrolo[1,2-a]pyrazin-6-ylmethoxy)benzaldehyde,

2-(imidazo[1,5-a]pyridin-6-ylmethoxy)-5-methoxybenzaldehyde,

3-formyl-4-(imidazo[1,2-a]pyridin-8-ylmethoxy)benzonitrile,

3-(imidazo[1,2-a]pyridin-8-ylmethyl)-1,3-dihydroisobenzofuran-1-ol,

2-(imidazo[1,2-a]pyridin-5-ylmethoxy)-5-methoxybenzaldehyde,

N-(2-formyl-4-methoxyphenyl)imidazo[1,2-a]pyridine-8-carboxamide,

N-(2-formylphenyl)imidazo[1,2-a]pyridine-8-carboxamide,

2-formyl-N-(imidazo[1,2-a]pyridin-8-yl)benzamide,

5-methoxy-2-(pyridin-3-ylmethoxy)benzaldehyde,

4-((2-formyl-3-hydroxyphenoxy)methyl)benzoic acid,

2-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)-5-methoxybenzaldehyde,

2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde,

2-((3-(2H-tetrazol-5-yl)benzyl)oxy)-6-hydroxybenzaldehyde,

2-((4-(2H-tetrazol-5-yl)benzyl)oxy)-6-hydroxybenzaldehyde,

methyl 4-((2-formylphenoxy)methyl)benzoate,

4-((2-formylphenoxy)methyl)benzoic acid,

methyl 3-((2-formylphenoxy)methyl)benzoate,

2-hydroxy-6-((2-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde,

2-hydroxy-6-((2-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde,

2-fluoro-6-((2-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde,

2-fluoro-6-((2-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde,

2-fluoro-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde, and

1-(2-formyl-3-hydroxyphenethyl)piperidine-4-carboxylic acid

or a tautomer or pharmaceutically acceptable salt thereof.