INHIBITORS OF SOLUTE CARRIER FAMILY 6A MEMBER 19 (SLC6A19) AND METHODS OF USE THEREOF

1 . A compound of formula (I):

or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein

one of R 1a and R 1b is

 and

the other of R 1a and R 1b is H, halo, —CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 cycloalkyl, or C 1-6 alkoxy, wherein the C 1-6 alkoxy of R 1a and R 1b is optionally substituted with one or more R a ;

R 2 and R 4 are each independently H, halo, —CN, C 1-6 alkyl, C 1-6 cycloalkyl, C 1-6 haloalkyl, or C 1-6 alkoxy, wherein the C 1-6 alkoxy of R 2 and R 4 is optionally substituted with one or more R a ;

R 3 and R 5 are each independently H, —OH, halo, —N(R w1 )(R w2 ), or C 1-6 alkyl, wherein the C 1-6 alkyl of R 3 and R 5 is optionally substituted with one or more —OH;

R 6 is C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-10 cycloalkyl, —N(R w1 )(R w2 ), C 6-20 aryl, 3-10 membered heterocyclyl, or 5-20 membered heteroaryl, wherein

the C 1-6 alkyl, C 6-20 aryl, and 5-20 membered heteroaryl of R 6 are each independently optionally substituted with one or more R a , and

the C 3-10 cycloalkyl, and 3-10 membered heterocyclyl of R 6 are each independently optionally substituted with one or more R b ;

R 7 is C 1-6 alkyl, C 1-6 cycloalkyl, or C 1-6 haloalkyl;

R 8 is independently at each occurrence, C 1-6 alkyl;

R 9 is independently at each occurrence, halo;

each R a is independently —OH, halo, —CN, C 1-6 alkyl, C 1-6 alkoxy, —N(R w1 )(R w2 ), —OR x , —C(O)R y , —SO 2 R z , C 3-10 cycloalkyl, C 6-20 aryl, 5-20 membered heteroaryl, or 3-10 membered heterocyclyl, wherein

the C 1-6 alkyl, C 3-10 cycloalkyl, and 3-10 membered heterocyclyl of R a are each optionally substituted with one or more R b , and

the C 6-20 aryl, and 5-20 membered heteroaryl of R a are each optionally substituted with one or more R c ;

each R b is independently —OH, oxo, halo, C 1-6 alkyl, C 1-6 alkoxy, —C(O)R y , or —SO 2 R z , wherein

the C 1-6 alkyl is optionally substituted with one or more R c ;

each R c is independently —OH, halo, —N(R w1 )(R w2 ), C 1-6 alkyl, —C 1-6 alkylN(R w1 )(R w2 ), or C 1-6 alkoxy;

R w1 and R w2 are independently at each occurrence H, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, or —C(O)R y ;

R x is independently at each occurrence, 3-10 membered heterocyclyl optionally substituted with one or more oxo or C 1-6 alkyl;

R y is independently at each occurrence, C 1-6 alkyl, C 1-6 haloalkyl; —NH 2 , —NH(C 1-6 alkyl), or —N(C 1-6 alkyl) 2 ;

R z is independently at each occurrence, C 1-6 alkyl;

X is absent or —C(O)—;

Y is absent or

n is an integer from 1 to 2;

p is an integer from 1 to 4;

q is an integer from 0 to 4; and

r is an integer from 0 to 11.

2 . The compound of claim 1 , wherein the compound is a compound of formula (I-A):

or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

3 . The compound of claim 1 , wherein the compound is a compound of formula (I-B):

or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

4 . The compound of claim 1 or claim 2 , wherein the compound is a compound of formula (I-C):

or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

5 . The compound of claim 1 or claim 2 , wherein the compound is a compound of formula (I-D):

or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.

6 . The compound of any one of claims 1-5 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein X is —C(O)—.

7 . The compound of any one of claims 1-6 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein n is 1.

8 . The compound of any one of claims 1-7 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein n is 2.

9 . The compound of any one of claims 1-8 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein p is an integer from 1 to 3.

10 . The compound of any one of claims 1-9 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein p is 1 or 2.

11 . The compound of any one of claims 1-10 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein p is 1.

12 . The compound of any one of claims 1-11 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 7 is C 1-3 alkyl, C 1-3 cycloalkyl, or C 1-3 haloalkyl.

13 . The compound of any one of claims 1-12 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 7 is C 1-3 alkyl.

14 . The compound of any one of claims 1-13 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 4 is H, halo, —CN, C 1-6 alkyl, C 1-6 cycloalkyl, C 1-6 haloalkyl.

15 . The compound of any one of claims 1-14 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 4 is H, halo, —CN, C 1-3 alkyl, C 1-3 cycloalkyl, C 1-3 haloalkyl, or C 1-3 alkoxy, wherein the C 1-3 alkoxy of R 2 and R 4 is optionally substituted with one or more R a .

16 . The compound of claim 2 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 1b is H, halo, —CN, H, halo, —CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 cycloalkyl, or C 1-3 alkoxy, wherein the C 1-3 alkoxy of R 1a and R 1b is optionally substituted with one or more R a .

17 . The compound of claim 3 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 1a is H, halo, —CN, H, halo, —CN, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 cycloalkyl, or C 1-3 alkoxy, wherein the C 1-3 alkoxy of R 1a and R 1b is optionally substituted with one or more R a .

18 . The compound of any one of claims 1-17 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 6 is C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 3-6 cycloalkyl, —N(R w1 )(R w2 ), C 6-10 aryl, 3-6 membered heterocyclyl, or 5-10 membered heteroaryl, wherein

the C 1-3 alkyl, C 6-10 aryl, and 5-10 membered heteroaryl of R 6 are each independently optionally substituted with one or more R a , and

the C 3-6 cycloalkyl, and 3-6 membered heterocyclyl of R 6 are each independently optionally substituted with one or more R b .

19 . The compound of any one of claims 1-18 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 6 is 5-20 membered heteroaryl optionally substituted with one or more R a .

20 . The compound of claim 19 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 6 is selected from the group consisting of

21 . The compound of any one of claims 1-18 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 6 is 3-10 membered heterocyclyl optionally substituted with one or more R b .

22 . The compound of claim 21 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 6 is selected from the group consisting of

23 . The compound of any one of claims 1-18 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 6 is C 6-20 aryl optionally substituted with one or more R a .

24 . The compound of claim 23 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 6 is selected from the group consisting of

25 . The compound of any one of claims 1-18 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 6 is C 3-10 cycloalkyl optionally substituted with one or more R b .

26 . The compound of claim 25 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 6 is selected from the group consisting of

27 . The compound of any one of claims 1-18 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 6 is C 1-6 alkyl optionally substituted with one or more R a .

28 . The compound of any one of claims 1-27 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 2 is H, halo, —CN, C 1-3 alkyl, C 1-4 cycloalkyl, C 1-3 haloalkyl.

29 . The compound of any one of claims 1-28 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 3 and R 5 are each independently H, —OH, halo, —N(R w1 )(R w2 ), or C 1-4 alkyl, wherein the C 1-4 alkyl is optionally substituted with one or more —OH.

30 . The compound of any one of claims 1-29 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R a is independently C 1-6 alkyl, C 6-20 aryl, 5-20 membered heteroaryl, or 3-10 membered heterocyclyl, wherein the C 1-6 alkyl, C 3-10 cycloalkyl, and 3-10 membered heterocyclyl of R a are each optionally substituted with one or more R b , and the C 6-20 aryl, and 5-20 membered heteroaryl of R a are each optionally substituted with one or more R c .

31 . The compound of any one of claims 1-30 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R b is independently C 1-6 alkyl optionally substituted with one or more R c .

32 . The compound of any one of claims 1-31 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R is independently —OH, halo, —N(R w1 )(R w2 ), C 1-3 alkyl, —C 1-3 alkylN(R w1 )(R w2 ), or C 1-3 alkoxy.

33 . The compound of any one of claims 1-32 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R w1 and R w2 are independently at each occurrence H, C 1-6 alkyl, C 1-6 haloalkyl, or C 3-10 cycloalkyl.

34 . The compound of claim 1 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the compound, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, is selected from Table 1.

35 . A process for preparing a compound of claim 1 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the process comprises:

reacting a compound of formula (I-1):

or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein

one of R 1c and R 1d is

 and

and the other of R 1c and R 1d is H, halo, —CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 cycloalkyl, or C 1-6 alkoxy, wherein the C 1-6 alkoxy of R 1a and R 1b is optionally substituted with one or more R a ;

R 2 and R 4 are each independently H, halo, —CN, C 1-6 alkyl, C 1-6 cycloalkyl, C 1-6 haloalkyl, or C 1-6 alkoxy, wherein the C 1-6 alkoxy of R 2 and R 4 is optionally substituted with one or more R a ;

R 3 and R 5 are each independently H, —OH, halo, —N(R w1 )(R w2 ), or C 1-6 alkyl, wherein C 1-6 alkyl of R 3 and R 5 is optionally substituted with one or more —OH;

R 7 is C 1-6 alkyl, C 1-6 cycloalkyl, or C 1-6 haloalkyl;

R 8 is independently at each occurrence, C 1-6 alkyl;

R 9 is independently at each occurrence, halo;

each R a is independently —OH, halo, —CN, C 1-6 alkyl, C 1-6 alkoxy, —N(R w1 )(R w2 ), —OR x , —C(O)R y , —SO 2 R z , C 3-10 cycloalkyl, C 6-20 aryl, 5-20 membered heteroaryl, or 3-10 membered heterocyclyl, wherein

the C 1-6 alkyl, C 3-10 cycloalkyl, and 3-10 membered heterocyclyl of R a are each optionally substituted with one or more R b , and

the C 6-20 aryl, and 5-20 membered heteroaryl of R a are each optionally substituted with one or more R c ;

each R b is independently —OH, oxo, halo, C 1-6 alkyl, C 1-6 alkoxy, —C(O)R y , or —SO 2 R z , wherein

the C 1-6 alkyl is optionally substituted with one or more R c ;

each R c is independently —OH, halo, —N(R w1 )(R w2 ), C 1-6 alkyl, —C 1-6 alkylN(R w1 )(R w2 ), or C 1-6 alkoxy;

R w1 and R w2 are independently at each occurrence H, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, —C(O)R y ;

R x is independently at each occurrence, 3-10 membered heterocyclyl optionally substituted with one or more oxo or C 1-6 alkyl;

R y is independently at each occurrence, C 1-6 alkyl, C 1-6 haloalkyl; —NH 2 , —NH(C 1-6 alkyl), or —N(C 1-6 alkyl) 2 ;

R z is independently at each occurrence, C 1-6 alkyl;

Y is absent or

n is an integer from 1 to 2;

p is an integer from 1 to 4;

q is an integer from 0 to 4; and

r is an integer from 0 to 11;

with a compound of formula (I-2):

or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:

Y 1 is —C(O)OH or —C(O)-halo;

R 6 is C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-10 cycloalkyl, —N(R w1 )(R w2 ), C 6-20 aryl, 3-10 membered heterocyclyl, or 5-20 membered heteroaryl, wherein

the C 1-6 alkyl, C 6-20 aryl, and 5-20 membered heteroaryl of R 6 are each independently optionally substituted with one or more R a , and

the C 3-10 cycloalkyl, and 3-10 membered heterocyclyl of R 6 are each independently optionally substituted with one or more R b ;

each R a is independently —OH, halo, —CN, C 1-6 alkyl, C 1-6 alkoxy, —N(R w1 )(R w2 ), —OR x , —C(O)R y , —SO 2 R z , C 3-10 cycloalkyl, C 6-20 aryl, 5-20 membered heteroaryl, or 3-10 membered heterocyclyl, wherein

the C 1-6 alkyl, C 3-10 cycloalkyl, and 3-10 membered heterocyclyl of R a are each optionally substituted with one or more R b , and

the C 6-20 aryl, and 5-20 membered heteroaryl of R a are each optionally substituted with one or more R c ;

each R b is independently —OH, oxo, halo, C 1-6 alkyl, C 1-6 alkoxy, —C(O)R y , or —SO 2 R z , wherein

the C 1-6 alkyl is optionally substituted with one or more R c ;

each R c is independently —OH, halo, —N(R w1 )(R w2 ), C 1-6 alkyl, —C 1-6 alkylN(R w1 )(R w2 ), or C 1-6 alkoxy;

R w1 and R w2 are independently at each occurrence H, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, —C(O)R y ;

R x is independently at each occurrence, 3-10 membered heterocyclyl optionally substituted with one or more oxo or C 1-6 alkyl;

R y is independently at each occurrence, C 1-6 alkyl, C 1-6 haloalkyl; —NH 2 , —NH(C 1-6 alkyl), or —N(C 1-6 alkyl) 2 ; and

R z is independently at each occurrence, C 1-6 alkyl;

in the presence of one or more coupling reagents.

36 . The process of claim 35 , wherein the one or more coupling reagents comprises EDCI, HOBt and/or DIEA.

37 . A process for preparing a compound of claim 1 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein the process comprises:

reacting a compound of formula (II-1):

or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:

one of R 1c and R 1d is

 and

and the other of R 1c and R 1d is H, halo, —CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 cycloalkyl, or C 1-6 alkoxy, wherein the C 1-6 alkoxy of R 1a and R 1b is optionally substituted with one or more R a ;

R 2 and R 4 are each independently H, halo, —CN, C 1-6 alkyl, C 1-6 cycloalkyl, C 1-6 haloalkyl, or C 1-6 alkoxy, wherein the C 1-6 alkoxy of R 2 and R 4 is optionally substituted with one or more R a ;

R 3 and R 5 are each independently H, —OH, halo, —N(R w1 )(R w2 ), or C 1-6 alkyl, wherein C 1-6 alkyl of R 3 and R 5 is optionally substituted with one or more —OH;

R 9 is independently at each occurrence, halo;

each R a is independently —OH, halo, —CN, C 1-6 alkyl, C 1-6 alkoxy, —N(R w1 )(R w2 ), —OR x , —C(O)R y , —SO 2 R z , C 3-10 cycloalkyl, C 6-20 aryl, 5-20 membered heteroaryl, or 3-10 membered heterocyclyl, wherein

the C 1-6 alkyl, C 3-10 cycloalkyl, and 3-10 membered heterocyclyl of R a are each optionally substituted with one or more R b , and

the C 6-20 aryl, and 5-20 membered heteroaryl of R a are each optionally substituted with one or more R c ;

each R b is independently —OH, oxo, halo, C 1-6 alkyl, C 1-6 alkoxy, —C(O)R y , or —SO 2 R z , wherein

the C 1-6 alkyl is optionally substituted with one or more R c ;

each R c is independently —OH, halo, —N(R w1 )(R w2 ), C 1-6 alkyl, —C 1-6 alkylN(R w1 )(R w2 ), or C 1-6 alkoxy;

R w1 and R w2 are independently at each occurrence H, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, —C(O)R y ;

R x is independently at each occurrence, 3-10 membered heterocyclyl optionally substituted with one or more oxo or C 1-6 alkyl;

R y is independently at each occurrence, C 1-6 alkyl, C 1-6 haloalkyl; —NH 2 , —NH(C 1-6 alkyl), or —N(C 1-6 alkyl) 2 ;

R z is independently at each occurrence, C 1-6 alkyl;

Q 1 H or —C(O)-LG;

LG is a leaving group;

Y is absent or

p is an integer from 1 to 4;

q is an integer from 0 to 4; and

with a compound of formula (I-2):

or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:

Y 2 is —H;

R 6 is C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-10 cycloalkyl, —N(R w1 )(R w2 ), C 6-20 aryl, 3-10 membered heterocyclyl, or 5-20 membered heteroaryl, wherein

the C 1-6 alkyl, C 6-20 aryl, and 5-20 membered heteroaryl of R 6 are each independently optionally substituted with one or more R a , and

the C 3-10 cycloalkyl, and 3-10 membered heterocyclyl of R 6 are each independently optionally substituted with one or more R b ;

R 7 is C 1-6 alkyl, C 1-6 cycloalkyl, or C 1-6 haloalkyl;

R 8 is independently at each occurrence, C 1-6 alkyl;

n is an integer from 1 to 2;

r is an integer from 0 to 11.

each R a is independently —OH, halo, —CN, C 1-6 alkyl, C 1-6 alkoxy, —N(R w1 )(R w2 ), —OR x , —C(O)R y , —SO 2 R z , C 3-10 cycloalkyl, C 6-20 aryl, 5-20 membered heteroaryl, or 3-10 membered heterocyclyl, wherein

the C 1-6 alkyl, C 3-10 cycloalkyl, and 3-10 membered heterocyclyl of R a are each optionally substituted with one or more R b , and

the C 6-20 aryl, and 5-20 membered heteroaryl of R a are each optionally substituted with one or more R c ;

each R b is independently —OH, oxo, halo, C 1-6 alkyl, C 1-6 alkoxy, —C(O)R y , or —SO 2 R z , wherein

the C 1-6 alkyl is optionally substituted with one or more R c ;

each R c is independently —OH, halo, —N(R w1 )(R w2 ), C 1-6 alkyl, —C 1-6 alkylN(R w1 )(R w2 ), or C 1-6 alkoxy;

R w1 and R w2 are independently at each occurrence H, C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, —C(O)R y ;

R x is independently at each occurrence, 3-10 membered heterocyclyl optionally substituted with one or more oxo or C 1-6 alkyl;

R y is independently at each occurrence, C 1-6 alkyl, C 1-6 haloalkyl; —NH 2 , —NH(C 1-6 alkyl), or —N(C 1-6 alkyl) 2 ;

R z is independently at each occurrence, C 1-6 alkyl; and

X is absent or —C(O)—;

in the presence of one or more coupling reagents.

38 . The process of claim 37 , wherein the one or more coupling reagents comprises a base.

39 . The process of claim 37 , wherein the one or more coupling reagents comprises a carbonate ester.

40 . The process of claim 39 , wherein the carbonate ester is triphosgene.

41 . The process of any one of claims 37-40 , wherein LG is an alkoxy group optionally substituted with one or more halo.

42 . A pharmaceutical composition comprising (i) a compound of any one of claims 1-34 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and (ii) one or more pharmaceutically acceptable excipients.

43 . A method of modulating SLC6A19 in a cell, comprising exposing the cell to an effective amount of a compound of any one of claims 1-34 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition of claim 42 .

44 . A method of inhibiting SLC6A19 in a cell, comprising exposing the cell to an effective amount of a compound of any one of claims 1-34 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition of claim 42 .

45 . A method of reducing systemic phenylalanine, tyrosine, glutamine, or glycine levels in an individual in need thereof, comprising administering to the individual an effective amount of a compound of any one of claims 1-34 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition of claim 42 .

46 . A method of treating a SLC6A19-mediated disease, disorder, or condition in an individual in need thereof, comprising administering to the individual an effective amount of a compound of any one of claims 1-34 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition of claim 42 .

47 . The method of claim 46 , wherein the disease, disorder, or condition is selected from the group consisting of phenylketonuria (PKU), chronic kidney disease (CKD), metabolic syndrome, metabolic diseases, hyperphenylalaninemia, tyrosinemia (Type I, II, or III), nonketotic hyperglycinemia, isovaleric acidemia, methylmalonic acidemia, propionic acidemia, maple syrup urine disease, DNAJC12 deficiency, urea cycle disorders, hyperammonemia, diabetes, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, obesity related disorders, and neurodevelopmental and autism-spectrum disorders.

48 . The method of claim 46 or claim 47 , wherein the disease, disorder, or condition is selected from the group consisting of phenylketonuria (PKU), chronic kidney disease (CKD), methabolic syndrome, and metabolic diseases.

49 . The method of claim 46 , wherein the disease, disorder, or condition is associated with abnormal levels of amino acids.

50 . The method of claim 46, or claim 49 , wherein the disease, disorder, or condition is associated with a genetic defect in phenylalanine hydroxylase.

51 . A kit, comprising (i) a compound of any one of claims 1-34 , or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, or a pharmaceutical composition of claim 43 , and (ii) instructions for use in treating an SLC6A19-mediated disease, disorder, or condition in an individual in need thereof.

52 . The kit of claim 51 , wherein the disease, disorder, or condition is associated with abnormal levels of amino acids.

53 . The kit of claim 51, or claim 52 , wherein the disease, disorder, or condition is associated with a genetic defect in phenylalanine hydroxylase.

54 . The kit of claim 51 , wherein the disease, disorder, or condition is selected from the group consisting of phenylketonuria (PKU), chronic kidney disease (CKD), metabolic syndrome, metabolic diseases, hyperphenylalaninemia, tyrosinemia (Type I, II, or III), nonketotic hyperglycinemia, isovaleric acidemia, methylmalonic acidemia, propionic acidemia, maple syrup urine disease, DNAJC12 deficiency, urea cycle disorders, hyperammonemia, diabetes, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, obesity related disorders, and neurodevelopmental and autism-spectrum disorders.

55 . The kit of claim 51 , wherein the individual has a genetic defect in phenylalanine hydroxylase.