US 2024/0199546 A1 · INHIBITORS OF SOLUTE CARRIER FAMILY 6A MEMBER 19 (SLC6A19) AND METHODS OF USE THEREOF

A compound of formula (I-H):

or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:
m is an integer from 1 to 4;
n is an integer from 0 to 4;
X is —O—, —S—, —C(R12a)(R12b)—, —N(H)—, or —N(C1-6alkyl)-;
R3 is C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, —C(O)C1-6alkyl, C3-10cycloalkyl, —N(R4)2, 5-20 membered heteroaryl, —C1-6alkyl(5-20 membered heteroaryl), or 4-10 membered heterocyclyl, wherein each R3 is optionally substituted with one or more Ra, and wherein when R3 is 6-10 membered heteroaryl, the 6-10 membered heteroaryl is unsubstituted;
each R4 is independently H, C1-6alkyl, C1-6haloalkyl, —C1-6alkyl(5-20 membered heteroaryl), or C3-10cycloalkyl, or
both R4 are taken together with the N atom to which they are attached to form a 4-10 membered heterocyclyl optionally substituted with one or more Ra;
R5 and R7 are each independently H, halo, C1-6alkyl, C1-6alkoxy, C1-6thioalkyl, C3-10cycloalkyl, C1-6haloalkyl, or 5-20 membered heteroaryl, wherein
the C1-6alkyl, C1-6alkoxy, or C3-10cycloalkyl of R5 and R7 are each independently optionally substituted with one or more halo or CN;
R6 and R9 are each independently H or halo;
R11a and R11b are each independently at each occurrence, H or C1-6alkyl, or
one of R11a and R11b is H or C1-6alkyl, and the other of R11a and R11b is taken together with one of R12a or R12b to form a C3-10cycloalkyl;
R12a and R12b are each independently, H or C1-6alkyl, or
one of R12a and R12b is H or C1-6alkyl, and the other of R12a and R12b is taken together with one of R11a or R11b to form a C3-10cycloalkyl;
each Ra is independently D, —OH, oxo, —CN, halo, C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, —O—C1-6haloalkyl, —NH2, —NH(C1-6alkyl), —N(C1-6alkyl)2, —C(O)NH2, —C(O)NH(C1-6alkyl), —C(O)N(C1-6alkyl)2, 4-10 membered heterocyclyl, C3-10cycloalkyl, or —O—C3-10cycloalkyl, wherein
the C1-6alkyl, C1-6alkoxy, 4-10 membered heterocyclyl, C3-10cycloalkyl, or —O—C3-10cycloalkyl of Ra is optionally substituted with one or more Rb;
each Rb is independently D, —OH, halo, C1-6alkyl, or C1-6alkoxy
Y1, Y2, Y3, Y4 and Y5 are each independently —C—, —CH—, —CH2—, —N—, —NH—, —S—, or —O—;
s is an integer from 0-6;
t is 1 or 2;
and
represents a single or double bond.

19 more elements

A process for preparing a compound of formula (I′):

or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:
m is an integer from 1 to 4;
n is an integer from 0 to 4;
X is —O—, —S—, —C(R12a)(R12b)—, —N(H)—, or —N(C1-6alkyl)-;
R1 is —NH—, —O—, or —S—;
R2 is H;
R3 is C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, —N(R4)2, or 4-10 membered heterocyclyl, wherein each R3 is optionally substituted with one or more Ra;
each R4 is independently H, C1-6alkyl, C1-6haloalkyl, or C3-10cycloalkyl, or
both R4 are taken together with the N atom to which they are attached to form a 4-10 membered heterocyclyl optionally substituted with one or more Ra;
R5 and R7 are each independently H, halo, C1-6alkyl, C1-6alkoxy, C3-10cycloalkyl, or C1-6haloalkyl, wherein
the C1-6alkyl of R5 and R7 are each independently optionally substituted with one or more halo or CN;
R6 and R9 are each independently H or halo;
R8 is —C(O)N(R4)2, C3-10cycloalkyl, C6-20aryl, 3-10 membered heterocyclyl, or 5-20 membered heteroaryl, wherein each R8 is optionally substituted with one or more Ra;
R10 is H;
R11a and R11b are each independently at each occurrence, H or C1-6alkyl, or
one of R11a and R11b is H or C1-6alkyl, and the other of R11a and R11b is taken together with one of R12a or R12b to form a C3-10cycloalkyl;
R12a and R12b are each independently, H or C1-6alkyl, or
one of R12a and R12b is H or C1-6alkyl, and the other of R12a and R12b is taken together with one of R11a or R11b to form a C3-10cycloalkyl;
each Ra is independently —OH, oxo, —CN, halo, C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, —O—C1-6haloalkyl, —NH2, —NH(C1-6alkyl), —N(C1-6alkyl)2, —C(O)NH2, —C(O)NH(C1-6alkyl), —C(O)N(C1-6alkyl)2, 4-10 membered heterocyclyl, C3-10cycloalkyl, or —O—C3-10cycloalkyl, wherein
the C1-6alkyl, C1-6alkoxy, 4-10 membered heterocyclyl, C3-10cycloalkyl, or —O—C3-10cycloalkyl, of Ra is optionally substituted with one or more Rb;
and
each Rb is independently D, —OH, halo, C1-6alkyl, or C1-6alkoxy,
wherein the process comprises:
(a) reacting a compound of formula (I′-1):
or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:
Q1 is halo, boronic acid, or boronic ester;
PG is absent, or a protecting group;
m is an integer from 1 to 4;
R1 is —N—, —NH—, —O—, or —S—;
R2 is H;
R3 is C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, —N(R4)2, or 4-10 membered heterocyclyl, wherein each R3 is optionally substituted with one or more Ra;
each R4 is independently H, C1-6alkyl, C1-6haloalkyl, or C3-10cycloalkyl, or
both R4 are taken together with the N atom to which they are attached to form a 4-10 membered heterocyclyl optionally substituted with one or more Ra;
R5 and R7 are each independently H, halo, C1-6alkyl, C1-6alkoxy, C3-10cycloalkyl, or C1-6haloalkyl, wherein
the C1-6alkyl of R5 and R7 are each independently optionally substituted with one or more halo or CN;
R6 and R9 are each independently H, or halo;
R10 is H;
and
each Ra is independently —OH, oxo, —CN, halo, C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, —O—C1-6haloalkyl, —NH2, —NH(C1-6alkyl), —N(C1-6alkyl)2, —C(O)NH2, —C(O)NH(C1-6alkyl), —C(O)N(C1-6alkyl)2, 4-10 membered heterocyclyl, C3-10cycloalkyl, or —O—C3-10cycloalkyl, wherein
the C1-6alkyl, C1-6alkoxy, 4-10 membered heterocyclyl, C3-10cycloalkyl, or —O—C3-10cycloalkyl, of Ra is optionally substituted with one or more Rb;
and
each Rb is independently D, —OH, halo, C1-6alkyl, or C1-6alkoxy;
with a compound of formula (I′-2):
or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:
Y1 is H, hydrazone, boronic acid, boronic ester, or halo;
n is an integer from 0 to 4;
X is —O—, —S—, —C(R12a)(R12b)—, —N(H)—, or —N(C1-6alkyl)-;
R8 is —C(O)N(R4)2, C3-10cycloalkyl, C6-20aryl, 3-10 membered heterocyclyl, or 5-20 membered heteroaryl, wherein each R8 is optionally substituted with one or more Ra;
R11a and R11b are each independently at each occurrence, H, or C1-6alkyl, or taken together with one of R12a or R12b to form a C3-10cycloalkyl;
R12a and R12b are each independently, H, or C1-6alkyl, or
one of R12a and R12b is H, or C1-6alkyl, and the other of R12a and R12b is taken together with R11a or R11b to form a C3-10cycloalkyl;
and
each Ra is independently —OH, oxo, —CN, halo, C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, —O—C1-6haloalkyl, —NH2, —NH(C1-6alkyl), —N(C1-6alkyl)2, —C(O)NH2, —C(O)NH(C1-6alkyl), —C(O)N(C1-6alkyl)2, 4-10 membered heterocyclyl, C3-10cycloalkyl, or —O—C3-10cycloalkyl, wherein
the C1-6alkyl, C1-6alkoxy, 4-10 membered heterocyclyl, C3-10cycloalkyl, or —O—C3-10cycloalkyl, of Ra is optionally substituted with one or more Rb;
and
each Rb is independently D, —OH, halo, C1-6alkyl, or C1-6alkoxy;
in the presence of one or more coupling reagent, to provide a compound of formula (I′-3):
or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:
PG is absent or a protecting group;
m is an integer from 1 to 4;
n is an integer from 0 to 4;
X is —O—, —S—, —C(R12a)(R12b)—, —N(H)—, or —N(C1-6alkyl)-;
R1 is —N—NH—, —O—, or —S—;
R2 is H;
R3 is C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, —N(R4)2, or 4-10 membered heterocyclyl, wherein each R3 is optionally substituted with one or more Ra;
each R4 is independently H, C1-6alkyl, C1-6haloalkyl, or C3-10cycloalkyl, or
both R4 are taken together with the N atom to which they are attached to form a 4-10 membered heterocyclyl optionally substituted with one or more Ra;
R5 and R7 are each independently H, halo, C1-6alkyl, C1-6alkoxy, C3-10cycloalkyl, or C1-6haloalkyl, wherein
the C1-6alkyl of R5 and R7 are each independently optionally substituted with one or more halo or CN;
R6 and R9 are each independently H, or halo;
R8 is —C(O)N(R4)2, C3-10cycloalkyl, C6-20aryl, 3-10 membered heterocyclyl, or 5-20 membered heteroaryl, wherein each R8 is optionally substituted with one or more Ra;
R10 is H;
R11a and R11b are each independently at each occurrence, H, or C1-6alkyl, or taken together with one of R12a or R12b to form a C3-10cycloalkyl;
R12a and R12b are each independently, H, or C1-6alkyl, or one of R12a and R12b is H, or C1-6alkyl, and the other of R12a and R12b is taken together with R11a or R11b to form a C3-10cycloalkyl;
each Ra is independently —OH, oxo, —CN, halo, C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, —O—C1-6haloalkyl, —NH2, —NH(C1-6alkyl), —N(C1-6alkyl)2, —C(O)NH2, —C(O)NH(C1-6alkyl), —C(O)N(C1-6alkyl)2, 4-10 membered heterocyclyl, C3-10cycloalkyl, or —O—C3-10cycloalkyl, wherein
the C1-6alkyl, C1-6alkoxy, 4-10 membered heterocyclyl, C3-10cycloalkyl, or —O—C3-10cycloalkyl, of Ra is optionally substituted with one or more Rb;
and
each Rb is independently D, —OH, halo, C1-6alkyl, or C1-6alkoxy;
followed by,
(b) optionally contacting the compound of formula (I′-3) with a deprotecting agent;
to provide a compound of formula (I′).

78 more elements

A process for preparing a compound of formula (I′):

or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:
m is an integer from 1 to 4;
n is an integer from 0 to 4;
X is —O—, —S—, —C(R12a)(R12b)—, —N(H)—, or —N(C1-6alkyl)-;
R1 is —NH—, —O—, or —S—;
R2 is H;
R3 is C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, —N(R4)2, or 4-10 membered heterocyclyl, wherein each R3 is optionally substituted with one or more Ra;
each R4 is independently H, C1-6alkyl, C1-6haloalkyl, or C3-10cycloalkyl, or
both R4 are taken together with the N atom to which they are attached to form a 4-10 membered heterocyclyl optionally substituted with one or more Ra;
R5 and R7 are each independently H, halo, C1-6alkyl, C1-6alkoxy, C3-10cycloalkyl, or C1-6 haloalkyl, wherein
the C1-6alkyl of R5 and R7 are each independently optionally substituted with one or more halo or CN;
R6 and R9 are each independently H or halo;
R8 is —C(O)N(R4)2, C3-10cycloalkyl, C6-20aryl, 3-10 membered heterocyclyl, or 5-20 membered heteroaryl, wherein each R8 is optionally substituted with one or more Ra;
R10 is H;
R11a and R11b are each independently at each occurrence, H or C1-6alkyl, or
one of R11a and R11b is H or C1-6alkyl, and the other of R11a and R11b is taken together with one of R12a or R12b to form a C3-10cycloalkyl;
R12a and R12b are each independently, H or C1-6alkyl, or
one of R12a and R12b is H or C1-6alkyl, and the other of R12a and R12b is taken together with one of R11a or R11b to form a C3-10cycloalkyl;
each Ra is independently —OH, oxo, —CN, halo, C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, —O—C1-6haloalkyl, —NH2, —NH(C1-6alkyl), —N(C1-6alkyl)2, —C(O)NH2, —C(O)NH(C1-6alkyl), —C(O)N(C1-6alkyl)2, 4-10 membered heterocyclyl, C3-10cycloalkyl, or —O—C3-10cycloalkyl, wherein
the C1-6alkyl, C1-6alkoxy, 4-10 membered heterocyclyl, C3-10cycloalkyl, or —O—C3-10cycloalkyl, of Ra is optionally substituted with one or more Rb;
and
each Rb is independently D, —OH, halo, C1-6alkyl, or C1-6alkoxy,
wherein the process comprises:
(a) reacting a compound of formula (IV′-1):
or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:
PG is absent or a protecting group;
Q2 is H, or (═O);
m is an integer from 1 to 4;
X is —O—, —S—, —C(R12a)(R12b)—, —N(H)—, or —N(C1-6alkyl)-;
R1 is —N—, —NH—, —O—, or —S—;
R2 is H;
R3 is C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, —N(R4)2, or 4-10 membered heterocyclyl, wherein each R3 is optionally substituted with one or more Ra;
each R4 is independently H, C1-6alkyl, C1-6haloalkyl, or C3-10cycloalkyl, or
both R4 are taken together with the N atom to which they are attached to form a 4-10 membered heterocyclyl optionally substituted with one or more Ra;
R5 and R7 are each independently H, halo, C1-6alkyl, C1-6alkoxy, C3-10cycloalkyl, or C1-6haloalkyl, wherein
the C1-6alkyl of R5 and R7 are each independently optionally substituted with one or more halo or CN;
R6 and R9 are each independently H, or halo;
R10 is H;
R12a and R12b are each independently, H, or C1-6alkyl;
and
each Ra is independently —OH, oxo, —CN, halo, C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, —O—C1-6haloalkyl, —NH2, —NH(C1-6alkyl), —N(C1-6alkyl)2, —C(O)NH2, —C(O)NH(C1-6alkyl), —C(O)N(C1-6alkyl)2, 4-10 membered heterocyclyl, C3-10cycloalkyl, or —O—C3-10cycloalkyl, wherein
the C1-6alkyl, C1-6alkoxy, 4-10 membered heterocyclyl, C3-10cycloalkyl, or —O—C3-10cycloalkyl, of Ra is optionally substituted with one or more Rb;
and
each Rb is independently D, —OH, halo, C1-6alkyl, or C1-6alkoxy;
with a compound of formula (II′-2):
or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:
Y2 is OH, (═O), halo, triphenylphosphonium salt, or sulfonic ester;
n is an integer from 0 to 4;
R8 is —C(O)N(R4)2, C3-10cycloalkyl, C6-20aryl, 3-10 membered heterocyclyl, or 5-20 membered heteroaryl, wherein each R8 is optionally substituted with one or more Ra;
R11a and R11b are each independently at each occurrence, H, or C1-6alkyl;
and
each Ra is independently —OH, oxo, —CN, halo, C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, —O—C1-6haloalkyl, —NH2, —NH(C1-6alkyl), —N(C1-6alkyl)2, —C(O)NH2, —C(O)NH(C1-6alkyl), —C(O)N(C1-6alkyl)2, 4-10 membered heterocyclyl, C3-10cycloalkyl, or —O—C3-10cycloalkyl, wherein
the C1-6alkyl, C1-6alkoxy, 4-10 membered heterocyclyl, C3-10cycloalkyl, or —O—C3-10cycloalkyl, of Ra is optionally substituted with one or more Rb;
and
each Rb is independently D, —OH, halo, C1-6alkyl, or C1-6alkoxy;
in the presence of one or more coupling reagents, to provide a compound of formula (I′-3):
or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:
PG is absent or a protecting group;
m is an integer from 1 to 4;
n is an integer from 0 to 4;
X is —O—, —S—, —C(R12a)(R12b)—, —N(H)—, or —N(C1-6alkyl)-;
R1 is —N—NH—, —O—, or —S—;
R2 is H;
R3 is C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, —N(R4)2, or 4-10 membered heterocyclyl, wherein each R3 is optionally substituted with one or more Ra;
each R4 is independently H, C1-6alkyl, C1-6haloalkyl, or C3-10cycloalkyl, or
both R4 are taken together with the N atom to which they are attached to form a 4-10 membered heterocyclyl optionally substituted with one or more Ra;
R5 and R7 are each independently H, halo, C1-6alkyl, C1-6alkoxy, C3-10cycloalkyl, or C1-6haloalkyl, wherein
the C1-6alkyl of R5 and R7 are each independently optionally substituted with one or more halo or CN;
R6 and R9 are each independently H, or halo;
R8 is —C(O)N(R4)2, C3-10cycloalkyl, C6-20aryl, 3-10 membered heterocyclyl, or 5-20 membered heteroaryl, wherein each R8 is optionally substituted with one or more Ra;
R10 is H;
R11a and R11b are each independently at each occurrence, H, or C1-6alkyl, or taken together with one of R12a or R12b to form a C3-10cycloalkyl;
R12a and R12b are each independently, H, or C1-6alkyl, or
one of R12a and R12b is H, or C1-6alkyl, and the other of R12a and R12b is taken together with R11a or R11b to form a C3-10cycloalkyl;
each Ra is independently —OH, oxo, —CN, halo, C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, —O—C1-6haloalkyl, —NH2, —NH(C1-6alkyl), —N(C1-6alkyl)2, —C(O)NH2, —C(O)NH(C1-6alkyl), —C(O)N(C1-6alkyl)2, 4-10 membered heterocyclyl, C3-10cycloalkyl, or —O—C3-10cycloalkyl, wherein
the C1-6alkyl, C1-6alkoxy, 4-10 membered heterocyclyl, C3-10cycloalkyl, or —O—C3-10cycloalkyl, of Ra is optionally substituted with one or more Rb;
and
each Rb is independently D, —OH, halo, C1-6alkyl, or C1-6alkoxy;
followed by,
(b) optionally contacting the compound of formula (I′-3) with a deprotecting agent;
to provide a compound of formula (I′).

78 more elements

A process for preparing a compound of formula (I′):

or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:
m is an integer from 1 to 4;
n is an integer from 0 to 4;
X is —O—, —S—, —C(R12a)(R12b)—, —N(H)—, or —N(C1-6alkyl)-;
R1 is —NH—, —O—, or —S—;
R2 is H;
R3 is C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, —N(R4)2, or 4-10 membered heterocyclyl, wherein each R3 is optionally substituted with one or more Ra;
each R4 is independently H, C1-6alkyl, C1-6haloalkyl, or C3-10cycloalkyl, or
both R4 are taken together with the N atom to which they are attached to form a 4-10 membered heterocyclyl optionally substituted with one or more Ra;
R5 and R7 are each independently H, halo, C1-6alkyl, C1-6alkoxy, C3-10cycloalkyl, or C1-6haloalkyl, wherein
the C1-6alkyl of R5 and R7 are each independently optionally substituted with one or more halo or CN;
R6 and R9 are each independently H or halo;
R8 is —C(O)N(R4)2, C3-10cycloalkyl, C6-20aryl, 3-10 membered heterocyclyl, or 5-20 membered heteroaryl, wherein each R8 is optionally substituted with one or more Ra;
R10 is H;
R11a and R11b are each independently at each occurrence, H or C1-6alkyl, or
one of R11a and R11b is H or C1-6alkyl, and the other of R11a and R11b is taken together with one of R12a or R12b to form a C3-10cycloalkyl;
R12a and R12b are each independently, H or C1-6alkyl, or
one of R12a and R12b is H or C1-6alkyl, and the other of R12a and R12b is taken together with one of R11a or R11b to form a C3-10cycloalkyl;
each Ra is independently —OH, oxo, —CN, halo, C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, —O—C1-6haloalkyl, —NH2, —NH(C1-6alkyl), —N(C1-6alkyl)2, —C(O)NH2, —C(O)NH(C1-6alkyl), —C(O)N(C1-6alkyl)2, 4-10 membered heterocyclyl, C3-10cycloalkyl, or —O—C3-10cycloalkyl, wherein
the C1-6alkyl, C1-6alkoxy, 4-10 membered heterocyclyl, C3-10cycloalkyl, or —O—C3-10cycloalkyl, of Ra is optionally substituted with one or more Rb;
and
each Rb is independently D, —OH, halo, C1-6alkyl, or C1-6alkoxy,
wherein the process comprises:
reacting a compound of formula (III′-1):
or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:
Q3 is H;
m is an integer from 1 to 4;
n is an integer from 0 to 4;
X is —O—, —S—, —C(R12a)(R12b)—, —N(H)—, or —N(C1-6alkyl)-;
R1 is —NH—, —O—, or —S—;
R2 is H;
each R4 is independently H, C1-6alkyl, C1-6haloalkyl, or C3-10cycloalkyl, or
both R4 are taken together with the N atom to which they are attached to form a 4-10 membered heterocyclyl optionally substituted with one or more Ra;
R5 and R7 are each independently H, halo, C1-6alkyl, C1-6alkoxy, C3-10cycloalkyl, or C1-6haloalkyl, wherein
the C1-6alkyl of R5 and R7 are each independently optionally substituted with one or more halo or CN;
R6 and R9 are each independently H, or halo;
R8 is —C(O)N(R4)2, C3-10cycloalkyl, C6-20aryl, 3-10 membered heterocyclyl, or 5-20 membered heteroaryl, wherein each R8 is optionally substituted with one or more Ra;
R10 is H;
R11a and R11b are each independently at each occurrence, H, or C1-6alkyl, or taken together with one of R12a or R12b to form a C3-10cycloalkyl;
R12a and R12b are each independently, H, or C1-6alkyl, or
one of R12a and R12b is H, or C1-6alkyl, and the other of R12a and R12b is taken together with R11a or R11b to form a C3-10cycloalkyl;
and
each Ra is independently —OH, oxo, —CN, halo, C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, —O—C1-6haloalkyl, —NH2, —NH(C1-6alkyl), —N(C1-6alkyl)2, —C(O)NH2, —C(O)NH(C1-6alkyl), —C(O)N(C1-6alkyl)2, 4-10 membered heterocyclyl, C3-10cycloalkyl, or —O—C3-10cycloalkyl, wherein
the C1-6alkyl, C1-6alkoxy, 4-10 membered heterocyclyl, C3-10cycloalkyl, or —O—C3-10cycloalkyl, of Ra is optionally substituted with one or more Rb;
and
each Rb is independently D, —OH, halo, C1-6alkyl, or C1-6alkoxy;
with a compound of formula (III′-2):
or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:
Y3 is —C(O)OH, or —C(O)-halo;
R3 is C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, —N(R4)2, or 4-10 membered heterocyclyl, wherein each R3 is optionally substituted with one or more Ra;
and
each Ra is, independently at each occurrence, —OH, halo, C1-6alkyl, C1-6haloalkyl, or C3-10cycloalkyl;
in the presence of one or more coupling reagent, to provide a compound of formula (I′).

50 more elements

Inhibitors of solute carrier family 6a member 19 (slc6a19) and methods of use thereof

Life of this patent

Inhibitors of solute carrier family 6a member 19 (slc6a19) and methods of use thereof

Life of this patent

Abstract

Claims41