US2023061736A1PendingUtilityA1
Gpr119 agonists
Est. expiryOct 7, 2039(~13.2 yrs left)· nominal 20-yr term from priority
A61P 3/00A61K 45/06A61K 31/506C07D 405/14C07D 401/04C07D 403/14C07H 15/26C07D 401/12C07D 401/14
66
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Claims
Abstract
This disclosure is directed, at least in part, to GPR119 agonists useful for the treatment of conditions or disorders involving the gut-brain axis. In some embodiments, the GPR119 agonists are gut-restricted compounds. In some embodiments, the condition or disorder is a metabolic disorder, such as diabetes, obesity, nonalcoholic steatohepatitis (NASH), or a nutritional disorder such as short bowel syndrome.
Claims
exact text as granted — not AI-modified1 . A compound of Formula (I):
or a pharmaceutically acceptable salt, solvate, stereoisomer, or prodrug thereof,
wherein:
K is
R 1 is hydrogen, —OH, C 1-8 alkyl, C 3-8 cycloalkyl, or 3- to 8-membered heterocycloalkyl, wherein the alkyl, cycloalkyl, and heterocycloalkyl are unsubstituted or substituted by 1-3 substituents independently selected from halogen, —OH, and —O(C 1-6 alkyl);
each R 2 and R 3 is independently hydrogen, C 1-6 alkyl, or C 1-6 fluoroalkyl;
or R 2 and R 3 on the same carbon atom are taken together to form ═O;
R 4 is hydrogen, C 1-8 alkyl, C 1-8 fluoroalkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 3-8 cycloalkyl, C 5-8 cycloalkenyl, 4- to 8-membered heterocycloalkyl, —[(CH 2 ) r —Z] t —R 6 , —[(CHR d ) r —Z] t —R 6 , or —[(C(R d ) 2 ) r —Z] t —R 6 ; wherein each alkyl, fluoroalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, and 4- to 8-membered heterocycloalkyl is unsubstituted or substituted by 1-6 R c groups;
R 5 is C 1-8 alkyl, C 1-8 fluoroalkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 3-8 cycloalkyl, C 5-8 cycloalkenyl, 4- to 8-membered heterocycloalkyl, —[(CH 2 ) r —Z] t —R 6 , —[(CHR d ) r —Z] t —R 6 , or —[(C(R d ) 2 ) r —Z] t —R 6 ; wherein each alkyl, fluoroalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, and 4- to 8-membered heterocycloalkyl is substituted by 1-6 R c groups;
each Z is independently —CH 2 O—, —CH 2 NR d —, —CH 2 N + (R d ) 2 —, —NH—C(═O)—NH—, —C(═O)NH—, —CH 2 S(═O) 2 —, or —CH 2 S(═O)—;
each r is independently 1-6;
each t is independently 1-6;
R 6 is hydrogen, C 1-8 alkyl, C 1-8 fluoroalkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 3-8 cycloalkyl, C 5-8 cycloalkenyl, or 4- to 8-membered heterocycloalkyl, wherein the alkyl, fluoroalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, or 4- to 8-membered heterocycloalkyl is unsubstituted or substituted by 1-6 R c groups;
or R 4 and R 5 are taken together with the nitrogen to which they are attached to form a 4- to 8-membered heterocycloalkyl, which is unsubstituted or substituted by 1-6 R c groups;
R 7 is hydrogen, C 1-4 alkyl, or C 1-4 fluoroalkyl;
R 8 is C 1-8 alkyl, C 1-8 fluoroalkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 3-8 cycloalkyl, C 5-8 cycloalkenyl, 4- to 8-membered heterocycloalkyl, —[(CH 2 ) r —Z] t —R 6 , —[(CHR d ) r —Z] t —R 6 , or —[(CR d 2 ) r —Z] t —R 6 ; wherein each alkyl, fluoroalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, and 4- to 8-membered heterocycloalkyl is substituted by 1-6 R e groups;
or R 8 is —(C 1-8 alkyl)-NH—R 9 , —(C 1-8 alkyl)-C(═O)NH—R 9 , —(C 1-8 alkyl)-C(═O)—N(R 9 ) 2 , or —(C 1-8 alkyl)-NHC(═O)NH—R 9 ; wherein the alkyl is unsubstituted or substituted by 1-6 R c groups;
each R 9 is independently C 1-8 alkyl, or C 1-8 fluoroalkyl which is substituted by 1-6 R c groups;
or two R 9 are taken together with the nitrogen to which they are attached to form a 4- to 6-membered heterocycloalkyl, which is substituted by 1-6 R c groups;
each R c is independently —OH, —CH 2 OH, —CH 2 CH 2 OH, —NH 2 , —CH 2 NH 2 , —NH(R d ), —CH 2 NH(R d ), —N(R d ) 2 , —CH 2 N(R d ) 2 , —N(R d ) 3 + , —C(═O)OH, —CH 2 C(═O)OH, —CH 2 CH 2 C(═O)OH, —S(═O) 2 OH, —S(═O)OH, —S(═O) 2 NH 2 , —P(═O)(OH) 2 , —P(═O)(OH)(R d ), —P(═O)(OH)(H), P(═O)(OH)(OR d ), —B(OH) 2 , —B(OR d )(OH), —NHCONHS(═O) 2 (R d ), —N(R d )CONHS(═O) 2 (R d ), —NHCON(R d )S(═O) 2 (R d ), —C(═O)NHS(═O) 2 (R d ), —S(═O) 2 NHC(═O)R d , —NHC(═NH)NH 2 , —NHC(═NH)NHR d , —NHC(═NH)N(R d ) 2 , —N(R d )C(═NH)NH 2 , —N(R d )C(═NH)NH(R d ), —N(R d )C(═NH)N(R d ) 2 , —NHC(═N(R d ))NH 2 , —NHC(═N(R d ))NHR d , —NHC(═N(R d ))N(R d ) 2 , —N(R d )C(═N(R d ))NH 2 , —N(R d )C(═N(R d ))NHR d , —N(R d )C(═N(R d ))N(R d ) 2 , —NHC(═NH)NHC(═NH)NH 2 , —N(R d )C(═NH)NHC(═NH)NH 2 ,
or a 4- to 6-membered heterocycle which is unsubstituted or substituted with 1, 2, 3, or 4 substituents selected from C 1-6 alkyl, —O—(C 1-6 alkyl), —OH, ═O and ═S;
each R d is independently C 1-6 alkyl, C 1-6 fluoroalkyl, or C 3-6 cycloalkyl;
each R e is independently —OH, —CH 2 OH, —CH 2 CH 2 OH, —N(R d ) 3 + , —C(═O)OH, —CH 2 C(═O)OH, —CH 2 CH 2 C(═O)OH, —S(═O) 2 OH, —S(═O)OH, —S(═O) 2 NH 2 , —P(═O)(OH) 2 , —P(═O)(OH)(R d ), —P(═O)(OH)(H), —P(═O)(OH)(OR d ), —B(OH) 2 , —B(OR d )(OH), —NHCONHS(═O) 2 (R d ), —N(R d )CONHS(═O) 2 (R d ), —NHCON(R d )S(═O) 2 (R d ), —C(═O)NHS(═O) 2 (R d ), —S(O) 2 NHC(O)R d , —NHC(═NH)NH 2 , —NHC(═NH)NHR d , —NHC(═NH)N(R d ) 2 , —N(R d )C(═NH)NH 2 , N(R d )C(═NH)NH(R d ), —N(R d )C(═NH)N(R d ) 2 , —NHC(═N(R d ))NH 2 , —NHC(═N(R d ))NR d , —NHC(═N(R d ))N(R d ) 2 , —N(R d )C(═N(R d ))NH 2 , —N(R d )C(═N(R d ))NHR d , —N(R d )C(═N(R d ))N(R d ) 2 , —NHC(═NH)NHC(═NH)NH 2 , N(R d )C(═NH)NHC(═NH)NH 2 ,
or a 4- to 6-membered heterocycle which is unsubstituted or substituted with 1, 2, 3, or 4 substituents selected from C 1-6 alkyl, —O—(C 1-6 alkyl), —OH, ═O and ═S;
Ring A is phenyl or 5-6 membered monocyclic heteroaryl;
each R a is independently halogen, —CN, C 1-6 alkyl, C 1-6 fluoroalkyl, or C 3-6 cycloalkyl;
X, when K is
is —O—, —NR N —, *—CH 2 O—, *—CH 2 NR N —, *—C(═O)O—, *—C(═O)NR N —, *—CH 2 C(═O)O—, *—CH 2 C(═O)NR N —, *—OC(═O)—, *—NR N C(═O)—, *—CH 2 OC(═O)—, or *—CH 2 NR N C(═O)—, where * represents the attachment point to Ring A;
R N is hydrogen or C 1-4 alkyl;
or X, when K is
is —O—, —NR N —, *—CH 2 O—, *—CH 2 NR N —, *—C(═O)O—, *—C(═O)NR N —, *—CH 2 C(═O)O—, *—CH 2 C(═O)NR N —, *—OC(═O)—, *—CH 2 OC(═O)—, or *—CH 2 NR N C(═O)—, where * represents the attachment point to Ring A;
R N is hydrogen or C 1-4 alkyl;
each R 11 is independently hydrogen, fluorine, —OH, C 1-6 alkyl, or C 1-6 alkoxy;
each R 12 is independently hydrogen, fluorine, or C 1-6 alkyl;
or, when K is
two R 11 are taken together with the intervening atoms to which they are attached to form a C 3-6 cycloalkyl;
or, when K is
two R 11 are taken together with the intervening atoms to which they are attached to form a C 4-6 cycloalkyl;
R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , and R 20 are each independently hydrogen, C 1-6 alkyl, C 1-6 alkoxy, or C 1-6 fluoroalkyl;
or R 13 and R 17 or R 13 and R 19 or R 15 and R 19 are taken together with the intervening atoms to which they are attached to form a ring;
R 21 is hydrogen, C 1-6 alkyl, or C 1-6 fluoroalkyl;
or R 21 and one R 11 are taken together with the intervening atoms to which they are attached to form a C 3-6 cycloalkyl;
W is phenyl or 5-6 membered monocyclic heteroaryl, wherein the phenyl or heteroaryl is unsubstituted or substituted with 1, 2, or 3 substituents selected from R b ;
each R b is independently halogen, —OH, —CN, —C(O)OH, —C(O)O(C 1-6 alkyl), C 1-6 alkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, phenyl, or 5- to 6-membered heteroaryl; wherein each alkyl, alkoxy, and cycloalkyl is unsubstituted or substituted with 1, 2, or 3 substituents selected from halogen, —OH, C 1-6 alkyl, and C 1-6 alkoxy;
or W is —C(═O)O—R 22 ;
R 22 is C 1-6 alkyl, C 3-6 cycloalkyl, or 3- to 6-membered heterocycloalkyl, wherein the alkyl, cycloalkyl, and heterocycloalkyl are unsubstituted or substituted by 1-3 substituents independently selected from fluorine, —OH, C 1-6 alkyl, C 1-6 haloalkyl or C 3-6 cycloalkyl;
m is 1-4;
n is 0-4;
p is 1 or 2;
q is 1 or 2; and
s is 1 or 2.
2 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, stereoisomer, or prodrug thereof, wherein:
X is —O—, *—CH 2 O—, *—C(═O)O—, or *—CH 2 C(═O)O—, where * represents the attachment point to Ring A; each R 11 is independently hydrogen, fluorine, —OH, C 1-6 alkyl, or C 1-6 alkoxy; or, when K is
two R 11 on adjacent carbon atoms are taken together with the intervening atoms to which they are attached to form a cyclopropyl;
R 21 is hydrogen or C 1-6 alkyl; and
R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , and R 20 are each independently hydrogen or C 1-6 alkyl.
3 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, stereoisomer, or prodrug thereof, wherein:
X is —O—; each R 11 is hydrogen; each R 12 is hydrogen; R 21 is hydrogen; and R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , and R 20 are each hydrogen.
4 . (canceled)
5 . (canceled)
6 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, stereoisomer, or prodrug thereof, wherein the compound has the structure of Formula (Ia), or a pharmaceutically acceptable salt, or solvate thereof:
7 . (canceled)
8 . The compound of claim 6 , or a pharmaceutically acceptable salt, solvate, stereoisomer, or prodrug thereof, wherein:
W is 6-membered monocyclic heteroaryl, wherein the heteroaryl is unsubstituted or substituted with 1 or 2 substituents selected from R b ; and each R b is independently halogen, —C(O)OH, —C(O)O(C 1-6 alkyl), C 1-6 alkyl, C 1-6 alkoxy, or C 3-6 cycloalkyl; wherein each alkyl, alkoxy, and cycloalkyl is unsubstituted or substituted with 1, 2, or 3 substituents selected from halogen, —OH, C 1-6 alkyl, and C 1-6 alkoxy.
9 . (canceled)
10 . (canceled)
11 . The compound of claim 6 , or a pharmaceutically acceptable salt, solvate, stereoisomer, or prodrug thereof, wherein:
K is
12 . The compound of claim 11 , or a pharmaceutically acceptable salt, solvate, stereoisomer, or prodrug thereof, wherein:
R 1 is hydrogen, —OH, or C 1-8 alkyl, wherein the alkyl is unsubstituted or substituted by —OH or —O(C 1-6 alkyl); each R 2 and R 3 is hydrogen; or R 2 and R 3 on the same carbon atom are taken together to form ═O; R 4 is hydrogen or C 1-8 alkyl; R 5 is C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 3-8 cycloalkyl, C 5-8 cycloalkenyl, 4- to 8-membered heterocycloalkyl, —[(CH 2 ) r —Z] t —R 6 , —[(CR d ) r —Z] t —R 6 , or —[(C(R d ) 2 ) r —Z] t —R 6 ; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, and 4- to 8-membered heterocycloalkyl is substituted by 1-6 R c groups; p is 1; and q is 1.
13 . (canceled)
14 . (canceled)
15 . The compound of claim 11 , or a pharmaceutically acceptable salt, solvate, stereoisomer, or prodrug thereof, wherein:
R 4 is hydrogen or C 1-4 alkyl; R 5 is C 1-8 alkyl, —[(CH 2 ) r —Z] t —R 6 , —[(CHR d ) r —Z] t —R 6 , or —[(C(R d ) 2 ) r —Z] t —R 6 ; wherein the alkyl is substituted by 1-6 R c groups; each Z is independently —CH 2 O—, —CH 2 NR d —, or —NH—C(═O)—NH—; r is 1-3; t is 1-3; R 6 is hydrogen or C 1-8 alkyl, wherein the alkyl is substituted by 1-6 R c groups; and each R c is independently —OH, —CH 2 OH, —NH 2 , —N(R d ) 3 + , —C(═O)OH, or
16 . (canceled)
17 . The compound of claim 11 , or a pharmaceutically acceptable salt, solvate, stereoisomer, or prodrug thereof, wherein:
R 5 is C 1-8 alkyl which is substituted by 1-6 R c groups; and each R c is independently —OH, —CH 2 OH, —N(R d ) 3 + , —C(═O)OH, or
18 . The compound of claim 11 , or a pharmaceutically acceptable salt, solvate, stereoisomer, or prodrug thereof, wherein:
R 4 is hydrogen; and R 5 is C 1-8 alkyl which is substituted by 1-6 —OH groups.
19 . The compound of claim 11 , or a pharmaceutically acceptable salt, solvate, stereoisomer, or prodrug thereof, wherein:
R 4 and R 5 are taken together with the nitrogen to which they are attached to form a 4- to 8-membered heterocycloalkyl, which is unsubstituted or substituted by 1-6 R c groups.
20 . The compound of claim 11 , or a pharmaceutically acceptable salt, solvate, stereoisomer, or prodrug thereof, wherein:
R 4 and R 5 are taken together with the nitrogen to which they are attached to form a 5- or 6-membered heterocycloalkyl, which is unsubstituted or substituted by 1-3-OH groups.
21 . The compound of claim 6 , or a pharmaceutically acceptable salt, solvate, stereoisomer, or prodrug thereof, wherein:
K is
wherein
R 7 is hydrogen or C 1-4 alkyl;
R 8 is C 1-8 alkyl, C 3-8 cycloalkyl, —[(CH 2 ) r —Z] t —R 6 , —[(CHR d ) r —Z] t —R 6 , or —[(CR d 2 ) r —Z] t —R 6 ;
wherein the alkyl or cycloalkyl is substituted by 1-6 R e groups
each Z is independently —CH 2 O—, —CH 2 NR d —, —CH 2 N + (R d ) 2 —, or —NH—C(═O)—NH—;
R 6 is hydrogen, C 1-8 alkyl, C 3-8 cycloalkyl, or 4- to 8-membered heterocycloalkyl, wherein the alkyl, cycloalkyl, or 4- to 8-membered heterocycloalkyl is unsubstituted or substituted by 1-6 R c groups;
or R 8 is —(C 1-8 alkyl)-NH—R 9 , —(C 1-8 alkyl)-C(═O)NH—R 9 , —(C 1-8 alkyl)-C(═O)—N(R 9 ) 2 , or —(C 1-8 alkyl)-NHC(═O)NH—R 9 ; wherein the alkyl is unsubstituted or substituted by 1-6 R c groups;
each R 9 is independently C 1-8 alkyl which is substituted by 1-6 R c groups;
or two R 9 are taken together with the nitrogen to which they are attached to form a 4- to 6-membered heterocycloalkyl, which is substituted by 1-6 R c groups;
each R c is independently —OH, —CH 2 OH, —NH 2 , —N(R d ) 3 + , —C(═O)OH, —S(═O) 2 OH, —S(═O) 2 NH 2 , —P(═O)(OH) 2 , —P(═O)(OH)(R d ), —P(═O)(OH)(OR d ),
each R d is independently C 1-6 alkyl; and
each R e is independently —OH, —CH 2 OH, —N(R d ) 3 + , —C(═O)OH, —S(═O) 2 OH, —S(═O) 2 NH 2 , —P(═O)(OH) 2 , —P(═O)(OH)(R d ), —P(═O)(OH)(OR d ),
22 . (canceled)
23 . The compound of claim 21 , or a pharmaceutically acceptable salt, solvate, stereoisomer, or prodrug thereof, wherein:
each R c is independently —OH, —CH 2 OH, or —N(R d ) 3 + ; and R 8 is C 1-8 alkyl; wherein the alkyl is substituted by 1-6 R e groups; wherein each R e is independently —OH, —CH 2 OH, —N(R d ) 3 + , —S(═O) 2 OH, —S(═O) 2 NH 2 , or
or R 8 is —(C 1-8 alkyl)-NH—R 9 , —(C 1-8 alkyl)-C(═O)NH—R 9 , —(C 1-8 alkyl)-C(═O)—N(R 9 ) 2 , or —(C 1-8 alkyl)-NHC(═O)NH—R 9 ; wherein the alkyl is unsubstituted.
24 . (canceled)
25 . (canceled)
26 . (canceled)
27 . (canceled)
28 . (canceled)
29 . (canceled)
30 . (canceled)
31 . (canceled)
32 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, stereoisomer, or prodrug thereof, selected from:
2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-N-[5-[[2-hydroxy-1-(hydroxymethyl)ethyl]amino]pentyl]acetamide; 5-[[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]amino]pentyl-triethyl-ammonium; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-N-[5-[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]pentyl]acetamide; 5-[[2-[2,6-difluoro-4-[3-[1-(5-propylpyrimidin-2-yl)-4-piperidyl]propoxy]phenyl]acetyl]amino]pentyl-triethyl-ammonium; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]acetamide; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2,6-difluoro-phenyl]-N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]acetamide; 2-[4-[3-[1-(5-ethylpyrimidin-2-yl)-4-piperidyl]propoxy]-2,6-difluoro-phenyl]-N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]acetamide; 2-[2,6-difluoro-4-[3-[1-(5-propylpyrimidin-2-yl)-4-piperidyl]propoxy]phenyl]-N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]acetamide; 1-[3,3-bis(hydroxymethyl)azetidin-1-yl]-2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]ethanone; 2-[[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]amino]ethanesulfonic acid; 3-[[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]amino]propane-1-sulfonic acid; 4-[[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]amino]butane-1-sulfonic acid; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-N-(3-sulfamoylpropyl)acetamide; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-N-(4-sulfamoylbutyl)acetamide; 3-[[2-[4-[3-[1-(5-ethylpyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]amino]propyl-trimethyl-ammonium; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-N-[2-[rac-(2S,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxyethyl]acetamide; 6-[[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]amino]-N-[2-hydroxy-1-(hydroxymethyl)ethyl]hexanamide; 6-[[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]amino]-N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]hexanamide; 3-[[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]amino]-N-[2-hydroxy-1-(hydroxymethyl)ethyl]propenamide; 3-[[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]amino]-N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]propenamide; 4-[[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]amino]-N-[2-hydroxy-1-(hydroxymethyl)ethyl]butanamide; 4-[[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]amino]-N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]butanamide; 5-[[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]amino]-N-[2-hydroxy-1-(hydroxymethyl)ethyl]pentanamide; 5-[[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]amino]-N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]pentanamide; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-N-[6-[(3S,4S)-3,4-dihydroxypyrrolidin-1-yl]-6-oxo-hexyl]acetamide; 1-[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2,6-difluoro-phenyl]acetyl]-N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]azetidine-3-carboxamide; 1-[2-[2-fluoro-4-[3-[1-[5-(methoxymethyl)pyrimidin-2-yl]-4-piperidyl]propoxy]phenyl]acetyl]-N-[2-[[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]carbamoylamino]ethyl]azetidine-3-carboxamide; 1-[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]-N-[2-hydroxy-1-(hydroxymethyl)ethyl]azetidine-3-carboxamide; 1-[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]-N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]azetidine-3-carboxamide; 1-[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]-N-[2,3-dihydroxy-2-(hydroxymethyl)propyl]azetidine-3-carboxamide; 1-[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]-N-[2-[rac-(2S,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxyethyl]azetidine-3-carboxamide; 2-[1-[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]azetidin-3-yl]-N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]acetamide; 2-[1-[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]azetidin-3-yl]-N-[2,3-dihydroxy-2-(hydroxymethyl)propyl]acetamide; 2-[1-[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2,6-difluoro-phenyl]acetyl]azetidin-3-yl]-N-[2,3-dihydroxy-2-(hydroxymethyl)propyl]acetamide; 3-[1-[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]azetidin-3-yl]-N-[2,3-dihydroxy-2-(hydroxymethyl)propyl]propenamide; 3-[1-[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2,6-difluoro-phenyl]acetyl]azetidin-3-yl]-N-[2,3-dihydroxy-2-(hydroxymethyl)propyl]propenamide; 1-[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]-N-[rac-(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]azetidine-3-carboxamide; 2-[1-[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]azetidin-3-yl]-N-[rac-(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide; 1-[2-[2-fluoro-4-[3-[1-[5-(methoxymethyl)pyrimidin-2-yl]-4-piperidyl]propoxy]phenyl]acetyl]-N-[rac-(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]azetidine-3-carboxamide; 3-[[1-[2-[2,6-difluoro-4-[3-[1-(5-propylpyrimidin-2-yl)-4-piperidyl]propoxy]phenyl]acetyl]azetidine-3-carbonyl]amino]propyl-trimethyl-ammonium formate; 1-[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]-N-[2,3-dihydroxy-2-(hydroxymethyl)propyl]piperidine-4-carboxamide; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[3-[[[2,3-dihydroxy-2-(hydroxymethyl)propyl]amino]methyl]azetidin-1-yl]ethanone; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[3-[[[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]amino]methyl]azetidin-1-yl]ethanone; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[3-[[[3-hydroxy-2-(hydroxymethyl)propyl]amino]methyl]azetidin-1-yl]ethanone; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[3-[[rac-(3S,4S)-3,4-dihydroxypyrrolidin-1-yl]methyl]azetidin-1-yl]ethanone; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[3-[[rac-(3R,4R)-3,4-dihydroxypyrrolidin-1-yl]methyl]azetidin-1-yl]ethanone; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[3-[[rac-(3S,4R)-3,4-dihydroxypyrrolidin-1-yl]methyl]azetidin-1-yl]ethanone; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[3-[[[rac-(1R,2S,3R,4S)-2,3,4-trihydroxycyclopentyl]amino]methyl]azetidin-1-yl]ethanone; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[3-[[rac-(3R,5S)-3,4,5-trihydroxy-1-piperidyl]methyl]azetidin-1-yl]ethanone; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[3-[[2-[2-(2-hydroxyethoxy)ethoxy]ethylamino]methyl]azetidin-1-yl]ethanone; 1-[3-[[2-[2-(2-aminoethoxy)ethoxy]ethylamino]methyl]azetidin-1-yl]-2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]ethanone; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2,6-difluoro-phenyl]-1-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; 2-[4-[4-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]butoxy]-2-fluoro-phenyl]-1-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; 2-(4-(4-(1-(5-chloropyrimidin-2-yl)piperidin-4-yl)butoxy)-2,6-difluorophenyl)-1-(3-((((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)amino)methyl)azetidin-1-yl)ethan-1-one; 2-(4-(3-(1-(5-chloropyrimidin-2-yl)piperidin-4-yl)propoxy)-2-fluorophenyl)-1-(3-(2-((1,3-dihydroxypropan-2-yl)amino)ethyl)azetidin-1-yl)ethan-1-one; 2-(4-(3-(1-(5-chloropyrimidin-2-yl)piperidin-4-yl)propoxy)-2-fluorophenyl)-1-(3-(2-((3-hydroxy-2-(hydroxymethyl)propyl)amino)ethyl)azetidin-1-yl)ethan-1-one; 2-(4-(3-(1-(5-chloropyrimidin-2-yl)piperidin-4-yl)propoxy)-2-fluorophenyl)-1-(3-(2-((2,3-dihydroxy-2-(hydroxymethyl)propyl)amino)ethyl)azetidin-1-yl)ethan-1-one; 2-(4-(3-(1-(5-chloropyrimidin-2-yl)piperidin-4-yl)propoxy)-2-fluorophenyl)-1-(3-(2-((1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)amino)ethyl)azetidin-1-yl)ethan-1-one; 1-(2-((2-(1-(2-(4-(3-(1-(5-chloropyrimidin-2-yl)piperidin-4-yl)propoxy)-2-fluorophenyl)acetyl)azetidin-3-yl)ethyl)amino)ethyl)-3-(1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)urea; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[3-[2-[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]ethyl]azetidin-1-yl]ethanone; 2-(4-(3-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)propoxy)-2-fluorophenyl)-1-(3-(((3-hydroxy-2-(hydroxymethyl)propyl)amino)methyl)azetidin-1-yl)ethan-1-one; 1-(3-(((2,3-dihydroxy-2-(hydroxymethyl)propyl)amino)methyl)azetidin-1-yl)-2-(4-(3-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)propoxy)-2-fluorophenyl)ethan-1-one; 1-(3-(((1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)amino)methyl)azetidin-1-yl)-2-(4-(3-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)propoxy)-2-fluorophenyl)ethan-1-one; 1-(1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)-3-(2-(((1-(2-(4-(3-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)propoxy)-2-fluorophenyl)acetyl)azetidin-3-yl)methyl)amino)ethyl)urea; (2S,3R,4S,5S)-6-[[1-[2-[4-[3-[1-(5-ethylpyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]azetidin-3-yl]methylamino]-2,3,4,5-tetrahydroxy-hexanoic acid; 1-(3-(((2,3-dihydroxy-2-(hydroxymethyl)propyl)amino)methyl)azetidin-1-yl)-2-(4-(3-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)propoxy)-2,6-difluorophenyl)ethan-1-one; 1-(1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)-3-(2-(((1-(2-(4-(3-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)propoxy)-2,6-difluorophenyl)acetyl)azetidin-3-yl)methyl)amino)ethyl)urea; 2-(4-(3-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)propoxy)-2,6-difluorophenyl)-1-(3-((((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)amino)methyl)azetidin-1-yl)ethan-1-one; 2-(2-fluoro-4-(3-(1-(5-propylpyrimidin-2-yl)piperidin-4-yl)propoxy)phenyl)-1-(3-(((3-hydroxy-2-(hydroxymethyl)propyl)amino)methyl)azetidin-1-yl)ethan-1-one; 1-(3-(((2,3-dihydroxy-2-(hydroxymethyl)propyl)amino)methyl)azetidin-1-yl)-2-(2-fluoro-4-(3-(1-(5-propylpyrimidin-2-yl)piperidin-4-yl)propoxy)phenyl)ethan-1-one; 1-(3-(((1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)amino)methyl)azetidin-1-yl)-2-(2-fluoro-4-(3-(1-(5-propylpyrimidin-2-yl)piperidin-4-yl)propoxy)phenyl)ethan-1-one; 1-(1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)-3-(2-(((1-(2-(2-fluoro-4-(3-(1-(5-propylpyrimidin-2-yl)piperidin-4-yl)propoxy)phenyl)acetyl)azetidin-3-yl)methyl)amino)ethyl)urea; 2-(2-fluoro-4-(3-(1-(5-propylpyrimidin-2-yl)piperidin-4-yl)propoxy)phenyl)-1-(3-((((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)amino)methyl)azetidin-1-yl)ethan-1-one; 2-(2,6-difluoro-4-(3-(1-(5-propylpyrimidin-2-yl)piperidin-4-yl)propoxy)phenyl)-1-(3-(((2,3-dihydroxy-2-(hydroxymethyl)propyl)amino)methyl)azetidin-1-yl)ethan-1-one; 2-(2,6-difluoro-4-(3-(1-(5-propylpyrimidin-2-yl)piperidin-4-yl)propoxy)phenyl)-1-(3-(((1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)amino)methyl)azetidin-1-yl)ethan-1-one; 1-(2-(((1-(2-(2,6-difluoro-4-(3-(1-(5-propylpyrimidin-2-yl)piperidin-4-yl)propoxy)phenyl)acetyl)azetidin-3-yl)methyl)amino)ethyl)-3-(1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)urea; 2-(2,6-difluoro-4-(3-(1-(5-propylpyrimidin-2-yl)piperidin-4-yl)propoxy)phenyl)-1-(3-((((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)amino)methyl)azetidin-1-yl)ethan-1-one; 2-[2-fluoro-4-[3-[1-(5-methoxypyrimidin-2-yl)-4-piperidyl]propoxy]phenyl]-1-[3-[[[rac-(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; 2-[4-[3-[1-(5-ethoxypyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[3-[[[rac-(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; 1-[2-[[1-[2-[2-fluoro-4-[3-[1-[5-(methoxymethyl)pyrimidin-2-yl]-4-piperidyl]propoxy]phenyl]acetyl]azetidin-3-yl]methylamino]ethyl]-3-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]urea; (3R,5R)-7-[[1-[2-[2-fluoro-4-[3-[1-[5-(methoxymethyl)pyrimidin-2-yl]-4-piperidyl]propoxy]phenyl]acetyl]azetidin-3-yl]methylamino]-3,5-dihydroxy-heptanoic acid; 2-[2-fluoro-4-[3-[1-[5-(methoxymethyl)pyrimidin-2-yl]-4-piperidyl]propoxy]phenyl]-1-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; 2-[2-fluoro-4-[4-[1-[5-(methoxymethyl)pyrimidin-2-yl]-4-piperidyl]butoxy]phenyl]-1-[3-[[[rac-(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; 2-[2,6-difluoro-4-[4-[1-[5-(methoxymethyl)pyrimidin-2-yl]-4-piperidyl]butoxy]phenyl]-1-[3-[[[rac-(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; 2-[4-[2-[(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]cyclopropyl]ethoxy]-2-fluoro-phenyl]-1-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; methyl 2-[4-[3-[3-fluoro-4-[2-oxo-2-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethyl]phenoxy]propyl]-1-piperidyl]pyrimidine-5-carboxylate; 2-[4-[2-[1-(5-ethylpyrimidin-2-yl)-4-piperidyl]ethoxymethyl]-2-fluoro-phenyl]-1-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]cyclobutyl]ethanone; 2-[4-[2-[1-(5-ethylpyrimidin-2-yl)-4-piperidyl]ethoxymethyl]-3-fluoro-phenyl]-1-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]cyclobutyl]ethanone; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxymethyl]-2-fluoro-phenyl]-1-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; 2-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]ethyl 3-fluoro-4-[2-oxo-2-[3-[[[rac-(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethyl]benzoate; 2-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]ethyl 2-[3-fluoro-4-[2-oxo-2-[3-[[[rac-(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethyl]phenyl]acetate; 2-[2-fluoro-4-[3-[1-[5-(hydroxymethyl)pyrimidin-2-yl]-4-piperidyl]propoxy]phenyl]-1-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; 2-[2,6-difluoro-4-[3-[1-[5-(methoxymethyl)pyrimidin-2-yl]-4-piperidyl]propoxy]phenyl]-1-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; [rac-(1R,2R)-2-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]cyclopropyl]methyl 3-fluoro-4-[2-oxo-2-[3-[[[rac-(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethyl]benzoate; 2-[2-fluoro-4-[[(1R,2R)-2-[1-[5-(methoxymethyl)pyrimidin-2-yl]-4-piperidyl]cyclopropyl]methoxymethyl]phenyl]-1-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; 2-[2-fluoro-4-[2-[rac-(1S,2R)-2-[1-[5-(methoxymethyl)pyrimidin-2-yl]-4-piperidyl]cyclopropyl]ethoxy]phenyl]-1-[3-[[[rac-(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[(3S)-3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]pyrrolidin-1-yl]ethanone; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[(3S)-3-[[[2,3-dihydroxy-2-(hydroxymethyl)propyl]amino]methyl]pyrrolidin-1-yl]ethanone; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[(3R)-3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]pyrrolidin-1-yl]ethanone; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[(3R)-3-[[[2,3-dihydroxy-2-(hydroxymethyl)propyl]amino]methyl]pyrrolidin-1-yl]ethanone; (3R)-1-[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]-N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]pyrrolidine-3-carboxamide; (3S)-1-[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]-N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]pyrrolidine-3-carboxamide; 2-[4-[2-[7-(5-chloropyrimidin-2-yl)-7-azaspiro[3.5]nonan-2-yl]ethoxy]-2-fluoro-phenyl]-1-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; 2-[4-[3-[7-(5-chloropyrimidin-2-yl)-7-azaspiro[3.5]nonan-2-yl]propoxy]-2-fluoro-phenyl]-1-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; 2-[4-[4-[7-(5-chloropyrimidin-2-yl)-7-azaspiro[3.5]nonan-2-yl]butoxy]-2-fluoro-phenyl]-1-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; 2-[4-[[7-(5-chloropyrimidin-2-yl)-7-azaspiro[3.5]nonan-2-yl]methoxymethyl]-2-fluoro-phenyl]-1-[3-[[[2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; N-[2,3-dihydroxy-2-(hydroxymethyl)propyl]-2-[1-[2-[4-[3-[1-(5-ethoxypyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]azetidin-3-yl]acetamide; 2-[4-[4-[1-(5-chloropyrimidin-2-yl)-4-methyl-4-piperidyl]butoxy]-2-fluoro-phenyl]-1-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; 2-[4-[2-[6-(5-chloropyrimidin-2-yl)-6-azaspiro[2.5]octan-2-yl]ethoxy]-2-fluoro-phenyl]-1-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; 2-[4-[[6-(5-chloropyrimidin-2-yl)-6-azaspiro[2.5]octan-2-yl]methoxymethyl]-2-fluoro-phenyl]-1-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; isopropyl 4-[3-[3-fluoro-4-[2-oxo-2-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethyl]phenoxy]propyl]piperidine-1-carboxylate; 2-[4-[3-[(1R,5S)-3-(5-chloropyrimidin-2-yl)-3-azabicyclo[3.1.0]hexan-6-yl]propoxy]-2-fluoro-phenyl]-1-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; 2-[4-[3-[1-(5-ethoxypyrimidin-2-yl)-4-piperidyl]propoxy]-2,6-difluoro-phenyl]-1-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; 2-[4-[2-[7-(5-chloropyrimidin-2-yl)-7-azaspiro[3.5]nonan-2-yl]ethoxy]-2,6-difluoro-phenyl]-1-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; 2-[4-[3-[7-(5-chloropyrimidin-2-yl)-7-azaspiro[3.5]nonan-2-yl]propoxy]-2,6-difluoro-phenyl]-1-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; isopropyl 2-[3-[3-fluoro-4-[2-oxo-2-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethyl]phenoxy]propyl]-7-azaspiro[3.5]nonane-7-carboxylate; isopropyl 2-[2-[3-fluoro-4-[2-oxo-2-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethyl]phenoxy]ethyl]-7-azaspiro[3.5]nonane-7-carboxylate; (1-methylcyclopropyl) 4-[3-[3-fluoro-4-[2-oxo-2-[3-[[[rac-(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethyl]phenoxy]propyl]piperidine-1-carboxylate; 2-[4-[[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]cyclobutyl]methoxy]-2-fluoro-phenyl]-1-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[3-(methoxymethyl)-3-[[[r(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]pyrrolidin-1-yl]ethanone; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[3-[[[3-hydroxy-2,2-bis(hydroxymethyl)propyl]amino]methyl]-3-(methoxymethyl)pyrrolidin-1-yl]ethanone; 2-[4-[2-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]cyclobutyl]ethoxy]-2-fluoro-phenyl]-1-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; 2-[4-[2-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]cyclobutyl]ethoxy]-2,6-difluoro-phenyl]-1-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; [3-(trifluoromethyl)oxetan-3-yl] 4-[3-[3-fluoro-4-[2-oxo-2-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethyl]phenoxy]propyl]piperidine-1-carboxylate; [3-(trifluoromethyl)oxetan-3-yl] 4-[3-[3,5-difluoro-4-[2-oxo-2-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethyl]phenoxy]propyl]piperidine-1-carboxylate; (3S)-1-[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]-N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pyrrolidine-3-carboxamide; (3S)-1-[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2,6-difluoro-phenyl]acetyl]-N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pyrrolidine-3-carboxamide; (3S)-1-[2-[4-[3-[1-(5-ethoxypyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]-N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pyrrolidine-3-carboxamide; (3S)-1-[2-[4-[3-[1-(5-ethoxypyrimidin-2-yl)-4-piperidyl]propoxy]-2,6-difluoro-phenyl]acetyl]-N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pyrrolidine-3-carboxamide; (3S)-1-[2-[2,6-difluoro-4-[3-[1-[5-(methoxymethyl)pyrimidin-2-yl]-4-piperidyl]propoxy]phenyl]acetyl]-N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pyrrolidine-3-carboxamide; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2,6-difluoro-phenyl]-1-[(3S)-3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]pyrrolidin-1-yl]ethanone; 2-[4-[3-[1-(5-ethoxypyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[(3S)-3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]pyrrolidin-1-yl]ethanone; 2-[4-[3-[1-(5-ethoxypyrimidin-2-yl)-4-piperidyl]propoxy]-2,6-difluoro-phenyl]-1-[(3S)-3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]pyrrolidin-1-yl]ethanone; 2-[2,6-difluoro-4-[3-[1-[5-(methoxymethyl)pyrimidin-2-yl]-4-piperidyl]propoxy]phenyl]-1-[(3S)-3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]pyrrolidin-1-yl]ethanone; 1-[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]-3-(methoxymethyl)-N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pyrrolidine-3-carboxamide; 1-[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]-N-[3-hydroxy-2,2-bis(hydroxymethyl)propyl]-3-(methoxymethyl)pyrrolidine-3-carboxamide; 2-[4-[2-[7-(5-chloropyrimidin-2-yl)-7-azaspiro[3.5]nonan-3-yl]ethoxy]-2-fluoro-phenyl]-1-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; 2-[4-[2-[7-(5-chloropyrimidin-2-yl)-7-azaspiro[3.5]nonan-3-yl]ethoxy]-2,6-difluoro-phenyl]-1-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; isopropyl 3-[2-[3-fluoro-4-[2-oxo-2-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethyl]phenoxy]ethyl]-7-azaspiro[3.5]nonane-7-carboxylate; isopropyl 3-[2-[3,5-difluoro-4-[2-oxo-2-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethyl]phenoxy]ethyl]-7-azaspiro[3.5]nonane-7-carboxylate; 2-[4-[3-[6-(5-chloropyrimidin-2-yl)-6-azaspiro[2.5]octan-2-yl]propoxy]-2-fluoro-phenyl]-1-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; 2-[4-[3-[6-(5-chloropyrimidin-2-yl)-6-azaspiro[2.5]octan-2-yl]propoxy]-2,6-difluoro-phenyl]-1-[3-[[[2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; 2-[4-[3-[7-(5-chloropyrimidin-2-yl)-7-azaspiro[3.5]nonan-3-yl]propoxy]-2-fluoro-phenyl]-1-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; isopropyl 2-[3-[3-fluoro-4-[2-oxo-2-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethyl]phenoxy]propyl]-6-azaspiro[2.5]octane-6-carboxylate; isopropyl 2-[3-[3,5-difluoro-4-[2-oxo-2-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethyl]phenoxy]propyl]-6-azaspiro[2.5]octane-6-carboxylate; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[(3S)-3-[[[3-hydroxy-2,2-bis(hydroxymethyl)propyl]amino]methyl]pyrrolidin-1-yl]ethanone; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[(3S)-3-[[[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]amino]methyl]pyrrolidin-1-yl]ethanone; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2,6-difluoro-phenyl]-1-[(3S)-3-[[[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]amino]methyl]pyrrolidin-1-yl]ethanone; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2,6-difluoro-phenyl]-1-[(3S)-3-[[[2,3-dihydroxy-2-(hydroxymethyl)propyl]amino]methyl]pyrrolidin-1-yl]ethanone; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2,6-difluoro-phenyl]-1-[(3S)-3-[[[3-hydroxy-2,2-bis(hydroxymethyl)propyl]amino]methyl]pyrrolidin-1-yl]ethanone; 2-[4-[3-[1-(5-ethoxypyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[(3S)-3-[[[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]amino]methyl]pyrrolidin-1-yl]ethanone; 2-[4-[3-[1-(5-ethoxypyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[(3S)-3-[[[2,3-dihydroxy-2-(hydroxymethyl)propyl]amino]methyl]pyrrolidin-1-yl]ethanone; 2-[4-[3-[1-(5-ethoxypyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[(3S)-3-[[[3-hydroxy-2,2-bis(hydroxymethyl)propyl]amino]methyl]pyrrolidin-1-yl]ethanone; 2-[4-[3-[1-(5-ethoxypyrimidin-2-yl)-4-piperidyl]propoxy]-2,6-difluoro-phenyl]-1-[(3S)-3-[[[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]amino]methyl]pyrrolidin-1-yl]ethanone; 2-[4-[3-[1-(5-ethoxypyrimidin-2-yl)-4-piperidyl]propoxy]-2,6-difluoro-phenyl]-1-[(3S)-3-[[[2,3-dihydroxy-2-(hydroxymethyl)propyl]amino]methyl]pyrrolidin-1-yl]ethanone; 2-[4-[3-[1-(5-ethoxypyrimidin-2-yl)-4-piperidyl]propoxy]-2,6-difluoro-phenyl]-1-[(3S)-3-[[[3-hydroxy-2,2-bis(hydroxymethyl)propyl]amino]methyl]pyrrolidin-1-yl]ethanone; 2-[2,6-difluoro-4-[3-[1-[5-(methoxymethyl)pyrimidin-2-yl]-4-piperidyl]propoxy]phenyl]-1-[(3S)-3-[[[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]amino]methyl]pyrrolidin-1-yl]ethanone; 2-[2,6-difluoro-4-[3-[1-[5-(methoxymethyl)pyrimidin-2-yl]-4-piperidyl]propoxy]phenyl]-1-[(3S)-3-[[[2,3-dihydroxy-2-(hydroxymethyl)propyl]amino]methyl]pyrrolidin-1-yl]ethanone; 2-[2,6-difluoro-4-[3-[1-[5-(methoxymethyl)pyrimidin-2-yl]-4-piperidyl]propoxy]phenyl]-1-[(3S)-3-[[[3-hydroxy-2,2-bis(hydroxymethyl)propyl]amino]methyl]pyrrolidin-1-yl]ethanone; 2-[2-fluoro-4-[2-[(1S,2R)-2-[1-[5-(methoxymethyl)pyrimidin-2-yl]-4-piperidyl]cyclopropyl]ethoxy]phenyl]-1-[(3S)-3-[[[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]amino]methyl]pyrrolidin-1-yl]ethanone; 2-[2-fluoro-4-[2-[(1S,2R)-2-[1-[5-(methoxymethyl)pyrimidin-2-yl]-4-piperidyl]cyclopropyl]ethoxy]phenyl]-1-[(3S)-3-[[[2,3-dihydroxy-2-(hydroxymethyl)propyl]amino]methyl]pyrrolidin-1-yl]ethanone; 2-[2-fluoro-4-[2-[(1S,2R)-2-[1-[5-(methoxymethyl)pyrimidin-2-yl]-4-piperidyl]cyclopropyl]ethoxy]phenyl]-1-[(3S)-3-[[[3-hydroxy-2,2-bis(hydroxymethyl)propyl]amino]methyl]pyrrolidin-1-yl]ethanone; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[3-[2-[[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]amino]ethyl]azetidin-1-yl]ethanone; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[3-[[[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]amino]methyl]azetidin-1-yl]ethanone; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[3-[[[(2S,3R,4R)-2,3,4,5-tetrahydroxypentyl]amino]methyl]azetidin-1-yl]ethanone; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[3-[[[(2R,3S,4R)-2,3,4,5-tetrahydroxypentyl]amino]methyl]azetidin-1-yl]ethanone; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[(3R)-3-[[[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]amino]methyl]pyrrolidin-1-yl]ethanone; 2-[5-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-pyridyl]-1-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; 2-[5-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-3-fluoro-2-pyridyl]-1-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; 2-[[1-[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]azetidine-3-carbonyl]amino]ethanesulfonic acid; 3-[[1-[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]azetidine-3-carbonyl]amino]propane-1-sulfonic acid; 4-[[1-[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]azetidine-3-carbonyl]amino]butane-1-sulfonic acid; 5-[[1-[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]azetidine-3-carbonyl]amino]pentane-1-sulfonic acid; 6-[[1-[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]azetidine-3-carbonyl]amino]hexane-1-sulfonic acid; 2-[[2-[1-[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]azetidin-3-yl]acetyl]amino]ethanesulfonic acid; 3-[[2-[1-[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]azetidin-3-yl]acetyl]amino]propane-1-sulfonic acid; 4-[[2-[1-[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]azetidin-3-yl]acetyl]amino]butane-1-sulfonic acid; 2-[6-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-3-pyridyl]-1-[3-[[[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]amino]methyl]azetidin-1-yl]ethanone; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[3-hydroxy-3-[[[3-hydroxy-2,2-bis(hydroxymethyl)propyl]amino]methyl]pyrrolidin-1-yl]ethanone; 1-[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]-3-hydroxy-N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pyrrolidine-3-carboxamide; 1-[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]-3-hydroxy-N-[3-hydroxy-2,2-bis(hydroxymethyl)propyl]pyrrolidine-3-carboxamide; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[4-hydroxy-4-[[[3-hydroxy-2,2-bis(hydroxymethyl)propyl]amino]methyl]-1-piperidyl]ethanone; 2-[1-[2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]acetyl]-3-hydroxy-azetidin-3-yl]-N-[3-hydroxy-2,2-bis(hydroxymethyl)propyl]acetamide; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[3-hydroxy-3-[[[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]amino]methyl]azetidin-1-yl]ethanone; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[3-hydroxy-3-[[[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]amino]methyl]pyrrolidin-1-yl]ethanone; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2-fluoro-phenyl]-1-[4-hydroxy-4-[[[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]amino]methyl]-1-piperidyl]ethanone; 2-[4-[3-[1-(5-chloropyrimidin-2-yl)-4-piperidyl]propoxy]-2,6-difluoro-phenyl]-1-[3-hydroxy-3-[[[3-hydroxy-2,2-bis(hydroxymethyl)propyl]amino]methyl]pyrrolidin-1-yl]ethanone; 2-[4-[3-[1-(5-ethoxypyrimidin-2-yl)-4-piperidyl]propoxy]-2,6-difluoro-phenyl]-1-[3-hydroxy-3-[[[3-hydroxy-2,2-bis(hydroxymethyl)propyl]amino]methyl]pyrrolidin-1-yl]ethanone; and 2-[2,6-difluoro-4-[3-[1-[5-(methoxymethyl)pyrimidin-2-yl]-4-piperidyl]propoxy]phenyl]-1-[3-hydroxy-3-[[[3-hydroxy-2,2-bis(hydroxymethyl)propyl]amino]methyl]pyrrolidin-1-yl]ethanone; or a pharmaceutically acceptable salt, solvate, stereoisomer, or prodrug thereof.
33 . A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt, solvate, stereoisomer, or prodrug thereof, and at least one pharmaceutically acceptable excipient.
34 . A method of treating a condition or disorder involving the gut-brain axis in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt, solvate, stereoisomer, or prodrug thereof; wherein the condition or disorder is associated with GPR119 activity.
35 . (canceled)
36 . The method of claim 34 , wherein the condition or disorder is a metabolic disorder or a nutritional disorder.
37 . The method of claim 36 , wherein the condition or disorder is type 2 diabetes, hyperglycemia, metabolic syndrome, obesity, hypercholesterolemia, nonalcoholic steatohepatitis, hypertension, short bowel syndrome, intestinal failure, intestinal insufficiency, chemotherapy-induced enteritis, or radiation-induced enteritis.
38 . (canceled)
39 . (canceled)
40 . (canceled)
41 . (canceled)
42 . (canceled)
43 . The method of claim 34 , further comprising administering one or more additional therapeutic agents to the subject: wherein the one or more additional therapeutic agents are selected from a TGR5 agonist, a GPR40 agonist, an SSTR5 antagonist, an SSTR5 inverse agonist, a CCK1 agonist, a PDE4 inhibitor, a DPP-4 inhibitor, a GLP-1 receptor agonist, metformin, or a combination thereof.
44 . (canceled)
45 . (canceled)Cited by (0)
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