US 2025/0333379 A1Published application

Compounds Useful for Treating Liver Diseases

AssigneeAbionyx Pharma SA

InventorJean-Louis Henri Dasseux

Life of this patent

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Abstract

This invention provides compounds, for example, of Formulae (A)-(H) and (J)-(AA) and pharmaceutically acceptable salts, solvates, esters, amides, and prodrugs thereof. The invention further provides pharmaceutical compositions comprising a compound of the invention, and a pharmaceutically acceptable carrier or vehicle. The compounds and compositions disclosed herein are useful for treating or preventing various diseases and conditions, for example liver disease such as liver fibrosis, fatty liver disease, non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH), and kidney diseases such as acute kidney injury (AKI).

Claims18

Dependent claims

A compound:

(I) of Formula (A)
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
each R1 and R2 is independently —C1-C6 alkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, phenyl, or benzyl;
or
alternatively, R1 and R2 together with the carbon atom to which R1 and R2 are attached form a C3-C7 cycloalkyl group;
X is —CH2OH, —COOH, —COH, —COOR3, —COOCH2CONR4R5, —SO3H,
R3 is —C1-C6 alkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, phenyl, or benzyl;
each R4 and R5 is independently alkyl, aryl, or heteroaryl;
or alternatively, R4 and R5 together with the carbon atom to which R4 and R5 are attached form a heterocycle;
each R6 and R7 is independently H, —C1-C6 alkyl, —C2-C6 alkenyl, or —C2-C6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(II) of Formula (B):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
each R1 and R2 is independently —C1-C6 alkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, phenyl, or benzyl;
or alternatively, R1 and R2 together with the carbon atom to which R1 and R2 are attached form a C3-C7 cycloalkyl group;
X is —CH2OH, —COH, —COOCH2CONR4R5, —SO3H,
R3 is —C1-C6 alkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, phenyl, or benzyl;
each R4 and R5 is independently alkyl, aryl, or heteroaryl;
or alternatively, R4 and R5 together with the carbon atom to which R4 and R5 are attached form a heterocycle;
each R6 and R7 is independently H, —C1-C6 alkyl, —C2-C6 alkenyl, or —C2-C6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(III) having the structure:
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof;
(IV) having the structure:
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof;
(V) having the structure:
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof;
(VI) of Formula (C):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
R1 is phenyl, naphthyl, pyridyl, thienyl, furyl, quinolyl or benzothienyl, any of which is unsubstituted or substituted with C1-8 alkyl, C1-8 haloalkyl, C1-8 alkoxy, C1-8 haloalkoxy, C2-8 alkenyl, C2-8 alkynyl, halogen, C2-7 acyl, benzoyl, hydroxyl, nitro, amino, phenyl or pyridyl;
R2 is C2-8 alkyl, C1-8 haloalkyl, C2-8 alkenyl, C2-8 alkynyl, 3-7 membered cycloalkyl, C1-8 alkyl substituted with a 3-7 membered cycloalkyl, or C1-6 alkyl substituted with phenyl, naphthyl or pyridyl, any of which is unsubstituted or substituted with C1-8 alkyl, C1-8 haloalkyl, C1-8 alkoxy, C1-8 haloalkoxy, C2-8 alkenyl, C2-8 alkynyl, halogen, C2-7 acyl, benzoyl, hydroxyl, nitro, amino, phenyl or pyridyl;
A is oxygen, sulfur or NR9 in which R9 is hydrogen or C1-8 alkyl;
X is a C1-8 alkylene chain which is unsubstituted or substituted with C1-8 alkyl, C1-8 alkoxy or hydroxyl, and which has 0 or 1 double bonds;
Y is C(═O), C(═N—OR10), CH(OR11), CH═CH, C≡C, or C(═CH2) in which each of R10 and R11 is hydrogen or C1-8 alkyl;
each of R3, R4 and R5 is independently hydrogen, C1-8 alkyl, C1-8 haloalkyl, C1-8 alkoxy, C1-8 haloalkoxy, C2-8 alkenyl, C2-8 alkynyl, halogen, C2-7 acyl, benzoyl, hydroxyl, nitro, amino, phenyl, or pyridyl;
optionally wherein at least one of R3, R4, and R5 is not hydrogen;
B is CH or nitrogen;
Z is oxygen or sulfur;
each of R6 and R7 is independently hydrogen, C1-8 alkyl, or C1-8 haloalkyl;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(VII) of Formula (D);
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
each of R1 and R2 independently is a hydrogen, a halogen, nitro, C1-8 alkyl, C1-8 alkoxy, C1-8 haloalkyl having 1 to 3 halogens, C1-8 haloalkoxy having 1 to 3 halogens, C2-8 alkenyl, C2-8 alkynyl, 3-7 membered cycloalkyl, C1-8 alkyl substituted with 3-7 membered cycloalkyl, C6-10 aryl which is optionally substituted, arylalkyl group which has a C6-10 aryl moiety and C1-8 alkyl moiety, a heterocyclic group or a heterocyclic-alkyl group having a C1-8 alkyl group;
each occurrence of R3, R4, and R5 is independently a hydrogen or C1-8 alkyl;
A is an oxygen atom, a sulfur atom, or NR3;
each of X1, X2, and Z independently is C(═O), C(═O)NH, C(═N—OR4), CH(OR5), NH(C═O), NHSO2, SO2NH, CH═CH, C≡C, or a bond;
and
Y is C1-8 alkylene;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(VIII) of Formula (E):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
each of R11 and R12 independently is hydrogen, halogen, nitro, hydroxyl, amino, C1-8 alkyl, an C1-8 alkoxy, C1-8 haloalkyl group having 1 to 3 halogens, C1-8 haloalkoxy group having 1 to 3 halogens, C2-8 alkenyl, C2-8 alkynyl, a 3-7 membered cycloalkyl, C1-8 alkyl having a 3-7 membered cycloalkyl substituent, or phenyl, naphthyl, benzyl, phenethyl, pyridyl, thienyl, furyl, quinolyl, or benzothienyl group which optionally has a substituent which is a halogen atom, nitro, hydroxyl, amino, C1-8 alkyl, C1-8 alkoxy, C1-8 haloalkyl having 1 to 3 halogens, C1-8 haloalkoxy having 1 to 3 halogens, C2-8 alkenyl, C2-8 alkynyl, 3-7 membered cycloalkyl group, C1-8 alkyl group having a 3-7 membered cycloalkyl substituent, phenyl or pyridyl;
each of X1 and Z1 independently is C(═O), C(═O)NH, C(═N—OR14), CH(OR15), NH(C═O), NHSO2, SO2NH, CH═CH, C≡C, or a bond, wherein each of R14 and R15 is a hydrogen or C1-8 alkyl;
Y1 is C1-8 alkylene;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(IX) of Formula (F):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
A is O, S or NR7 in which R7 is hydrogen or C1-8 alkyl;
B1 is CW or N in which W is hydrogen or a bond;
B2 is O, S or NR8 in which R8 is hydrogen or C1-8 alkyl;
each of X1 and X2 is O, S, NH, NHC(═O), C(═O), C(═N—OR9), CH(OR10), C═C, C≡C or a bond wherein each of R9 and R10 is hydrogen or C1-8 alkyl;
Y is C1-8 alkylene, which is unsubstituted or substituted with C1-8 alkyl or C1-8 haloalkyl having 1-3 halogens;
Z is NH, O or S;
R1 is aryl, which is unsubstituted or substituted with C1-8 alkyl, C1-8 alkoxy, C1-8 haloalkyl having 1-3 halogens, hydroxyl, nitro, amino, phenyl, pyridyl or halogen, or a heterocyclic group having a five to eight membered ring comprising one to three hetero atoms each of which is independently nitrogen, oxygen or sulfur and the other atoms are carbon, optionally wherein a benzene ring is condensed with the heterocyclic ring;
R2 is C2-8 alkyl, C1-8 haloalkyl having with 1-3 halogens, C3-7 cycloalkyl, C2-8 alkenyl, C2-8 alkynyl, C1-4 alkyl substituted with aryl, which is unsubstituted or substituted with C1-8 alkyl, C1-8 alkoxy, C1-8 haloalkyl having 1-3 halogens, hydroxyl, nitro, amino, phenyl, pyridyl or halogen, or C1-4 alkyl substituted with a heterocyclic group having five to eight membered ring having one to three heteroatoms each of which is independently nitrogen, oxygen or sulfur;
R3 is halogen, trifluoromethyl, C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl;
each of R4 and R5 is hydrogen, C1-8 alkyl or C1-8 haloalkyl having 1-3 halogens;
each of Z and R3 is attached to the benzene ring, and X2 is not attached to the benzene ring;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(X) of Formula (G):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
each of R1 and R4, which are the same or different, is a hydrogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, halogen, C1-8 haloalkyl;
C1-8 haloalkoxy;
hydroxyl, nitro, C2-8 acyl group, C6-10 aryl, or a 5- or 6-membered heterocyclic group;
R2 is hydrogen;
R3 is C1-8 alkyl, or R3 is combined with R2 to form ═O or ═C(R7)(R8) in which each of R7 and R8 which are the same or different, is a hydrogen or C1-8 alkyl;
each of R5 and R6, which are the same or different, is a hydrogen atom, C1-8 alkyl, C1-8 haloalkyl;
X and Y are the same or different and each represents CH or N;
Z is oxygen or sulfur;
A is a 5-membered heterocyclic group which is pyrazole, thiophene, furan or pyrrole, wherein the heterocyclic group is unsubstituted or substituted with C1-8 alkyl having a substituent which is C1-8 alkyl, 3- to 7-membered cycloalkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, C1-8 alkyl group substituted with a 3- to 7-membered cycloalkyl group, C1-8 haloalkyl, C1-8 haloalkoxy, C6-10 aryl, 5- or 6-membered heterocyclic group, an aralkyl group having a C6-10 aryl moiety and a C1-8 alkylene moiety, or 5- or 6-membered heterocyclic group;
B is a C1-8 alkylene chain which is unsubstituted or substituted with C1-8 alkyl, 3- to 7-membered cycloalkyl group, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, halogen, C1-8 haloalkyl or C1-8 haloalkoxy, the alkylene group optionally having a double bond in the case that the alkylene group has 2 to 6 carbon atoms;
g is 0, 1, 2, 3, 4, or 5;
RX is CH2OH, COH, COOCH2CONRX4RX5 SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(XI) of Formula (H):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
each of R11 and R13, which are the same or different, is a hydrogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, halogen, C1-8 haloalkyl;
C1-8 haloalkoxy;
hydroxyl, nitro, C2-8 acyl group, C6-10 aryl, or a 5- or 6-membered heterocyclic group;
R12 is hydrogen, C1-8 alkyl, a 3- to 7-membered cycloalkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, C1-8 alkyl having a 3- to 7-membered cycloalkyl group substituent, C1-8 haloalkyl, C1-8 haloalkoxy, C6-10 aryl, a 5- or 6-membered heterocyclic group, an aralkyl group having a C6-10 aryl moiety and a C1-8 alkylene moiety, or a C1-8 alkyl group having a 5- or 6-membered heterocyclic substituent;
R14 and R15 are the same or different and each is a hydrogen atom, C1-8 alkyl, or C1-8 haloalkyl;
X1 is CH or N;
Z1 is oxygen or sulfur:
W1 is oxygen or CH2 when bond a is present and OH when bond a is absent;
g is 2, 3, or 4:
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(XII) of Formula (J):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
each of R21 and R23, which are the same or different, is a hydrogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, halogen, C1-8 haloalkyl;
C1-8 haloalkoxy;
hydroxyl, nitro, C2-8 acyl group, C6-10 aryl, or a 5- or 6-membered heterocyclic group;
R22 is hydrogen, C1-8 alkyl, a 3- to 7-membered cycloalkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, C1-8 alkyl having a 3- to 7-membered cycloalkyl group substituent, C1-8 haloalkyl, C1-8 haloalkoxy, C6-10 aryl, a 5- or 6-membered heterocyclic group, an aralkyl group having a C6-10 aryl moiety and a C1-8 alkylene moiety, or a C1-8 alkyl group having a 5- or 6-membered heterocyclic substituent;
R24 and R25 are the same or different and each is a hydrogen atom, C1-8 alkyl, or C1-8 haloalkyl;
X2 is CH or N;
Z2 is oxygen or sulfur;
W2 is oxygen or CH2 when bond a is present and OH when bond a is absent;
r is 2, 3, or 4;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(XIII) of Formula (K);
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
A is CH or nitrogen;
B, when bond a is present, is oxygen or C(R8)(R9) in which each of R8 and R9 is independently hydrogen or C1-8 alkyl;
B, when bond a is absent, is OH;
W1 is a bond, C(═O), or (C(R10)(R11)m in which each of R10 and R11 is independently a hydrogen or C1-8 alkyl group and m is 1, 2, or 3;
X and Y differ from each other, and each is an oxygen atom, a sulfur atom, a nitrogen atom, or CR12 in which R12 is a hydrogen or C1-8 alkyl;
Z1 is a bond, oxygen, sulfur, or C(R13)(R14) in which each of R13 and R14 is independently a hydrogen or C1-8 alkyl;
each of R1, R2, and R3, is independently a hydrogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, halogen, C1-8 haloalkyl;
C1-8 haloalkoxy;
hydroxyl, nitro, C2-8 acyl group, C6-10 aryl, or a 5- or 6-membered heterocyclic group;
each of R4 and R5 is independently hydrogen, C1-8 alkyl, C1-8 haloalkyl;
each of R6 and R7 is independently hydrogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, or C1-8 haloalkyl
r is 1, 2, 3, 4, or 5;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(XIV) of Formula (L):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
B, when bond a is present, is oxygen;
B, when bond a is absent, is OH;
W2 is a bond, C(═O), or CH2;
Z2 is oxygen or sulfur:
each of R21, R22, and R23 is independently a hydrogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, halogen, C1-8 haloalkyl;
C1-8 haloalkoxy;
hydroxyl, nitro, C2-8 acyl group, C6-10 aryl, or a 5- or 6-membered heterocyclic group;
each of R24 and R25 is independently hydrogen, C1-8 alkyl, C1-8 haloalkyl;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(XV) of Formula (M):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
each of W1 and W2 is independently nitrogen or CH;
X is nitrogen or CH;
Y is oxygen or sulfur;
Z is a bond, oxygen, sulfur or NR5, in which R5 is hydrogen or C1-8 alkyl;
each of R1 and R2 is independently hydrogen, halogen, hydroxyl, nitro, amino, C1-8 alkyl, 3- to 7-membered cycloalkyl group, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, C1-8 alkyl having a 3- to 7-membered cycloalkyl substituent, C1-8 haloalkyl, C1-8 haloalkoxy, C6-10 aryl, 5- or 6-membered heterocyclic group, an aralkyl group having C6-10 aryl moiety and a C1-8 alkylene, or C1-8 alkyl having a 5- or 6-membered heterocyclic substituent;
each of R3 and R4 is independently hydrogen, C1-8 alkyl, or C1-8 haloalkyl;
A is a 5-membered heterocycle which is pyrazole, thiophene, furan, isoxazole, isothiazole or pyrrole, in which the 5-membered heterocycle is unsubstituted or substituted with halogen, hydroxyl, nitro, amino, C1-8 alkyl, 3- to 7-membered cycloalkyl group, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, C1-8 alkyl having a 3- to 7-membered cycloalkyl substituent, C1-8 haloalkyl, C1-8 haloalkoxy, C6-10 aryl, a 5- or 6-membered heterocyclic group, an aralkyl group having a C6-10 aryl moiety and C1-8 alkylene moiety, or C1-8 alkyl group having a 5- or 6-membered heterocyclic substituent;
B is a bond or C1-8 alkylene which is unsubstituted or substituted with C1-8 alkyl, 3- to 7-membered cycloalkyl, C1-8 alkoxy or a halogen substituent, optionally wherein the C1-8 alkylene has a double or triple bond;
r is 0, 1, 2, or 3;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(XVI) of Formula (N):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
W3 is nitrogen or CH;
Z1 is oxygen or sulfur;
each of R11 and R12 is independently hydrogen, halogen, hydroxyl, nitro, amino, C1-8 alkyl, C1-8 alkoxy, C1-8 haloalkyl, or C1-8 haloalkoxy′
each of R13 and R14 is independently hydrogen or C1-8 alkyl;
A1 is a 5-membered heterocycle which is pyrazole or thiophene, in which the 5-membered heterocycle is unsubstituted or substituted with halogen, hydroxyl, nitro, amino, C1-8 alkyl, C1-8 alkoxy, C1-8 haloalkyl, or C1-8 haloalkoxy;
m is 2, 3, or 4;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(XVII) of Formula (O):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
each of W1 and W2 independently is CH or nitrogen;
X is NR5 or CR6R7;
wherein R5 is hydrogen, C1-8 alkyl, C1-8 haloalkyl, C1-8 alkyl substituted with C1-8 alkoxy, C3-7 cycloalkyl, C1-8 alkyl substituted with C3-7 cycloalkyl, C1-8 alkyl substituted with phenyl, C2-8 acyl, or C2-8 alkenyl, and each of R6 and R7 independently is hydrogen or C1-8 alkyl;
Y is (CR8R9)r, wherein each of R8 and R9 independently is hydrogen or C1-8 alkyl, and r is 1, 2, 3, or 4;
or
X and Y are combined to form CR10═CR11 or ethynylene, wherein each of R10 and R11 independently is hydrogen or C1-8 alkyl;
G, when bond a is present, is O, S or CR12R13, wherein each of R12 and R13 independently is hydrogen or C1-8 alkyl;
G, when bond a is absent, is OH;
A is a five-membered heterocyclic ring which is thiazole, oxazole, imidazole, pyrazole, thiophene, furan, or pyrrole, wherein the heterocyclic ring is unsubstituted or substituted with C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, halogen, C1-8 haloalkyl, C1-8 haloalkoxy, hydroxyl, nitro, C2-8 acyl, C6-10 aryl, or a five-membered or six-membered heterocyclic group;
B is a C1-8 alkylene, C2-8 alkenylene or C2-8 alkynylene chain, wherein the chain is unsubstituted or substituted with C1-8 alkyl, C3-7 cycloalkyl, C1-8 alkoxy, or halogen;
each of R1 and R2 independently is hydrogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, halogen, C1-8 haloalkyl, C1-8 haloalkoxy, hydroxyl, nitro, C2-8 acyl, C6-10 aryl, or a five-membered or six-membered heterocyclic group;
each of R3 and R4 independently is hydrogen or C1-8 alkyl;
m is 0, 1, 2, or 3;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(XVIII) of Formula (P);
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
Ga, when bond a is present, is O, S or CH2;
Ga, when bond a is absent, is OH;
Aa is five-membered heterocyclic ring which is thiazole, oxazole, or thiophene, wherein the five-membered heterocyclic ring is unsubstituted or is substituted with C1-8 alkyl, C1-8 alkoxy, halogen, C1-8 haloalkyl, C1-8 haloalkoxy, hydroxyl, nitro, or C2-8 acyl;
Ba is a C1-8 alkylene or C2-8 alkenylene chain;
each of R1a and R2a independently is hydrogen, C1-8 alkyl, C1-8 alkoxy, halogen, C1-8 haloalkyl, C1-8 haloalkoxy, hydroxyl, nitro, or C2-8 acyl;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(XIX) of Formula (Q);
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
Gb, when bond a is present, is O, S or CH2;
Gb, when bond a is absent, is OH;
Ab is five-membered heterocyclic ring which is thiazole, oxazole, or thiophene, wherein the five-membered heterocyclic ring is unsubstituted or is substituted with C1-8 alkyl, C1-8 alkoxy halogen, C1-8 haloalkyl, C1-8 haloalkoxy, hydroxyl, nitro, or C2-8 acyl;
Bb is a C1-8 alkylene or C2-8 alkenylene chain;
each of R1b and R2b independently is hydrogen, C1-8 alkyl, C1-8 alkoxy, halogen, C1-8 haloalkyl, C1-8 haloalkoxy, hydroxyl, nitro, or C2-8 acyl;
R3b is hydrogen or C1-8 alkyl;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(XX) of Formula (R):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
each of W1 and W2 is independently CH or N;
X is NR3 or CR4R5, in which R3 is C1-8 alkyl, C1-8 haloalkyl, C1-8 alkyl substituted with C1-8 alkoxy, C1-8 alkyl substituted with a 3-7 membered cycloalkyl, C1-8 alkyl substituted with a phenyl group, C2-8 acyl, or C2-8 alkenyl;
each of R4 and R5 is independently hydrogen or C1-8 alkyl;
Y is (CR6R7)r, in which each of R6 and R7 is independently hydrogen or C1-8 alkyl and r is 1, 2, 3, or 4;
A is a 5 or 6-membered heterocyclic group which is thiazole, oxazole, imidazole, pyrazole, thiophene, furan, pyrrole, pyridine or pyrimidine, or a phenyl group, wherein the 5 or 6-membered heterocyclic group or phenyl group is unsubstituted or substituted with C1-8 alkyl, 3-7 membered cycloalkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxyl, C1-8 alkyl group substituted with a 3-7 membered cycloalkyl group, C1-8 haloalkyl, C1-8 haloalkoxy, C6-10 aryl, a 5 or 6-membered heterocyclic group, aralkyl group comprising a C6-10 aryl group and a C1-8 alkyl group, or C1-8 alkyl group substituted with a 5 or 6-membered heterocyclic group;
B is a bond or C1-8 alkylene which is unsubstituted or substituted with C1-8 alkyl, a 3-7 membered cycloalkyl group, C1-8 alkoxy or a halogen, and which may have a double bond or triple bond when the carbon number of the alkylene chain is 2 or more;
D is N or CH;
E is O or S;
each of R1 and R2 is independently H, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, halogen, C1-8 haloalkyl, C1-8 haloalkoxy, nitro, C2-8 acyl, C6-10 aryl, or a 5 or 6-membered heterocyclic group;
m 0, 1, 2, or 3;
RX is CH2OH, COH, COOCH2CONRX4RX5 SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(XXI) of Formula(S):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
A1 is a 5 or 6-membered heterocyclic group which is thiazole, oxazole, pyridine or pyrimidine, or a phenyl group, wherein the 5 or 6-membered heterocyclic group or phenyl group is unsubstituted or substituted with C1-8 alkyl or C1-8 haloalkyl;
B1 is C2-4 alkylene;
each of R11 and R12 is independently H, C1-8 alkyl, halogen, or C1-8 haloalkyl;
R13 is C1-8 alkyl or C1-8 haloalkyl, optionally wherein the N to which R13 is attached is attached to the 6th position of benzisoxazole;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(XXII) of Formula (T):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
B2 is C2-4 alkylene;
R20 is C1-8 alkyl;
each of R21 and R22 is independently H, C1-8 alkyl, halogen, or C1-8 haloalkyl;
R23 is C1-8 alkyl or C1-8 haloalkyl, optionally wherein the N to which R23 is attached is attached to the 6th position of benzisoxazole;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(XXIII) of Formula (U);
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
R1 is hydrogen, halogen, hydroxyl, nitro, amino, cyano, carboxyl, C1-8 alkyl, C3-7 cycloalkyl, C2-C8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, C1-8 alkyl having a 3- to 7-membered cycloalkyl substituent, C1-8 haloalkyl, C1-8 alkyl having a C1-8 alkoxy substituent, C1-8 haloalkoxy, C2-8 acyl, C6-10 aryl group, a 5- or 6-membered heterocyclic group, an aralkyl group having a C6-10 aryl moiety and a C1-8 alkylene moiety, or a C1-8 alkyl group having a 5- or 6-membered heterocyclic substituent;
R2 is hydrogen, C1-8 alkyl, C2-8 alkenyl, C1-8 alkyl having a 3- to 7-membered cycloalkyl substituent, C1-8 haloalkyl, C1-8 alkyl group having a C1-8 alkoxy substituent, C2-8 acyl, C6-10 aryl, or an aralkyl group having a C6-10 aryl moiety and a C1-8 alkylene moiety;
each of R3, R4, R5 and R6 independently is hydrogen, C1-8 alkyl, or C1-8 haloalkyl;
X is oxygen, sulfur or NR7;
where R7 is hydrogen, C1-8 alkyl, C1-8 haloalkyl, an aralkyl group having a C6-10 aryl moiety and a C1-8 alkylene moiety, C2-8 acyl, or C2-8 alkenyl;
Y is oxygen, sulfur, NR8 or a bond, where R8 is hydrogen, C1-8 alkyl, C1-8 haloalkyl, C2-8 acyl, or C2-8 alkenyl;
p is 0 or 1;
A, when bond a is present, is oxygen CH2, N—NH2 or N—OR9, where R9 is hydrogen, C1-8 alkyl, C1-8 haloalkyl, C2-8 acyl, C2-8 alkenyl, or an aralkyl group having a C6-10 aryl moiety and a C1-8 alkylene moiety;
A, when bond a is absent, is OH;
B is, in the case of p=1, a benzene ring having or not having a substituent which is halogen, hydroxyl, nitro, amino, C1-8 alkyl, C3-7 cycloalkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, C1-8 alkyl having a 3- to 7-membered cycloalkyl substituent, C1-8 haloalkyl, C1-8 alkyl having a C1-8 alkoxy substituent, C1-8 haloalkoxy, C2-8 acyl, C6-10 aryl group, or an aralkyl group having a C6-10 aryl moiety and a C1-C8 alkylene moiety of 1-8 carbon atoms, and, in the case of p=0, a condensed ring which is indole, benzofuran, benzisoxazole or 1,2-benzisothiazole, in which said condensed ring has or does not have a substituent which is
halogen, hydroxyl, nitro, amino, C1-8 alkyl group, C3-7 cycloalkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, C1-8 alkyl having a 3- to 7-membered cycloalkyl substituent, C1-8 haloalkyl, C1-8 alkyl having a C1-C8 alkoxy substituent, C1-8 haloalkoxy group, C2-8 acyl, C6-10 aryl, or an aralkyl group having a C6-10 aryl moiety and a C1-8 alkylene moiety;
Y is bonded to the benzene ring of B;
(C(R3)(R4)m is bonded to the condensed ring of B at its 3-position;
m is an integer of 1 to 4;
n is 0, 1, 2, 3, 4, or 5;
Y is a bond in the case of n=0;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
and
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
(XXIV) of Formula (V):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
R11 is hydrogen, halogen, hydroxyl, nitro, amino, cyano, carboxyl, C1-8 alkyl, C3-7 cycloalkyl, C2-C8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, C1-8 alkyl having a 3- to 7-membered cycloalkyl substituent, C1-8 haloalkyl, C1-8 alkyl having a C1-8 alkoxy substituent, C1-8 haloalkoxy, C2-8 acyl, C6-10 aryl group, a 5- or 6-membered heterocyclic group, an aralkyl group having a C6-10 aryl moiety and a C1-8 alkylene moiety, or a C1-8 alkyl group having a 5- or 6-membered heterocyclic substituent;
R12 is hydrogen, C1-8 alkyl, C2-8 alkenyl, C1-8 alkyl having a 3- to 7-membered cycloalkyl substituent, C1-8 haloalkyl, C1-8 alkyl group having a C1-8 alkoxy substituent, C2-8 acyl, C6-10 aryl, or an aralkyl group having a C6-10 aryl moiety and a C1-8 alkylene moiety;
each of R13, R14, R15 and R16 independently is hydrogen, C1-8 alkyl, or C1-8 haloalkyl;
Y1 is oxygen, sulfur, NR18 or a bond, where R18 is hydrogen, C1-8 alkyl, C1-8 haloalkyl, C2-8 acyl, or C2-8 alkenyl;
A1, when bond a is present, is oxygen CH2, N—NH2 or N—OR19, where R19 is hydrogen, C1-8 alkyl, C1-8 haloalkyl, C2-8 acyl, C2-8 alkenyl, or an aralkyl group having a C6-10 aryl moiety and a C1-8 alkylene moiety;
A1, when bond a is absent, is OH;
Q1 is hydrogen, halogen, hydroxyl, nitro, amino, C1-8 alkyl group, C3-7 cycloalkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, C1-8 alkyl having a 3- to 7-membered cycloalkyl substituent, C1-8 haloalkyl, C1-8 alkyl having a C1-8 alkoxy substituent, C1-8 haloalkoxy, C2-8 acyl, C6-10 aryl, or an aralkyl group having a C6-10 aryl moiety and a C1-8 alkylene moiety;
r is 1, 2, 3, or 4;
s is 1, 2, 3, 4, or 5;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
(XXV) of Formula (W):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
R21 is hydrogen, halogen, hydroxyl, nitro, amino, cyano, carboxyl, C1-8 alkyl, C3-7 cycloalkyl, C2-C8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, C1-8 alkyl having a 3- to 7-membered cycloalkyl substituent, C1-8 haloalkyl, C1-8 alkyl having a C1-8 alkoxy substituent, C1-8 haloalkoxy, C2-8 acyl, C6-10 aryl group, a 5- or 6-membered heterocyclic group, an aralkyl group having a C6-10 aryl moiety and a C1-8 alkylene moiety, or a C1-8 alkyl group having a 5- or 6-membered heterocyclic substituent;
R22 is hydrogen, C1-8 alkyl, C2-8 alkenyl, C1-8 alkyl having a 3- to 7-membered cycloalkyl substituent, C1-8 haloalkyl, C1-8 alkyl group having a C1-8 alkoxy substituent, C2-8 acyl, C6-10 aryl, or an aralkyl group having a C6-10 aryl moiety and a C1-8 alkylene moiety;
each of R23, R24, R25 and R26 independently is hydrogen, C1-8 alkyl, or C1-8 haloalkyl;
Y2 is oxygen, sulfur, NR28 or a bond, where R28 is hydrogen, C1-8 alkyl, C1-8 haloalkyl, C2-8 acyl, or C2-8 alkenyl;
Q2 is hydrogen, halogen, hydroxyl, nitro, amino, C1-8 alkyl group, C3-7 cycloalkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, C1-8 alkyl having a 3- to 7-membered cycloalkyl substituent, C1-8 haloalkyl, C1-8 alkyl having a C1-8 alkoxy substituent, C1-8 haloalkoxy, C2-8 acyl, C6-10 aryl, or an aralkyl group having a C6-10 aryl moiety and a C1-8 alkylene moiety;
t is 1, 2, 3, or 4;
u is 1, 2, 3, 4, or 5;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
(XXVI) of Formula (X):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
R1 is hydrogen, halogen, C1-4 alkyl, C1-4 haloalkyl, CN, C1-4 alkoxy, C1-4 haloalkoxy, or C3-6 cycloalkyl;
Q1 is CH or N;
R2 is hydrogen, halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C3-6 cycloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, S(C1-4 alkyl), SO2(C1-4-alkyl), 5- or 6-membered heterocycle, aryl, 5-membered heteroaryl, C≡C—R2A, O(CH2)m R2B, NH(C1-4 alkyl), N(C1-4 alkyl)2, or C(O)(C1-4 alkyl), wherein aryl and heteroaryl are unsubstituted or substituted with halogen, OH, CN, C1-4 alkyl, formyl, acetyl, acetoxy, or carboxy, and wherein m is 1, 2, or 3;
x is 1 or 2;
R2A and R2B are each independently C1-4 alkyl, C1-4 haloalkyl, or C3-6 cycloalkyl;
each R20 is independently hydrogen, halogen, C1-4 alkyl, CN, or C1-4 alkoxy;
R3 is CH3 or CD3,
RX is CH2OH, COH, COOCH2CONRX4RX5 SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
and
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
(XXVII) of Formula (Y):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
R1 is hydrogen, halogen, C1-4 alkyl, C1-4 haloalkyl, CN, C1-4 alkoxy, C1-4 haloalkoxy, or C3-6 cycloalkyl;
Q1 is CH or N;
R2 is hydrogen, halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C3-6 cycloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, S(C1-4 alkyl), SO2(C1-4-alkyl), 5- or 6-membered heterocycle, aryl, 5-membered heteroaryl, C≡C—R2A, O(CH2)mR2B, NH(C1-4 alkyl), N(C1-4 alkyl)2, or C(O)(C1-4 alkyl), wherein aryl and heteroaryl are unsubstituted or substituted with halogen, OH, CN, C1-4 alkyl, formyl, acetyl, acetoxy, or carboxy, and wherein m is 1, 2, or 3;
x is 1 or 2;
R2A and R2B are each independently C1-4 alkyl, C1-4 haloalkyl, or C3-6 cycloalkyl;
each R20 is independently hydrogen, halogen, C1-4 alkyl, CN, or C1-4 alkoxy;
R3 is CH3 or CD3;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
and
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
(XXVIII) of Formula (Z);
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
R1 is hydrogen, halogen, C1-4 alkyl, C1-4 haloalkyl, CN, C1-4 alkoxy, C1-4 haloalkoxy, or C3-6 cycloalkyl;
Q1 is CH or N;
R2 is hydrogen, halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C3-6 cycloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, S(C1-4 alkyl), SO2 (C1-4-alkyl), 5- or 6-membered heterocycle, ryl, 5-membered heteroaryl, C≡C—R2A, O(CH2)mR2B, NH(C1-4 alkyl), N(C1-4 alkyl) 2, or C(O)(C1-4 alkyl), wherein aryl and heteroaryl are unsubstituted or substituted with halogen, OH, CN, C1-4 alkyl, formyl, acetyl, acetoxy, or carboxy, and wherein m is 1, 2, or 3;
x is 1 or 2;
R2A and R2B are each independently C1-4 alkyl, C1-4 haloalkyl, or C3-6 cycloalkyl;
each R20 is independently hydrogen, halogen, C1-4 alkyl, CN, or C1-4 alkoxy;
R3 is CH3 or CD3;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
and
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
(XXIX) of Formula (AA):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
L is (CH2)5, which is unsubstituted or substituted by one methyl group;
R1 is hydrogen, halogen, C1-4 alkyl, C1-4 haloalkyl, CN, C1-4 alkoxy, C1-4 haloalkoxy, or C3-6 cycloalkyl;
R2 is hydrogen, halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C3-6 cycloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, S(C1-4 alkyl), SO2(C1-4-alkyl), 5- or 6-membered heterocycle, aryl, 5-membered heteroaryl, C≡C—R2A, O(CH2)mR2B, NH(C1-4 alkyl), N(C1-4 alkyl)2, or C(O)(C1-4 alkyl), wherein aryl and heteroaryl are unsubstituted or substituted with halogen, OH, CN, C1-4 alkyl, formyl, acetyl, acetoxy, or carboxy, and wherein m is 1, 2, or 3;
x is 0 or 1;
R2A and R2B are each independently C1-4 alkyl, C1-4 haloalkyl, or C3-6 cycloalkyl;
R3 is C1-4 haloalkyl, NO2, CN, halogen, or C(O)O(C1-4 alkyl);
R20 is hydrogen, halogen, C1-4 alkyl, CN, or C1-4 alkoxy;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
and
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
(XXX) having the structure:
or pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof;
(XXXI) having the structure:
or pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof;
(XXXII) having the structure:
or pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof;
(XXXIII) having the structure
or pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof;
(XXXIV) having the structure
or pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof;
(XXXV) having the structure
or pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof;
or
(XXXVI) having the structure
or pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof.

420 more elements

Dependencies are inferred from the claim text.

Facts

Application: 19/175,821Filed 10 Apr 2025
Priority: 26 Sep 2019
Published: 30 Oct 2025
Term ends: Not estimatedThe source records don’t support an estimate.

Classification20 codes

C07C 323/19
Having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton: with…
A61P 3/06
Drugs for disorders of the metabolism: antihyperlipidemics
A61P 3/10
For glucose homeostasis: for hyperglycaemia, e.g. antidiabetics
A61P 13/12
Drugs for disorders of the urinary system: of the kidneys

Family

Application62/906,288Us provisional application · filed 26 Sep 2019
Application17/195,334Continuation in part · filed 8 Mar 2021
Application17/219,058Division · filed 31 Mar 2021
Application18/179,622Division · filed 7 Mar 2023
Application19/175,821Division
Application17/219,058Continuation in part
US 11,634,387 B2Related patent
US 12,297,168 B2Related patent
US 2021/0300890 A1Published application
US 2022/0363632 A1Published application
US 2023/0278952 A1Published application
US 2025/0333379 A1This patent

From the US filing history. Foreign family members aren’t listed.

Timeline

Citations

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Abstract

A compound:

(I) of Formula (A)
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
each R1 and R2 is independently —C1-C6 alkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, phenyl, or benzyl;
or
alternatively, R1 and R2 together with the carbon atom to which R1 and R2 are attached form a C3-C7 cycloalkyl group;
X is —CH2OH, —COOH, —COH, —COOR3, —COOCH2CONR4R5, —SO3H,
R3 is —C1-C6 alkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, phenyl, or benzyl;
each R4 and R5 is independently alkyl, aryl, or heteroaryl;
or alternatively, R4 and R5 together with the carbon atom to which R4 and R5 are attached form a heterocycle;
each R6 and R7 is independently H, —C1-C6 alkyl, —C2-C6 alkenyl, or —C2-C6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(II) of Formula (B):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
each R1 and R2 is independently —C1-C6 alkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, phenyl, or benzyl;
or alternatively, R1 and R2 together with the carbon atom to which R1 and R2 are attached form a C3-C7 cycloalkyl group;
X is —CH2OH, —COH, —COOCH2CONR4R5, —SO3H,
R3 is —C1-C6 alkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, phenyl, or benzyl;
each R4 and R5 is independently alkyl, aryl, or heteroaryl;
or alternatively, R4 and R5 together with the carbon atom to which R4 and R5 are attached form a heterocycle;
each R6 and R7 is independently H, —C1-C6 alkyl, —C2-C6 alkenyl, or —C2-C6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(III) having the structure:
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof;
(IV) having the structure:
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof;
(V) having the structure:
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof;
(VI) of Formula (C):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
R1 is phenyl, naphthyl, pyridyl, thienyl, furyl, quinolyl or benzothienyl, any of which is unsubstituted or substituted with C1-8 alkyl, C1-8 haloalkyl, C1-8 alkoxy, C1-8 haloalkoxy, C2-8 alkenyl, C2-8 alkynyl, halogen, C2-7 acyl, benzoyl, hydroxyl, nitro, amino, phenyl or pyridyl;
R2 is C2-8 alkyl, C1-8 haloalkyl, C2-8 alkenyl, C2-8 alkynyl, 3-7 membered cycloalkyl, C1-8 alkyl substituted with a 3-7 membered cycloalkyl, or C1-6 alkyl substituted with phenyl, naphthyl or pyridyl, any of which is unsubstituted or substituted with C1-8 alkyl, C1-8 haloalkyl, C1-8 alkoxy, C1-8 haloalkoxy, C2-8 alkenyl, C2-8 alkynyl, halogen, C2-7 acyl, benzoyl, hydroxyl, nitro, amino, phenyl or pyridyl;
A is oxygen, sulfur or NR9 in which R9 is hydrogen or C1-8 alkyl;
X is a C1-8 alkylene chain which is unsubstituted or substituted with C1-8 alkyl, C1-8 alkoxy or hydroxyl, and which has 0 or 1 double bonds;
Y is C(═O), C(═N—OR10), CH(OR11), CH═CH, C≡C, or C(═CH2) in which each of R10 and R11 is hydrogen or C1-8 alkyl;
each of R3, R4 and R5 is independently hydrogen, C1-8 alkyl, C1-8 haloalkyl, C1-8 alkoxy, C1-8 haloalkoxy, C2-8 alkenyl, C2-8 alkynyl, halogen, C2-7 acyl, benzoyl, hydroxyl, nitro, amino, phenyl, or pyridyl;
optionally wherein at least one of R3, R4, and R5 is not hydrogen;
B is CH or nitrogen;
Z is oxygen or sulfur;
each of R6 and R7 is independently hydrogen, C1-8 alkyl, or C1-8 haloalkyl;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(VII) of Formula (D);
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
each of R1 and R2 independently is a hydrogen, a halogen, nitro, C1-8 alkyl, C1-8 alkoxy, C1-8 haloalkyl having 1 to 3 halogens, C1-8 haloalkoxy having 1 to 3 halogens, C2-8 alkenyl, C2-8 alkynyl, 3-7 membered cycloalkyl, C1-8 alkyl substituted with 3-7 membered cycloalkyl, C6-10 aryl which is optionally substituted, arylalkyl group which has a C6-10 aryl moiety and C1-8 alkyl moiety, a heterocyclic group or a heterocyclic-alkyl group having a C1-8 alkyl group;
each occurrence of R3, R4, and R5 is independently a hydrogen or C1-8 alkyl;
A is an oxygen atom, a sulfur atom, or NR3;
each of X1, X2, and Z independently is C(═O), C(═O)NH, C(═N—OR4), CH(OR5), NH(C═O), NHSO2, SO2NH, CH═CH, C≡C, or a bond;
and
Y is C1-8 alkylene;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(VIII) of Formula (E):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
each of R11 and R12 independently is hydrogen, halogen, nitro, hydroxyl, amino, C1-8 alkyl, an C1-8 alkoxy, C1-8 haloalkyl group having 1 to 3 halogens, C1-8 haloalkoxy group having 1 to 3 halogens, C2-8 alkenyl, C2-8 alkynyl, a 3-7 membered cycloalkyl, C1-8 alkyl having a 3-7 membered cycloalkyl substituent, or phenyl, naphthyl, benzyl, phenethyl, pyridyl, thienyl, furyl, quinolyl, or benzothienyl group which optionally has a substituent which is a halogen atom, nitro, hydroxyl, amino, C1-8 alkyl, C1-8 alkoxy, C1-8 haloalkyl having 1 to 3 halogens, C1-8 haloalkoxy having 1 to 3 halogens, C2-8 alkenyl, C2-8 alkynyl, 3-7 membered cycloalkyl group, C1-8 alkyl group having a 3-7 membered cycloalkyl substituent, phenyl or pyridyl;
each of X1 and Z1 independently is C(═O), C(═O)NH, C(═N—OR14), CH(OR15), NH(C═O), NHSO2, SO2NH, CH═CH, C≡C, or a bond, wherein each of R14 and R15 is a hydrogen or C1-8 alkyl;
Y1 is C1-8 alkylene;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(IX) of Formula (F):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
A is O, S or NR7 in which R7 is hydrogen or C1-8 alkyl;
B1 is CW or N in which W is hydrogen or a bond;
B2 is O, S or NR8 in which R8 is hydrogen or C1-8 alkyl;
each of X1 and X2 is O, S, NH, NHC(═O), C(═O), C(═N—OR9), CH(OR10), C═C, C≡C or a bond wherein each of R9 and R10 is hydrogen or C1-8 alkyl;
Y is C1-8 alkylene, which is unsubstituted or substituted with C1-8 alkyl or C1-8 haloalkyl having 1-3 halogens;
Z is NH, O or S;
R1 is aryl, which is unsubstituted or substituted with C1-8 alkyl, C1-8 alkoxy, C1-8 haloalkyl having 1-3 halogens, hydroxyl, nitro, amino, phenyl, pyridyl or halogen, or a heterocyclic group having a five to eight membered ring comprising one to three hetero atoms each of which is independently nitrogen, oxygen or sulfur and the other atoms are carbon, optionally wherein a benzene ring is condensed with the heterocyclic ring;
R2 is C2-8 alkyl, C1-8 haloalkyl having with 1-3 halogens, C3-7 cycloalkyl, C2-8 alkenyl, C2-8 alkynyl, C1-4 alkyl substituted with aryl, which is unsubstituted or substituted with C1-8 alkyl, C1-8 alkoxy, C1-8 haloalkyl having 1-3 halogens, hydroxyl, nitro, amino, phenyl, pyridyl or halogen, or C1-4 alkyl substituted with a heterocyclic group having five to eight membered ring having one to three heteroatoms each of which is independently nitrogen, oxygen or sulfur;
R3 is halogen, trifluoromethyl, C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl;
each of R4 and R5 is hydrogen, C1-8 alkyl or C1-8 haloalkyl having 1-3 halogens;
each of Z and R3 is attached to the benzene ring, and X2 is not attached to the benzene ring;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(X) of Formula (G):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
each of R1 and R4, which are the same or different, is a hydrogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, halogen, C1-8 haloalkyl;
C1-8 haloalkoxy;
hydroxyl, nitro, C2-8 acyl group, C6-10 aryl, or a 5- or 6-membered heterocyclic group;
R2 is hydrogen;
R3 is C1-8 alkyl, or R3 is combined with R2 to form ═O or ═C(R7)(R8) in which each of R7 and R8 which are the same or different, is a hydrogen or C1-8 alkyl;
each of R5 and R6, which are the same or different, is a hydrogen atom, C1-8 alkyl, C1-8 haloalkyl;
X and Y are the same or different and each represents CH or N;
Z is oxygen or sulfur;
A is a 5-membered heterocyclic group which is pyrazole, thiophene, furan or pyrrole, wherein the heterocyclic group is unsubstituted or substituted with C1-8 alkyl having a substituent which is C1-8 alkyl, 3- to 7-membered cycloalkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, C1-8 alkyl group substituted with a 3- to 7-membered cycloalkyl group, C1-8 haloalkyl, C1-8 haloalkoxy, C6-10 aryl, 5- or 6-membered heterocyclic group, an aralkyl group having a C6-10 aryl moiety and a C1-8 alkylene moiety, or 5- or 6-membered heterocyclic group;
B is a C1-8 alkylene chain which is unsubstituted or substituted with C1-8 alkyl, 3- to 7-membered cycloalkyl group, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, halogen, C1-8 haloalkyl or C1-8 haloalkoxy, the alkylene group optionally having a double bond in the case that the alkylene group has 2 to 6 carbon atoms;
g is 0, 1, 2, 3, 4, or 5;
RX is CH2OH, COH, COOCH2CONRX4RX5 SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(XI) of Formula (H):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
each of R11 and R13, which are the same or different, is a hydrogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, halogen, C1-8 haloalkyl;
C1-8 haloalkoxy;
hydroxyl, nitro, C2-8 acyl group, C6-10 aryl, or a 5- or 6-membered heterocyclic group;
R12 is hydrogen, C1-8 alkyl, a 3- to 7-membered cycloalkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, C1-8 alkyl having a 3- to 7-membered cycloalkyl group substituent, C1-8 haloalkyl, C1-8 haloalkoxy, C6-10 aryl, a 5- or 6-membered heterocyclic group, an aralkyl group having a C6-10 aryl moiety and a C1-8 alkylene moiety, or a C1-8 alkyl group having a 5- or 6-membered heterocyclic substituent;
R14 and R15 are the same or different and each is a hydrogen atom, C1-8 alkyl, or C1-8 haloalkyl;
X1 is CH or N;
Z1 is oxygen or sulfur:
W1 is oxygen or CH2 when bond a is present and OH when bond a is absent;
g is 2, 3, or 4:
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(XII) of Formula (J):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
each of R21 and R23, which are the same or different, is a hydrogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, halogen, C1-8 haloalkyl;
C1-8 haloalkoxy;
hydroxyl, nitro, C2-8 acyl group, C6-10 aryl, or a 5- or 6-membered heterocyclic group;
R22 is hydrogen, C1-8 alkyl, a 3- to 7-membered cycloalkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, C1-8 alkyl having a 3- to 7-membered cycloalkyl group substituent, C1-8 haloalkyl, C1-8 haloalkoxy, C6-10 aryl, a 5- or 6-membered heterocyclic group, an aralkyl group having a C6-10 aryl moiety and a C1-8 alkylene moiety, or a C1-8 alkyl group having a 5- or 6-membered heterocyclic substituent;
R24 and R25 are the same or different and each is a hydrogen atom, C1-8 alkyl, or C1-8 haloalkyl;
X2 is CH or N;
Z2 is oxygen or sulfur;
W2 is oxygen or CH2 when bond a is present and OH when bond a is absent;
r is 2, 3, or 4;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(XIII) of Formula (K);
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
A is CH or nitrogen;
B, when bond a is present, is oxygen or C(R8)(R9) in which each of R8 and R9 is independently hydrogen or C1-8 alkyl;
B, when bond a is absent, is OH;
W1 is a bond, C(═O), or (C(R10)(R11)m in which each of R10 and R11 is independently a hydrogen or C1-8 alkyl group and m is 1, 2, or 3;
X and Y differ from each other, and each is an oxygen atom, a sulfur atom, a nitrogen atom, or CR12 in which R12 is a hydrogen or C1-8 alkyl;
Z1 is a bond, oxygen, sulfur, or C(R13)(R14) in which each of R13 and R14 is independently a hydrogen or C1-8 alkyl;
each of R1, R2, and R3, is independently a hydrogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, halogen, C1-8 haloalkyl;
C1-8 haloalkoxy;
hydroxyl, nitro, C2-8 acyl group, C6-10 aryl, or a 5- or 6-membered heterocyclic group;
each of R4 and R5 is independently hydrogen, C1-8 alkyl, C1-8 haloalkyl;
each of R6 and R7 is independently hydrogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, or C1-8 haloalkyl
r is 1, 2, 3, 4, or 5;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(XIV) of Formula (L):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
B, when bond a is present, is oxygen;
B, when bond a is absent, is OH;
W2 is a bond, C(═O), or CH2;
Z2 is oxygen or sulfur:
each of R21, R22, and R23 is independently a hydrogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, halogen, C1-8 haloalkyl;
C1-8 haloalkoxy;
hydroxyl, nitro, C2-8 acyl group, C6-10 aryl, or a 5- or 6-membered heterocyclic group;
each of R24 and R25 is independently hydrogen, C1-8 alkyl, C1-8 haloalkyl;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(XV) of Formula (M):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
each of W1 and W2 is independently nitrogen or CH;
X is nitrogen or CH;
Y is oxygen or sulfur;
Z is a bond, oxygen, sulfur or NR5, in which R5 is hydrogen or C1-8 alkyl;
each of R1 and R2 is independently hydrogen, halogen, hydroxyl, nitro, amino, C1-8 alkyl, 3- to 7-membered cycloalkyl group, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, C1-8 alkyl having a 3- to 7-membered cycloalkyl substituent, C1-8 haloalkyl, C1-8 haloalkoxy, C6-10 aryl, 5- or 6-membered heterocyclic group, an aralkyl group having C6-10 aryl moiety and a C1-8 alkylene, or C1-8 alkyl having a 5- or 6-membered heterocyclic substituent;
each of R3 and R4 is independently hydrogen, C1-8 alkyl, or C1-8 haloalkyl;
A is a 5-membered heterocycle which is pyrazole, thiophene, furan, isoxazole, isothiazole or pyrrole, in which the 5-membered heterocycle is unsubstituted or substituted with halogen, hydroxyl, nitro, amino, C1-8 alkyl, 3- to 7-membered cycloalkyl group, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, C1-8 alkyl having a 3- to 7-membered cycloalkyl substituent, C1-8 haloalkyl, C1-8 haloalkoxy, C6-10 aryl, a 5- or 6-membered heterocyclic group, an aralkyl group having a C6-10 aryl moiety and C1-8 alkylene moiety, or C1-8 alkyl group having a 5- or 6-membered heterocyclic substituent;
B is a bond or C1-8 alkylene which is unsubstituted or substituted with C1-8 alkyl, 3- to 7-membered cycloalkyl, C1-8 alkoxy or a halogen substituent, optionally wherein the C1-8 alkylene has a double or triple bond;
r is 0, 1, 2, or 3;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(XVI) of Formula (N):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
W3 is nitrogen or CH;
Z1 is oxygen or sulfur;
each of R11 and R12 is independently hydrogen, halogen, hydroxyl, nitro, amino, C1-8 alkyl, C1-8 alkoxy, C1-8 haloalkyl, or C1-8 haloalkoxy′
each of R13 and R14 is independently hydrogen or C1-8 alkyl;
A1 is a 5-membered heterocycle which is pyrazole or thiophene, in which the 5-membered heterocycle is unsubstituted or substituted with halogen, hydroxyl, nitro, amino, C1-8 alkyl, C1-8 alkoxy, C1-8 haloalkyl, or C1-8 haloalkoxy;
m is 2, 3, or 4;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(XVII) of Formula (O):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
each of W1 and W2 independently is CH or nitrogen;
X is NR5 or CR6R7;
wherein R5 is hydrogen, C1-8 alkyl, C1-8 haloalkyl, C1-8 alkyl substituted with C1-8 alkoxy, C3-7 cycloalkyl, C1-8 alkyl substituted with C3-7 cycloalkyl, C1-8 alkyl substituted with phenyl, C2-8 acyl, or C2-8 alkenyl, and each of R6 and R7 independently is hydrogen or C1-8 alkyl;
Y is (CR8R9)r, wherein each of R8 and R9 independently is hydrogen or C1-8 alkyl, and r is 1, 2, 3, or 4;
or
X and Y are combined to form CR10═CR11 or ethynylene, wherein each of R10 and R11 independently is hydrogen or C1-8 alkyl;
G, when bond a is present, is O, S or CR12R13, wherein each of R12 and R13 independently is hydrogen or C1-8 alkyl;
G, when bond a is absent, is OH;
A is a five-membered heterocyclic ring which is thiazole, oxazole, imidazole, pyrazole, thiophene, furan, or pyrrole, wherein the heterocyclic ring is unsubstituted or substituted with C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, halogen, C1-8 haloalkyl, C1-8 haloalkoxy, hydroxyl, nitro, C2-8 acyl, C6-10 aryl, or a five-membered or six-membered heterocyclic group;
B is a C1-8 alkylene, C2-8 alkenylene or C2-8 alkynylene chain, wherein the chain is unsubstituted or substituted with C1-8 alkyl, C3-7 cycloalkyl, C1-8 alkoxy, or halogen;
each of R1 and R2 independently is hydrogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, halogen, C1-8 haloalkyl, C1-8 haloalkoxy, hydroxyl, nitro, C2-8 acyl, C6-10 aryl, or a five-membered or six-membered heterocyclic group;
each of R3 and R4 independently is hydrogen or C1-8 alkyl;
m is 0, 1, 2, or 3;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(XVIII) of Formula (P);
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
Ga, when bond a is present, is O, S or CH2;
Ga, when bond a is absent, is OH;
Aa is five-membered heterocyclic ring which is thiazole, oxazole, or thiophene, wherein the five-membered heterocyclic ring is unsubstituted or is substituted with C1-8 alkyl, C1-8 alkoxy, halogen, C1-8 haloalkyl, C1-8 haloalkoxy, hydroxyl, nitro, or C2-8 acyl;
Ba is a C1-8 alkylene or C2-8 alkenylene chain;
each of R1a and R2a independently is hydrogen, C1-8 alkyl, C1-8 alkoxy, halogen, C1-8 haloalkyl, C1-8 haloalkoxy, hydroxyl, nitro, or C2-8 acyl;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(XIX) of Formula (Q);
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
Gb, when bond a is present, is O, S or CH2;
Gb, when bond a is absent, is OH;
Ab is five-membered heterocyclic ring which is thiazole, oxazole, or thiophene, wherein the five-membered heterocyclic ring is unsubstituted or is substituted with C1-8 alkyl, C1-8 alkoxy halogen, C1-8 haloalkyl, C1-8 haloalkoxy, hydroxyl, nitro, or C2-8 acyl;
Bb is a C1-8 alkylene or C2-8 alkenylene chain;
each of R1b and R2b independently is hydrogen, C1-8 alkyl, C1-8 alkoxy, halogen, C1-8 haloalkyl, C1-8 haloalkoxy, hydroxyl, nitro, or C2-8 acyl;
R3b is hydrogen or C1-8 alkyl;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(XX) of Formula (R):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
each of W1 and W2 is independently CH or N;
X is NR3 or CR4R5, in which R3 is C1-8 alkyl, C1-8 haloalkyl, C1-8 alkyl substituted with C1-8 alkoxy, C1-8 alkyl substituted with a 3-7 membered cycloalkyl, C1-8 alkyl substituted with a phenyl group, C2-8 acyl, or C2-8 alkenyl;
each of R4 and R5 is independently hydrogen or C1-8 alkyl;
Y is (CR6R7)r, in which each of R6 and R7 is independently hydrogen or C1-8 alkyl and r is 1, 2, 3, or 4;
A is a 5 or 6-membered heterocyclic group which is thiazole, oxazole, imidazole, pyrazole, thiophene, furan, pyrrole, pyridine or pyrimidine, or a phenyl group, wherein the 5 or 6-membered heterocyclic group or phenyl group is unsubstituted or substituted with C1-8 alkyl, 3-7 membered cycloalkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxyl, C1-8 alkyl group substituted with a 3-7 membered cycloalkyl group, C1-8 haloalkyl, C1-8 haloalkoxy, C6-10 aryl, a 5 or 6-membered heterocyclic group, aralkyl group comprising a C6-10 aryl group and a C1-8 alkyl group, or C1-8 alkyl group substituted with a 5 or 6-membered heterocyclic group;
B is a bond or C1-8 alkylene which is unsubstituted or substituted with C1-8 alkyl, a 3-7 membered cycloalkyl group, C1-8 alkoxy or a halogen, and which may have a double bond or triple bond when the carbon number of the alkylene chain is 2 or more;
D is N or CH;
E is O or S;
each of R1 and R2 is independently H, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, halogen, C1-8 haloalkyl, C1-8 haloalkoxy, nitro, C2-8 acyl, C6-10 aryl, or a 5 or 6-membered heterocyclic group;
m 0, 1, 2, or 3;
RX is CH2OH, COH, COOCH2CONRX4RX5 SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(XXI) of Formula(S):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
A1 is a 5 or 6-membered heterocyclic group which is thiazole, oxazole, pyridine or pyrimidine, or a phenyl group, wherein the 5 or 6-membered heterocyclic group or phenyl group is unsubstituted or substituted with C1-8 alkyl or C1-8 haloalkyl;
B1 is C2-4 alkylene;
each of R11 and R12 is independently H, C1-8 alkyl, halogen, or C1-8 haloalkyl;
R13 is C1-8 alkyl or C1-8 haloalkyl, optionally wherein the N to which R13 is attached is attached to the 6th position of benzisoxazole;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(XXII) of Formula (T):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
B2 is C2-4 alkylene;
R20 is C1-8 alkyl;
each of R21 and R22 is independently H, C1-8 alkyl, halogen, or C1-8 haloalkyl;
R23 is C1-8 alkyl or C1-8 haloalkyl, optionally wherein the N to which R23 is attached is attached to the 6th position of benzisoxazole;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
and
n is 0, 1, 2, 3, or 4;
(XXIII) of Formula (U);
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
R1 is hydrogen, halogen, hydroxyl, nitro, amino, cyano, carboxyl, C1-8 alkyl, C3-7 cycloalkyl, C2-C8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, C1-8 alkyl having a 3- to 7-membered cycloalkyl substituent, C1-8 haloalkyl, C1-8 alkyl having a C1-8 alkoxy substituent, C1-8 haloalkoxy, C2-8 acyl, C6-10 aryl group, a 5- or 6-membered heterocyclic group, an aralkyl group having a C6-10 aryl moiety and a C1-8 alkylene moiety, or a C1-8 alkyl group having a 5- or 6-membered heterocyclic substituent;
R2 is hydrogen, C1-8 alkyl, C2-8 alkenyl, C1-8 alkyl having a 3- to 7-membered cycloalkyl substituent, C1-8 haloalkyl, C1-8 alkyl group having a C1-8 alkoxy substituent, C2-8 acyl, C6-10 aryl, or an aralkyl group having a C6-10 aryl moiety and a C1-8 alkylene moiety;
each of R3, R4, R5 and R6 independently is hydrogen, C1-8 alkyl, or C1-8 haloalkyl;
X is oxygen, sulfur or NR7;
where R7 is hydrogen, C1-8 alkyl, C1-8 haloalkyl, an aralkyl group having a C6-10 aryl moiety and a C1-8 alkylene moiety, C2-8 acyl, or C2-8 alkenyl;
Y is oxygen, sulfur, NR8 or a bond, where R8 is hydrogen, C1-8 alkyl, C1-8 haloalkyl, C2-8 acyl, or C2-8 alkenyl;
p is 0 or 1;
A, when bond a is present, is oxygen CH2, N—NH2 or N—OR9, where R9 is hydrogen, C1-8 alkyl, C1-8 haloalkyl, C2-8 acyl, C2-8 alkenyl, or an aralkyl group having a C6-10 aryl moiety and a C1-8 alkylene moiety;
A, when bond a is absent, is OH;
B is, in the case of p=1, a benzene ring having or not having a substituent which is halogen, hydroxyl, nitro, amino, C1-8 alkyl, C3-7 cycloalkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, C1-8 alkyl having a 3- to 7-membered cycloalkyl substituent, C1-8 haloalkyl, C1-8 alkyl having a C1-8 alkoxy substituent, C1-8 haloalkoxy, C2-8 acyl, C6-10 aryl group, or an aralkyl group having a C6-10 aryl moiety and a C1-C8 alkylene moiety of 1-8 carbon atoms, and, in the case of p=0, a condensed ring which is indole, benzofuran, benzisoxazole or 1,2-benzisothiazole, in which said condensed ring has or does not have a substituent which is
halogen, hydroxyl, nitro, amino, C1-8 alkyl group, C3-7 cycloalkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, C1-8 alkyl having a 3- to 7-membered cycloalkyl substituent, C1-8 haloalkyl, C1-8 alkyl having a C1-C8 alkoxy substituent, C1-8 haloalkoxy group, C2-8 acyl, C6-10 aryl, or an aralkyl group having a C6-10 aryl moiety and a C1-8 alkylene moiety;
Y is bonded to the benzene ring of B;
(C(R3)(R4)m is bonded to the condensed ring of B at its 3-position;
m is an integer of 1 to 4;
n is 0, 1, 2, 3, 4, or 5;
Y is a bond in the case of n=0;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
and
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
(XXIV) of Formula (V):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
R11 is hydrogen, halogen, hydroxyl, nitro, amino, cyano, carboxyl, C1-8 alkyl, C3-7 cycloalkyl, C2-C8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, C1-8 alkyl having a 3- to 7-membered cycloalkyl substituent, C1-8 haloalkyl, C1-8 alkyl having a C1-8 alkoxy substituent, C1-8 haloalkoxy, C2-8 acyl, C6-10 aryl group, a 5- or 6-membered heterocyclic group, an aralkyl group having a C6-10 aryl moiety and a C1-8 alkylene moiety, or a C1-8 alkyl group having a 5- or 6-membered heterocyclic substituent;
R12 is hydrogen, C1-8 alkyl, C2-8 alkenyl, C1-8 alkyl having a 3- to 7-membered cycloalkyl substituent, C1-8 haloalkyl, C1-8 alkyl group having a C1-8 alkoxy substituent, C2-8 acyl, C6-10 aryl, or an aralkyl group having a C6-10 aryl moiety and a C1-8 alkylene moiety;
each of R13, R14, R15 and R16 independently is hydrogen, C1-8 alkyl, or C1-8 haloalkyl;
Y1 is oxygen, sulfur, NR18 or a bond, where R18 is hydrogen, C1-8 alkyl, C1-8 haloalkyl, C2-8 acyl, or C2-8 alkenyl;
A1, when bond a is present, is oxygen CH2, N—NH2 or N—OR19, where R19 is hydrogen, C1-8 alkyl, C1-8 haloalkyl, C2-8 acyl, C2-8 alkenyl, or an aralkyl group having a C6-10 aryl moiety and a C1-8 alkylene moiety;
A1, when bond a is absent, is OH;
Q1 is hydrogen, halogen, hydroxyl, nitro, amino, C1-8 alkyl group, C3-7 cycloalkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, C1-8 alkyl having a 3- to 7-membered cycloalkyl substituent, C1-8 haloalkyl, C1-8 alkyl having a C1-8 alkoxy substituent, C1-8 haloalkoxy, C2-8 acyl, C6-10 aryl, or an aralkyl group having a C6-10 aryl moiety and a C1-8 alkylene moiety;
r is 1, 2, 3, or 4;
s is 1, 2, 3, 4, or 5;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
(XXV) of Formula (W):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
R21 is hydrogen, halogen, hydroxyl, nitro, amino, cyano, carboxyl, C1-8 alkyl, C3-7 cycloalkyl, C2-C8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, C1-8 alkyl having a 3- to 7-membered cycloalkyl substituent, C1-8 haloalkyl, C1-8 alkyl having a C1-8 alkoxy substituent, C1-8 haloalkoxy, C2-8 acyl, C6-10 aryl group, a 5- or 6-membered heterocyclic group, an aralkyl group having a C6-10 aryl moiety and a C1-8 alkylene moiety, or a C1-8 alkyl group having a 5- or 6-membered heterocyclic substituent;
R22 is hydrogen, C1-8 alkyl, C2-8 alkenyl, C1-8 alkyl having a 3- to 7-membered cycloalkyl substituent, C1-8 haloalkyl, C1-8 alkyl group having a C1-8 alkoxy substituent, C2-8 acyl, C6-10 aryl, or an aralkyl group having a C6-10 aryl moiety and a C1-8 alkylene moiety;
each of R23, R24, R25 and R26 independently is hydrogen, C1-8 alkyl, or C1-8 haloalkyl;
Y2 is oxygen, sulfur, NR28 or a bond, where R28 is hydrogen, C1-8 alkyl, C1-8 haloalkyl, C2-8 acyl, or C2-8 alkenyl;
Q2 is hydrogen, halogen, hydroxyl, nitro, amino, C1-8 alkyl group, C3-7 cycloalkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, C1-8 alkyl having a 3- to 7-membered cycloalkyl substituent, C1-8 haloalkyl, C1-8 alkyl having a C1-8 alkoxy substituent, C1-8 haloalkoxy, C2-8 acyl, C6-10 aryl, or an aralkyl group having a C6-10 aryl moiety and a C1-8 alkylene moiety;
t is 1, 2, 3, or 4;
u is 1, 2, 3, 4, or 5;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
(XXVI) of Formula (X):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
R1 is hydrogen, halogen, C1-4 alkyl, C1-4 haloalkyl, CN, C1-4 alkoxy, C1-4 haloalkoxy, or C3-6 cycloalkyl;
Q1 is CH or N;
R2 is hydrogen, halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C3-6 cycloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, S(C1-4 alkyl), SO2(C1-4-alkyl), 5- or 6-membered heterocycle, aryl, 5-membered heteroaryl, C≡C—R2A, O(CH2)m R2B, NH(C1-4 alkyl), N(C1-4 alkyl)2, or C(O)(C1-4 alkyl), wherein aryl and heteroaryl are unsubstituted or substituted with halogen, OH, CN, C1-4 alkyl, formyl, acetyl, acetoxy, or carboxy, and wherein m is 1, 2, or 3;
x is 1 or 2;
R2A and R2B are each independently C1-4 alkyl, C1-4 haloalkyl, or C3-6 cycloalkyl;
each R20 is independently hydrogen, halogen, C1-4 alkyl, CN, or C1-4 alkoxy;
R3 is CH3 or CD3,
RX is CH2OH, COH, COOCH2CONRX4RX5 SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
and
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
(XXVII) of Formula (Y):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
R1 is hydrogen, halogen, C1-4 alkyl, C1-4 haloalkyl, CN, C1-4 alkoxy, C1-4 haloalkoxy, or C3-6 cycloalkyl;
Q1 is CH or N;
R2 is hydrogen, halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C3-6 cycloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, S(C1-4 alkyl), SO2(C1-4-alkyl), 5- or 6-membered heterocycle, aryl, 5-membered heteroaryl, C≡C—R2A, O(CH2)mR2B, NH(C1-4 alkyl), N(C1-4 alkyl)2, or C(O)(C1-4 alkyl), wherein aryl and heteroaryl are unsubstituted or substituted with halogen, OH, CN, C1-4 alkyl, formyl, acetyl, acetoxy, or carboxy, and wherein m is 1, 2, or 3;
x is 1 or 2;
R2A and R2B are each independently C1-4 alkyl, C1-4 haloalkyl, or C3-6 cycloalkyl;
each R20 is independently hydrogen, halogen, C1-4 alkyl, CN, or C1-4 alkoxy;
R3 is CH3 or CD3;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
and
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
(XXVIII) of Formula (Z);
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
R1 is hydrogen, halogen, C1-4 alkyl, C1-4 haloalkyl, CN, C1-4 alkoxy, C1-4 haloalkoxy, or C3-6 cycloalkyl;
Q1 is CH or N;
R2 is hydrogen, halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C3-6 cycloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, S(C1-4 alkyl), SO2 (C1-4-alkyl), 5- or 6-membered heterocycle, ryl, 5-membered heteroaryl, C≡C—R2A, O(CH2)mR2B, NH(C1-4 alkyl), N(C1-4 alkyl) 2, or C(O)(C1-4 alkyl), wherein aryl and heteroaryl are unsubstituted or substituted with halogen, OH, CN, C1-4 alkyl, formyl, acetyl, acetoxy, or carboxy, and wherein m is 1, 2, or 3;
x is 1 or 2;
R2A and R2B are each independently C1-4 alkyl, C1-4 haloalkyl, or C3-6 cycloalkyl;
each R20 is independently hydrogen, halogen, C1-4 alkyl, CN, or C1-4 alkoxy;
R3 is CH3 or CD3;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
and
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
(XXIX) of Formula (AA):
or a pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof, wherein:
L is (CH2)5, which is unsubstituted or substituted by one methyl group;
R1 is hydrogen, halogen, C1-4 alkyl, C1-4 haloalkyl, CN, C1-4 alkoxy, C1-4 haloalkoxy, or C3-6 cycloalkyl;
R2 is hydrogen, halogen, CN, C1-4 alkyl, C1-4 haloalkyl, C3-6 cycloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, S(C1-4 alkyl), SO2(C1-4-alkyl), 5- or 6-membered heterocycle, aryl, 5-membered heteroaryl, C≡C—R2A, O(CH2)mR2B, NH(C1-4 alkyl), N(C1-4 alkyl)2, or C(O)(C1-4 alkyl), wherein aryl and heteroaryl are unsubstituted or substituted with halogen, OH, CN, C1-4 alkyl, formyl, acetyl, acetoxy, or carboxy, and wherein m is 1, 2, or 3;
x is 0 or 1;
R2A and R2B are each independently C1-4 alkyl, C1-4 haloalkyl, or C3-6 cycloalkyl;
R3 is C1-4 haloalkyl, NO2, CN, halogen, or C(O)O(C1-4 alkyl);
R20 is hydrogen, halogen, C1-4 alkyl, CN, or C1-4 alkoxy;
RX is CH2OH, COH, COOCH2CONRX4RX5, SO3H,
each RX4 and RX5 is independently alkyl, aryl, or heteroaryl;
or alternatively, RX4 and RX5 together with the carbon atom to which RX4 and RX5 are attached form a heterocycle;
and
each RX6 and RX7 is independently H, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
(XXX) having the structure:
or pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof;
(XXXI) having the structure:
or pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof;
(XXXII) having the structure:
or pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof;
(XXXIII) having the structure
or pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof;
(XXXIV) having the structure
or pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof;
(XXXV) having the structure
or pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof;
or
(XXXVI) having the structure
or pharmaceutically acceptable salt, solvate, ester, amide, or prodrug thereof.

420 more elements

Facts

Application

19/175,821Filed 10 Apr 2025

Priority

26 Sep 2019

Published

30 Oct 2025

Term ends

Not estimatedThe source records don’t support an estimate.

Classification20 codes

C07C 323/19
Having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton: with…
A61P 3/06
Drugs for disorders of the metabolism: antihyperlipidemics
A61P 3/10
For glucose homeostasis: for hyperglycaemia, e.g. antidiabetics
A61P 13/12
Drugs for disorders of the urinary system: of the kidneys

Family

Application62/906,288Us provisional application · filed 26 Sep 2019

Application17/195,334Continuation in part · filed 8 Mar 2021

Application17/219,058Division · filed 31 Mar 2021

Application18/179,622Division · filed 7 Mar 2023

Application19/175,821Division

Application17/219,058Continuation in part

US 11,634,387 B2Related patent

US 12,297,168 B2Related patent

US 2021/0300890 A1Published application

US 2022/0363632 A1Published application

US 2023/0278952 A1Published application

US 2025/0333379 A1This patent

From the US filing history. Foreign family members aren’t listed.