US 10,626,081 B2Granted

Farnesoid X receptor agonists and uses thereof

AssigneeMetacrine, Inc.

InventorsNicholas D. Smith, Steven P. Govek, Johnny Y. Nagasawa

Life of this patent

Estimating the term…

Abstract

Described herein are compounds that are farnesoid X receptor agonists, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds in the treatment of conditions, diseases, or disorders associated with farnesoid X receptor activity.

Claims18

Dependent claims

A compound that has the structure of Formula (II), or a pharmaceutically acceptable salt or solvate thereof:

wherein
R1 and R2 are each independently selected from H, D, F, CH3, and CF3;
R3 is cyclohexyl that is substituted with R12;
R12 is selected from D, halogen, —CN, —NO2, —OR10, —SR10, —S(═O)R11, —S(═O)2R11, —S(═O)2N(R10)2, —NR10S(═O)2R11, —C(═O)R11, —OC(═O)R11, —CO2R10, —OCO2R11, —N(R10)2, —C(═O)N(R10)2, —OC(═O)N(R10)2, —NR10C(═O)R11, —NR10C(═O)OR11, unsubstituted or substituted C1-C10alkyl, unsubstituted or substituted C1-C10fluoroalkyl, unsubstituted or substituted C2-C10alkenyl, unsubstituted or substituted C2-C10alkynyl, unsubstituted or substituted C1-C10heteroalkyl, unsubstituted or substituted C3-C10cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, and -L4-L5-R13;
L4 is absent, —O—, —S—, —S(═O)—, —S(═O)2—, —NR10—, —C(═O)—, —C(═O)NH—, —NHC(═O)—, —C(═O)O—, —OC(═O)—, —OC(═O)NH—, —NHC(═O)NH—, —NHC(═O)O—, —(CH2)r—, or —(OCH2CH2)r—, and r is 1, 2, 3, or 4;
L5 is absent, unsubstituted or substituted C1-C10alkylene, unsubstituted or substituted C1-C10heteroalkylene, unsubstituted or substituted C2-C10alkenylene, unsubstituted or substituted C2-C10alkynylene, unsubstituted or substituted C3-C10cycloalkylene, unsubstituted or substituted C2-C10heterocycloalkylene, unsubstituted or substituted arylene, or unsubstituted or substituted heteroarylene;
R13 is H, halogen, —N(R10)2, unsubstituted or substituted C1-C10alkyl, unsubstituted or substituted C1-C10alkenyl, unsubstituted or substituted C1-C10alkynyl, unsubstituted or substituted C1-C10cycloalkyl, unsubstituted or substituted C1-C10heterocycloalkyl, unsubstituted or substituted aryl, or unsubstituted or substituted heteroaryl;
R4 is -L3-Y;
L3 is —C(R5)(R6)—, —C(R6)═C(R8)—, —C≡C—, —O—C(R7)(R8)—, or —C(R5)(R6)—O—;
R5 and R7 are each independently selected from H, D, C1-C4alkyl, and C3-C6cycloalkyl;
R6 and R8 are each independently selected from H, D, C1-C4alkyl, or C3-C6cycloalkyl;
Y is —CH2OR9, —C(═O)OR9,
R9 is selected from H, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C2-C6alkenyl, substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted phenyl, and substituted or unsubstituted heterocycle;
L1 is absent, —O—, —S—, —S—CH2—, —CH2—S—, —CH2—, —CH═CH—, —C═C—, —NR10, —NR10—CH2—, or —CH2—NR10—;
A is CRA, or N;
each RA is independently selected from H, D, halogen, —CN, —OH, —OR10, C1-C6alkyl, or C1-C6fluoroalkyl;
B is CRB, or N;
each RB is independently selected from H, D, halogen, —CN, —OH, —OR10, C1-C6alkyl, or C1-C6fluoroalkyl;
ring C is phenyl;
or ring C is a monocyclic heteroaryl selected from furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, triazolylene, tetrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, or triazinyl;
or ring C is a bicyclic heteroaryl selected from indolizinyl, azaindolizinyl, indolyl, azaindolyl, indazolyl, azaindazolyl, benzimidazolyl, azabenzimidazolyl, benzotriazolyl, azabenzotriazolyl, benzoxazolyl, azabenzoxazolyl, benzisoxazolyl, azabenzisoxazolyl, benzofuranyl, azabenzofuranyl, benzothienyl, azabenzothienyl, benzothiazolyl, azabenzothiazolyl, and purinyl;
each RC is independently selected from H, D, halogen, —CN, —OH, —OR10, —SR10, —S(═O)R11, —NO2, —N(R10)2, —S(═O)2R11, —NHS(═O)2R11, —S(═O)2N(R10)2, —C(═O)R11, —OC(═O)R11, —CO2R10, —OCO2R11, —C(═O)N(R10)2, —OC(═O)N(R10)2, —NR10C(═O)N(R10)2, —NR10C(═O)R11, —NR10C(═O)OR11, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C2-C6alkenyl, substituted or unsubstituted C2-C6alkynyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted phenyl and substituted or unsubstituted monocyclic heteroaryl;
each R10 is independently selected from H, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted monocyclic heteroaryl, and substituted or unsubstituted benzyl;
or two R10 on the same N atom are taken together with the N atom to which they are attached to form a N-containing heterocycle;
each R11 is independently selected from substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted monocyclic heteroaryl, and substituted or unsubstituted benzyl;
m is 0, 1, or 2;
n is 0, 1, or 2;
and
p is 0, 1, 2, 3, or 4.

26 more elements

A compound that has the structure of Formula (VI), or a pharmaceutically acceptable salt or solvate thereof:

wherein
R1 and R2 are each independently selected from H, D, F, CH3, and CF3;
R3 is cyclohexyl that is substituted with R12;
each R12 is independently selected from D, halogen, —CN, —NO2, —OR10, —SR10, —S(═O)R11, —S(═O)2R11, —S(═O)2N(R10)2, —NR10S(═O)2R11, —C(═O)R11, —OC(═O)R11, —CO2R10, —OCO2R11, —N(R10)2, —C(═O)N(R10)2, —OC(═O)N(R10)2, —NR10C(═O)R11, —NR10C(═O)OR11, unsubstituted or substituted C1-C10alkyl, unsubstituted or substituted C1-C10fluoroalkyl, unsubstituted or substituted C2-C10alkenyl, unsubstituted or substituted C2-C10alkynyl, unsubstituted or substituted C1-C10heteroalkyl, unsubstituted or substituted C3-C10cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, and -L5-L6-R13;
L5 is absent, —O—, —S—, —S(═O)—, —S(═O)2—, —NR10—, —C(═O)—, —C(═O)NH—, —NHC(═O)—, —C(═O)O—, —OC(═O)—, —OC(═O)NH—, —NHC(═O)NH—, —NHC(═O)O—, —(CH2)r—, or —(OCH2CH2)r—, and r is 1, 2, 3, or 4;
L6 is absent, unsubstituted or substituted C1-C10alkylene, unsubstituted or substituted C1-C10heteroalkylene, unsubstituted or substituted C2-C10alkenylene, unsubstituted or substituted C2-C10alkynylene, unsubstituted or substituted C3-C10cycloalkylene, unsubstituted or substituted C2-C10heterocycloalkylene, unsubstituted or substituted arylene, or unsubstituted or substituted heteroarylene;
R13 is H, halogen, —N(R10)2, unsubstituted or substituted C1-C10alkyl, unsubstituted or substituted C1-C10alkenyl, unsubstituted or substituted C1-C10alkynyl, unsubstituted or substituted C1-C10cycloalkyl, unsubstituted or substituted C1-C10heterocycloalkyl, unsubstituted or substituted aryl, or unsubstituted or substituted heteroaryl;
ring A is phenyl, cyclohexyl, pyridinyl, pyrimidinyl, pyrazinyl, or pyridazinyl;
each RA is independently selected from H, D, halogen, —CN, —OH, —OR10, C1-C6alkyl, and C1-C6fluoroalkyl;
L1 is absent, —O—, —S—, —S—CH2—, —CH2—S—, —CH2—, —CH═CH—, —C—═C—, —NR10, —NR10—CH2—, or —CH2—NR10—;
ring C is phenyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, or triazinyl;
each RC is independently selected from H, D, halogen, —CN, —OH, —OR10, —SR10, —S(═O)R11, —NO2, —N(R10)2, —S(═O)2R11, —NHS(═O)2R11, —S(═O)2N(R10)2, —C(═O)R11, —OC(═O)R11, —CO2R10, —OCO2R11, —C(═O)N(R10)2, —OC(═O)N(R10)2, —NR10C(═O)N(R10)2, —NR10C(═O)R11, —NR10C(═O)OR11, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C2-C6alkenyl, substituted or unsubstituted C2-C6alkynyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted phenyl and substituted or unsubstituted monocyclic heteroaryl;
ring B is phenyl, pyridinyl, pyrimidinyl, pyrazinyl, or pyridazinyl;
each RB is independently selected from H, D, halogen, —CN, —OH, —OR10, C1-C6alkyl, and C1-C6fluoroalkyl;
R5 and R7 are each independently selected from H, D, C1-C4alkyl and C3-C6cycloalkyl;
or R5 and R7 are taken together with the intervening atoms to form a double bond;
R6 and R8 are each independently selected from H, D, C1-C4alkyl, and C3-C6cycloalkyl;
Y is —CH2OR9, —C(═O)OR9, —CH2C(═O)OR9,
each R9 is independently selected from H, substituted or unsubstituted C2-C6alkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C2-C6alkenyl, substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted phenyl, and substituted or unsubstituted heterocycle;
each R10 is independently selected from H, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted monocyclic heteroaryl, and substituted or unsubstituted benzyl;
or two R10 on the same N atom are taken together with the N atom to which they are attached to form a N-containing heterocycle;
each R11 is independently selected from substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted monocyclic heteroaryl, and substituted or unsubstituted benzyl;
m is 0, 1, or 2;
n is 0, 1, or 2;
and
p is 0, 1, 2, 3, or 4.

23 more elements

A compound selected from the group consisting of:

(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)pivalamido)-phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)butyramido)-phenyl)acrylate;
(E)-Methyl 3-(3-(((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)(ethoxycarbonyl)amino)phenyl)acrylate;
(E)-Methyl 3-(3-(4-cyano-N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)benzamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)tetrahydro-2H-pyran-4-carboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)oxetane-3-carboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-3,3-dimethylbutanamido)phenyl)acrylate;
(E)-Methyl 3-(3-((1r,4r)-N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-4-methoxycyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-((1s,4s)-N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-4-methoxycyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-4-methoxybenzamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cycloheptanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(-N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)adamantane-1-carboxamido)phenyl)acrylate;
(E)-methyl 3-(3-(N-(4-cyclohexylbenzyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-3,4-difluorobenzamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-4-fluorobenzamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-1-methylcyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)-5-fluorophenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)bicyclo[2.2.1]heptane-2-carboxamido)-5-fluorophenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-4-methyltetrahydro-2H-pyran-4-carboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-2-methoxybenzamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-1,1-dioxidotetrahydro-2H-thiopyran-4-carboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)tetrahydro-2H-thiopyran-4-carboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-3-methoxybenzamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-1-(methylsulfonyl)azetidine-3-carboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-4-(2-morpholinoethoxy)benzamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-4-(methylthio)cyclohexanecarboxamido)phenyl)acrylate;
cis-(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-4-(methylsulfonyl)cyclohexanecarboxamido)phenyl)acrylate;
trans-(E)-methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-4-(methylsulfonyl)cyclohexanecarboxamido)phenyl)acrylate;
trans-4-(((4′-(Dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)(3-((E)-3-methoxy-3-oxoprop-1-en-1-yl)phenyl)carbamoyl)cyclohexanecarboxylic acid;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-6-oxopiperidine-3-carboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-2-oxopiperidine-4-carboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-1-oxidotetrahydro-2H-thiopyran-4-carboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-4-(methylsulfinyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-4-hydroxybenzamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-4-(2-hydroxyethoxy)benzamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-3-hydroxy-2,2-dimethylpropanamido)phenyl)acrylate;
(E)-Methyl 3-(3-(3-chloro-N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-2,2-dimethylpropanamido)phenyl)acrylate;
trans-(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-2-hydroxycyclohexanecarboxamido)phenyl)acrylate;
cis-(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-2-hydroxycyclohexanecarboxamido)phenyl)acrylate;
cis-(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-3-hydroxycyclohexanecarboxamido)phenyl)acrylate;
trans-(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-3-hydroxycyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclopentanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclobutanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)amino)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-4-oxocyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)tetrahydro-2H-pyran-2-carboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-1,4-dioxane-2-carboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)tetrahydro-2H-pyran-3-carboxamido)phenyl)acrylate;
cis-(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-4-hydroxycyclohexane carboxamido)phenyl)acrylate;
trans-(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-4-hydroxycyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-3′-methyl-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((2′-methyl-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(pyridin-4-yl)benzyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-cyano-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)-phenyl)acrylate;
(E)-Methyl 3-(3-(N-((3′-cyano-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)-phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-fluoro-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)-phenyl)acrylate;
(E)-Methyl 3-(3-(N-((3′-fluoro-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)-phenyl)acrylate;
(E)-Methyl 3-(3-(N-((2′-fluoro-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)-phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(1-methyl-1H-pyrazol-4-yl)benzyl)cyclohexanecarboxamido)-phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(pyridin-3-yl)benzyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((3′-(trifluoromethoxy)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(3,5-dimethylisoxazol-4-yl)benzyl)cyclohexanecarboxamido)-phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-isopropoxy-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((2′-fluoro-4′-methoxy-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-chloro-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((3′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(6-(dimethylamino)pyridin-3-yl)benzyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)-5-methylphenyl)acrylate;
(E)-Methyl 3-(5-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)-2-methylphenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)-2-methylphenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)-4-methylphenyl)acrylate;
Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)propanoate;
(E)-N-((4′-(Dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-N-(3-(3-methoxyprop-1-en-1-yl)phenyl)cyclohexanecarboxamide;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)but-2-enoate;
(E)-Methyl 3-(3-(N-(1-(4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)ethyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((3′-isopropyl-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(pyrrolidin-1-yl)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(1H-indazol-5-yl)benzyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-methyl 3-(3-(N-((4′-(dimethylamino)-2-fluoro-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-methyl 3-(3-(N-((4′-(dimethylamino)-3-fluoro-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-methoxy-3′-methyl-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-2-methyl-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-3-methyl-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((3′-hydroxy-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((2′-hydroxy-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-hydroxy-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((3′-methoxy-4′-methyl-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((2′,6′-difluoro-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-((tert-butoxycarbonyl)(methyl)amino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(methylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(1-methyl-1H-indol-5-yl)benzyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-methoxy-3′-methyl-[1,1′-biphenyl]-4-yl)methyl)isonicotinamido)phenyl)acrylate;
(E)-Methyl 4′-((N-(3-(3-methoxy-3-oxoprop-1-en-1-yl)phenyl)cyclohexanecarboxamido)methyl)-[1,1′-biphenyl]-3-carboxylate;
(E)-Methyl 4′-((N-(3-(3-methoxy-3-oxoprop-1-en-1-yl)phenyl)cyclohexanecarboxamido)methyl)-[1,1′-biphenyl]-4-carboxylate;
(E)-Methyl 3-(3-(N-((4′-(methylsulfonyl)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-tert-Butyl 4-(((4′-methoxy-3′-methyl-[1,1′-biphenyl]-4-yl)methyl)(3-(3-methoxy-3-oxoprop-1-en-1-yl)phenyl)carbamoyl)piperidine-1-carboxylate;
(E)-Methyl 3-(3-(N-((3′-(hydroxymethyl)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(hydroxymethyl)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((3′-(methylsulfonyl)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(benzo[d][1,3]dioxol-5-yl)benzyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((3′-chloro-4′-methoxy-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((2-cyano-4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((3-cyano-4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-2-ethyl-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-3-ethyl-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-methoxy-3′-methyl-[1,1′-biphenyl]-4-yl)methyl)piperidine-4-carboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(1-acetyl-N-((4′-methoxy-3′-methyl-[1,1′-biphenyl]-4-yl)methyl)piperidine-4-carboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-methoxy-3′-methyl-[1,1′-biphenyl]-4-yl)methyl)-1-(methylsulfonyl)piperidine-4-carboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)-2-methylacrylate;
(E)-Methyl 3-(3-(N-((3′-cyano-4′-methoxy-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(pyridin-2-yl)benzyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((2′-cyano-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(thiazol-2-yl)benzyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(thiazol-4-yl)benzyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(thiazol-5-yl)benzyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-isopropyl-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(prop-1-en-2-yl)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((3′-cyano-4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-3′-fluoro-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(1-methyl-1H-benzo[d]imidazol-5-yl)benzyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-methyl 3-(3-(N-((4′-(dimethylamino)-3′-methoxy-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)benzyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(azetidin-1-yl)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(2-(dimethylamino)pyrimidin-5-yl)benzyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(5-(dimethylamino)pyrazin-2-yl)benzyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(6-(dimethylamino)pyridazin-3-yl)benzyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(N-methylmethylsulfonamido)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((3′-fluoro-4′-(methylsulfonyl)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((2′-fluoro-4′-(methylsulfonyl)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(benzo[d]thiazol-6-yl)benzyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((3′-chloro-4′-(methylsulfonyl)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(benzo[d]oxazol-5-yl)benzyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(benzo[d]oxazol-6-yl)benzyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(benzo[d]isoxazol-6-yl)benzyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(benzo[d]thiazol-5-yl)benzyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(benzo[d]isoxazol-5-yl)benzyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(benzo[d]isothiazol-6-yl)benzyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(benzo[d]isothiazol-5-yl)benzyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(3-fluoro-1-methyl-1H-indazol-5-yl)benzyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(3-methylbenzo[d]isothiazol-6-yl)benzyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(4-methylpiperazin-1-yl)benzyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-morpholinobenzyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(piperidin-1-yl)benzyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(piperazin-1-yl)benzyl)cyclohexanecarboxamido)phenyl) acrylate;
(E)-Methyl 3-(3-(N-(naphthalen-1-ylmethyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-([1,1′-biphenyl]-2-ylmethyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-([1,1′-biphenyl]-3-ylmethyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-iso-Propyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Ethyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)-5-ethylphenyl)acrylate;
(E)-2-Hydroxyethyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Cyclohexyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Isobutyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-2-Methoxyethyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-2-(Dimethylamino)ethyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-(Tetrahydrofuran-2-yl)methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-2,2,2-Trifluoroethyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Benzyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)-5-methoxyphenyl)acrylate;
(E)-Methyl 3-(3-cyano-5-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-chloro-5-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)-5-(trifluoromethyl)phenyl)acrylate;
Methyl 3-(3-(N-((4′-(Dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)propiolate;
(E)-3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexane carboxamido)phenyl)acrylic acid;
(E)-3-(3-((1s,4s)-N-((4′-(Dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-4-hydroxycyclohexanecarboxamido)phenyl)acrylic acid;
Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)-5-methylphenyl)propanoate;
Methyl 3-(5-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)-2-methylphenyl)propanoate;
Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)-2-methylphenyl)propanoate;
Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)-4-methylphenyl)propanoate;
Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)butanoate;
Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)-2-methylpropanoate;
(E)-Methyl 3-(3-(trans-4-((tert-butoxycarbonyl)amino)-N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(trans-4-amino-N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(trans-4(4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-4-((methoxycarbonyl)amino)cyclohexanecarboxamido)phenyl)acrylate;
trans-(E)-Methyl 3-(3-(4-acetamido-N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)cyclohexanecarboxamido)phenyl)acrylate;
trans-(E)-Methyl 3-(3-(N-((4′-(dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-4-(methylsulfonamido)cyclohexanecarboxamido)phenyl)acrylate;
N-((4′-(Dimethylamino)-[1,1′-biphenyl]-4-yl)methyl)-N-(3-(3-methylbut-2-en-1-yl)phenyl)cyclohexanecarboxamide;
(E)-Methyl 3-(3-(N-(4-benzamidobenzyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(N-methylbenzamido)benzyl)cyclohexanecarboxamido)phenyl)acrylate;
(E)-Methyl 3-(3-(N-(4-(benzylamino)benzyl)cyclohexanecarboxamido)phenyl)acrylate;
and
(E)-Methyl 3-(3-(N-(4-(benzyl(methyl)amino)benzyl)cyclohexanecarboxamido)phenyl)acrylate;
or a pharmaceutically acceptable salt, or solvate thereof.

182 more elements

Dependencies are inferred from the claim text.

Facts

Application: 15/758,709Filed 16 Sep 2016 · us provisional application
Priority: 16 Sep 2015
Published: US 2018/0244606 A130 Aug 2018
Granted: 21 Apr 2020
Term ends: Not estimatedThe source records don’t support an estimate.

Classification88 codes

C07C 233/54
With the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring:…
A61K 31/16
Medicinal preparations containing organic active ingredients: amides, e.g. hydroxamic acids
A61K 31/216
Of carboxylic acids: of acids having aromatic rings, e.g. benactizyne, clofibrate
A61K 31/27
Esters, e.g. nitroglycerine, selenocyanates: of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine

Family

Application62/219,422Us provisional application · filed 16 Sep 2015
US 2018/0244606 A1Pre-grant publication · published 30 Aug 2018
US 10,626,081 B2This patent

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

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Abstract

A compound that has the structure of Formula (II), or a pharmaceutically acceptable salt or solvate thereof:

wherein
R1 and R2 are each independently selected from H, D, F, CH3, and CF3;
R3 is cyclohexyl that is substituted with R12;
R12 is selected from D, halogen, —CN, —NO2, —OR10, —SR10, —S(═O)R11, —S(═O)2R11, —S(═O)2N(R10)2, —NR10S(═O)2R11, —C(═O)R11, —OC(═O)R11, —CO2R10, —OCO2R11, —N(R10)2, —C(═O)N(R10)2, —OC(═O)N(R10)2, —NR10C(═O)R11, —NR10C(═O)OR11, unsubstituted or substituted C1-C10alkyl, unsubstituted or substituted C1-C10fluoroalkyl, unsubstituted or substituted C2-C10alkenyl, unsubstituted or substituted C2-C10alkynyl, unsubstituted or substituted C1-C10heteroalkyl, unsubstituted or substituted C3-C10cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heteroaryl, and -L4-L5-R13;
L4 is absent, —O—, —S—, —S(═O)—, —S(═O)2—, —NR10—, —C(═O)—, —C(═O)NH—, —NHC(═O)—, —C(═O)O—, —OC(═O)—, —OC(═O)NH—, —NHC(═O)NH—, —NHC(═O)O—, —(CH2)r—, or —(OCH2CH2)r—, and r is 1, 2, 3, or 4;
L5 is absent, unsubstituted or substituted C1-C10alkylene, unsubstituted or substituted C1-C10heteroalkylene, unsubstituted or substituted C2-C10alkenylene, unsubstituted or substituted C2-C10alkynylene, unsubstituted or substituted C3-C10cycloalkylene, unsubstituted or substituted C2-C10heterocycloalkylene, unsubstituted or substituted arylene, or unsubstituted or substituted heteroarylene;
R13 is H, halogen, —N(R10)2, unsubstituted or substituted C1-C10alkyl, unsubstituted or substituted C1-C10alkenyl, unsubstituted or substituted C1-C10alkynyl, unsubstituted or substituted C1-C10cycloalkyl, unsubstituted or substituted C1-C10heterocycloalkyl, unsubstituted or substituted aryl, or unsubstituted or substituted heteroaryl;
R4 is -L3-Y;
L3 is —C(R5)(R6)—, —C(R6)═C(R8)—, —C≡C—, —O—C(R7)(R8)—, or —C(R5)(R6)—O—;
R5 and R7 are each independently selected from H, D, C1-C4alkyl, and C3-C6cycloalkyl;
R6 and R8 are each independently selected from H, D, C1-C4alkyl, or C3-C6cycloalkyl;
Y is —CH2OR9, —C(═O)OR9,
R9 is selected from H, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C2-C6alkenyl, substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted phenyl, and substituted or unsubstituted heterocycle;
L1 is absent, —O—, —S—, —S—CH2—, —CH2—S—, —CH2—, —CH═CH—, —C═C—, —NR10, —NR10—CH2—, or —CH2—NR10—;
A is CRA, or N;
each RA is independently selected from H, D, halogen, —CN, —OH, —OR10, C1-C6alkyl, or C1-C6fluoroalkyl;
B is CRB, or N;
each RB is independently selected from H, D, halogen, —CN, —OH, —OR10, C1-C6alkyl, or C1-C6fluoroalkyl;
ring C is phenyl;
or ring C is a monocyclic heteroaryl selected from furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, triazolylene, tetrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, or triazinyl;
or ring C is a bicyclic heteroaryl selected from indolizinyl, azaindolizinyl, indolyl, azaindolyl, indazolyl, azaindazolyl, benzimidazolyl, azabenzimidazolyl, benzotriazolyl, azabenzotriazolyl, benzoxazolyl, azabenzoxazolyl, benzisoxazolyl, azabenzisoxazolyl, benzofuranyl, azabenzofuranyl, benzothienyl, azabenzothienyl, benzothiazolyl, azabenzothiazolyl, and purinyl;
each RC is independently selected from H, D, halogen, —CN, —OH, —OR10, —SR10, —S(═O)R11, —NO2, —N(R10)2, —S(═O)2R11, —NHS(═O)2R11, —S(═O)2N(R10)2, —C(═O)R11, —OC(═O)R11, —CO2R10, —OCO2R11, —C(═O)N(R10)2, —OC(═O)N(R10)2, —NR10C(═O)N(R10)2, —NR10C(═O)R11, —NR10C(═O)OR11, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C2-C6alkenyl, substituted or unsubstituted C2-C6alkynyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted phenyl and substituted or unsubstituted monocyclic heteroaryl;
each R10 is independently selected from H, substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted monocyclic heteroaryl, and substituted or unsubstituted benzyl;
or two R10 on the same N atom are taken together with the N atom to which they are attached to form a N-containing heterocycle;
each R11 is independently selected from substituted or unsubstituted C1-C6alkyl, substituted or unsubstituted C1-C6heteroalkyl, substituted or unsubstituted C1-C6fluoroalkyl, substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted monocyclic heteroaryl, and substituted or unsubstituted benzyl;
m is 0, 1, or 2;
n is 0, 1, or 2;
and
p is 0, 1, 2, 3, or 4.

26 more elements

Facts

Application

15/758,709Filed 16 Sep 2016 · us provisional application

Priority

16 Sep 2015

Published

US 2018/0244606 A130 Aug 2018

Granted

21 Apr 2020

Term ends

Not estimatedThe source records don’t support an estimate.

Classification88 codes

C07C 233/54
With the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring:…
A61K 31/16
Medicinal preparations containing organic active ingredients: amides, e.g. hydroxamic acids
A61K 31/216
Of carboxylic acids: of acids having aromatic rings, e.g. benactizyne, clofibrate
A61K 31/27
Esters, e.g. nitroglycerine, selenocyanates: of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine