US 11,173,145 B2Granted

Compounds useful as inhibitors of indoleamine 2,3-dioxygenase and/or tryptophan dioxygenase

AssigneeBoard of Regents, The University of Texas System

InventorsRichard T. Lewis, Matthew Hamilton, Philip Jones, Alessia Petrocchi, Naphtali Reyna, Jason Cross, Michelle Han, Michael Soth, Timothy McAfoos, Martin Tremblay

Life of this patent

Estimating the term…

Abstract

Compounds of formula (VII), which are useful as inhibitors of indoleamine 2,3-dioxygenase and/or tryptophan dioxygenase, are provided. Also provided are pharmaceutical compositions, kits comprising said compounds, and methods and uses pertaining to said compounds.

Claims27

Dependent claims

A compound of formula (VII),

or a pharmaceutically acceptable salt thereof, wherein one but not both of the dashed bonds may optionally be a carbon-carbon double bond, and wherein:
W is selected from C and CH;
a is selected from 0 and 1;
b is selected from 0, 1, and 2;
c is selected from 0 and 1;
d is selected from 0 and 1;
e is selected from 0 and 1;
f is selected from 0, 1, and 2;
A is selected from O, C(O), and S(O)2;
J is in each case independently selected from oxo, OH, CN, halogen, and C1-3-alkyl;
X1 is selected from C(R8)(R9), N(R10), O, and S;
X2 is selected from C(R11)(R12), N(R13) and O;
Y is selected from
C6-10-aryl, and
5- to 10-membered heteroaryl comprising 1, 2, 3, or 4 ring heteroatoms selected from N, S, and O,
wherein said aryl and heteroaryl are optionally substituted by one or more groups independently selected from R14;
R1 is selected from
H,
(G)n-(C1-6-alkyl),
(G)n-(C3-8-cycloalkyl),
N3,
(G)n-heterocycloalkyl, wherein said heterocycloalkyl is a 3- to 6-membered heterocycloalkyl comprising 1, 2, or 3 ring heteroatoms selected from N, S, and O,
(G)n-(C5-8-cycloalkenyl),
(G)n-heterocycloalkenyl, wherein said heterocycloalkenyl is a 5- to 6-membered heterocycloalkenyl comprising 1, 2, or 3 ring heteroatoms selected from N, S, and O,
(G)n-(C6-10-aryl), and
(G)n-heteroaryl, wherein said heteroaryl is a 5- to 10-membered heteroaryl comprising 1, 2, 3, or 4 ring heteroatoms selected from N, S, and O,
wherein G in each case is independently selected from C(R8)(R9), C(O), S(O)2, C(O)NR10, and S(O)2NR10;
and wherein n in each case is selected from 0 and 1, and
wherein said alkyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl, and heteroaryl are optionally substituted by one or more groups independently selected from R15;
R2, R3, R4, R6, R7, R8, R9, R11, and R12 are in each case independently selected from
H,
halogen,
CN,
OH,
(C0-4-alkyl)-SO2R17,
(C0-4-alkyl)-N(R18)2,
(C0-4-alkyl)-NHCOR19,
(C0-4-alkyl)-NHSO2R20,
(C0-4-alkyl)-CON(R21)2,
(C0-4-alkyl)-CO2R22,
(C0-4-alkyl)-SO2N(R23)2,
C1-6-alkyl,
O—(C1-6-alkyl),
C3-8-cycloalkyl,
3- to 6-membered heterocycloalkyl comprising 1, 2, or 3 ring heteroatoms selected from N, S, and O,
C5-8-cycloalkenyl,
5- to 6-membered heterocycloalkenyl comprising 1, 2, or 3 ring heteroatoms selected from N, S, and O,
C6-10-aryl, and
5- to 10-membered heteroaryl comprising 1, 2, 3, or 4 ring heteroatoms selected from N, S, and O, or
one or both geminal R3 and R4 pairs, taken together with the carbon atom to which they are attached, independently forms a 3- to 6-membered cycloalkyl group or a 3- to 6-membered heterocycloalkyl group which comprises 1, 2, or 3 ring heteroatoms selected from N, S, and O,
wherein said alkyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl, and heteroaryl are optionally substituted by one or more groups independently selected from R16;
R5, R10 and R13 are in each case independently selected from
H,
C1-6-alkyl,
C3-8-cycloalkyl,
3- to 6-membered heterocycloalkyl comprising 1, 2, or 3 ring heteroatoms selected from N, S, and O,
C5-8-cycloalkenyl,
5- to 6-membered heterocycloalkenyl comprising 1, 2, or 3 ring heteroatoms selected from N, S, and O,
C6-10-aryl, and
5- to 10-membered heteroaryl comprising 1, 2, 3, or 4 ring heteroatoms selected from N, S, and O,
optionally wherein one of R3 and R5, together with one of R11 and R13 and the atoms intervening between them, may form a 5- or 6-membered cycloalkyl, cycloalkenyl or aryl group, or a 5- or 6-membered heterocycloalkyl, heterocycloalkenyl or heteroaryl group which comprises 1, 2, 3, or 4 ring heteroatoms selected from N, S, and O;
wherein said alkyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl, and heteroaryl are optionally substituted by one or more groups independently selected from R24;
any two R14 substituents on adjacent ring atoms may, together with the ring atoms to which they are attached, independently form a 5- or 6-membered cyclic group optionally comprising 1, 2, or 3 ring heteroatoms selected from N, S, and O, which cyclic group is optionally substituted by one or more groups independently selected from halogen, C1-4-alkyl, and C1-4-haloalkyl, and
any remaining R14 is in each case independently selected from
halogen,
CN,
OH,
C1-6-alkyl,
O—(C1-6-alkyl),
O—(C1-6-haloalkyl),
O—(C1-6-alkyl-C3-6-cycloalkyl),
(C0-4-alkyl)-SO2R17,
(C0-4-alkyl)-N(R18)2,
(C0-4-alkyl)-NHCOR19,
(C0-4-alkyl)-NHSO2R20,
(C0-4-alkyl)-CON(R21)2,
(C0-4-alkyl)-CO2R22,
(C0-4-alkyl)-SO2N(R23)2, and
(C0-4-alkyl)-heteroaryl,
wherein said heteroaryl is a 5- to 10-membered heteroaryl comprising 1, 2, 3, or 4 ring heteroatoms selected from N, S, and O;
R15 is in each case independently selected from halogen,
CN,
OH,
oxo,
NO2,
C1-6-alkyl,
C2-6-alkenyl,
C2-6-alkynyl,
(C0-4-alkyl)-O—(C1-6-alkyl),
(C0-4-alkyl)-SO2R17,
(C0-4-alkyl)-N(R18)2,
(C0-4-alkyl)-NHCOR19,
(C0-4-alkyl)-NHSO2R20,
(C0-4-alkyl)-CON(R21)2,
(C0-4-alkyl)-CO2R22,
(C0-4-alkyl)-SO2N(R23)2,
(C0-4-alkyl)-heteroaryl, wherein said heteroaryl is a 5- to 10-membered heteroaryl comprising 1, 2, 3, or 4 ring heteroatoms selected from N, S, and O,
(C0-4-alkyl)-heterocycloalkenyl, wherein said heterocycloalkenyl is a 5- to 10-membered heterocycloalkenyl comprising 1 or 2 ring heteroatoms selected from N and O,
(C0-4-alkyl)-heterocycloalkyl, wherein said heterocycloalkyl is a 4- to 6-membered heterocycloalkyl comprising 1 or 2 ring heteroatoms selected from N and O,
(C0-4-alkyl)-aryl, wherein said aryl is a 6- to 10-membered aryl,
(C0-4-alkyl)-cycloalkenyl, wherein said cycloalkenyl is a 5- to 8-membered cycloalkenyl, and
(C0-4-alkyl)-cycloalkyl, wherein said cycloalkyl is a 3- to 8-membered cycloalkyl,
wherein said alkyl, alkenyl, alkynyl, heteroaryl, heterocycloalkenyl, heterocycloalkyl, aryl, cycloalkenyl, and cycloalkyl are optionally substituted by one or more groups independently selected from halogen, OH, O—(C1-4-alkyl), oxo, C(O)—(C1-4-alkyl), C(O)O—(C1-4-alkyl), and NH2;
R16 and R24 are in each case independently selected from
halogen,
CN,
OH,
C1-6-alkyl,
O—(C1-6-alkyl),
(C0-4-alkyl)-SO2R17,
(C0-4-alkyl)-N(R18)2,
(C0-4-alkyl)-NHCOR19,
(C0-4-alkyl)-NHSO2R20,
(C0-4-alkyl)-CON(R21)2,
(C0-4-alkyl)-CO2R22,
(C0-4-alkyl)-SO2N(R23)2,
(C0-4-alkyl)-heteroaryl, wherein said heteroaryl is a 5- to 10-membered heteroaryl comprising 1, 2, 3, or 4 ring heteroatoms selected from N, S, and O,
(C0-4-alkyl)-heterocycloalkenyl, wherein said heterocycloalkenyl is a 5- to 6-membered heterocycloalkenyl comprising 1 or 2 ring heteroatoms selected from N and O,
(C0-4-alkyl)-heterocycloalkyl, wherein said heterocycloalkyl is a 4- to 6-membered heterocycloalkyl comprising 1 or 2 ring heteroatoms selected from N and O,
(C0-4-alkyl)-aryl, wherein said aryl is a 6- to 10-membered aryl,
(C0-4-alkyl)-cycloalkenyl, wherein said cycloalkenyl is a 5- to 8-membered cycloalkenyl, and
(C0-4-alkyl)-cycloalkyl, wherein said cycloalkyl is a 3- to 8-membered cycloalkyl,
wherein said alkyl, heteroaryl, heterocycloalkenyl, heterocycloalkyl, aryl, cycloalkenyl, and cycloalkyl are optionally substituted by one or more groups independently selected from halogen;
and
R17 to R23 are in each case independently selected from
H,
C1-6-alkyl,
C3-8-cycloalkyl,
3- to 6-membered heterocycloalkyl comprising 1, 2, or 3 ring heteroatoms selected from N, S, and O,
C5-8-cycloalkenyl,
5- to 6-membered heterocycloalkenyl comprising 1, 2, or 3 ring heteroatoms selected from N, S, and O,
C6-10-aryl, and
5- to 10-membered heteroaryl comprising 1, 2, 3, or 4 ring heteroatoms selected from N, S, and O,
wherein any pair of R18 groups attached to the same nitrogen atom, taken together with the intervening nitrogen atom, may form a 3- to 10-membered heterocycloalkyl or heterocycloalkenyl group comprising 1, 2, or 3 ring heteroatoms selected from N, S, and O,
wherein any pair of R21 groups attached to the same nitrogen atom, taken together with the intervening nitrogen atom, may form a 3- to 10-membered heterocycloalkyl or heterocycloalkenyl group comprising 1, 2, or 3 ring heteroatoms selected from N, S, and O,
wherein any pair of R23 groups attached to the same nitrogen atom, taken together with the intervening nitrogen atom, may form a 3- to 10-membered heterocycloalkyl or heterocycloalkenyl group comprising 1, 2, or 3 ring heteroatoms selected from N, S, and O,
wherein each said alkyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl, and heteroaryl is optionally and independently substituted by one or more groups independently selected from halogen, OH, C1-6-alkyl, and C1-6-haloalkyl.

134 more elements

A compound selected from

4-chloro-N-(1-((1R,3r,5S,6r)-3-hydroxybicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3r,5S,6r)-3-(quinolin-4-yloxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-hydroxybicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(quinolin-4-yloxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((6-fluoroquinazolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(6-fluoro-4-oxoquinazolin-3(4H)-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide
2-(4-chlorophenyl);
—N-((1R,3s,5S,6r)-3-((6-fluoroquinolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)acetamide;
(1R,5S)—N-(4-chlorophenyl)-3-(quinolin-4-yloxy)bicyclo[3.1.0]hexane-6-carboxamide;
4-chloro-N-(((1R,3s,5S,6r)-3-((6-fluoroquinolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)methyl)benzamide;
1-(4-chlorophenyl)-3-((1R,3s,5S,6r)-3-((6-fluoroquinolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)urea;
2-(4-chlorophenyl)-5-(3-(quinolin-4-yloxy)bicyclo[3.1.0]hexan-6-yl)-1,3,4-oxadiazole;
4-((6-(2-(4-chlorophenoxy)ethyl)bicyclo[3.1.0]hexan-3-yl)oxy)-6-fluoro-2-(trifluoromethyl)quinoline;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((6-fluoroquinazolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)ethyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(4-fluorophenoxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((2-methylpyridin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
(1R,5S)—N-(4-chlorobenzyl)-3-(quinolin-4-yloxy)bicyclo[3.1.0]hexane-6-carboxamide;
(1R,5S)—N-(4-chlorobenzyl)-3-((6-fluoro-2-(trifluoromethyl)quinolin-4-yl)oxy)bicyclo[3.1.0]hexane-6-carboxamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((6-fluoropyridin-3-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((6-fluoroquinolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((6-fluoro-2-methylquinolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((7-chloroquinazolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((6-fluoro-2-(trifluoromethyl)quinolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(((1R,3s,5S,6s)-3-((6-fluoroquinolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)methyl)benzamide;
4-chloro-N-(((1R,3s,5S,6s)-3-((6-fluoro-2-(trifluoromethyl)quinolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)methyl)benzamide;
4-chloro-N-(3-((6-fluoro-2-(trifluoromethyl)quinolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)benzamide;
4-chloro-N-(3-(quinolin-4-yloxy)bicyclo[3.1.0]hexan-6-yl)benzamide;
1-(4-bromophenyl)-N-(3-(quinolin-4-yloxy)bicyclo[3.1.0]hexan-6-yl)methanesulfonamide;
4-chloro-N-(3-(quinolin-4-yloxy)bicyclo[3.1.0]hexan-6-yl)benzenesulfonamide;
1-(4-chlorophenyl)-3-((1R,3r,5S,6r)-3-((6-fluoroquinolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)urea;
2-(4-chlorophenyl)-N-((1R,5S)-3-(quinolin-4-yloxy)bicyclo[3.1.0]hexan-6-yl)acetamide;
2-(4-chlorophenyl)-N-((1R,3r,5S)-3-((6-fluoroquinolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)acetamide;
4-chloro-N-(((1R,3r,5S,6r)-3-((6-fluoroquinolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)methyl)benzamide;
4-chloro-N-(((1R,3r,5S,6r)-3-((4-chloroquinolin-6-yl)oxy)bicyclo[3.1.0]hexan-6-yl)methyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(7-fluoro-4-oxoquinazolin-3(4H)-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((7-fluoroquinazolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(5-fluoro-4-oxoquinazolin-3(4H)-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((5-fluoroquinazolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
N-(1-((1R,3s,5S,6r)-3-((1,5-naphthyridin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)-4-chlorobenzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((3-fluoropyridin-2-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((6-methylpyridin-2-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((3-methylpyridin-2-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(2,5-difluorophenoxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(quinolin-8-yloxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(2,6-difluorophenoxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
N-(1-((1R,3s,5S,6r)-3-(2-(2-amino-2-oxoethyl)phenoxy)bicyclo[3.1.0]hexan-6-yl)propyl)-4-chlorobenzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(cinnolin-4-yloxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(4-oxocinnolin-1(4H)-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(2-((dimethylamino)methyl)phenoxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(quinolin-3-yloxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
N-(1-((1R,3s,5S,6r)-3-(1H-pyrazolo[4,3-c]pyridin-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)-4-chlorobenzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((5-fluoro-2-methylpyrimidin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(7-chloro-4-oxoquinazolin-3(4H)-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((5-fluoropyrimidin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
N-(1-((1R,3s,5S,6r)-3-((1,6-naphthyridin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)-4-chlorobenzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((7-fluoroquinolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((4-chloroquinolin-7-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((5-fluoropyridin-3-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(quinazolin-4-yloxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((2-chloropyridin-3-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
2-(4-chlorophenyl)-N-((1R,3s,5S,6r)-3-((6-fluoroquinazolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)acetamide;
2-(4-chlorophenyl)-N-((1R,3s,5S,6r)-3-(6-fluoro-4-oxoquinazolin-3(4H)-yl)bicyclo[3.1.0]hexan-6-yl)acetamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(6-fluoro-4-oxoquinazolin-3(4H)-yl)bicyclo[3.1.0]hexan-6-yl)ethyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((6-fluoroquinazolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)ethyl)benzamide;
4-chloro-N-(((1R,3s,5S,6r)-3-(6-fluoro-4-oxoquinazolin-3(4H)-yl)bicyclo[3.1.0]hexan-6-yl)methyl)benzamide;
4-cyano-N-(1-((1R,3s,5S,6r)-3-((6-fluoroquinazolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-cyano-N-(1-((1R,3s,5S,6r)-3-(6-fluoro-4-oxoquinazolin-3(4H)-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
N-(1-((1R,3s,5S,6r)-3-((6-fluoroquinazolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)-2-methoxypyrimidine-5-carboxamide;
2,2-difluoro-N-(1-((1R,3s,5S,6r)-3-((6-fluoroquinazolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzo[d][1,3]dioxole-5-carboxamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((7-fluoroquinazolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)ethyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((3-methylpyridin-2-yl)oxy)bicyclo[3.1.0]hexan-6-yl)ethyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(phthalazin-1-yloxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-morpholinobicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
N-(1-((1R,3s,5S,6r)-3-(6-fluoro-4-oxoquinazolin-3(4H)-yl)bicyclo[3.1.0]hexan-6-yl)propyl)-6-methoxynicotinamide;
5-chloro-N-(1-((1R,3s,5S,6r)-3-(6-fluoro-4-oxoquinazolin-3(4H)-yl)bicyclo[3.1.0]hexan-6-yl)propyl)picolinamide;
5-cyano-N-(1-((1R,3s,5S,6r)-3-(6-fluoro-4-oxoquinazolin-3(4H)-yl)bicyclo[3.1.0]hexan-6-yl)propyl)picolinamide;
5-chloro-N-(1-((1R,5S)-3-(cinnolin-4-yloxy)bicyclo[3.1.0]hexan-6-yl)propyl)picolinamide;
N-(1-((1R,3s,5S,6r)-3-((6-fluoroquinazolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)-6-methoxynicotinamide;
2-(4-chlorophenyl)-N-((1R,3s,5S,6r)-3-(cinnolin-4-yloxy)bicyclo[3.1.0]hexan-6-yl)acetamide;
N-(1-((1R,3s,5S,6r)-3-(cinnolin-4-yloxy)bicyclo[3.1.0]hexan-6-yl)propyl)-4-cyanobenzamide;
N-(1-((1R,3s,5S,6r)-3-(1H-1,2,4-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)-4-chlorobenzamide;
N-(1-((1R,3s,5S,6r)-3-(cinnolin-4-yloxy)bicyclo[3.1.0]hexan-6-yl)propyl)-5-cyanopicolinamide;
5-cyano-N-(1-((1R,3s,5S,6r)-3-(4-oxocinnolin-1(4H)-yl)bicyclo[3.1.0]hexan-6-yl)propyl)picolinamide;
ethyl 3-(4-chlorobenzamido)-3-((1R,3s,5S,6r)-3-(cinnolin-4-yloxy)bicyclo[3.1.0]hexan-6-yl)propanoate;
2-(4-chlorophenyl)-N-((1R,3s,5S,6r)-3-(4-oxocinnolin-1(4H)-yl)bicyclo[3.1.0]hexan-6-yl)acetamide;
2-(4-chlorophenyl)-N-((1R,3s,5S,6r)-3-(cinnolin-4-yloxy)bicyclo[3.1.0]hexan-6-yl)-N-methylacetamide;
4-cyano-N-(2-((1R,5S)-3-(4-oxocinnolin-1(4H)-yl)bicyclo[3.1.0]hexan-6-yl)propan-2-yl)benzamide;
N-(2-((1R,5S)-3-(cinnolin-4-yloxy)bicyclo[3.1.0]hexan-6-yl)propan-2-yl)-4-cyanobenzamide;
N-(1-((1R,3s,5S,6r)-3-(1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)-4-chlorobenzamide;
N-(1-((1R,3s,5S,6r)-3-azidobicyclo[3.1.0]hexan-6-yl)propyl)-4-chlorobenzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(4-cyclopropyl-1H-1,2,3-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((4-chloro-2-methylpyridin-3-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((3-fluoro-2-methylpyridin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
1-((1R,3s,5S,6r)-6-(1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)-1H-1,2,3-triazole-4-carboxylic acid;
1-((1R,3s,5S,6r)-6-(1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)-1H-1,2,3-triazole-4-carboxamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((tetrahydro-2H-pyran-4-yl)methoxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(4-(2-hydroxypropan-2-yl)-1H-1,2,3-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(4-(pyrrolidine-1-carbonyl)-1H-1,2,3-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
N-(1-((1R,3s,5S,6r)-3-(1H-benzo[d][1,2,3]triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)-4-chlorobenzamide;
N-(1-((1R,3s,5S,6r)-3-(2H-benzo[d][1,2,3]triazol-2-yl)bicyclo[3.1.0]hexan-6-yl)propyl)-4-chlorobenzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((tetrahydro-2H-pyran-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-cyano-N-(1-((1R,3s,5S,6r)-3-((7-fluoroquinazolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)ethyl)benzamide;
4-chloro-N—((S)-1-((1R,3R,5S,6r)-3-(cinnolin-4-yloxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N—((R)-1-((1R,3S,5S,6r)-3-(cinnolin-4-yloxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-cyano-N-(1-((1R,3r,5S,6r)-3-hydroxybicyclo[3.1.0]hexan-6-yl)ethyl)benzamide;
4-cyano-N-(1-((1R,3s,5S,6r)-3-hydroxybicyclo[3.1.0]hexan-6-yl)ethyl)benzamide;
4-cyano-N-(1-((1R,3s,5S,6r)-3-((6-fluoroquinazolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)ethyl)benzamide;
4-cyano-N-(1-((1R,3s,5S,6r)-3-(6-fluoro-4-oxoquinazolin-3(4H)-yl)bicyclo[3.1.0]hexan-6-yl)ethyl)benzamide;
N-(1-((1R,5S,6R)-bicyclo[3.1.0]hex-2-en-6-yl)propyl)-4-chlorobenzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(2,3-dioxoindolin-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
N-(1-((1R,3s,5S,6r)-3-((6-fluoroquinazolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)ethyl)-6-methoxynicotinamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(phenylsulfonamido)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
N-((1R,3s,5S,6r)-6-(1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)picolinamide;
N-((1R,3s,5S,6r)-6-(1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)quinoline-2-carboxamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(3,3-difluoro-2-oxoindolin-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-cyano-N-(1-((1R,3s,5S,6r)-3-(7-fluoro-4-oxoquinazolin-3(4H)-yl)bicyclo[3.1.0]hexan-6-yl)ethyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(5-fluoro-2-oxoindolin-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(3,3-dimethyl-2,5-dioxopyrrolidin-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((6-fluoroquinazolin-4-yl)amino)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
N-(1-((1R,3s,5S,6r)-3-((7-fluoroquinazolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)ethyl)-6-methoxynicotinamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(6-fluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3r,5S,6r)-3-((6-fluoroquinolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3r,5S,6r)-3-((4-chloroquinolin-6-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
N-(1-((1R,3s,5S,6r)-3-hydroxybicyclo[3.1.0]hexan-6-yl)ethyl)-6-methoxynicotinamide;
4-cyano-N-(1-((1R,3s,5S,6r)-3-(4-cyclopropyl-1H-1,2,3-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)ethyl)benzamide;
4-cyano-N—((R)-1-((1R,3S,5S,6r)-3-((6-fluoroquinazolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)ethyl)benzamide;
4-cyano-N—((S)-1-((1R,3R,5S,6r)-3-((6-fluoroquinazolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)ethyl)benzamide;
4-cyano-N—((R)-1-((1R,3S,5S,6r)-3-((7-fluoroquinazolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)ethyl)benzamide;
4-cyano-N—((S)-1-((1R,3R,5S,6r)-3-((7-fluoroquinazolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)ethyl)benzamide;
Ethyl 3-(4-chlorobenzamido)-3-((1R,3s,5S,6r)-3-((6-fluoroquinazolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propanoate;
N-(1-((1R,3s,5S,6r)-3-(cinnolin-4-yloxy)bicyclo[3.1.0]hexan-6-yl)ethyl)-4-cyanobenzamide;
4-cyano-N-(1-((1R,3s,5S,6r)-3-(4-oxocinnolin-1(4H)-yl)bicyclo[3.1.0]hexan-6-yl)ethyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((6-fluoroquinazolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)-3-hydroxypropyl)benzamide;
4-chloro-N-(1-((1R,3r,5S,6r)-3-(cinnolin-4-yloxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(cinnolin-4-yloxy)bicyclo[3.1.0]hexan-6-yl)-3-hydroxypropyl)benzamide;
4-chloro-N-(3-hydroxy-1-((1R,3s,5S,6r)-3-(4-oxocinnolin-1(4H)-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N—((R)-1-((1R,3S,5S,6r)-3-(4-(2-hydroxypropan-2-yl)-1H-1,2,3-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N—((S)-1-((1R,3R,5S,6r)-3-(4-(2-hydroxypropan-2-yl)-1H-1,2,3-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
N-((1R,3s,5S,6r)-6-(1-(4-cyanobenzamido)ethyl)bicyclo[3.1.0]hexan-3-yl)picolinamide;
N-((1R,3s,5S,6r)-6-(1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)-5-fluoropicolinamide;
N-((1R,3s,5S,6r)-6-(1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)nicotinamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(4-(prop-1-en-2-yl)-1H-1,2,3-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
3-(4-chlorobenzamido)-3-((1R,3s,5S,6r)-3-((6-fluoroquinazolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propanoic acid;
N-((1R,3s,5S,6r)-6-(1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)pyrimidine-4-carboxamide;
6-chloro-N-((1R,3s,5S,6r)-6-(1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)pyrazine-2-carboxamide;
N-((1R,3s,5S,6r)-6-(1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)pyridazine-3-carboxamide;
N-((1R,3s,5S,6r)-6-(1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)pyrazine-2-carboxamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(5-cyclopropyl-1H-1,2,3-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(5-(2-hydroxypropan-2-yl)-1H-1,2,3-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(5-(hydroxymethyl)-1H-1,2,3-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
N-((1R,3s,5S,6r)-6-(1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)piperazine-1-carboxamide;
N-((1R,3s,5S,6r)-6-(1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)morpholine-4-carboxamide;
3-chloro-N-((1R,3s,5S,6r)-6-(1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)-4-(trifluoromethyl)picolinamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(methylsulfonamido)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((1-methylcyclopropane)-1-sulfonamido)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(1,3-dioxoisoindolin-2-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(6-fluoro-1H-indazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(6-fluoro-2H-indazol-2-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
N-((1R,3s,5S,6r)-6-(1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)-5-methoxypicolinamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(5-ethyl-1H-1,2,3-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(cyano(phenyl)methyl)bicyclo[3.1.0]hexan-6-yl) propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(4-ethyl-1H-1,2,3-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(4-cyclopropyl-1H-1,2,3-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)-2-hydroxyethyl)benzamide;
Methyl 2-(4-chlorobenzamido)-2-((1R,3s,5S,6r)-3-(4-cyclopropyl-1H-1,2,3-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)acetate;
N-((1R,3s,5S,6r)-6-(1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)-5-fluoronicotinamide;
N-((1R,3s,5S,6r)-6-(1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)-3,5-difluoropicolinamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(3-cyclopropyl-4H-1,2,4-triazol-4-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(4-cyclopropyl-1H-1,2,3-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)-2-methoxyethyl)benzamide;
N-(1-((1R,3s,5S,6r)-3-(1H-pyrazolo[3,4-c]pyridin-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)-4-chlorobenzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(1-oxoisoindolin-2-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(5,6-dichloro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
N-((1R,3s,5S,6r)-6-(1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)-1H-pyrazole-4-carboxamide;
N-(1-((1R,3s,5S,6r)-3-(6-bromo-1H-benzo[d][1,2,3]triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)-4-chlorobenzamide;
N-(1-((1R,3s,5S,6r)-3-(5-bromo-2H-benzo[d][1,2,3]triazol-2-yl)bicyclo[3.1.0]hexan-6-yl)propyl)-4-chlorobenzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
N-(1-((1R,3s,5S,6r)-3-(4H-imidazo[4,5-b]pyridin-4-yl)bicyclo[3.1.0]hexan-6-yl)propyl)-4-chlorobenzamide;
N-(1-((1R,3s,5S,6r)-3-(1H-imidazo[4,5-b]pyridin-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)-4-chlorobenzamide;
N-(1-((1R,3s,5S,6r)-3-(3H-imidazo[4,5-b]pyridin-3-yl)bicyclo[3.1.0]hexan-6-yl)propyl)-4-chlorobenzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(2-oxooxazolidin-3-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3r,5S,6r)-3-(4-cyclopropyl-1H-1,2,3-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3r,5S,6r)-3-(4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
N-((1R,3s,5S,6r)-6-(1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)-3-fluoropicolinamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(3-methyl-3-(pyridin-2-yl)ureido)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
Ethyl 2-(((1R,3s,5S,6r)-6-(1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)amino)-2-phenylacetate;
4-chloro-N-(1-((1R,3r,5S,6r)-3-(5-cyclopropyl-1H-1,2,3-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(5-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((6-fluoro-1H-benzo[d]imidazol-2-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(4-fluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(7-fluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide
N-(1-((1R,3s,5S,6r)-3-(1H-imidazo[4,5-c]pyridin-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)-4-chlorobenzamide;
N-(1-((1R,3s,5S,6r)-3-(3H-imidazo[4,5-c]pyridin-3-yl)bicyclo[3.1.0]hexan-6-yl)propyl)-4-chlorobenzamide;
N-(1-((1R,3s,5S,6r)-3-(5H-imidazo[4,5-c]pyridin-5-yl)bicyclo[3.1.0]hexan-6-yl)propyl)-4-chlorobenzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(5-fluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(4-phenyl-1H-imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(2-methyl-1H-imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
methyl (S/R)-2-((1R,3S,5S,6S)-6-((R/S)-1-(4-chlorobenzamido)propyl)bicyclo [3.1.0]hexan-3-yl)-2-phenylacetate;
methyl (S/R)-2-((1R,3R,5S,6S)-6-((S/R)-1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)-2-phenylacetate;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(4-phenyl-2H-1,2,3-triazol-2-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(7-fluoro-2H-indazol-2-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(7-fluoro-1H-indazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(5-fluoro-2H-indazol-2-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(5-fluoro-1H-indazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(4-fluoro-2H-indazol-2-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(4-fluoro-1H-indazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
N-(1-((1R,3s,5S,6r)-3-(2H-pyrazolo[3,4-b]pyridin-2-yl)bicyclo[3.1.0]hexan-6-yl)propyl)-4-chlorobenzamide;
N-(1-((1R,3s,5S,6r)-3-(1H-pyrazolo[3,4-b]pyridin-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)-4-chlorobenzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(4,6-difluoro-2H-benzo[d][1,2,3]triazol-2-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide
4-chloro-N-(1-((1R,3r,5S,6r)-3-(4-(methoxymethyl)-1H-1,2,3-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3r,5S,6r)-3-(4-((2-methoxyethoxy)methyl)-1H-1,2,3-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3r,5S,6r)-3-(4-(ethoxymethyl)-1H-1,2,3-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
2-(((1R,3s,5S,6r)-6-(1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)amino)-2-phenylacetic acid;
3-chloro-N-((1R,3s,5S,6r)-6-(1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)picolinamide;
N-((1R,3s,5S,6r)-6-(1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)-4-(trifluoromethyl)nicotinamide;
N-((1R,3r,5S,6r)-6-(1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)-3-fluoropicolinamide;
N-((1R,3r,5S,6r)-6-(1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)-5-fluoropicolinamide;
3-chloro-N-((1R,3r,5S,6r)-6-(1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)-4-(trifluoromethyl)picolinamide;
N-((1R,3s,5S,6r)-6-(1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)-2-methylnicotinamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((2-(methylamino)-2-oxo-1-phenylethyl)amino)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
N-((1R,3s,5S,6r)-6-(1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)-4-(trifluoromethyl)picolinamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(pyridin-2-ylamino)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((5-fluoropyridin-2-yl)amino)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
2-((1R,3s,5S,6r)-6-(1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)-2-phenylacetic acid;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(5-fluoro-1H-indol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N—((R/S)-1-((1R,3S,5S,6S)-3-((S/R)-2-(methylamino)-2-oxo-1-phenylethyl) bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N—((R/S)-1-((1R,3S,5S,6S)-3-((R/S)-2-(methylamino)-2-oxo-1-phenylethyl) bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(4-(1,3-dioxoisoindolin-2-yl)-1H-1,2,3-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
3-(1-((1R,3s,5S,6r)-6-(1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)-1H-1,2,3-triazol-4-yl)azetidine-1-carboxylate;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(6-cyano-3H-imidazo[4,5-b]pyridin-3-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(6-cyano-1H-imidazo[4,5-b]pyridin-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((5-fluoro-3-nitropyridin-2-yl)amino)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
N-(1-((1R,3s,5S,6r)-3-(4-(azetidin-3-yl)-1H-1,2,3-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)-4-chlorobenzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(4-(dimethylamino)-1H-1,2,3-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
N-(1-((1R,3s,5S,6r)-3-(4-amino-1H-1,2,3-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)-4-chlorobenzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(6-fluoro-3H-imidazo[4,5-b]pyridin-3-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-cyano-N-(1-((1R,3s,5S,6r)-3-(4-(methoxymethyl)-1H-1,2,3-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)ethyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((3,5-difluoro-2-nitrophenyl)amino)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((2,3-difluoro-6-nitrophenyl)amino)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(6,7-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(4,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N—((R)-1-((1R,3S,5S,6r)-3-(6-fluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N—((S)-1-((1R,3S,5S,6r)-3-(6-fluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((7-chloroquinazolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,5R,6S)-3-(5-(trifluoromethyl)pyridin-3-yl)bicyclo[3.1.0]hex-2-en-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,5R,6S)-3-(7-fluoroquinazolin-4-yl)bicyclo[3.1.0]hex-2-en-6-yl)propyl)benzamide;
N-(1-((1R,3s,5S,6r)-3-(4-acetamido-1H-1,2,3-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)-4-chlorobenzamide;
N-(1-((1R,3s,5S,6r)-3-(4-(1-acetylazetidin-3-yl)-1H-1,2,3-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)-4-chlorobenzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(5-cyclopropyl-1H-1,2,4-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N—((R)-1-((1R,3S,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(4-cyclopropyl-1H-imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3S,5S,6r)-3-(4-(propen-2-yl)-1H-1,2,3-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(pyrazol-1-yl)bicyclo[3.1.0]hexan-6-yl)ethyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((2,4-difluoro-6-nitrophenyl)amino)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N—((R)-1-((1R,3S,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)ethyl)benzamide;
4-chloro-N—((R)-1-((1R,3S,5S,6r)-3-(6-fluoroquinolin-4-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(5,7-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-cyano-N—((R)-1-((1R,3S,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((4-cyano-2-nitrophenyl)amino)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-((4-chloro-2-nitrophenyl)amino)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(5-cyano-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(1-((1R,3s,5S,6r)-3-(5-chloro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N—((R)-1-((1R,3S,5S,6r)-3-(6-chloro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-cyano-N—((R)-1-((1R,3S,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)ethyl)benzamide;
4-chloro-N—((R)-1-((1R,3S,5S,6r)-3-(6-fluoro-2-methyl-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N—((R)-1-((1R,3S,5S,6r)-3-(6-fluoro-2-(trifluoromethyl)-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-cyano-N—((R)-1-((1R,3S,5S,6r)-3-(6-fluoroquinolin-4-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-cyano-N—((R)-1-((1R,3S,5S,6r)-3-(6-fluoroquinolin-4-yl)bicyclo[3.1.0]hexan-6-yl)ethyl)benzamide;
4-chloro-N—((R)-1-((1R,3S,5S,6r)-3-(6-fluoroquinazolin-4-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
N-(4-chlorophenyl)-2-((1R,3s,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propanamide;
4-chloro-N—((R)-1-((1R,3S,5S,6r)-3-(6-cyano-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
N-((1R)-1-((1R,5S,6r)-3-azidobicyclo[3.1.0]hexan-6-yl)propyl)-4-cyanobenzamide;
4-chloro-N—((R)-1-((1R,3S,5S,6r)-3-((5-chloro-2-nitrophenyl)amino)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N—((R)-1-((1R,3S,5S,6r)-3-(6-fluoroquinolin-4-yl)bicyclo[3.1.0]hexan-6-yl)ethyl)benzamide;
4-chloro-N—((R)-1-((1R,3R,5S,6r)-3-(6-fluoroquinolin-4-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N-(2-((1R,3s,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propan-2-yl)benzamide;
4-cyano-N—((R)-1-((1R,3S,5S,6r)-3-(6-cyano-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
N—((R)-1-((1R,3S,5S,6r)-3-(6-chloro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)-4-cyanobenzamide;
diethyl 2-((1R,3S,5S,6r)-6-((R)-1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)malonate;
4-chloro-N—((R)-1-((1R,3S,5S,6r)-3-(1,3-dihydroxypropan-2-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N—((R)-1-((1R,3S,5S,6r)-3-(1-cyclopropyl-1H-pyrazol-4-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-cyano-N—((R)-1-((1R,3S,5S,6r)-3-(6-cyano-2-methyl-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
N—((R)-1-((1R,3S,5S,6r)-3-(6-chloro-2-methyl-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)-4-cyanobenzamide;
4-cyano-N-((1R)-1-((1R,3S,5S,6r)-3-(4-(tetrahydrofuran-3-yl)-1H-1,2,3-triazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-cyano-N—((R)-1-((1R,3R,5S,6r)-3-hydroxybicyclo[3.1.0]hexan-6-yl)ethyl)benzamide;
4-cyano-N—((R)-1-((1R,3S,5S,6r)-3-hydroxybicyclo[3.1.0]hexan-6-yl)ethyl)benzamide;
(R)—N-(4-chlorophenyl)-2-((1R,3S,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propanamide;
(S)—N-(4-chlorophenyl)-2-((1R,3R,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propanamide;
dimethyl 1-((1R,3S,5S,6r)-6-((R)-1-(4-cyanobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)-1H-1,2,3-triazole-4,5-dicarboxylate;
4-chloro-N-(((1R,3s,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)methyl)benzamide;
4-cyano-N-(((1R,3s,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)methyl)benzamide;
4-chloro-N—((R)-1-((1R,3R,5S,6r)-3-(5-cyclopropylpyridin-3-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N—((R)-1-((1R,3S,5S,6r)-3-(4-iodo-1H-pyrazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N—((R)-1-((1R,3S,5S,6r)-3-(4-vinyl-1H-pyrazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
N—((R)-1-((1R,3S,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)-4-fluorobenzamide;
4-chloro-N—((R)-1-((1R,3S,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)-3-fluorobenzamide;
N—((R)-1-((1R,3S,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)-2-methylisonicotinamide;
N—((R)-1-((1R,3S,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)-2-methylthiazole-4-carboxamide;
3-chloro-N—((R)-1-((1R,3S,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
N—((R)-1-((1R,3S,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)-6-methylnicotinamide;
N—((R)-1-((1R,3S,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)-3-fluorobenzamide;
3-cyano-N—((R)-1-((1R,3S,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
N-(((1R,3s,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)methyl)-4-fluorobenzamide;
4-chloro-N-(((1R,3s,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)methyl)-3-fluorobenzamide;
3-chloro-N-(((1R,3s,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)methyl)benzamide;
N-(((1R,3s,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)methyl)-6-methylnicotinamide;
N-(((1R,3s,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)methyl)-6-methoxynicotinamide;
N-(((1R,3s,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)methyl)-1-methyl-1H-pyrazole-4-carboxamide;
N-(((1R,3s,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)methyl)-3-fluorobenzamide;
3-cyano-N-(((1R,3s,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)methyl)benzamide;
N-(((1R,3s,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)methyl)-4-methylbenzamide;
N-(((1R,3s,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)methyl)-3-methylbenzamide;
N—((R)-1-((1R,3S,5S,6r)-3-(1H-pyrazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)-4-chlorobenzamide;
4-chloro-N—((R)-1-((1R,3S,5S,6r)-3-(4-cyano-1H-pyrazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
methyl 1-((1R,3S,5S,6r)-6-((R)-1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)-1H-pyrazole-4-carboxylate;
N-((1R,3S,5S,6r)-6-((R)-1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)-3-fluoropicolinamide;
1-((1R,3S,5S,6r)-6-((R)-1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)-1H-pyrazole-4-carboxylic acid;
N—((R)-1-((1R,3S,5S,6r)-3-(4-bromo-1H-pyrazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)-4-chlorobenzamide;
4-chloro-N—((R)-1-((1R,3S,5S,6r)-3-(4-methyl-1H-pyrazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N—((R)-1-((1R,3S,5S,6r)-3-((2-cyanophenyl)amino)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N—((R)-1-((1R,3S,5S,6r)-3-(4-(trifluoromethyl)-1H-pyrazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
N-((1R,3S,5S,6r)-6-((R)-1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)picolinamide;
N-((1R,3S,5S,6r)-6-((R)-1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)-5-fluoronicotinamide;
N-((1R,3S,5S,6r)-6-((R)-1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)nicotinamide;
4-chloro-N—((R)-1-((1R,3S,5S,6r)-3-((6-fluoroquinazolin-4-yl)amino)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N—((R)-1-((1R,3S,5S,6r)-3-((6-ethynylquinazolin-4-yl)amino)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N—((R)-1-((1R,3S,5S,6r)-3-((6-methylquinazolin-4-yl)amino)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
N-(4-chlorophenyl)-2-((1R,3s,5S,6r)-3-((6-fluoroquinazolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propanamide;
N-(4-chlorophenyl)-2-((1R,3s,5S,6r)-3-((6-fluorocinnolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propanamide;
4-chloro-2-(((1R,3S,5S,6r)-6-((R)-1-(4-chlorobenzamido)ethyl)bicyclo[3.1.0]hexan-3-yl)oxy)benzoic acid;
4-chloro-N—((R)-1-((1R,3S,5S,6r)-3-(5-cyclopropyl-1H-pyrazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
4-chloro-N—((R)-1-((1R,3S,5S,6r)-3-(3-cyclopropyl-1H-pyrazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
1-(4-chlorophenyl)-3-((R)-1-((1R,3S,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)urea;
N-(4-chloro-3-fluorophenyl)-2-((1R,3s,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propanamide;
2-(((1R,3S,5S,6r)-6-((R)-1-(4-chlorobenzamido)propyl)bicyclo[3.1.0]hexan-3-yl)amino)benzoic acid;
N-(4-chlorophenyl)-2-((1R,3s,5S,6r)-3-((6-fluoroquinolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propanamide;
4-chloro-N—((R)-1-((1R,3S,5S,6r)-3-(4-cyclopropyl-1H-pyrazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)benzamide;
1-(4-chloro-3-fluorophenyl)-3-((R)-1-((1R,3S,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propyl)urea;
(R)—N-(4-chlorophenyl)-2-((1R,3S,5S,6r)-3-((6-fluoroquinazolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propanamide;
(S)—N-(4-chlorophenyl)-2-((1R,3R,5S,6r)-3-((6-fluoroquinazolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propanamide;
N—((R)-1-((1R,3S,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl) propyl)-1-(trifluoromethyl)cyclopropane-1-carboxamide;
1-((R)-1-((1R,3S,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl) propyl)-3-(oxetan-3-yl)urea;
N—((R)-1-((1R,3S,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl) propyl)-3,3-difluoroazetidine-1-carboxamide;
N—((R)-1-((1R,3S,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl) propyl)-4,4-difluoropiperidine-1-carboxamide;
N—((R)-1-((1R,3S,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl) propyl)morpholine-4-carboxamide;
1-cyclopropyl-3-((R)-1-((1R,3S,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl) propyl)urea;
(R)—N-(4-chlorophenyl)-2-((1R,3s,5S,6r)-3-((6-fluorocinnolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propanamide;
(S)—N-(4-chlorophenyl)-2-((1R,3s,5S,6r)-3-((6-fluorocinnolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propanamide;
(R)—N-(4-chloro-3-fluorophenyl)-2-((1R,3s,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propanamide;
(S)—N-(4-chloro-3-fluorophenyl)-2-((1R,3s,5S,6r)-3-(5,6-difluoro-1H-benzo[d]imidazol-1-yl)bicyclo[3.1.0]hexan-6-yl)propanamide;
(R)—N-(4-chlorophenyl)-2-((1R,3s,5S,6r)-3-((6-fluoroquinolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propanamide;
and
(S)—N-(4-chlorophenyl)-2-((1R,3s,5S,6r)-3-((6-fluoroquinolin-4-yl)oxy)bicyclo[3.1.0]hexan-6-yl)propanamide;
or a pharmaceutically acceptable salt thereof.

354 more elements

Dependencies are inferred from the claim text.

Facts

Application: 16/478,076Filed 16 Jan 2018 · us provisional application
Priority: 17 Jan 2017
Published: US 2019/0365718 A15 Dec 2019
Granted: 16 Nov 2021
Term ends: Not estimatedThe source records don’t support an estimate.

Classification87 codes

A61K 31/015
Hydrocarbons: carbocyclic
A61K 31/4192
Having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole: 1,2,3-Triazoles
A61K 31/166
Having aromatic rings, e.g. colchicine, atenolol, progabide: having the carbon of a carboxamide group directly attached to the aromatic ring, e.g.…
A61K 31/18
Amides, e.g. hydroxamic acids: sulfonamides

Family

Application62/447,368Us provisional application · filed 17 Jan 2017
Application62/458,777Us provisional application · filed 14 Feb 2017
Application62/528,366Us provisional application · filed 3 Jul 2017
US 2019/0365718 A1Pre-grant publication · published 5 Dec 2019
US 11,173,145 B2This patent

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

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Abstract

A compound of formula (VII),

or a pharmaceutically acceptable salt thereof, wherein one but not both of the dashed bonds may optionally be a carbon-carbon double bond, and wherein:
W is selected from C and CH;
a is selected from 0 and 1;
b is selected from 0, 1, and 2;
c is selected from 0 and 1;
d is selected from 0 and 1;
e is selected from 0 and 1;
f is selected from 0, 1, and 2;
A is selected from O, C(O), and S(O)2;
J is in each case independently selected from oxo, OH, CN, halogen, and C1-3-alkyl;
X1 is selected from C(R8)(R9), N(R10), O, and S;
X2 is selected from C(R11)(R12), N(R13) and O;
Y is selected from
C6-10-aryl, and
5- to 10-membered heteroaryl comprising 1, 2, 3, or 4 ring heteroatoms selected from N, S, and O,
wherein said aryl and heteroaryl are optionally substituted by one or more groups independently selected from R14;
R1 is selected from
H,
(G)n-(C1-6-alkyl),
(G)n-(C3-8-cycloalkyl),
N3,
(G)n-heterocycloalkyl, wherein said heterocycloalkyl is a 3- to 6-membered heterocycloalkyl comprising 1, 2, or 3 ring heteroatoms selected from N, S, and O,
(G)n-(C5-8-cycloalkenyl),
(G)n-heterocycloalkenyl, wherein said heterocycloalkenyl is a 5- to 6-membered heterocycloalkenyl comprising 1, 2, or 3 ring heteroatoms selected from N, S, and O,
(G)n-(C6-10-aryl), and
(G)n-heteroaryl, wherein said heteroaryl is a 5- to 10-membered heteroaryl comprising 1, 2, 3, or 4 ring heteroatoms selected from N, S, and O,
wherein G in each case is independently selected from C(R8)(R9), C(O), S(O)2, C(O)NR10, and S(O)2NR10;
and wherein n in each case is selected from 0 and 1, and
wherein said alkyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl, and heteroaryl are optionally substituted by one or more groups independently selected from R15;
R2, R3, R4, R6, R7, R8, R9, R11, and R12 are in each case independently selected from
H,
halogen,
CN,
OH,
(C0-4-alkyl)-SO2R17,
(C0-4-alkyl)-N(R18)2,
(C0-4-alkyl)-NHCOR19,
(C0-4-alkyl)-NHSO2R20,
(C0-4-alkyl)-CON(R21)2,
(C0-4-alkyl)-CO2R22,
(C0-4-alkyl)-SO2N(R23)2,
C1-6-alkyl,
O—(C1-6-alkyl),
C3-8-cycloalkyl,
3- to 6-membered heterocycloalkyl comprising 1, 2, or 3 ring heteroatoms selected from N, S, and O,
C5-8-cycloalkenyl,
5- to 6-membered heterocycloalkenyl comprising 1, 2, or 3 ring heteroatoms selected from N, S, and O,
C6-10-aryl, and
5- to 10-membered heteroaryl comprising 1, 2, 3, or 4 ring heteroatoms selected from N, S, and O, or
one or both geminal R3 and R4 pairs, taken together with the carbon atom to which they are attached, independently forms a 3- to 6-membered cycloalkyl group or a 3- to 6-membered heterocycloalkyl group which comprises 1, 2, or 3 ring heteroatoms selected from N, S, and O,
wherein said alkyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl, and heteroaryl are optionally substituted by one or more groups independently selected from R16;
R5, R10 and R13 are in each case independently selected from
H,
C1-6-alkyl,
C3-8-cycloalkyl,
3- to 6-membered heterocycloalkyl comprising 1, 2, or 3 ring heteroatoms selected from N, S, and O,
C5-8-cycloalkenyl,
5- to 6-membered heterocycloalkenyl comprising 1, 2, or 3 ring heteroatoms selected from N, S, and O,
C6-10-aryl, and
5- to 10-membered heteroaryl comprising 1, 2, 3, or 4 ring heteroatoms selected from N, S, and O,
optionally wherein one of R3 and R5, together with one of R11 and R13 and the atoms intervening between them, may form a 5- or 6-membered cycloalkyl, cycloalkenyl or aryl group, or a 5- or 6-membered heterocycloalkyl, heterocycloalkenyl or heteroaryl group which comprises 1, 2, 3, or 4 ring heteroatoms selected from N, S, and O;
wherein said alkyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl, and heteroaryl are optionally substituted by one or more groups independently selected from R24;
any two R14 substituents on adjacent ring atoms may, together with the ring atoms to which they are attached, independently form a 5- or 6-membered cyclic group optionally comprising 1, 2, or 3 ring heteroatoms selected from N, S, and O, which cyclic group is optionally substituted by one or more groups independently selected from halogen, C1-4-alkyl, and C1-4-haloalkyl, and
any remaining R14 is in each case independently selected from
halogen,
CN,
OH,
C1-6-alkyl,
O—(C1-6-alkyl),
O—(C1-6-haloalkyl),
O—(C1-6-alkyl-C3-6-cycloalkyl),
(C0-4-alkyl)-SO2R17,
(C0-4-alkyl)-N(R18)2,
(C0-4-alkyl)-NHCOR19,
(C0-4-alkyl)-NHSO2R20,
(C0-4-alkyl)-CON(R21)2,
(C0-4-alkyl)-CO2R22,
(C0-4-alkyl)-SO2N(R23)2, and
(C0-4-alkyl)-heteroaryl,
wherein said heteroaryl is a 5- to 10-membered heteroaryl comprising 1, 2, 3, or 4 ring heteroatoms selected from N, S, and O;
R15 is in each case independently selected from halogen,
CN,
OH,
oxo,
NO2,
C1-6-alkyl,
C2-6-alkenyl,
C2-6-alkynyl,
(C0-4-alkyl)-O—(C1-6-alkyl),
(C0-4-alkyl)-SO2R17,
(C0-4-alkyl)-N(R18)2,
(C0-4-alkyl)-NHCOR19,
(C0-4-alkyl)-NHSO2R20,
(C0-4-alkyl)-CON(R21)2,
(C0-4-alkyl)-CO2R22,
(C0-4-alkyl)-SO2N(R23)2,
(C0-4-alkyl)-heteroaryl, wherein said heteroaryl is a 5- to 10-membered heteroaryl comprising 1, 2, 3, or 4 ring heteroatoms selected from N, S, and O,
(C0-4-alkyl)-heterocycloalkenyl, wherein said heterocycloalkenyl is a 5- to 10-membered heterocycloalkenyl comprising 1 or 2 ring heteroatoms selected from N and O,
(C0-4-alkyl)-heterocycloalkyl, wherein said heterocycloalkyl is a 4- to 6-membered heterocycloalkyl comprising 1 or 2 ring heteroatoms selected from N and O,
(C0-4-alkyl)-aryl, wherein said aryl is a 6- to 10-membered aryl,
(C0-4-alkyl)-cycloalkenyl, wherein said cycloalkenyl is a 5- to 8-membered cycloalkenyl, and
(C0-4-alkyl)-cycloalkyl, wherein said cycloalkyl is a 3- to 8-membered cycloalkyl,
wherein said alkyl, alkenyl, alkynyl, heteroaryl, heterocycloalkenyl, heterocycloalkyl, aryl, cycloalkenyl, and cycloalkyl are optionally substituted by one or more groups independently selected from halogen, OH, O—(C1-4-alkyl), oxo, C(O)—(C1-4-alkyl), C(O)O—(C1-4-alkyl), and NH2;
R16 and R24 are in each case independently selected from
halogen,
CN,
OH,
C1-6-alkyl,
O—(C1-6-alkyl),
(C0-4-alkyl)-SO2R17,
(C0-4-alkyl)-N(R18)2,
(C0-4-alkyl)-NHCOR19,
(C0-4-alkyl)-NHSO2R20,
(C0-4-alkyl)-CON(R21)2,
(C0-4-alkyl)-CO2R22,
(C0-4-alkyl)-SO2N(R23)2,
(C0-4-alkyl)-heteroaryl, wherein said heteroaryl is a 5- to 10-membered heteroaryl comprising 1, 2, 3, or 4 ring heteroatoms selected from N, S, and O,
(C0-4-alkyl)-heterocycloalkenyl, wherein said heterocycloalkenyl is a 5- to 6-membered heterocycloalkenyl comprising 1 or 2 ring heteroatoms selected from N and O,
(C0-4-alkyl)-heterocycloalkyl, wherein said heterocycloalkyl is a 4- to 6-membered heterocycloalkyl comprising 1 or 2 ring heteroatoms selected from N and O,
(C0-4-alkyl)-aryl, wherein said aryl is a 6- to 10-membered aryl,
(C0-4-alkyl)-cycloalkenyl, wherein said cycloalkenyl is a 5- to 8-membered cycloalkenyl, and
(C0-4-alkyl)-cycloalkyl, wherein said cycloalkyl is a 3- to 8-membered cycloalkyl,
wherein said alkyl, heteroaryl, heterocycloalkenyl, heterocycloalkyl, aryl, cycloalkenyl, and cycloalkyl are optionally substituted by one or more groups independently selected from halogen;
and
R17 to R23 are in each case independently selected from
H,
C1-6-alkyl,
C3-8-cycloalkyl,
3- to 6-membered heterocycloalkyl comprising 1, 2, or 3 ring heteroatoms selected from N, S, and O,
C5-8-cycloalkenyl,
5- to 6-membered heterocycloalkenyl comprising 1, 2, or 3 ring heteroatoms selected from N, S, and O,
C6-10-aryl, and
5- to 10-membered heteroaryl comprising 1, 2, 3, or 4 ring heteroatoms selected from N, S, and O,
wherein any pair of R18 groups attached to the same nitrogen atom, taken together with the intervening nitrogen atom, may form a 3- to 10-membered heterocycloalkyl or heterocycloalkenyl group comprising 1, 2, or 3 ring heteroatoms selected from N, S, and O,
wherein any pair of R21 groups attached to the same nitrogen atom, taken together with the intervening nitrogen atom, may form a 3- to 10-membered heterocycloalkyl or heterocycloalkenyl group comprising 1, 2, or 3 ring heteroatoms selected from N, S, and O,
wherein any pair of R23 groups attached to the same nitrogen atom, taken together with the intervening nitrogen atom, may form a 3- to 10-membered heterocycloalkyl or heterocycloalkenyl group comprising 1, 2, or 3 ring heteroatoms selected from N, S, and O,
wherein each said alkyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl, and heteroaryl is optionally and independently substituted by one or more groups independently selected from halogen, OH, C1-6-alkyl, and C1-6-haloalkyl.

134 more elements

Facts

Application

16/478,076Filed 16 Jan 2018 · us provisional application

Priority

17 Jan 2017

Published

US 2019/0365718 A15 Dec 2019

Granted

16 Nov 2021

Term ends

Not estimatedThe source records don’t support an estimate.

Classification87 codes

A61K 31/015
Hydrocarbons: carbocyclic
A61K 31/4192
Having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole: 1,2,3-Triazoles
A61K 31/166
Having aromatic rings, e.g. colchicine, atenolol, progabide: having the carbon of a carboxamide group directly attached to the aromatic ring, e.g.…
A61K 31/18
Amides, e.g. hydroxamic acids: sulfonamides

Family

Application62/447,368Us provisional application · filed 17 Jan 2017

Application62/458,777Us provisional application · filed 14 Feb 2017

Application62/528,366Us provisional application · filed 3 Jul 2017

US 2019/0365718 A1Pre-grant publication · published 5 Dec 2019

US 11,173,145 B2This patent

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