US 2014/0179676 A1Published application

Heterocyclic nuclear hormone receptor modulators

AssigneeAbbVie Inc.

InventorsKevin P. Cusack, Thomas D. Gordon, Michael Z. Hoemann, David C. Ihle, Bin Li, Gloria Y. Lo Schiavo, Gagandeep K. Somal, Michael Friedman, Martin E. Hayes, Wouter Iwema Bakker

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Abstract

The invention provides a compound of Formula (I) pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein the variable are defined herein. The compounds of the invention are useful for treating immunological and oncological conditions.

Claims21

Dependent claims

A compound represented by the following formula:

or a pharmaceutically acceptable salt, pro-drug or solvate thereof, wherein:
Ring 1 is heterocyclic or heteroaromatic;
X is N, N(R4′), C(R4), C(R4)(R4), S or O;
Y is N, N(R4′), C(R4), S, O or C(═O);
Z is N(R4′), C(R4)C(R4) or C(R4);
A is, N(R3′), C(R3)(R3) or C(═O);
G and J are independently S, S(O), S(O)2, O, C(R1)(R2), N(R3) or C(═O) provided that at least one of G and J are C(R1)(R2) or C(═O);
E is N(R4′), S, S(O), S(O)2, O, C(R1)(R2), or C(═O);
L is N(R5), C(R5)(R5) or C(R5)(R5);
or L is C(R5) or C(R5′) and J is C(R1) or N;
M and Q are independently N, C or CH;
provided that
X, Y, and Z are not each heteroatoms at the same time;
not more than three of A, E, G, J, L, M and Q are heteroatoms;
M and Q are not both N;
adjacent atoms do not form S—S, S—O, O—O or —C(═O)—C(═O) bonds;
at least one of X, Y and Z is C(R4) or C(═O);
when Q is N, X is not S or O;
when J is S, O, S(O) or N(R3), L is not N(R5);
R1 and R2, for each occurrence, is independently —H, CF3, CN, —C(═O)NH2, OH, an optionally substituted (C1-C6)alkyl, optionally substituted (C3-C6)cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl or optionally substituted heterocyclyl;
or R1 and R2, together with the carbon to which they attach, form an optionally substituted (C3-C6)carbocyclic ring spiro to ring 2 or an optionally substituted heterocyclic ring spiro to ring 2;
R3 is independently —H, CF3, CN, OH, —NRaRb, an optionally substituted (C1-C6)alkyl, optionally substituted (C2-C6)alkenyl, optionally substituted (C2-C6)alkynyl, an optionally substituted aryl, an optionally substituted (C3-C6)cycloalkyl, an optionally substituted heteroaryl, an optionally substituted heterocyclyl, or an optionally substituted benzyl;
R3′ is independently —H, an optionally substituted (C1-C6)alkyl, optionally substituted (C2-C6)alkenyl, optionally substituted (C2-C6)alkynyl, an optionally substituted aryl, an optionally substituted (C3-C6)cycloalkyl, an optionally substituted heteroaryl, an optionally substituted heterocyclyl, or an optionally substituted benzyl;
R4 is independently H, —CF3, —CN, —OH, —NRaRb, an optionally substituted (C1-C6)alkyl, an optionally substituted (C2-C6)alkenyl, an optionally substituted (C2-C6)alkynyl, an optionally substituted (C1-C6)alkoxy, an optionally substituted aryl, an optionally substituted (C3-C6)cycloalkyl, an optionally substituted heteroaryl, or an optionally substituted heterocyclyl;
R4′ is independently —H, an optionally substituted (C1-C8)alkyl, an optionally substituted (C2-C6)alkenyl, an optionally substituted (C2-C6)alkynyl, an optionally substituted (C3-C6)cycloalkyl, an optionally substituted heterocyclyl, an optionally substituted aryl, or an optionally substituted heteroaryl;
provided that R4′ is not an optionally substituted benzisoxazolyl, an optionally substituted isobenzazolyl, an optionally substituted quinazolinyl, an optionally substituted isoquinolinyl or an optionally substituted phthalazinyl;
R5 is independently —H, OH, F, CF3, CN, optionally substituted (C1-C6)alkyl, optionally substituted (C2-C6)alkenyl, optionally substituted (C2-C6)alkynyl, optionally substituted (C3-C6)cycloalkyl, —(CH2)m-optionally substituted aryl, —(CH2)n-optionally substituted heterocyclyl, or —(CH2)n-optionally substituted heteroaryl;
or both R5, together with the carbon to which they are attached, form a carbocyclic spirocyclic ring;
R5′ is —R5′a—R5′b—R5′c wherein R5′a is attached to the ring and
R5′a is optionally substituted phenyl or optionally substituted heteroaryl;
R5′b is a bond or —C(═O)N(H) wherein the —C(═O) is attached to R5′a;
and
R5′c is optionally substituted isoxazolyl, optionally substituted oxazolyl, optionally substituted phenyl, optionally substituted pyrazolyl, optionally substituted pyridazinyl, optionally substituted pyridinyl, optionally substituted pyrimidinyl, optionally substituted pyrido[2,3-b]pyrazinyl, tetrazolyl, optionally substituted 1,3,5-thiadiazolyl, or 1,2,4-triazolyl;
Ra and Rb are independently H and optionally substituted (C1-C6)alkyl;
and
n, for each occurrence, is independently 0, 1, 2 or 3;
provided that when the compound is
then R5 is not unsubstituted phenyl or phenyl substituted by COOH, Cl, F, OH, NO2 or two OCH3;
provided that when M and Q are both CH or M and Q are both C and Ring 1 contains two nitrogen atoms, Ring 2 is not
provided that not more than one of X, Y and Z is substituted by phenyl;
and
provided that the compound is not
wherein
R1 and R2 are independently H or CH3;
R4′ is H, optionally substituted (C1-C8)alkyl, —CH2C(O)OCH2CH3, optionally substituted (C3-C8)cycloalkyl, optionally substituted benzyl, optionally substituted pyridinyl,
optionally substituted pyrimidinyl,

43 more elements

A compound selected from

4-(2,6-dichlorophenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(4-chloro-2-(trifluoromethyl)phenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(2,4-dichlorophenyl)-1,3,6,6-tetramethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(4-chloro-2-methoxyphenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
3-chloro-N,N-dimethyl-4-(1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)aniline;
4-(3-chloropyridin-4-yl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(2,4-dichlorophenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(2,4-dimethylphenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(4-methoxy-2-methylphenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(4-fluoro-2-methylphenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
1-methyl-4-(2-methyl-4-(trifluoromethoxy)phenyl)-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(4-chloro-2-methylphenyl)-2-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-2H-pyrazolo[3,4-e][1,4]thiazepine;
1-methyl-3-(pyridin-2-yl)-4-o-tolyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
3-(5-bromopyridin-2-yl)-4-(2,4-dichlorophenyl)-1-methyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(2,4-dichlorophenyl)-1-methyl-3-(thiazol-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(2,4-dichlorophenyl)-1,6,6-trimethyl-3-(thiazol-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(2,4-dichlorophenyl)-1-methyl-3-(pyridin-4-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
3-(4-bromopyridin-2-yl)-4-(4-chloro-2-methylphenyl)-1-methyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(2,5-dimethylphenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(5-chloro-3-methylpyridin-2-yl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(4-chloro-2-methylphenyl)-3-(4-methoxypyridin-2-yl)-1-methyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(4-chlorophenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(4-chloro-2-methylphenyl)-3-(4-chloropyridin-2-yl)-1-methyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(4-bromophenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(5-bromo-3-methylthiophen-2-yl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(5-bromo-2-methylphenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(5-methoxy-2-methylphenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
5-(4-(4-bromo-2-methylphenyl)-1-methyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-3-yl)-3-methylisoxazole;
4-(4-bromo-2-methylphenyl)-1-ethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(4-(2,4-dichlorophenyl)-1-methyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-3-yl)-N,N-dimethylaniline;
4-(2,4-dichlorophenyl)-1,6,6-trimethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(2,3-dimethylphenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(5-bromo-2-methylthiophen-3-yl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(4-chloro-5-methoxy-2-methylphenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-benzyl-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine hydrochloride;
4-(2-bromo-4-chlorophenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(4-chloro-2-cyclopropylphenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(4-chloro-2-(fluoromethyl)phenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(5-chloro-2-methylphenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
1-methyl-4-(2-methyl-4-(trifluoromethyl)phenyl)-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
3-methyl-4-(1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)phenol;
3-(4-(4-chloro-2-methylphenyl)-1-methyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-3-yl)-5-methylisoxazole;
4-(4-bromo-2-methylphenyl)-3-(pyridin-2-yl)-4,6,7,8-tetrahydroisoxazolo[5,4-e][1,4]thiazepine;
4-(5-chloro-2-methylphenyl)-3-cyclopropyl-1,6,6-trimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(4-chloro-2-methoxyphenyl)-3-cyclopropyl-1,6,6-trimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine hydrochloride;
4-(4-chloro-2-(trifluoromethyl)phenyl)-3-cyclopropyl-1,6,6-trimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine hydrochloride;
3-cyclopropyl-4-(2,5-dimethylphenyl)-1,6,6-trimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(5-chloro-3-methylpyridin-2-yl)-3-cyclopropyl-1,6,6-trimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(4-bromo-2-methylphenyl)-3-cyclopropyl-1,6-dimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(4-bromo-2-methylphenyl)-3-cyclopropyl-1,6-dimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(4-chloro-2-fluorophenyl)-3-cyclopropyl-1,6,6-trimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine hydrochloride;
(Z)-4-(5-bromo-2-methylphenyl)-3-cyclopropyl-1,6,6-trimethyl-4,6-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(5-bromo-2-methylphenyl)-3-cyclopropyl-1,6,6-trimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
3-cyclopropyl-4-(4-fluoro-2-methylphenyl)-1,6,6-trimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(4-chloro-2-methylphenyl)-1,3,6,6-tetramethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(4-bromo-2-methylphenyl)-1,3,6,6-tetramethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(4-chloro-2-methylphenyl)-1,3-dimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(4-bromo-2-chlorophenyl)-1,3,6,6-tetramethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
1,3,6,6-tetramethyl-4-(2-methyl-4-(trifluoromethyl)phenyl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(4-bromo-2-methylphenyl)-1,3,6-trimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(2,4-dichlorophenyl)-3,6,6-trimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(2,4-dichlorophenyl)-3-isopropyl-1,6,6-trimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine hydrochloride;
4′-(2,4-dichlorophenyl)-1′,3′-dimethyl-1′,4′,7′,8′-tetrahydrospiro[cyclopentane-1,6′-pyrazolo[3,4-e][1,4]thiazepine];
4′-(2,4-dichlorophenyl)-1′,3′-dimethyl-1′,4′,7′,8′-tetrahydrospiro[cyclobutane-1,6′-pyrazolo[3,4-e][1,4]thiazepine];
4′-(2,4-dichlorophenyl)-1′,3′-dimethyl-1′,2,3,4′,5,6,7′,8′-octahydrospiro[pyran-4,6′-pyrazolo[3,4-e][1,4]thiazepine];
4-(2,4-dichlorophenyl)-1,3,6,6-tetramethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(3-bromo-2-methylphenyl)-3-cyclopropyl-1,6,6-trimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(4-chloro-2-methylphenyl)-1-cyclopentyl-3,6,6-trimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
1,3,6,6-tetramethyl-4-(2-methyl-4-(methylsulfonyl)phenyl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(4-chloro-2-methylphenyl)-1-methyl-3-(tetrahydrofuran-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(4-chloro-2-methylphenyl)-1-methyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-3-ol;
3-cyclopropyl-4-(2,4-dichlorophenyl)-1,6,6-trimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
1,3-dimethyl-4-(4-(p-tolyloxy)phenyl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine2;
4-(1H-indazol-5-yl)-1,3-dimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
3-cyclopentyl-4-(2,4-dichlorophenyl)-1-methyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
1,3,6,6-tetramethyl-4-(4-(p-tolyloxy)phenyl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
3-cyclopentyl-4-(2,4-dichlorophenyl)-1,6,6-trimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(2,4-dichlorophenyl)-1,3-dimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(3-methoxyphenyl)-1,3-dimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
3-(4-chlorophenyl)-4-(2,4-dichlorophenyl)-1-methyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(2,4-dichlorophenyl)-1-methyl-3-phenyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(2,4-dichlorophenyl)-3-isopropyl-1-methyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
3-tert-butyl-4-(2,4-dichlorophenyl)-1-methyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(2,4-dichlorophenyl)-1-methyl-3-(pyridin-3-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(2,4-dichlorophenyl)-1-methyl-3-p-tolyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
3-(4-tert-butylphenyl)-4-(2,4-dichlorophenyl)-1-methyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(2,4-dichlorophenyl)-3-(3,4-dichlorophenyl)-1-methyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(2,4-dichlorophenyl)-3-(3,5-difluorophenyl)-1-methyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(2,4-dichlorophenyl)-1-methyl-3-(trifluoromethyl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(2,4-dichlorophenyl)-3-isobutyl-1-methyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(2,4-dichlorophenyl)-3-(2,4-difluorophenyl)-1-methyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(2,4-dichlorophenyl)-3-(4-fluorophenyl)-1-methyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(2,4-dichlorophenyl)-1-methyl-3-(4-(trifluoromethoxy)phenyl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
1,3-dimethyl-4-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(4-methoxyphenyl)-1,3-dimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(2-methoxyphenyl)-1,3-dimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
1,3-dimethyl-4-(pyridin-3-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
2-(4-(4-chlorophenyl)-1,3-dimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-6-yl)ethanol;
4-(2,4-dichlorophenyl)-1-methyl-3-(thiophen-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
1,3-dimethyl-4-(1H-pyrazol-3-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(4-chloro-2-fluorophenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
methyl 3-chloro-4-[1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepin-4-yl]benzoate;
methyl 4-(1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)benzoate;
methyl 3-methyl-4-(1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)benzoate;
methyl 4-(1,3,6,6-tetramethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)benzoate;
methyl 5-methyl-4-(1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)thiophene-2-carboxylate;
methyl 6-(4-(2,4-dichlorophenyl)-1-methyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-3-yl)nicotinate;
3-chloro-N-(2-methyl-3-pyridyl)-4-[1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydro-pyrazolo[3,4-e][1,4]thiazepin-4-yl]benzamide;
6-(4-(2,4-dichlorophenyl)-1-methyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-3-yl)-N-(2-methylpyridin-3-yl)nicotinamide;
4-(1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-N-(2-methylpyridin-3-yl)benzamide;
4-methyl-5-(1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-N-(2-methylpyridin-3-yl)thiophene-2-carboxamide;
4-methyl-3-(1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-N-(2-methylpyridin-3-yl)benzamide;
5-methyl-4-(1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-N-(2-methylpyridin-3-yl)thiophene-2-carboxamide;
4-methyl-3-[1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepin-4-yl]benzonitrile;
3-methyl-4-((4S,6S)-1,3,6-trimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)benzonitrile;
3-methyl-4-((4R,6R)-1,3,6-trimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)benzonitrile;
4-((4R,6S)-3-cyclopropyl-1,6-dimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylbenzonitrile;
4-((4S,6R)-3-cyclopropyl-1,6-dimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylbenzonitrile;
4-((4S,6S)-3-cyclopropyl-1,6-dimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylbenzonitrile;
4-((4R,6R)-3-cyclopropyl-1,6-dimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylbenzonitrile;
3-(3-cyclopropyl-1,6,6-trimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-4-methylbenzonitrile;
3-methyl-4-(1,3,6,6-tetramethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)benzonitrile;
4-(1,7-dimethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylbenzonitrile;
3-methyl-4-(1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)benzonitrile;
3-methyl-4-(3-(pyridin-2-yl)-4,6,7,8-tetrahydroisoxazolo[5,4-e][1,4]thiazepin-4-yl)benzonitrile;
4-(1-ethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylbenzonitrile;
3-methyl-4-((4R,6S)-1,3,6-trimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)benzonitrile;
3-methyl-4-((4S,6R)-1,3,6-trimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)benzonitrile;
3-methyl-N-(3-pyridyl)-4-(1,3,6,6-tetramethyl-7,8-dihydro-4H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)benzamide;
3-(3-cyclopropyl-1,6,6-trimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-4-methyl-N-(2-methylpyridin-3-yl)benzamide;
3-chloro-4-(1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-N-(pyridin-3-yl)benzamide;
4-(1-ethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methyl-N-(2-methylpyridin-3-yl)benzamide;
3-methyl-N-(2-methylpyridin-3-yl)-4-(1,3,6,6-tetramethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)benzamide;
3-chloro-4-[1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepin-4-yl]benzamide;
3-chloro-N-methyl-4-(1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)benzamide;
6-(4-(2,4-dichlorophenyl)-1-methyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-3-yl)-N-methylnicotinamide;
3-methyl-4-(1,3,6,6-tetramethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)benzamide;
6-(4-(2,4-dichlorophenyl)-1-methyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-3-yl)nicotinamide;
4-(4-bromo-2-methyl-phenyl)-1,7-dimethyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine;
4-(4-bromo-2-methyl-phenyl)-1,7-dimethyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine;
(4R,7R)-4-(4-chloro-2-methylphenyl)-1,3,6,6-tetramethyl-7-phenyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
(4S,7S)-4-(4-chloro-2-methylphenyl)-1,3,6,6-tetramethyl-7-phenyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(4-chloro-2-methylphenyl)-7-isopropyl-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(2,4-dichlorophenyl)-1,3,6,6-tetramethyl-7,8-dihydro-4H-pyrazolo[3,4-e][1,4]thiazepine 5-oxide;
4-(2,4-Dichloro-phenyl)-1-methyl-3-pyridin-2-yl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine 5-oxide;
4-(2,4-Dichloro-phenyl)-1-methyl-3-pyridin-2-yl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine 5,5-dioxide;
4-(2,4-Dichloro-phenyl)-1,3,6,6-tetramethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine 5,5-dioxide;
(R)-4-(4-Chloro-2-methylphenyl)-1,3,6,6-tetramethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
(S)-4-(4-Chloro-2-methylphenyl)-1,3,6,6-tetramethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
(S)-4-(4-bromo-2-chlorophenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
(R)-4-(4-bromo-2-chlorophenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
(R)-4-(4-chloro-2-fluorophenyl)-3-cyclopropyl-1,6,6-trimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
(S)-4-(4-chloro-2-fluorophenyl)-3-cyclopropyl-1,6,6-trimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
3-((S)-4-(2,4-dichlorophenyl)-3,6,6-trimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-1-yl)-1,1,1-trifluoropropan-2-ol;
(R)-4-(4-chloro-2-methylphenyl)-1,3,6,6-tetramethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
(S)-4-(4-chloro-2-methylphenyl)-1,3,6,6-tetramethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
(S)-3-chloro-N-(2-methylpyridin-3-yl)-4-(1,3,6,6-tetramethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)benzamide;
(R)-3-chloro-N-(2-methylpyridin-3-yl)-4-(1,3,6,6-tetramethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)benzamide;
2-((4R,6S)-4-(4-chloro-2-methylphenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-6-yl)ethanol;
2-((4R,6R)-4-(4-chloro-2-methylphenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-6-yl)ethanol;
2-((4S,6R)-4-(4-chloro-2-methylphenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-6-yl)ethanol;
2-((4S,6S)-4-(4-chloro-2-methylphenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-6-yl)ethanol;
2-((4R,6R)-4-(4-chloro-2-methylphenyl)-1,3-dimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-6-yl)ethanol;
2-((4R,6S)-4-(4-chloro-2-methylphenyl)-1,3-dimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-6-yl)ethanol;
2-((4S,6S)-4-(4-chloro-2-methylphenyl)-1,3-dimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-6-yl)ethanol;
2-((4S,6R)-4-(4-chloro-2-methylphenyl)-1,3-dimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-6-yl)ethanol;
4-(4-chloro-2-methyl-phenyl)-3-cyclopropyl-1,6,6-trimethyl-7,8-dihydro-4H-pyrazolo[3,4-e][1,4]thiazepine;
(4S)-4-(4-chloro-2-methyl-phenyl)-3-cyclopropyl-1,6,6-trimethyl-7,8-dihydro-4H-pyrazolo[3,4-e][1,4]thiazepine;
(4R)-4-(4-chloro-2-methyl-phenyl)-3-cyclopropyl-1,6,6-trimethyl-7,8-dihydro-4H-pyrazolo[3,4-e][1,4]thiazepine;
4-(4-chloro-2-methyl-phenyl)-1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine;
(4R)-4-(4-chloro-2-methyl-phenyl)-1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine;
(4S)-4-(4-chloro-2-methyl-phenyl)-1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine;
3-chloro-N-(2-methyl-3-pyridyl)-4-[1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydro-pyrazolo[3,4-e][1,4]thiazepin-4-yl]benzamide;
3-chloro-N-(2-methyl-3-pyridyl)-4-[(4R)-1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepin-4-yl]benzamide;
3-chloro-N-(2-methyl-3-pyridyl)-4-[(4S)-1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepin-4-yl]benzamide;
3-methyl-N-(2-methyl-3-pyridyl)-4-[1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydro-pyrazolo[3,4-e][1,4]thiazepin-4-yl]benzamide;
(R)-3-methyl-4-(1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-N-(2-methylpyridin-3-yl)benzamide;
(S)-3-methyl-4-(1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-N-(2-methylpyridin-3-yl)benzamide;
(4R,7S)-4-(4-chloro-2-methylphenyl)-1,7-dimethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
(4R,7R)-4-(4-chloro-2-methylphenyl)-1,7-dimethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
(4S,7S)-4-(4-chloro-2-methylphenyl)-1,7-dimethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
(4S,7R)-4-(4-chloro-2-methylphenyl)-1,7-dimethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(4-chloro-2-methyl-phenyl)-1-methyl-3-(1H-pyrazol-5-yl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine;
3-chloro-4-[1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepin-4-yl]benzoic;
6-[4-(2,4-dichlorophenyl)-1-methyl-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepin-3-yl]pyridine-3-carboxylic acid;
1-[4-[1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepin-4-yl]-1-piperidyl]ethanone;
5:
(2-methyl-3-pyridyl)-[4-[1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepin-4-yl]-1-piperidyl]methanone;
N-(2-methyl-3-pyridyl)-4-[1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepin-4-yl]piperidine-1-carboxamide;
1-methyl-4-[2-methyl-4-(3-pyridylmethoxy)phenyl]-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine;
1-methyl-4-[2-methyl-4-[(2-methyl-3-pyridyl)methoxy]phenyl]-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine;
2-[4-(2,4-dichlorophenyl)-1-methyl-3-(2-pyridyl)-6,7-dihydro-4H-pyrazolo[3,4-e][1,4]thiazepin-8-yl]acetic acid;
2-[4-(2,4-dichlorophenyl)-1-methyl-3-(2-pyridyl)-6,7-dihydro-4H-pyrazolo[3,4-e][1,4]thiazepin-8-yl]acetamide;
4-(4-chloro-2-methyl-phenyl)-1-methyl-3-(6-methyl-2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine;
[4-(4-chloro-2-methyl-phenyl)-1-methyl-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepin-3-yl]trifluoromethanesulfonate;
4-(4-chloro-2-vinyl-phenyl)-1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine;
4-(4-chloro-2-ethyl-phenyl)-1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine;
1-methyl-4-(2-methyl-4-methylsulfonyl-phenyl)-3-(2-pyridyl)-4,6,7,8-tetrahydro-pyrazolo[3,4-e][1,4]thiazepine;
4-(2,4-dichlorophenyl)-1-methyl-3-[(2S)-pyrrolidin-2-yl]-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine;
4-(4-chloro-2-methyl-phenyl)-1-methyl-3-[(2S)-pyrrolidin-2-yl]-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine;
2-[3-chloro-4-[1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepin-4-yl]phenyl]propan-2-ol;
4-(2-chlorophenyl)-1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine;
4-(2-chloro-4-methyl-phenyl)-1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine;
4-(2,4-dichlorophenyl)-1,3,6,6,8-pentamethyl-4H-pyrazolo[3,4-e][1,4]thiazepin-7-one;
4-(2,4-dichlorophenyl)-1,3,6,6-tetramethyl-4,7-dihydropyrazolo[3,4-e][1,4]thiazepine-8-carbaldehyde;
3-[4-(2,4-dichlorophenyl)-1,3,6,6-tetramethyl-4,7-dihydropyrazolo[3,4-e][1,4]thiazepin-8-yl]-1,1,1-trifluoro-propan-2-ol;
3-[4-(2,4-dichlorophenyl)-3,6,6-trimethyl-7,8-dihydro-4H-pyrazolo[3,4-e][1,4]thiazepin-1-yl]-1,1,1-trifluoro-propan-2-ol;
3-[4-(2,4-dichlorophenyl)-3,6,6-trimethyl-7,8-dihydro-4H-pyrazolo[3,4-e][1,4]thiazepin-2-yl]-1,1,1-trifluoro-propan-2-ol;
4-(2,4-dichlorophenyl)-1,3,6,6,8-pentamethyl-4,7-dihydropyrazolo[3,4-e][1,4]thiazepine hydrochloride;
4-(4-chloro-2-methyl-phenyl)-1-methyl-3-(2-pyridyl)-4,8-dihydropyrazolo[3,4-e][1,4]thiazepin-7-one;
4-(2,4-dichlorophenyl)-1,3,6,6-tetramethyl-4,8-dihydropyrazolo[3,4-e][1,4]thiazepin-7-one;
4-(4-bromo-2-methylphenyl)-1-ethyl-3-(pyrimidin-4-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(1-(4-fluorophenyl)-6-methyl-1H-indazol-5-yl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
methyl 4-(1,7-dimethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylbenzoate;
3-cyano-4-((4R,7R)-1,7-dimethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-N-(2-methylpyridin-3-yl)benzamide;
(R)-3-methyl-4-(1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)benzonitrile;
(S)-3-methyl-4-(1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)benzonitrile;
(S)-4-(1-ethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylbenzonitrile;
2-(4-((4S,7R)-1,7-dimethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenoxy)acetonitrile;
2-(4-((4S,7R)-1,7-dimethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenoxy)acetamide;
3-(4-((4R,7S)-1-ethyl-7-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)prop-2-yn-1-ol;
3-(4-((4R,7R)-1-ethyl-7-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)prop-2-yn-1-ol;
3-(4-((4S,7R)-1-ethyl-7-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)prop-2-yn-1-ol;
3-(4-((4S,7S)-1-ethyl-7-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)prop-2-yn-1-ol;
4-(4-((4R,7S)-1-ethyl-7-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)-2-methylbut-3-yn-2-ol;
4-(4-((4R,7R)-1-ethyl-7-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)-2-methylbut-3-yn-2-ol;
4-(4-((4S,7R)-1-ethyl-7-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)-2-methylbut-3-yn-2-ol;
4-(4-((4S,7S)-1-ethyl-7-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)-2-methylbut-3-yn-2-ol;
3-(4-((4R,7S)-1-ethyl-7-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)propan-1-ol;
3-(4-((4R,7R)-1-ethyl-7-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)propan-1-ol;
3-(4-((4S,7R)-1-ethyl-7-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)propan-1-ol;
3-(4-((4S,7S)-1-ethyl-7-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)propan-1-ol;
4-(4-((4R,7S)-1-ethyl-7-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)-2-methylbutan-2-ol;
4-(4-((4R,7R)-1-ethyl-7-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)-2-methylbutan-2-ol;
4-(4-((4S,7S)-1-ethyl-7-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)-2-methylbutan-2-ol;
4-(4-((4S,7R)-1-ethyl-7-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)-2-methylbutan-2-ol;
4-(4-((4R,7S)-1,7-dimethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)-2-methylbutan-2-ol;
4-(4-((4S,7S)-1,7-dimethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)-2-methylbutan-2-ol;
4-(4-((4R,7R)-1,7-dimethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)-2-methylbutan-2-ol;
4-(4-((4S,7R)-1,7-dimethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)-2-methylbutan-2-ol;
4-((4R,7S)-1-ethyl-7-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylbenzamide;
4-((4S,7R)-1-ethyl-7-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylbenzamide;
4-((4R,7R)-1-ethyl-7-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylbenzamide;
4-((4S,7S)-1-ethyl-7-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylbenzamide;
3-(4-((4R,7S)-1,7-dimethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)propan-1-ol;
3-(4-((4R,7R)-1,7-dimethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)propan-1-ol;
3-(4-((4S,7R)-1,7-dimethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)propan-1-ol;
3-(4-((4S,7S)-1,7-dimethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)propan-1-ol;
4-(4-((4R,7S)-1,7-dimethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)but-3-yn-1-ol;
4-(4-((4S,7S)-1,7-dimethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)but-3-yn-1-ol;
4-(4-((4S,7R)-1,7-dimethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)but-3-yn-1-ol;
4-(4-((4R,7R)-1,7-dimethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)but-3-yn-1-ol;
4-((4S,7R)-1,7-dimethyl-3-(pyrimidin-4-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methyl-N-(2-methylpyridin-3-yl)benzamide;
4-((4S,7S)-1,7-dimethyl-3-(pyrimidin-4-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methyl-N-(2-methylpyridin-3-yl)benzamide;
4-((4R,7S)-1,7-dimethyl-3-(pyrimidin-4-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methyl-N-(2-methylpyridin-3-yl)benzamide;
4-((4R,7R)-1,7-dimethyl-3-(pyrimidin-4-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methyl-N-(2-methylpyridin-3-yl)benzamide;
(R)-4-(1-ethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methyl-N-(2-methylpyridin-3-yl)benzamide;
(S)-4-(1-ethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methyl-N-(2-methylpyridin-3-yl)benzamide;
2-((4R,7R)-4-(4-bromo-2-methylphenyl)-1,7-dimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-3-yl)-1,3,4-oxadiazole;
2-((4S,7S)-4-(4-bromo-2-methylphenyl)-1,7-dimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-3-yl)-1,3,4-oxadiazole;
2-((4R,7R)-4-(4-bromo-2-methylphenyl)-1,7-dimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-3-yl)-1,3,4-oxadiazole;
2-((4S,7S)-4-(4-bromo-2-methylphenyl)-1,7-dimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-3-yl)-1,3,4-oxadiazole;
3-(4-((4R,7S)-1-ethyl-7-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)-N,N-dimethylprop-2-yn-1-amine;
3-(4-((4R,7S)-1-ethyl-7-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)-N,N-dimethylprop-2-yn-1-amine;
4-(4-((4S,7S)-1-ethyl-7-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)-2-methylbut-3-yn-2-amine;
4-(4-((4S,7R)-1-ethyl-7-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)-2-methylbut-3-yn-2-amine;
(R)-4-(1-ethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-N-(2-methylpyridin-3-yl)-3-(trifluoromethyl)benzamide;
3-(4-((4R,7R)-1,7-dimethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)prop-2-yn-1-ol;
3-(4-((4S,7R)-1,7-dimethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)prop-2-yn-1-ol;
3-(4-((4S,7S)-1,7-dimethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)prop-2-yn-1-ol;
4-(1,3-dimethyl-7-oxo-1,4,5,6,7,8-hexahydropyrazolo[3,4-b]azepin-4-yl)-3-methyl-N-(2-methylpyridin-3-yl)benzam;
4-(4-((4R,7R)-1-ethyl-7-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)-2-methylbutan-2-amine;
4-(4-((4S,7S)-1-ethyl-7-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)-2-methylbutan-2-amine;
4-(1-ethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methyl-N-(3-methylisoxazol-5-yl)benzamide;
4-(1-ethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methyl-N-(1-methyl-1H-pyrazol-5-yl)benzamide;
N-(1,3-dimethyl-1H-pyrazol-5-yl)-4-(1-ethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylbenzamide;
4-(1-ethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methyl-N-(1,3,4-thiadiazol-2-yl)benzamide;
4-(1-ethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methyl-N-(5-methyl-1,3,4-thiadiazol-2-yl)benzamide;
4-(1-ethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methyl-N-(4H-1,2,4-triazol-3-yl)benzamide;
4-(1-ethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methyl-N-(1H-tetrazol-5-yl)benzamide;
N-(4-cyano-3-methylisoxazol-5-yl)-4-(1-ethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylbenzamide;
N-(4-cyano-1H-pyrazol-3-yl)-4-(1-ethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylbenzamide;
N-(4-cyano-5-methyl-1H-pyrazol-3-yl)-4-(1-ethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylbenzamide;
N-(2-chloropyridin-3-yl)-4-(1-ethyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylbenzamide;
4-(2-chloro-4-(5-(methylsulfonyl)pyridin-3-yl)phenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(2-chloro-4-(pyrimidin-5-yl)phenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
4-(2-chloro-4-(pyridazin-4-yl)phenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
5-(3-chloro-4-(1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)phenyl)nicotinonitrile;
(2-(4-(3-chloro-4-(1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)phenyl)-1H-pyrazol-1-yl)ethyl)morpholine;
4-(2-chloro-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)phenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
5-(3-chloro-4-(1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)phenyl)nicotinamide;
5-(3-chloro-4-(1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)phenyl)-N-methylnicotinamide;
4-(3-chloro-4-(1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)phenyl)nicotinonitrile;
3-(3-chloro-4-(1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)phenyl)isonicotinonitrile;
4-(2-chloro-4-(pyrido[2,3-b]pyrazin-7-yl)phenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
(5-(3-chloro-4-(1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)phenyl)pyridin-3-yl)(morpholino)methanone;
4-(2-chloro-4-(6-(methylsulfonyl)pyridin-3-yl)phenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
1-(4-(5-(3-chloro-4-(1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)phenyl)pyridin-2-yl)piperazin-1-yl)ethanone;
4-(2-chloro-4-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)phenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
3-(4-(3-chloro-4-(1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)phenyl)-1H-pyrazol-1-yl)propanenitrile;
2-(4-(3-chloro-4-(1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)phenyl)-1H-pyrazol-1-yl)acetamide;
3-(4-(3-chloro-4-(1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)phenyl)-1H-pyrazol-1-yl)propanamide;
4-(5-(3-chloro-4-(1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)phenyl)pyrimidin-2-yl)morpholine;
4-(4-bromo-2-methylphenyl)-1-ethyl-3-(pyridin-2-yl)-4,5,6,8-tetrahydropyrazolo[3,4-b]azepin-7(1H)-one;
4-(4-bromo-2-methylphenyl)-1,3-dimethyl-4,5,6,8-tetrahydropyrazolo[3,4-b]azepin-7(1H)-one;
4-(4-bromo-2-methylphenyl)-1-ethyl-3-(pyridin-2-yl)-1,4,5,6,7,8-hexahydropyrazolo[3,4-b]azepine;
4-(4-bromophenyl)-1-ethyl-3-(pyridin-2-yl)-1,4,5,6,7,8-hexahydropyrazolo[3,4-b]azepine;
rac-2-((4S,6S,7R)-4-(4-chloro-2-methylphenyl)-1,3,7-trimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-6-yl)ethanol;
2-((4R,6R,7S)-4-(4-chloro-2-methylphenyl)-1,3,7-trimethyl-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-6-yl)ethanol;
rac-(4R,7R)-4-(4-bromo-2-methylphenyl)-1-methyl-3-(pyridin-2-yl)-7-(trifluoromethyl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
rac-(4R,7S)-4-(4-bromo-2-methylphenyl)-1-methyl-3-(pyridin-2-yl)-7-(trifluoromethyl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine;
rac-(4R,7S)-4-(4-bromo-2-methylphenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine-7-carboxamide;
rac-(4R,7S)-4-(4-bromo-2-methylphenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine-7-carbonitrile;
rac-2-((4R,7S)-4-(4-bromo-2-methylphenyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7-yl)acetonitrile;
4-((4S,7R)-7-(hydroxymethyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methyl-N-(2-methylpyridin-3-yl)benzamide;
4-((4R,7S)-7-(hydroxymethyl)-1-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methyl-N-(2-methylpyridin-3-yl)benzamide;
rac-4-(1-(4-fluorophenyl)-6-methyl-1H-indazol-5-yl)-1-methyl-3-(pyridin-2-yl)-6,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7(4H)-one;
1-methyl-4-(6-methyl-1-(2-methylpyridin-4-yl)-1H-indazol-5-yl)-3-(pyridin-2-yl)-6,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7(4H)-one;
4-(1-(4-fluorophenyl)-6-methyl-1H-indazol-5-yl)-1-methyl-3-(pyridin-2-yl)-6,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7(4H)-one;
4-(6-chloro-1-(2-methylpyridin-4-yl)-1H-indazol-5-yl)-1-methyl-3-(pyridin-2-yl)-6,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7(4H)-one;
1-methyl-4-(1-(2-methylpyridin-4-yl)-1H-indazol-5-yl)-3-(pyridin-2-yl)-6,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7(4H)-one;
4-(6-chloro-1-(4-fluorophenyl)-1H-indazol-5-yl)-1-methyl-3-(pyridin-2-yl)-6,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7(4H)-one;
4-(1-(4-fluorophenyl)-1H-indazol-5-yl)-1-methyl-3-(pyridin-2-yl)-6,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7(4H)-one;
4-(6-fluoro-1-(2-methylpyridin-4-yl)-1H-indazol-5-yl)-1-methyl-3-(pyridin-2-yl)-6,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7(4H)-one;
4-(6-fluoro-1-(4-fluorophenyl)-1H-indazol-5-yl)-1-methyl-3-(pyridin-2-yl)-6,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7(4H)-one;
1-methyl-4-(1-(2-methylpyridin-4-yl)-6-(trifluoromethyl)-1H-indazol-5-yl)-3-(pyridin-2-yl)-6,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7(4H)-one;
4-(1-(4-fluorophenyl)-6-(trifluoromethyl)-1H-indazol-5-yl)-1-methyl-3-(pyridin-2-yl)-6,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7(4H)-one;
1-ethyl-4-(6-methyl-1-(2-methylpyridin-4-yl)-1H-indazol-5-yl)-3-(pyridin-2-yl)-6,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7(4H)-one;
4-(6-chloro-1-(2-methylpyridin-4-yl)-1H-indazol-5-yl)-1-ethyl-3-(pyridin-2-yl)-6,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7(4H)-one;
1-ethyl-4-(1-(2-methylpyridin-4-yl)-1H-indazol-5-yl)-3-(pyridin-2-yl)-6,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7(4H)-one;
1-ethyl-4-(6-fluoro-1-(2-methylpyridin-4-yl)-1H-indazol-5-yl)-3-(pyridin-2-yl)-6,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7(4H)-one;
1-ethyl-4-(1-(2-methylpyridin-4-yl)-6-(trifluoromethyl)-1H-indazol-5-yl)-3-(pyridin-2-yl)-6,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7(4H)-one;
1-ethyl-4-(1-(4-fluorophenyl)-6-methyl-1H-indazol-5-yl)-3-(pyridin-2-yl)-6,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7(4H)-one;
(Z)-3-(1-aminobuta-1,3-dien-1-yl)-4-(6-chloro-1-(4-fluorophenyl)-1H-indazol-5-yl)-1-ethyl-6,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7(4H)-one;
(Z)-3-(1-aminobuta-1,3-dien-1-yl)-1-ethyl-4-(1-(4-fluorophenyl)-1H-indazol-5-yl)-6,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7(4H)-one;
1-ethyl-4-(6-fluoro-1-(4-fluorophenyl)-1H-indazol-5-yl)-3-(pyridin-2-yl)-6,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7(4H)-one;
1-ethyl-4-(1-(4-fluorophenyl)-6-(trifluoromethyl)-1H-indazol-5-yl)-3-(pyridin-2-yl)-6,8-dihydro-1H-pyrazolo[3,4-e][1,4]thiazepin-7(4H)-one;
rac-4-((4R,7R)-7-hydroxy-1-methyl-3-(pyridin-2-yl)-7-(trifluoromethyl)-1,4,5,6,7,8-hexahydrocyclohepta[c]pyrazol-4-yl)-3-methyl-N-(2-methylpyridin-3-yl)benzamide;
4-(4-chloro-2-methyl-phenyl)-1-methyl-3-(2-pyridyl)-4,8-dihydropyrazolo[3,4-e][1,4]thiazepin-7-one;
or
rac-4-((4R,7S)-7-hydroxy-1-methyl-3-(pyridin-2-yl)-7-(trifluoromethyl)-1,4,5,6,7,8-hexahydrocyclohepta[c]pyrazol-4-yl)-3-methyl-N-(2-methylpyridin-3-yl)benzamide,
or a pharmaceutically acceptable salt, pro-drug or solvate thereof.

339 more elements

Dependencies are inferred from the claim text.

Facts

Application: 14/135,793Filed 20 Dec 2013
Priority: CN PCT/CN2013/0015055 Dec 2013
Published: 26 Jun 2014
Term ends: Not estimatedThe source records don’t support an estimate.

Classification14 codes

C07D 513/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 5/38
Drugs for disorders of the endocrine system: of the suprarenal hormones
A61P 5/44
Of the suprarenal hormones: glucocorticosteroids; Drugs increasing or potentiating the activity of glucocorticosteroids
A61P 29/00
Non-central analgesic, antipyretic or antiinflammatory agents

Family

Application61/740,931Us provisional application · filed 21 Dec 2012
US 9,150,592 B2Related patent
US 2014/0179676 A1This patent

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

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Abstract

A compound represented by the following formula:

or a pharmaceutically acceptable salt, pro-drug or solvate thereof, wherein:
Ring 1 is heterocyclic or heteroaromatic;
X is N, N(R4′), C(R4), C(R4)(R4), S or O;
Y is N, N(R4′), C(R4), S, O or C(═O);
Z is N(R4′), C(R4)C(R4) or C(R4);
A is, N(R3′), C(R3)(R3) or C(═O);
G and J are independently S, S(O), S(O)2, O, C(R1)(R2), N(R3) or C(═O) provided that at least one of G and J are C(R1)(R2) or C(═O);
E is N(R4′), S, S(O), S(O)2, O, C(R1)(R2), or C(═O);
L is N(R5), C(R5)(R5) or C(R5)(R5);
or L is C(R5) or C(R5′) and J is C(R1) or N;
M and Q are independently N, C or CH;
provided that
X, Y, and Z are not each heteroatoms at the same time;
not more than three of A, E, G, J, L, M and Q are heteroatoms;
M and Q are not both N;
adjacent atoms do not form S—S, S—O, O—O or —C(═O)—C(═O) bonds;
at least one of X, Y and Z is C(R4) or C(═O);
when Q is N, X is not S or O;
when J is S, O, S(O) or N(R3), L is not N(R5);
R1 and R2, for each occurrence, is independently —H, CF3, CN, —C(═O)NH2, OH, an optionally substituted (C1-C6)alkyl, optionally substituted (C3-C6)cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl or optionally substituted heterocyclyl;
or R1 and R2, together with the carbon to which they attach, form an optionally substituted (C3-C6)carbocyclic ring spiro to ring 2 or an optionally substituted heterocyclic ring spiro to ring 2;
R3 is independently —H, CF3, CN, OH, —NRaRb, an optionally substituted (C1-C6)alkyl, optionally substituted (C2-C6)alkenyl, optionally substituted (C2-C6)alkynyl, an optionally substituted aryl, an optionally substituted (C3-C6)cycloalkyl, an optionally substituted heteroaryl, an optionally substituted heterocyclyl, or an optionally substituted benzyl;
R3′ is independently —H, an optionally substituted (C1-C6)alkyl, optionally substituted (C2-C6)alkenyl, optionally substituted (C2-C6)alkynyl, an optionally substituted aryl, an optionally substituted (C3-C6)cycloalkyl, an optionally substituted heteroaryl, an optionally substituted heterocyclyl, or an optionally substituted benzyl;
R4 is independently H, —CF3, —CN, —OH, —NRaRb, an optionally substituted (C1-C6)alkyl, an optionally substituted (C2-C6)alkenyl, an optionally substituted (C2-C6)alkynyl, an optionally substituted (C1-C6)alkoxy, an optionally substituted aryl, an optionally substituted (C3-C6)cycloalkyl, an optionally substituted heteroaryl, or an optionally substituted heterocyclyl;
R4′ is independently —H, an optionally substituted (C1-C8)alkyl, an optionally substituted (C2-C6)alkenyl, an optionally substituted (C2-C6)alkynyl, an optionally substituted (C3-C6)cycloalkyl, an optionally substituted heterocyclyl, an optionally substituted aryl, or an optionally substituted heteroaryl;
provided that R4′ is not an optionally substituted benzisoxazolyl, an optionally substituted isobenzazolyl, an optionally substituted quinazolinyl, an optionally substituted isoquinolinyl or an optionally substituted phthalazinyl;
R5 is independently —H, OH, F, CF3, CN, optionally substituted (C1-C6)alkyl, optionally substituted (C2-C6)alkenyl, optionally substituted (C2-C6)alkynyl, optionally substituted (C3-C6)cycloalkyl, —(CH2)m-optionally substituted aryl, —(CH2)n-optionally substituted heterocyclyl, or —(CH2)n-optionally substituted heteroaryl;
or both R5, together with the carbon to which they are attached, form a carbocyclic spirocyclic ring;
R5′ is —R5′a—R5′b—R5′c wherein R5′a is attached to the ring and
R5′a is optionally substituted phenyl or optionally substituted heteroaryl;
R5′b is a bond or —C(═O)N(H) wherein the —C(═O) is attached to R5′a;
and
R5′c is optionally substituted isoxazolyl, optionally substituted oxazolyl, optionally substituted phenyl, optionally substituted pyrazolyl, optionally substituted pyridazinyl, optionally substituted pyridinyl, optionally substituted pyrimidinyl, optionally substituted pyrido[2,3-b]pyrazinyl, tetrazolyl, optionally substituted 1,3,5-thiadiazolyl, or 1,2,4-triazolyl;
Ra and Rb are independently H and optionally substituted (C1-C6)alkyl;
and
n, for each occurrence, is independently 0, 1, 2 or 3;
provided that when the compound is
then R5 is not unsubstituted phenyl or phenyl substituted by COOH, Cl, F, OH, NO2 or two OCH3;
provided that when M and Q are both CH or M and Q are both C and Ring 1 contains two nitrogen atoms, Ring 2 is not
provided that not more than one of X, Y and Z is substituted by phenyl;
and
provided that the compound is not
wherein
R1 and R2 are independently H or CH3;
R4′ is H, optionally substituted (C1-C8)alkyl, —CH2C(O)OCH2CH3, optionally substituted (C3-C8)cycloalkyl, optionally substituted benzyl, optionally substituted pyridinyl,
optionally substituted pyrimidinyl,

43 more elements

Facts

Application

14/135,793Filed 20 Dec 2013

Priority

CN PCT/CN2013/0015055 Dec 2013

Published

26 Jun 2014

Term ends

Not estimatedThe source records don’t support an estimate.

Classification14 codes

C07D 513/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 5/38
Drugs for disorders of the endocrine system: of the suprarenal hormones
A61P 5/44
Of the suprarenal hormones: glucocorticosteroids; Drugs increasing or potentiating the activity of glucocorticosteroids
A61P 29/00
Non-central analgesic, antipyretic or antiinflammatory agents