Indazole derivatives as CRF antagonists

A pharmaceutical composition comprising a therapeutically effective amount of at least one compound of formula I

• 24
• wherein:
• R1 is —NRaRb, —CRcRdRe, CO2Ra, or —C(O)NRaRb;
• or R1 is hydrogen, cycloalkenyl, aryl, or heteroaryl, where each aryl or heteroaryl is optionally substituted with one or more substituents independently selected from C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 alkylsulfonyl, halogen, haloalkyl, cyano, nitro, —C(O)NRa′Rb′, and —NRa′Rb′, where Ra′ and Rb′ are each independently selected from the group consisting of hydrogen, C1-9 alkyl, and C1-9 alkylcarbonyl;
• R2 is hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-3 alkyl, C1-6 alkylcarbonyl, C1-6 alkylsulfonyl, aryl, or arylalkyl, wherein said aryl or arylalkyl is optionally substituted with one or more substituents independently selected from C1-6 alkyl, haloalkyl, C1-6 alkoxy, and halogen;
• R3 is aryl or heteroaryl, each optionally substituted with one or more substituents independently selected from the group consisting of C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 alkylsulfonyl, aminosulfonyl, monoalkylaminosulfonyl, dialkylaminosulfonyl, halogen, haloalkyl, cyano, nitro, and —NRa″Rb″, where Ra″ and Rb″ are each independently selected from the group consisting of hydrogen, C1-9 alkyl, and C1-9 alkylcarbonyl;
• Ra and Rb are each independently selected from the group consisting of hydrogen, C1-9 alkyl, hydroxyalkyl, C1-6 alkoxyalkyl, C1-6 alkylthioalkyl, carboxyalkyl, acyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-3 alkyl, di-C3-6 cycloalkylC1-3 alkyl, C1-6 heteroalkyl, aminoalkyl, aminocarbonylalkyl, cyanoalkyl, C5-8 heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, phenylalkyl, diphenylalkyl, and C1-3 alkyl substituted with both a C3-6 cycloalkyl and a phenyl group, wherein each of said cycloalkyl, phenyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C1-6 alkyl, haloalkyl, C1-6 alkoxy, amino, alkylamino, dialkylamino, hydroxyalkyl, cyano, acylamino, alkylsulfonyl, alkylsulfonyloxy, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl;
• or
• Ra and Rb are taken together with the nitrogen to which they are attached form an heterocyclyl or heteroaryl ring selected from the group consisting of pyrrolidine, piperidine, homopiperidine, tetrahydropyridine, 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydroisoquinoline, tetrahydropyrimidine, hexahydropyrimidine, pyrazolidine, piperazine, morpholine, imidazoline, pyrrole, pyrazole, and imidazole, where each of said rings is optionally substituted with one or more substituents selected from the group consisting of hydroxy, oxo, alkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, aminoalkyl, acyl, acylaminio, aminocarbonyl, aminocarbonylalkyl, aminocarbonylamino, aminosulfonyl, alkylsulfonylamino, aminosulfonylamino, and phenyl, wherein each of said phenyl groups is optionally substituted with one or more groups independently selected from C1-6 alkyl, haloalkyl, C1-6 alkoxy, amino, alkylamino, dialkylamino, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl, or is contained in a pyrrolidinyl, piperidinyl, morpholinyl, or piperazinyl group;
• Rc is hydrogen, hydroxy, C1-6 alkoxy, or —NRa′″Rb′″;
• Rd and Re are each independently selected from the group consisting of hydrogen, C1-9 alkyl, hydroxyalkyl, C1-6 alkoxyalkyl, C1-6 alkylthioalkyl, heteroalkyl, heterocyclyl, heterocyclylalkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-3 alkyl, di-C3-6 cycloalkyl-C1-3 alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, phenylalkyl, diphenyl-C1-3alkyl, and C1-3 alkyl substituted with both a C3-6 cycloalkyl and a phenyl group, wherein each of said cycloalkyl, phenyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C1-6 alkyl, haloalkyl, C1-6 alkoxy, amino, alkylamino, dialkylamino, and halogen;
• or
• Rc and Rd are taken together to form a divalent group selected from C1-6 alkylidenyl, C1-6 heteroalkylidenyl, C3-6 cycloalkylidenyl, C3-6 cycloalkyl-alkylidenyl, C3-6 cycloalkyl-C1-3 alkyl-alkylidenyl, C3-6 heterocyclylidenyl, C3-6 heterocyclyl-C1-3 alkylidenyl, C3-6 heterocyclylalkyl-C1-3 alkylidenyl, aryl-C1-3 alkylidenyl, aryl-C1-3alkyl-alkylidenyl, heteroaryl-C1-3alkylidenyl, and heteroarylalkyl-CI -3 alkylidenyl, wherein each of said cycloalkyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from C1-6 alkyl, haloalkyl, C1-6 alkoxy, amino, alkylamino, dialkylamino, and halogen;
• or
• Rd and Re are taken together with the carbon to which they are attached to form a cycloalkyl or heterocyclyl ring;
• Ra″ and Rb′″ are each independently selected from the group consisting of hydrogen, C1-9 alkyl, hydroxyalkyl, C1-6 alkoxyalkyl, C1-6 alkylthioalkyl, carboxyalkyl, acyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-3 alkyl, di-C3-6 cycloalkyl-C1-3 alkyl, C1-6 heteroalkyl, aminoalkyl, aminocarbonylalkyl, cyanoalkyl, C5-8 heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, phenylalkyl, diphenyl-C1-3 alkyl, and C1-3 alkyl substituted with both a C3-6 cycloalkyl and a phenyl group, wherein each of said cycloalkyl, phenyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C1-6 alkyl, haloalkyl, C1-6 alkoxy, amino, alkylamino, dialkylamino, hydroxyalkyl, cyano, acylamino, alkylsulfonyl, alkylsulfonyloxy, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl;
• or
• Ra′″ and Rb′″ are taken together with the nitrogen to which they are attached form an heterocyclyl or heteroaryl ring selected from the group consisting of pyrrolidine, piperidine, homopiperidine, tetrahydropyridine, 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydroisoquinoline, tetrahydropyrimidine, hexahydropyrimidine, pyrazolidine, piperazine, morpholine, imidazoline, pyrrole, pyrazole, and imidazole, where each of said rings is optionally substituted with one or more substituents selected from the group consisting of hydroxy, oxo, alkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, aminoalkyl, acyl, acylamino, aminocarbonyl, aminocarbonylalkyl, aminocarbonylamino, aminosulfonyl, alkylsulfonylamino, aminosulfonylamino, and phenyl, wherein each of said phenyl groups is optionally substituted with one or more groups independently selected from C1-6alkyl, haloalkyl, C1-6alkoxy, amino, alkylamino, dialkylamino, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl, or is contained in a pyrrolidinyl, piperidinyl, morpholinyl, or piperazinyl group;
• or individual isomers, racemic or non-racemic mixtures of isomers, or pharmaceutically acceptable salts thereof;
• in admixture with at least one pharmaceutically acceptable carrier.

A method for treating a subject having a disease state that is alleviated by treatment with a CRF receptor antagonist, which comprises administering to such a subject a therapeutically effective amount of a compound of formula I

• 25
• wherein:
• R1 is —NRaRb, —CRcRdRe, CO2Ra, or —C(O)NRaRb;
• or R1 is hydrogen, cycloalkenyl, aryl, or heteroaryl, where each aryl or heteroaryl is optionally substituted with one or more substituents independently selected from C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 alkylsulfonyl, halogen, haloalkyl, cyano, nitro, —C(O)NRa′Rb′, and —NRa′Rb′, where Ra′″ and Rb′ are each independently selected from the group consisting of hydrogen, C1-9 alkyl, and C1-9alkylcarbonyl;
• R2 is hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-3 alkyl, C1-3 alkylcarbonyl, C1-6 alkylsulfonyl, aryl, or arylalkyl, wherein said aryl or arylalkyl is optionally substituted with one or more substituents independently selected from C1-6 alkyl, haloalkyl, C1-6 alkoxy, and halogen;
• R3 is aryl or heteroaryl, each optionally substituted with one or more substituents independently selected from the group consisting of C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 alkylsulfonyl, aminosulfonyl, monoalkylaminosulfonyl, dialkylaminosulfonyl, halogen, haloalkyl, cyano, nitro, and —NRa″Rb″, where Ra″ and Rb″ are each independently selected from the group consisting of hydrogen, C1-9 alkyl, and C1-9 alkylcarbonyl;
• Ra and Rb are each independently selected from the group consisting of hydrogen, C1-9 alkyl, hydroxyalkyl, C1-6 alkoxyalkyl, C1-6 alkylthioalkyl, carboxyalkyl, acyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-3 alkyl, di-C3-6 cycloalkylC1-3 alkyl, C1-6 heteroalkyl, aminoalkyl, aminocarbonylalkyl, cyanoalkyl, C5-8 heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, phenylalkyl, diphenylalkyl, and C1-3 alkyl substituted with both a C3-6 cycloalkyl and a phenyl group, wherein each of said cycloalkyl, phenyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C1-6 alkyl, haloalkyl, C1-6 alkoxy, amino, alkylamino, dialkylamino, hydroxyalkyl, cyano, acylamino, alkylsulfonyl, alkylsulfonyloxy, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl;
• or
• Ra and Rb are taken together with the nitrogen to which they are attached form an heterocyclyl or heteroaryl ring selected from the group consisting of pyrrolidine, piperidine, homopiperidine, tetrahydropyridine, 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydroisoquinoline, tetrahydropyrimidine, hexahydropyrimidine, pyrazolidine, piperazine, morpholine, imidazoline, pyrrole, pyrazole, and imidazole, where each of said rings is optionally substituted with one or more substituents selected from the group consisting of hydroxy, oxo, alkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, aminoalkyl, acyl, acylamino, aminocarbonyl, aminocarbonylalkyl, aminocarbonylamino, aminosulfonyl, alkylsulfonylamino, aminosulfonylamino, and phenyl, wherein each of said phenyl groups is optionally substituted with one or more groups independently selected from C1-6 alkyl, haloalkyl, C1-6 alkoxy, amino, alkylamino, dialkylamino, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl, or is contained in a pyrrolidinyl, piperidinyl, morpholinyl, or piperazinyl group;
• Rc is hydrogen, hydroxy, C1-6 alkoxy, or —NRa′″Rb′″;
• Rd and Re are each independently selected from the group consisting of hydrogen, C1-9 alkyl, hydroxyalkyl, C1-6 alkoxyalkyl, C1-6 alkylthioalkyl, heteroalkyl, heterocyclyl, heterocyclylalkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-3 alkyl, di-C3-6 cycloalkyl-C1-3 alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, phenylalkyl, diphenyl-C1-3alkyl, and C1-3 alkyl substituted with both a C3-6 cycloalkyl and a phenyl group, wherein each of said cycloalkyl, phenyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C1-6 alkyl, haloalkyl, C1-6 alkoxy, amino, alkylamino, dialkylamino, and halogen;
• or
• Rc and Rd are taken together to form a divalent group selected from C1-6 alkylidenyl, C1-6 heteroalkylidenyl, C3-6 cycloalkylidenyl, C3-6 cycloalkyl-alkylidenyl, C3-6 cycloalkyl-C1-3 alkyl-alkylidenyl, C3-6 heterocyclylidenyl, C3-6 heterocyclyl-C1-3 alkylidenyl, C3-6 heterocyclylalkyl-C1-3 alkylidenyl, aryl-C1-3 alkylidenyl, aryl-C1-3alkyl-alkylidenyl, heteroaryl-C1-3alkylidenyl, and heteroarylalkyl-C1-3 alkylidenyl, wherein each of said cycloalkyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from C1-6 alkyl, haloalkyl, C1-6 alkoxy, amino, alkylamino, dialkylamino, and halogen;
• or
• Rd and Re are taken together with the carbon to which they are attached to form a cycloalkyl or heterocyclyl ring;
• Ra′″ and Rb′″ are each independently selected from the group consisting of hydrogen, C1-9 alkyl, hydroxyalkyl, C1-6 alkoxyalkyl, C1-6 alkylthioalkyl, carboxyalkyl, acyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-3 alkyl, di-C3-6 cycloalkyl-C1-3 alkyl, C1-6 heteroalkyl, aminoalkyl, aminocarbonylalkyl, cyanoalkyl, C5-8 heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, phenylalkyl, diphenyl-C1-3 alkyl, and C1-3 alkyl substituted with both a C3-6 cycloalkyl and a phenyl group, wherein each of said cycloalkyl, phenyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C1-6 alkyl, haloalkyl, C1-6 alkoxy, amino, alkylamino, dialkylamino, hydroxyalkyl, cyano, acylamino, alkylsulfonyl, alkylsulfonyloxy, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl;
• or
• Ra′″ and Rb′″ are taken together with the nitrogen to which they are attached form an heterocyclyl or heteroaryl ring selected from the group consisting of pyrrolidine, piperidine, homopiperidine, tetrahydropyridine, 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydroisoquinoline, tetrahydropyrimidine, hexahydropyrimidine, pyrazolidine, piperazine, morpholine, imidazoline, pyrrole, pyrazole, and imidazole, where each of said rings is optionally substituted with one or more substituents selected from the group consisting of hydroxy, oxo, alkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, aminoalkyl, acyl, acylamino, aminocarbonyl, aminocarbonylalkyl, aminocarbonylamino, aminosulfonyl, alkylsulfonylamino, aminosulfonylamino, and phenyl, wherein each of said phenyl groups is optionally substituted with one or more groups independently selected from C1-6 alkyl, haloalkyl, C1-6 alkoxy, amino, alkylamino, dialkylamino, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl, or is contained in a pyrrolidinyl, piperidinyl, morpholinyl, or piperazinyl group;
• or individual isomers, racemic or non-racemic mixtures of isomers, or pharmaceutically acceptable salts thereof.

A compound of Formula II

• 26
• wherein:
• R1 is —NRaRb, —CRcRdRe, CO2Ra;
• or, R1 is hydrogen, cycloalkenyl, aryl, or heteroaryl, where each aryl or heteroaryl is optionally substituted with one or more substituents independently selected from C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 alkylsulfonyl, halogen, haloalkyl, cyano, nitro, —C(O)NRa′Rb′, and —NRa′Rb′, where Ra′ and Rb′ are each independently selected from the group consisting of hydrogen, C1-9 alkyl, and C1-9 alkylcarbonyl;
• R2 is hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-3 alkyl, C1-6 alkylcarbonyl, C1-6 alkylsulfonyl, aryl, or arylalkyl, wherein said aryl or arylalkyl is optionally substituted with one or more substituents independently selected from C1-6 alkyl, haloalkyl, C1-6 alkoxy, and halogen;
• R3 is aryl or heteroaryl, each optionally substituted with one or more substituents independently selected from the group consisting of C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 alkylsulfonyl, aminosulfonyl, monoalkylaminosulfonyl, dialkylaminosulfonyl, halogen, haloalkyl, cyano, nitro, and —NRa″Rb″, where Ra″ and Rb″ are each independently selected from the group consisting of hydrogen, C1-9 alkyl, and C1-9 alkylcarbonyl;
• Ra and Rb are each independently selected from the group consisting of hydrogen, C1-9alkyl, hydroxyalkyl, C1-6 alkoxyalkyl, C1-6 alkylthioalkyl, carboxyalkyl, acyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-3 alkyl, di-C3-6 cycloalkylC1-3 alkyl, C1-6 heteroalkyl, aminoalkyl, aminocarbonylalkyl, cyanoalkyl, C5-8 heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, phenylalkyl, diphenylalkyl, and C1-3 alkyl substituted with both a C3-6 cycloalkyl and a phenyl group, wherein each of said cycloalkyl, phenyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C1-6 alkyl, haloalkyl, C1-6 alkoxy, amino, alkylamino, dialkylamino, hydroxyalkyl, cyano, acylamino, alkylsulfonyl, alkylsulfonyloxy, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl;
• or
• Ra and Rb are taken together with the nitrogen to which they are attached form an heterocyclyl or heteroaryl ring selected from the group consisting of pyrrolidine, piperidine, homopiperidine, tetrahydropyridine, 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydroisoquinoline, tetrahydropyrimidine, hexahydropyrimidine, pyrazolidine, piperazine, morpholine, imidazoline, pyrrole, pyrazole, and imidazole, where each of said rings is optionally substituted with one or more substituents selected from the group consisting of hydroxy, oxo, alkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, aminoalkyl, acyl, acylamino, aminocarbonyl, aminocarbonylalkyl, aminocarbonylamino, aminosulfonyl, alkylsulfonylamino, aminosulfonylamino, and phenyl, wherein each of said phenyl groups is optionally substituted with one or more groups independently selected from C1-6 alkyl, haloalkyl, C1-6 alkoxy, amino, alkylamino, dialkylamino, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl, or is contained in a pyrrolidinyl, piperidinyl, morpholinyl, or piperazinyl group;
• Rc is hydrogen, hydroxy, C1-6 alkoxy, or —NRa′″Rb′″;
• Rd and Re are each independently selected from the group consisting of hydrogen, C1-9alkyl, hydroxyalkyl, C1-6 alkoxyalkyl, C1-6 alkylthioalkyl, heteroalkyl, heterocyclyl, heterocyclylalkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C,3 alkyl, di-C3-6 cycloalkyl-C1-3 alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, phenylalkyl, diphenyl-C1-3 alkyl, and C1-3 alkyl substituted with both a C3-6 cycloalkyl and a phenyl group, wherein each of said cycloalkyl, phenyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C1-4 alkyl, haloalkyl, C1-6 alkoxy, amino, alkylamino, dialkylamino, and halogen;
• or
• Rc and Rd are taken together to form a divalent group selected from C1-6 alkylidenyl, C1-6 heteroalkylidenyl, C3-6 cycloalkylidenyl, C3-6 cycloalkyl-alkylidenyl, C3-6 cycloalkyl-C1-3 alkyl-alkylidenyl, C3-6 heterocyclylidenyl, C3-6 heterocyclyl-C1-3 alkylidenyl, C3-6 heterocyclylalkyl-C1-3 alkylidenyl, aryl-C1-3 alkylidenyl, aryl-C1-3 alkyl-alkylidenyl, heteroaryl-C1-3 alkylidenyl, and heteroarylalkyl-C1-3 alkylidenyl, wherein each of said cycloalkyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from C1-6 alkyl, haloalkyl, C1-6 alkoxy, amino, alkylamino, dialkylamino, and halogen;
• or
• Rd and Re are taken together with the carbon to which they are attached to form a cycloalkyl or heterocyclyl ring;
• Ra′″ and Rb′″ are each independently selected from the group consisting of hydrogen, C1-9 alkyl, hydroxyalkyl, C1-6 alkoxyalkyl, C1-6 alkylthioalkyl, carboxyalkyl, acyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-3 alkyl, di-C3-6 cycloalkyl-C1-3 alkyl, C1-6 heteroalkyl, aminoalkyl, aminocarbonylalkyl, cyanoalkyl, C5-8 heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, phenylalkyl, diphenyl-C1-3 alkyl, and C1-3 alkyl substituted with both a C3-6 cycloalkyl and a phenyl group, wherein each of said cycloalkyl, phenyl, aryl, or heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of C1-6 alkyl, haloalkyl, C1-6 alkoxy, amino, alkylamino, dialkylamino, hydroxyalkyl, cyano, acylamino, alkylsulfonyl, alkylsulfonyloxy, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl;
• or
• Ra′″ and Rb′″ are taken together with the nitrogen to which they are attached form an heterocyclyl or heteroaryl ring selected from the group consisting of pyrrolidine, piperidine, homopiperidine, tetrahydropyridine, 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydroisoquinoline, tetrahydropyrimidine, hexahydropyrimidine, pyrazolidine, piperazine, morpholine, imidazoline, pyrrole, pyrazole, and imidazole, where each of said rings is optionally substituted with one or more substituents selected from the group consisting of hydroxy, oxo, alkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, aminoalkyl, acyl, acylamino, aminocarbonyl, aminocarbonylalkyl, aminocarbonylamino, aminosulfonyl, alkylsulfonylamino, aminosulfonylamino, and phenyl, wherein each of said phenyl groups is optionally substituted with one or more groups independently selected from C1-6 alkyl, haloalkyl, C1-6 alkoxy, amino, alkylamino, dialkylamino, and halogen, and each of said amino groups is optionally monosubstituted or disubstituted with alkyl, or is contained in a pyrrolidinyl, piperidinyl, morpholinyl, or piperazinyl group;
• or,
• individual isomers, racemic or non-racemic mixtures of isomers, or pharmaceutically acceptable salts thereof;
• with the proviso that if R1 is —CRcRdRe, R2 is hydrogen or alkyl, R3 is a 5- or 6-membered heteroaromatic ring, and
• (i) Rc is hydrogen and one of Rd and Re is hydrogen or alkyl, then the other of Rd and Rc is other than hydrogen or alkyl if the number of carbon atoms in Rd and Re together are zero to three;
• or,
• (ii) Re is hydrogen and one of Rd and Re is hydrogen or alkyl, then the other of Rd and Re is other than alkoxy, alkoxyalkyl, heterocyclyl, heterocyclylalkyl, or heteroalkyl;
• or,
• (iii) Rc is NRa′″Rb′″ and one of Ra′″ and Rb′″ is hydrogen or C1-3 alkyl, then the other of Ra′″ and Rb′″ is other than hydrogen or C1-3 alkyl.