| 主权项 |
1. A method of treating a subject suffering from or diagnosed with a disorder selected from the group consisting of: anxiety and post-traumatic stress disorder, comprising administering to the subject in need of such treatment an effective amount of a compound of Formula (I):wherein:
Z is —N— or >CH; R1 is —H or —C1-4alkyl; Ar1 is 2-thiazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, each unsubstituted or substituted at a carbon ring member with one or two Ra moieties;
where each Ra moiety is independently selected from the group consisting of —C1-4alkyl, —C2-4alkenyl, —OH, —OC1-4alkyl, halo, —CF3, —OCF3, —SCF3, —SH, —S(O)0-2C1-4alkyl, —OSO2C1-4alkyl, —CO2C1-4alkyl, —CO2H, —COC1-4alkyl, —N(Rb)Rc, —SO2NRbRc, —NRbSO2Rc, —C(═O)NRbRc, —NO2, and —CN, wherein Rb and Rc are each independently —H or —C1-4alkyl; and Ar2 is:
(a) phenanthrenyl, pyrenyl, fluorenyl, naphthyl, or N—Rd-9H-carbazolyl moieties, wherein Rd is selected from the group consisting of —H, —C1-4alkyl, and phenyl, each said moiety unsubstituted or substituted with one, two, or three Re substituents,wherein each Re substituent is independently selected from the group consisting of —C1-4alkyl, —C2-4alkenyl, —OH, —OC1-4alkyl, halo, —CF3, —OCF3, —SCF3, —SH, —S(O)0-2C1-4alkyl, —OSO2C1-4alkyl, —CO2C1-4alkyl, —CO2H, —COC1-4alkyl, —N(Rb)Rc, —SO2NRbRc, —NRbSO2Rc, —C(═O)NRbRc, —NO2, and —CN, wherein Rb and Rc are as previously defined;(b) phenyl fused at two adjacent ring carbon atoms to a group selected from the group consisting of —(CH2)3-5— having 0 or 1 double bonds, —OCH2CH2O—, —OCF2O— and —OCH2O— to form a fused ring structure, unsubstituted or substituted with one, two, or three Re substituents as previously defined;(c) Ar6, where Ar6 is a 6-membered monocyclic heteroaryl having carbon as a point of attachment, with one or two nitrogen heteroatoms, unsubstituted or substituted with one, two, or three Re substituents as previously defined;(d) a 9- or 10-membered fused bicyclic heteroaryl having one heteroatom selected from the group consisting of N, O, and S, with a carbon atom as point of ring attachment, and optionally having up to four additional carbon ring atoms replaced with nitrogen, said fused bicyclic heteroaryl having not more than five heteroatoms, and unsubstituted or substituted with one, two, or three Re substituents as previously defined;(e) phenyl substituted at the 3- or 4-position with Rg, and optionally further substituted with one, two, or three substituents Rh,wherein each Rg is independently selected from the group consisting of —C2-8alkyl, —C2-8alkenyl, —OC3-8cycloalkyl, —OC3-8heterocycloalkyl, and —O—C2-10alkyl optionally substituted with —NRiRj, wherein Ri and Rj are each independently —H or —C1-8alkyl, or Ri and Rj are taken together with the nitrogen ring atom of attachment to form a 5-, 6-, or 7-membered heterocycloalkyl ring optionally having one additional carbon ring atom replaced with O, S, >NH, or >NC1-4alkyl; andeach Rh substituent is independently selected from the group consisting of —C1-4alkyl, —C2-4alkenyl, —OH, —OC1-4alkyl, halo, —CF3, —OCF3, —SCF3, —SH, —S(O)0-2C1-4alkyl, —OSO2C1-4alkyl, —CO2C1-4alkyl, —CO2H, —COC1-4alkyl, —N(Rb)Rc, —SO2NRbRc, —NRbSO2Rc, —C(═O)NRbRc, —NO2, and —CN, wherein Rb and Rc are as previously defined;(f) phenyl substituted at the 3- or 4-position with -L—Ar3, wherein:
L is a linker selected from the group consisting of —(CH2)1-3—, —CH═CH—, —O—, —OCH2—, —CH2O—, —NH—, >NC1-4alkyl, >S(═O)0-2, —OSO2—, —C≡C—, —C(═O)—, and a covalent bond; andAr3 is a moiety selected from the group consisting of:
(1) phenyl, naphthyl, and phenanthrenyl,(2) Ar6′, where Ar6′ is a 6-membered monocyclic heteroaryl having carbon as a point of attachment, having one or two nitrogen heteroatoms,(3) Ar5′, where Ar5′ is a 5-membered monocyclic heteroaryl having carbon as a point of attachment, with one heteroatom selected from the group consisting of O, S, >NH, and >NRf, wherein Rf is —C1-8alkyl or —C0-3phenalkyl, and having zero, one, two, or three additional nitrogen heteroatoms, and(4) a 9- or 10-membered fused bicyclic heteroaryl, having one heteroatom selected from the group consisting of N, O, and S, with a carbon as point of ring attachment, and optionally having up to four additional carbon ring atoms replaced with nitrogen, said fused bicyclic heteroaryl having not more than five heteroatoms;where each of the moieties (1) through (4) is optionally di-substituted on adjacent carbons with —OC1-4alkyleneO—, —(CH2)2-3NH—, —(CH2)1-2NH(CH2)—, —(CH2)2-3N(C1-4alkyl)—, or —(CH2)1-2N(C1-4alkyl)(CH2)— to form a fused ring structure, and is optionally further substituted with one, two, or three substituents Rk,wherein each Rk substituent is independently selected from the group consisting of —C1-4alkyl, —C2-4alkenyl, —OH, —OC1-4alkyl, halo, —CF3, —OCF3, —SCF3, —SH, —S(O)0-2C1-4alkyl, —OSO2C1-4alkyl, —CO2C1-4alkyl, —CO2H, —COC1-4alkyl, —N(Rb)Rc, —SO2NRbRc, —NRbSO2Rc, —C(═O)NRbRc, —NO2, and —CN, wherein Rb and Rc are as previously defined;(g) 2-hydroxyphenyl or 2-methoxyphenyl, unsubstituted or substituted with one, two, or three substituents RI,wherein each RI substituent is independently selected from the group consisting of —CH3, 6-C2-4alkyl, 6-C2-4alkenyl, —OH, —OCH3, 6-OC2-6alkyl, halo, —CF3, —OCF3, —SCF3, —SH, —SC1-4alkyl, —SO2C1-4alkyl, —CO2C1-4alkyl, —CO2H, —COC1-4alkyl, —N(Rb)Rc, —SO2NRbRc, —NRbSO2Rc, —C(═O)NRbRc, —NO2, and —CN, wherein Rb and Rc are as previously defined;(h) 4-halophenyl, unsubstituted or substituted with one, two, or three substituents Rm,wherein each Rm substituent is independently selected from the group consisting of —CH3, 2-C2-4alkyl, 2-C2-4alkenyl, 3-hydroxy, 4-hydroxy, —OCH3, 2-OC2-6alkyl, halo, —CF3, —OCF3, —SCF3, —SH, —SC1-4alkyl, —SO2C1-4alkyl, —CO2C1-4alkyl, —CO2H, —COC1-4alkyl, —N(Rb)Rc, —SO2NRbRc, —NRbSO2Rc, —C(═O)NRbRc, —NO2, and —CN, wherein Rb and Rc are as previously defined; or(i) 2-bromophenyl, 3-methylphenyl, 3-methoxyphenyl, 4-methoxyphenyl, or 3,4-dimethoxyphenyl;or a pharmaceutically acceptable salt of such compound. |
