US 6,982,268 B2 | ||
Substituted imidazolylmethyl pyridine and pyrazine derivatives GABAA receptor ligands | ||
Linghong Xie, Guilford, Conn. (US); Manuka Ghosh, Brandford, Conn. (US); and George Maynard, Clinton, Conn. (US) | ||
Assigned to Neurogen Corporation, Branford, Conn. (US) | ||
Filed on May 07, 2003, as Appl. No. 10/431,257. | ||
Claims priority of provisional application 60/379117, filed on May 08, 2002. | ||
Prior Publication US 2003/0220348 A1, Nov. 27, 2003 | ||
Int. Cl. A61K 31/4965 (2006.01); A61K 31/44 (2006.01); A01N 43/40 (2006.01); C07D 403/00 (2006.01); C07D 401/00 (2006.01) |
U.S. Cl. 514—255.05 | 20 Claims |
1. A compound of the formula: ![]() or a pharmaceutically acceptable salt thereof, wherein: W represents CH or N;
R1 represents 5- to 10-membered aryl or heteroaryl, each of which is unsubstituted or substituted with from 1 to 4 groups independently
selected from R5;
R2 represents C1–C8alkoxy, C1–C8alkyl, C2–C8alkenyl, C2–C8alkynyl, C3–C10cycloalkyl, heterocycloalkyl, (C3–C10cycloalkyl) C1–C8alkyl, heterocycloalkyl) C1–C8alkyl, or 5- or 6-membered aryl or heteroaryl, each of which is unsubstituted or substituted with from 1 to 3 substituents
independently selected from R5, where each heterocycloalkyl is a ring having from 3–10 ring members and contains at least one atom selected from N, S, and
O, the remaining ring members being carbon atoms;
R3 and R4 are each independently selected from:
(a) hydrogen, halogen, nitro and cyano; and
(b) groups of the formula:
![]() wherein:
(i) G is a bond, C1–C8alkyl, —NH—, —N(RB)—, (RB)N— —O—, —C(═O)—, —C(═O)NH—, —C(═O)NRB—, —S(O)m—, —CH2C(═O)—, —S(O)mNH—, —S(O)mNRB—, —NHC(═O)—, —C(═NRB), HC═N—, —NRBC(═O)—, —NHS(O)m— or NRBS(O)—;
(ii) RA and RB are independently selected from C1–C8alkyl, C2–C8alkenyl, C2–C8alkynyl and 3- to 12-membered carbocycles and 3- to 12-membered heterocycles,
where each of the carbocycles and heterocycles has 1 ring or 2 fused, pendant or spiro rings,
each heterocycle has at least one ring that comprises at least one heteroatom selected from N, O, and S, the remaining heterocycle
members being carbon atoms,
each of the carbocycles and heterocycles is unsubstituted or substituted with from 1 to 4 substituents independently selected
from R5; and
(iii) m is 0, 1 or 2; and
R5 is independently selected at each occurrence from halogen, hydroxy, nitro, cyano, amino, C1–C8alkyl, C1–C8alkoxy, mono- and di(C1–C8alkyl)amino, C3–C10cycloalkyl, (C3–C10cycloalkyl)alkyl, (C3–C10cycloalkyl)alkoxy, heterocycloalkyl, C1–C8alkenyl, C1–C8alkynyl, halo(C1–C8)alkyl, halo(C1–C8)alkoxy, oxo, amino(C1–C8)alkyl and mono- and di(C1–C8alkyl)amino (C1–C8)alkyl, where each heterocycloalkyl is a ring having from 3–10 ring members and at least one atom selected from N, S, and
O, and the remaining ring members are carbon atoms.
|