Amide derivatives as NMDA receptor antagonists

Details Amide derivatives as NMDA receptor antagonists Amide derivatives as NMDA receptor antagonists

2008-04-29

2008-04-29

Chang, Celia (Department: 1625)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

C546S199000, C548S218000

Reexamination Certificate

active

07365083

ABSTRACT:
Compounds having NR2B selective NMDA receptor antagonist activity are disclosed of the formula (I)whereintwo of the neighboring R1, R2, R3and R4groups form an oxo-oxazolidine ring fused to the benzene ring of the indole nucleus,and the other two of R1, R2, R3and R4groups are hydrogen atoms,R5and R6together with the nitrogen between them form a saturated or unsaturated, 4-6 membered heterocyclic ring, which is substituted by phenoxy, phenyl-(C1-C4alkyl), phenyl-(C1-C4alkoxy), phenoxy-(C1-C4alkyl), or benzoyl, optionally substituted on the aromatic ring by one or more halogen atoms, cyano or hydroxy groups, C1-C4alkyl or C1-C4alkoxy groups,X is NH—,Y is a —CH— group,or pharmaceutically acceptable salts thereof formed with acids or bases.

REFERENCES:
patent: 5866589 (1999-02-01), Romero et al.
patent: 6476041 (2002-11-01), Thompson et al.
patent: 0 105 763 (1984-04-01), None
patent: WO 96/18628 (1995-11-01), None
patent: WO 98/14427 (1997-08-01), None
patent: WO 00/00197 (1999-06-01), None
patent: WO 00/12074 (1999-08-01), None
patent: WO 00/42213 (2000-01-01), None
Sobol et al. “Preclinical evaluation . . . ” Neuropharmacology v.51, p. 933-946 (2006).
Borza et al. “Indole-2-carboxamines . . . ” Bioorg. Med. Chem. v.13, p. 3859-3861 (2003).
Borza et al. “Selective NR1/2B . . . ” J. Med. Chem. v.50 p. 901-014 (2007).
Johnson, M.I., Bunge, R.P. (1992), 51-75, Primary cell cultures of peripheral and central neurons and glia.
Helva. Chim. Acta., 51, 1616 (1968).
Helva. Chim. Acta., 77, 100 (1994).
J. Chem. Soc. 1605-1608 (1948).
Tetrahedron 54, 13981 (1998).
Helva. Chim. Acta., 135 (1949).
Bioorganic & Medicinal Chemistry Letters 10 (2000) 483-486; Karen Milkiewicz et al; The design, synthesis and activity . . . .
Protein Science (1997) 6:1412-1417; Nickolay Chirgadze et al; The crystal structure of human a-thrombin . . . .
J. Med. Chem. 1996, 39, 3769-3789; Donna Romero et al; Targeting delavirdine/atevirdine resistant HIV-1: . . . .
J. Med. Chem. 1999, 42, 4140-4149; Michael Genin et al; Synthesis and structure—activity relationships . . . .
XP-002191279 Chem. Abstracts (Indian J. Chem 1970).
XP-002191278 Chem. Abstract Svce Columbus Ohio (Acta Pol. Pharm 1974).
“Synthesis and biological evaluation of novel piperiodine . . . ” by Lubisch et al. (Biorg. & Med. Chem. Letters Oct. 2000.
“The reduction of aromatic nitro groups . . . ” by Scheuermann et al (Tetrahedron Letters 41/2000).
Ennis et al “Preparation of dioxino[2,3-e]indole . . . ” CA 115:279812 (1991).
Font et al “Indoles and pyridazino[4,5-b]indoles . . . ” CA 124:164316 (1996).
Berger et al “Preparation of substituted aromatic . . . ” CA 135:92639 (2001).
Andersson et al “Preparation of heterocyclic pharmaceutical . . . ” CA 2001:816656 (2001).
Pabel et al “Synthesis and resolution of racemic eliprodil . . . ” Bioorganic & Med. Chem. Letters 10 (2000) 1377-1380.
J. Med. Chem. 1978, vol. 21, No. 3, pp. 309-312; Piperidylalkylindoles. 1. Hypotensive activity . . . .
J. Med. Chem. 1992, 35, pp. 4903-4910; Ketanserin analogues: structure-affinity relationships for . . . .
TINS, vol. 10, No. 7, 1987, pp. 299-302; Excitotoxicity and the NMDA receptor.
Curr. Pharm. Des. 1999, 5, pp. 381-404; Antagonists selective for NMDA receptors containing . . . .
Stroke, 28, 1997, pp. 2244-2251; Effect of CP101,606, a novel NR2B subunit antagonist . . . .
Brain Res. 792, 1998, pp. 291-298; Effects of the NMDA antagonist CP-98,113 on regional . . . .
Exp. Neurol. 163, 2000, pp. 239-243; Antiparkinsonian actions of CP-101,606, an antagonist . . . .
Neuropharmacology 38, 1999, pp. 611-623; Selective NMDA NR2B antagonists Induce . . . .
Drug News Perspect 11, 1998, pp. 523-569; Glutamate in CNS disorders as a target for . . . .
Eur. J. Neuroscience, vol. 10, 1998, pp. 1704-1715; Developmental changes in localization . . . .
Meth. Cell. Biol. 40, 1994, pp. 155-181; Practical aspects of measuring . . . .
J. Chem. Soc., 321, 1938, pp. 321-329; The unsaturation and tautomeric . . . .
J. Am. Chem. Soc., 80, 1958, pp. 1657-1662; Synthesis of some substituted . . . .
J. Org. Chem., 64, 1999, pp. 3763-3766; A practical synthesis of . . . .
J. Med. Chem., 18, 926 (1975).

Affiliated with

Also associated with

Rating

Amide derivatives as NMDA receptor antagonists does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Amide derivatives as NMDA receptor antagonists, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Amide derivatives as NMDA receptor antagonists will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2745627