Indole derivatives as MCP-1 receptor antagonists

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

Reexamination Certificate

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C548S492000

Reexamination Certificate

active

06984657

ABSTRACT:
A compound of Formula I,wherein: R1is hydrogen, halo, methyl, ethyl or methoxy; R2is hydrogen, halo, methyl, ethyl or methoxy; R3is a halo group, lower alkyl, lower alkenyl, lower alkynyl, alkoxy, trifluoromethyl, nitro, cyano, trifluoromethoxy, C(O)R7, or S(O)nR7where n is 0, 1 or 2 and R7is an alkyl group; R4is a halo, trifluoromethyl, methylthio, methoxy, trifluoromethoxy or lower alkyl, lower alkenyl or lower alkynyl or COR8where R8is lower alkyl; R6is hydrogen, halo, lower alkyl, lower alkenyl, lower alkynyl or COR9where R9is lower alkyl; provided that when R1is hydrogen, halo or methoxy, R2is hydrogen, halo, methyl, ethyl or methoxy, R5and R6are both hydrogen, and one of R3or R4is not halo or trifluoromethyl; or a pharmaceutically acceptable salt or prodrug thereof. These compounds have useful activity for the treatment of inflammatory disease, specifically in antagonizing an MCP-1 mediated effect in a warm-blooded animal such as a human being.

REFERENCES:
patent: 3557142 (1971-01-01), Bell
patent: 3776923 (1973-12-01), Remers et al.
patent: 3997557 (1976-12-01), Helsley et al.
patent: 4529724 (1985-07-01), Ho
patent: 4608384 (1986-08-01), Wierzbicki et al.
patent: 4721725 (1988-01-01), Biller et al.
patent: 4751231 (1988-06-01), Halczenko et al.
patent: 4965369 (1990-10-01), Maetzel et al.
patent: 5081145 (1992-01-01), Guindon et al.
patent: 5190968 (1993-03-01), Gillard et al.
patent: 5254563 (1993-10-01), Huth et al.
patent: 5272145 (1993-12-01), Prasit et al.
patent: 5273980 (1993-12-01), Frenette et al.
patent: 5288743 (1994-02-01), Brooks et al.
patent: 5290798 (1994-03-01), Gillard et al.
patent: 5308850 (1994-05-01), Gillard et al.
patent: 5389650 (1995-02-01), Frenette et al.
patent: 5399699 (1995-03-01), Kolasa et al.
patent: 5482960 (1996-01-01), Berryman et al.
patent: 5684032 (1997-11-01), Elliott et al.
patent: 5852046 (1998-12-01), Lang et al.
patent: 5955492 (1999-09-01), Thompson et al.
patent: 6184235 (2001-02-01), Connor et al.
patent: 6337344 (2002-01-01), Defossa et al.
patent: 6737435 (2004-05-01), Kettle et al.
patent: 298 913 (1992-03-01), None
patent: 0 077 209 (1983-04-01), None
patent: 0 186 367 (1986-07-01), None
patent: 0 189 690 (1986-08-01), None
patent: 0 419 049 (1991-03-01), None
patent: 0 480 659 (1992-04-01), None
patent: 0 535 923 (1993-04-01), None
patent: 0 535 924 (1993-04-01), None
patent: 0 535 925 (1993-04-01), None
patent: 0 535 926 (1993-04-01), None
patent: 0 639 573 (1995-02-01), None
patent: 0 822 185 (1998-02-01), None
patent: 0 275 667 (1998-07-01), None
patent: 2 565 981 (1985-12-01), None
patent: 63284177 (1988-11-01), None
patent: 4273857 (1992-09-01), None
patent: WO 86/00896 (1986-02-01), None
patent: WO 92/04343 (1992-03-01), None
patent: WO 93/12780 (1993-07-01), None
patent: WO 93/16069 (1993-08-01), None
patent: WO 93/20078 (1993-10-01), None
patent: WO 93/25546 (1993-12-01), None
patent: WO 94/14434 (1994-07-01), None
patent: WO 96/03377 (1996-02-01), None
patent: WO 96/31492 (1996-10-01), None
patent: WO 96/33171 (1996-10-01), None
patent: WO 96/37467 (1996-11-01), None
patent: WO 96/37469 (1996-11-01), None
patent: WO 97/12613 (1997-04-01), None
patent: WO 97/12615 (1997-04-01), None
patent: WO 97/30704 (1997-08-01), None
patent: WO 97/35572 (1997-10-01), None
patent: WO 98/06703 (1998-02-01), None
patent: WO 99/07351 (1999-02-01), None
patent: WO 99/07678 (1999-02-01), None
patent: WO 00/46196 (2000-08-01), None
Berman, J.W. et al. Localization of Monocyte Chemoattractant Peptide- I Expression in the Central Nervous System in Experimental Autoimmune Encephalomyelitis and Trauma in the Rat.J. Immunol.156, 3017-3023 (1996).
Bobosik, V. & Krutosikova, A. Synthesis of N-Phenylsulfonyl Protected Furo[3,2-b]Pyyroles.Collect. Czech. Chem. Commun.59, 499-502 (1994).
Dandarova, M. 13C NMR Spectra of Some Substituted Furo[3,2-b]pyrroles.Magnetic Resonance Chem.28, 830-831 (1990).
Deleuran, M. et al. Localization of monocyte chemotactic and activating factor (MCAF/MCP-1) in psoriasis.J. Dermatological Sci.13, 228-236 (1996).
Grimm, M.C. et al. Enhanced expression and production of monocyte chemoattractant protein-1 in inflammatory bowel disease mucosa.J. Leukocyte Biol.59, 804-812 (Jun. 1996).
Harrison, C.-A. et al. Cyclopenta [b] indoles. Part 2. Model studies towards the tremorgenic mycotoxins.J. Chem. Soc. Perkin Trans.1131-1136 (1995).
Hartman, G.D. & Halczenko, W. The Synthesis of 5-Alkylaminomethylthieno[2,3-b]pyrrole-5-sulfonamides.Heterocycles29, 1943-1949 (1989).
Jones, M.L. et al. Potential Role of Monocyte Chemoaltractant Protein I/JE in Monocyte/Macrophage-Dependent IgA Immune Complex Alveolitis in the Rat.J. Immunol.149, 2147-2154 (Sep. 15, 1992).
Kataoka, K. et al. Homopiperazines as cell migration inhibitors.Chemical Abstracts,Columbus Ohio, US 123, 667 (Oct. 2, 1995).
Koch, A.E. et al. Enhanced Production of Monocyte Chemoattractant Protein-1 Rheumatoid Arthritis.J. Clin. Invest.90, 772-779 (Sep. 1992).
Korobehenko, L.V. et al. Synthesis and antiviral activity of pyrrolecarboxylic acids and their derivatives.Chemical AbstractsColumbus, Ohio, Access No.: 119:62465 (1999).
Krutosikova, A & Dandarova, M. Substituted Vinyl Azides in Synthesis of Furo[3,2-b:4,5-b]-Dipyrroles and Pyrrolo[2′3′:4,5]Furo[3,2-c]Pyridines.Heterocycles37, 1695-1700 (1994).
Krutosikova, A. & Dandarova, M. Reactions of Methyl 2-Formylfuro[3,2-b]pyrrole-5-carboxylates.Chem. Papers50, 72-76 (1996).
Krutosikova, A. & Hanes, M. Substituted 4-Benzylfuro[3,2-b]Pyrroles.Collect. Czech Chem.57, 1487-1494 (1992).
Krutosikova, A. et al. Condensed O-, N-Heterocycles by the Transformation of Azidoacrylates.Chemical Monthly123, 807-815 (1992).
Krutosikova, A. et al. Derivatives of Furo[3,2-b]Pyrrole.Collect. Czech. Chem. Commun.59, 473-481 (1994).
Krutosikova, A. et al. Substituted Vinyl Azides in the Synthesis of Condensed Nitrogen Heterocycles.Chem. Papers48, 268-273 (1994).
Krutosikova, A. et al. Synthesis and Reactions of Furo[3,2-b]Pyrrole Type Aldehydes.Collect. Czech. Chem. Commune.58, 2139-2149 (1993).
Murakami, Y. et al. Direct Regioselective Vinylation of Indoles Using Palladium (II) Chloride.Heterocycles22, 1493-1496 (1984).
Rosenmund, P. et al. Decarboxylations of Some 1-Alkyl-2-carboxy-3-indolacetic Acids and Synthesis of a 5-Thiocyanato-2,3-dihydroindole.Chem. Ber.108, 3538-3542 (1975)-Abstract only.
Troschutz, R. & Hoffmann, A. Synthesis of Substituted 3-Amino-4-cyano-1-oxo-1,2,5,10-tetrahy-droazepino[3,4-b]indoles.J. Heterocyclic Chem.34, 1431 (1997).
Yokoyama, Y. et al. New Synthetic Method for Dehydrotryptophan Derivatives. Synthesis Studies on Indoles and Related Compounds, XXIV.Chem. Pharm. Bull.42, 832-838 (1994).
Krutosikova, A. et al. Synthesis and Reactions of Furo[2,3-b]pyrroles. Molecules 2, 69-79 (1997).
Yokoyama, Y. et al. Palladium-Catalyzed Cross-Coupling Reaction: Direct Allylation of Aryl Bromides with Allyl Acetate. Tetrahedron Letters 26, 6457-6460 (1985).

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