Compounds and methods for modulating CXCR3 function

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...

Reexamination Certificate

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

C544S128000, C544S287000, C544S290000, C546S141000, C514S309000, C514S266210

Reexamination Certificate

active

06992084

ABSTRACT:
The invention provides compounds and compositions of the formula:wherein,the subscript n is an integer of from 0 to 4;Ar is a member selected from the group consisting of substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl,R1is a member selected from the group consisting of substituted or unsubstituted (C5–C15)alkyl and (C8–C14)acyl group;R2is a member selected from the group consisting of substituted or unsubstituted (C1–C8)alkyl;each R3is independently a substituentY is a member selected from the group consisting of substituted or unsubstituted (C2–C8)alkylene and substituted or unsubstituted (C2–C8)heteroalkylene;Z is —NR4R5R4and R5are independently selected from the group consisting of hydrogen and (C1–C8)alkyl or taken together with the nitrogen atom to which each is attached to form a heterocyclyl or heteroaryl;These compounds and compositions bind to the CXCR3 chemokine receptor and are useful for treating diseases and conditions responsive to the modulation of CXCR3 activity, such as multiple sclerosis, rheumatoid arthritis, psoriasis, cancer, infectious disease, angiogenesis, and graft rejection.

REFERENCES:
patent: 5919776 (1999-07-01), Hagmann et al.
patent: 5948775 (1999-09-01), Koko et al.
patent: WO 98/02151 (1998-01-01), None
patent: WO 00/00491 (2000-01-01), None
patent: WO 01/30768 (2001-05-01), None
patent: WO 01/31335 (2001-05-01), None
patent: WO 01/98278 (2001-12-01), None
Power et al. (Current Opinion in Pharmacology, vol. 1, issue 4, Aug. 1, 2001, pp. 417-424).
Schall,Cytokine, 3:165-183 (1991).
Schall et al.,Curr. Opin. Immunol., 6:865-873 (1994).
Horuk,Trends Pharm. Sci. 15:159-165 (1994).
J.K. Padia et al., “Design and Synthesis of Novel Nonpeptide CCK-B Receptor Antagonists”,Biorganic&Medicinal Chemistry Letters7:(7) pp 805-810 (1997).
Thomas J. Schall, Biology of the Rantes/SIS Cytokine Family,Cytokine, US Academic Press Ltd., :3(3),pp 165-183, XP002062534 (May 1, 1991).
Padia et al., Novel Nonpeptide CCK-B Antagonist: Design and Development of Quinazolinone Derivatives as Potent, Selective, and Orally Active CCK-B Antagonists,Journal of Medical Chemistry, 41:(7), pp1042-1049 XP002158593 (Mar. 26, 1998).
Two pages of ComGenex Compound Catalog (online).
Michael T. Liu et al.; Neutralization of the Chemokine CXCL10 Reduces Inflammatory Cell Invasion and Demyelination and Improves Neurological Function in a Viral Model of Multiple Sclerosis, The American Assoc of Immunology, pp. 4091-4097, 2001.
Torben L. Sorensen et al.; Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients; Journal of Clinical Investigation Mar. 1999 vol. 103 No. 6, pp 807-815.
Konstantin E. Balashov et al.; CCR5+and CXCR3+T cells are increased in multiple sclerosis and their ligands MIP-1α and IP-10 are expressed in demyelinating brain lesions; Communicated by Dvid W. Talmage, Proc. Natl. Acad. Sci. USA, vol. 96, pp 6873-6878, Jun. 1999 Immunology.
Craig Gerard and Barrett J. Rollins; Chemokines and disease; Nature Immunology, vol. 2 No. 2 Feb. 2001m http:/Immunol.nature.com, pp108-115.
James B. Rottman et al.; Potential Role of the Chemokine Receptors CXCR3, CCR4, and the Integrin αEβ7 in the Pathogenesis of Psoriasis Vulgaris; Laboratory Investigation Mar. 2001 vol. 81, No. 3, pp. 335-347.
Carlo Agostini et al., CXC Chemokines IP-10 and Mig Expression and Direct Migration of Pulmonary and Direct Migration of Pulmonary CD8+/CXCR3+ T Cells in the Lungs of Patients with HIV Infection and T-Cell Alveolitis; Am J Respir Crit Med vol. 162, pp1466-1473, 2000.
Wayne W. Hancock et al., Requirement of the Chemokine Receptor CXCR3 for Acute Allograft Rejection; J. Exp. Med. © The Rockefelle University Press vol. 192, No. 10, Nov. 20, 2000, pp. 1515-1519.
Press Release Dec. 10, 2003; Tularik Initiates Phase 2 Clinical Trial of T487 in Psoriasis; San Francisco, CA, pp. 1-2.

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

Compounds and methods for modulating CXCR3 function does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Compounds and methods for modulating CXCR3 function, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Compounds and methods for modulating CXCR3 function will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-3551062

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.