Methods relating to the treatment of fibrosis

Abstract

The invention provides α-helix mimetic structures of formula (I) with the definitions of A, B, D, E, G, W, R1 and R2 as set out in the description and a chemical library relating thereto. The compounds, pharmaceutical compositions comprising the compounds, and methods of the invention using the compounds, relate to the reversal of fibrotic conditions, such as pulmonary fibrosis.

Description

CROSS REFERENCE TO RELATED APPLICATION(S)[0001]The present application is a continuation of PCT International Patent Application No. PCT / US2006 / 009191, filed Mar. 15, 2006, which claims priority from U.S. Provisional Application No. 60 / 663,499, filed Mar. 18, 2005, both of which are hereby incorporated by reference in their entirety.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT[0002]This invention was made with government support under grant R01 HL073722 awarded by the National Institutes of Health. The government has certain rights in the invention.[0003]The subject matter of this application was made with support from the United States Government under The National Institutes of Health, Grant No. R01 HL073722. The U.S. Government may have certain rights.TECHNICAL FIELD[0004]The present invention relates generally to α-helix mimetic structures and to a chemical library relating thereto. The invention also relates to applications in the treatment of diseases and ph...

AI Technical Summary

Benefits of technology

[0023]The compound V (ICG-001) is useful for treating fibrosis as described in Example 1.

[0024]These and other aspects of this invention will be apparent upon reference to the attached figures and followin...

Problems solved by technology

It is believed that death due to IPF is greatly underreported and the considerable morbidity of IPF is not recognized.

Pulmonary fibrosis leads to progressive scarring and lung destruction.

The fibrosis is refractory to corticosteroids and no effective therapy currently exists.

While advances in molecular biology and computational chemistry have led to increased interest in what has been termed “rational drug design”, such techniques have not proven as fast or reliable as initially predicted.

Initially, combinatorial chemistry libraries were generally limited to members of peptide or nucleotide origin.

However, such cyclized peptides are generally still quite flexible and are poorly bioavailable, and thus have met with only limited success.

Anti-inflammatory therapies (e.g. corticosteroids, interferon-γ) to treat pulmonary fibrosis have been disappointing to date due to limited efficacy and severe adverse side effects.

No drugs have been approved for the treatment of any fibrotic disease in the United States.

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