Affinity small molecules for the EPO receptor

Abstract

Compounds are provided that complex with the modulating domain of erythropoietin receptor (EPO-R) for use with EPO-R to determine the presence of EPO-R, the ability of other molecules to bind to the modulating domain in competitive assays and to induce a signal by EPO-R into a cell when bound by the subject compounds in a physiological environment. The compounds are characterized by having a six-membered heterocyclic ring comprising at least one nitrogen atom and include substituted triazolopyrimidine, pyridazinone, pyridine and piperidine.

Description

[0001] This application is a continuation of provisional patent applications, Nos. 60 / 393,361; 60 / 393,360 and 60 / 394,110, all filed on Jul. 3, 2002, the entire contents of each of which is incorporated herein by reference.STATEMENT TO COMPUTER DISK AND SEQUENCE LISTING[0002] This application includes a sequence listing of 2 sequences and a computer disk labeled "Sequence Listing for application entitled "Affinity Small Molecules for the EPO Receptor" by Lennart Olsson and Tatjana Naranda" containing files "REC105-SEQLIST.prj" dated "Jul. 2, 2003" with 990 bytes, which is the PatentIn project file generated using PatentIn Version 3.0 software provided by the USPTO, and "REC105-SEQLIST.doc", dated "Jul. 2, 2003" with 21 kilobytes, which is the generated sequence listing from the PatentIn project file REC105-SEQLIST.prj using PatentIn Version 3.0 software, all which are herein incorporated. The information recorded in computer readable format on the incorporated computer disk labeled "...

AI Technical Summary

Problems solved by technology

In many situations, the level of treatment is compromised by the adverse effect on the red blood cell count, so that the desired therapy cannot be administered.

EPO is a large glycosylated protein that is expensive and difficult to manufacture, purify and formulate.

It is also degraded by proteases when in the blood, so that a substantial portion of the administered EPO is lost.

However, the peptide is small and will be rapidly degraded in the blood.

Also, it suffers from the inconvenience of requiring injection.

When a patient suffers from acute renal failure or when chronic renal failure develops, the inadequate renal production of erythropoietin results in hypoplastic anemia.

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