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Pyrimidylaminobenzamide Derivatives For Sytemic Mastocytosis

a technology of pyrimidylaminobenzamide and sytemic mastocytosis, which is applied in the direction of drug compositions, extracellular fluid disorders, immunological disorders, etc., can solve the problems of increased bone marrow mast cell and eosinophil content, poor prognosis, and elevated serum alkaline phosphatas

Inactive Publication Date: 2008-07-24
ALLAND LEILA +3
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In general, mast cell leukemia is a terminal disease with survival measured in months and no effective therapy to date.
In both indolent and aggressive SM without AHNMD, increased bone marrow mast cell and eosinophil content, elevated serum alkaline phosphatase, anemia, and hepatosplenomegaly have been associated with poor prognosis (Tefferi and Pardanani 2004).

Method used

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  • Pyrimidylaminobenzamide Derivatives For Sytemic Mastocytosis
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  • Pyrimidylaminobenzamide Derivatives For Sytemic Mastocytosis

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Embodiment Construction

[0085]A Phase II, open-label study was designed to evaluate the safety and efficacy of Compound (II) administered orally 400 mg twice daily. SM patients meeting specific disease criteria and with a clinical indication for treatment were enrolled. The results are based on preliminary data for the first 23 pts in this study. Results: The median age was 49 (range 33-78) yrs and the median time from diagnosis of SM was 27 (range 1 to 292) months. For those with data available, 13 / 17 pts had a c-kit D816V mutation in bone marrow cells. The median exposure to Compound (II) was 144 days. Treatment is ongoing for 18 (78%) pts; 5 (22%) discontinued, 3 (13%) for adverse events and 2 (9%) withdrew consent. Three (13%) responses were reported (2 incomplete remission and 1 minor response), based on serum tryptase, bone marrow mast cell counts and improvement of clinical symptoms. Baseline mutation data are available for 2 of the 3 responding pts and revealed the c-kit D816V mutation. These data ...

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Abstract

The present invention relates to the use of pyrimidylaminobenzamide derivatives for the preparation of a drug for the treatment of systemic mastocytosis.

Description

SUMMARY OF THE INVENTION[0001]The present invention relates to the use of pyrimidylaminobenzamide derivatives for the preparation of a drug for the treatment of systemic mastocyctosis. The present invention also relates to a method of treating systemic mastocyctosis.BACKGROUND OF THE INVENTION[0002]Systemic mastocytosis (SM) can be classified into indolent SM (little or no evidence of impaired organ function), aggressive SM (presence of impaired organ function), SM associated hematologic non-mast cell disease (SM-AHNMD) and mast cell leukemia. Clinical presentation in adult SM is heterogenous and includes skin disease (usually urticaria pigmentosa), mast cell mediator-release symptoms (headache, flushing, lightheadedness, syncope, anaphylaxis, etc), and direct or indirect organ damage (bone pain from lytic bone lesions, osteoporosis or bone fractures, hepatosplenomegaly, cytopenia from bone marrow involvement). In addition, around 20% of patients with SM may display significant and ...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/506A61P35/04
CPCA61K31/506A61P7/00A61P11/00A61P11/02A61P17/00A61P17/04A61P25/00A61P35/00A61P35/02A61P35/04A61P37/00A61P37/08A61P43/00C07D401/04C07D401/14
Inventor ALLAND, LEILAFABBRO, DORIANOMESTAN, JURGENMANLEY, PAUL W.
Owner ALLAND LEILA
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