Methods and compositions for the treatment of cancer, tumors, and tumor-related disorders
a technology for cancer and tumors, applied in the field of combination compositions, can solve the problems of limited benefit of additional conventional treatment, serious and often life-threatening conditions of cancer, tumors, tumor-related disorders, etc., and achieve the effects of increasing or maintaining the same effect, decreasing the dosage, and increasing the therapeutic
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example 1
Synthesis of 2-(4-ethoxyphenyl)-4-methyl-1-(4-sulfamoylphenyl)-pyrrole
[0422]
[0423]Substituted benzaldehyde undergoes dehydration condensation by reaction with aniline compound A in an inert solvent at a temperature of between 5° C. to 200° C. to give aldimine compound B. Trimethylsilyl cyanide is then reacted with aldimine compound B in the presence of a Lewis acid to afford anilinonitrile C. An α-β-unsaturated aldehyde is then reacted with anilinonitrile C to afford compound D which then undergoes dehydration and dehydrogencyanation under basic conditions in a modification of the method described in Ann Chem. 589, 176 (1954).
example 2
Synthesis of Erlotinib
[0424]
[0425]Starting material compound H is heated in a suspension of metal alkali and solvent, then heated to give compound I. Starting material alcohol F, is placed in a solvent mixture of thionyl chloride, methylene chloride and dimethylformamide to give the chloride G. Chloride G is then coupled with compound I to give erlotinib J.
example 3
Pharmacokinetics and Metabolism of 2-(4-ethoxyphenyl)-4-methyl-1-(4-sulfamoylphenyl)-pyrrole
[0426]Orally administered 2-(4-ethoxyphenyl)-4-methyl-1-(4-sulfamoylphenyl)-pyrrole was rapidly absorbed in all species examined (mice, rats, dogs, and monkeys). Peak plasma concentrations were achieved between 1 and 3 hours after a dose of 5 mg / kg. The elimination half life (t1 / 2) was 4-5 hours in rodents and dogs, and approximately 2 hours in monkeys. Oral availability was greatest in rodent, and was reduced in dogs and monkeys (59 and 34% respectively). Pharmacokinetics in human subjects demonstrated a linear dose exposure relationship from doses of 2 mg to 800 mg given orally. The half-life in human subjects is 15-18 hours.
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