Nitrosourea derivatives having antitumour activity and pharmaceutical compositions containing the same

Abstract

Abstract Translated from English Nitroso-urees nouvelles et hautement efficaces utiles dans le traitement de tumeurs chez les mammiferes. Le degre eleve de selective des composes est attribue au positionnement de certains groupes electronegatifs sur le carbone (Beta) sur l'extremite non nitrosee de la molecule. Par hypothese, ceci pourrait influencer favorablement la liaison de l'hydrogene sur certains sites presentant une activite enzymatiques, en eliminant ainsi de maniere plus selective le maintien enzymatique de proteines, masquant les antigenes des surfaces des cellules tumorales, ce qui a son tour empeche la destruction par le systeme immunitaire normal du tissu neoplastique. L'activite de ces composes apparait en outre comme etant superieure a celle du MeCCNU(1-(4-trans-methylcyclohexyle)-3-(2-chloroethyle)-3-nitroso-uree), un compose tres actif utilise couramment dans la chimiotherapie du cancer. Les composes selon la formule generale suivante sont decrits: (FORMULE) ainsi que les sels derives pharmaceutiquement acceptables, ou hal represente du chlore ou du fluor; R est un groupe hydroxy, halogene, acide carboxylique ou des derives de ceux-ci; n varie entre 4 et 7, le groupe cycycloalkyle pouvant etre facultativement substitue avec un ou plusieurs groupes methyle ou groupes hydroxyle. New and highly effective nitro-ureas useful in the treatment of mammalian tumors. The high degree of selective compounds is attributed to the positioning of certain electronegative groups on carbon (Beta) on the non-nitrosed end of the molecule. Hypothetically, this could favorably influence the binding of hydrogen to certain sites exhibiting enzymatic activity, thus eliminating in a more selective way the enzymatic maintenance of proteins, masking the antigens of the surfaces of tumor cells, which in turn prevents the destruction by the normal immune system of neoplastic tissue. The activity of these compounds also appears to be superior to that of MeCCNU (1- (4-trans-methylcyclohexyle) -3- (2-chloroethyle) -3-nitroso-uree), a very active compound commonly used in the cancer chemotherapy. The compounds according to the following general formula are described: (FORMULA) as well as the pharmaceutically acceptable derivative salts, or hal represents chlorine or fluorine; R is hydroxy, halogen, carboxylic acid or derivatives thereof; n varies between 4 and 7, the cycycloalkyl group possibly being optionally substituted with one or more methyl groups or hydroxyl groups.

Inventors

• 👤 Andrew Welebir

Bibliographic Details