N,N'-Dialkyl-1,2-bis(hydroxyphenyl)ethylenediamines and N,N-dialkyl-4,5-bis(4-hydroxyphenyl)imidazolidines: syntheses and evaluation of their mammary tumor inhibiting activity.

Abstract

Diastereomeric N,N'-dialkyl-1,2-bis(hydroxyphenyl)ethylenediamines (5) were synthesized and tested for their affinity for the estradiol receptor. Only the (+/-)-1,2-bis(4-hydroxyphenyl)ethylenediamines with the alkyl groups C3H7 [(+/-)-5c, Ka = 1.1 x 19(6))], C4H9 [(+/-)-5e,Ka = 3.6 x 10(6)], and C5H11 [(+/-)-5h, Ka = 2.2 x 10(6)] showed a marked affinity, which is mainly due to the (+) enantiomers [e.g., (+)-5e, Ka = 2.1 x 10(7)]. No enhancement of affinity by cyclization to imidazolidines [e.g., (+/-)-trans-7a, Ka = 1.2 x 10(7)] was observed. These compounds [e.g., (+/-)-, (+)-, and (-)-5e], which did not produce any uterine response in the mouse, were able to inhibit weakly the growth of the DMBA-induced mammary carcinoma of the rat. The inhibitory effect of (+/-)-5e against MCF-7 cells, which can be overcome by hexestrol, makes a direct antiestrogenic mode of action probable, since general cytotoxic effects and a central action could be ruled out.

• Authors: E von Angerer, G Egginger, G Kranzfelder, H Bernhauer, H Schönenberger
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 25 Issue 7 Pg. 832-7 (Jul 1982) ISSN: 0022-2623 [Print] United States
• PMID: 6809943 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Ethylenediamines
• Imidazoles
• Receptors, Estradiol
• Receptors, Estrogen
• 9,10-Dimethyl-1,2-benzanthracene
• Thymidine

Topics

• 9,10-Dimethyl-1,2-benzanthracene
• Animals
• Antineoplastic Agents (chemical synthesis)
• Breast Neoplasms
• Cell Division (drug effects)
• Cells, Cultured
• Chemical Phenomena
• Chemistry
• Ethylenediamines (chemical synthesis, pharmacology)
• Female
• Humans
• Imidazoles (chemical synthesis, pharmacology)
• Mammary Neoplasms, Experimental (chemically induced, drug therapy)
• Rats
• Receptors, Estradiol
• Receptors, Estrogen (metabolism)
• Stereoisomerism
• Thymidine (metabolism)