Bis(3-hydroxyphenyl)alkane compounds

Six title compds. I (R = C1-6 alkyl, R1 = H, Me), useful in treating mammary tumors, were prepd. from 3-MeOC6H4CHO and alkylmagnesium halides. Thus, Grignard reaction of MeI with 3-MeOC6H4CHO gave 85.4% 3-MeOC6H4CH(OH)Me which was treated with HCl to give 73.3% 3-MeOC6H4CHClMe. Grignard reaction of this with EtBr gave 17.9% (3-MeOC6H4CHMe)2, ether cleavage of which with MeMgI or pyridine-HCl gave 77.0 or 92.0% I (R =Me, R1 = OH), resp. Mammary tumor-inhibiting, uterotropic, and antiuterotropic activities of I were tabulated

Antiestrogens. Synthesis and evaluation of mammary tumor inhibiting activity of 1,1,2,2-tetraalkyl-1,2 -diphenylethanes

Among the newly synthesized 1,1,2,2-tetraalkyl-1,2-diphenylethanes, 1,1,2,2-tetramethyl-1,2-bis(4'-hydroxyphenyl)ethane (23) and 1,1,2,2-tetramethyl-1,2-bis(3'-hydroxyphenyl)ethane (26) were the most active compounds regarding estradiol receptor affinity, exhibiting Ka values of 0.73 X 10(8) and 0.67 X 10(8) M-1, respectively. In vivo, 23 and 26 showed only very small uterotrophic activity in the mouse. They strongly inhibited (73%) the estrone-stimulated mouse uterine growth. Tested on the 9,10-dimethyl-1,2-benzanthracene induced hormone-dependent mammary adenocarcinoma of the Sprague-Dawley rat, compounds 23 and 26 exhibited a dose-dependent inhibition of the tumor growth, having a strong effect at a dose of 20 (mg/kg)/day (compound 23)

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

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

Studies on the mammary tumor inhibiting effect of cis-bis(glycylglycin ethyl ester)platinum(II) chloride

In vivo, cis-dichlorodiammineplatinum(II) (I) [15663-27-1] and cis-dichlorobis(glycylglycine Et ester)platinum(II) (II) [60426-60-0] inhibited the DMBA-induced hormone-dependent mammary carcinoma of the SD rat. In vitro, a marked effect on DNA synthesis by mammary tumor cells and an inhibition of estradiol-receptor interaction by I and II were demonstrated. Binding to DNA and inhibition of the proliferation-stimulating effect of endogenous estrogens by blocking the hormone receptors are discussed as modes of action of I and II

Potential antiestrogens. Synthesis and evaluation of mammary tumor inhibiting activity of 1,2-dialkyl-1,2-bis(3'-hydroxyphenyl)ethanes

The syntheses of the meso-1,2-dialkyl-1,2-bis(3'-hydroxyphenyl)ethanes [alkyl substituent: CH3 (I) [78682-42-5], C2H5 (II) [71953-72-5], C3H7 (III) [78682-43-6], C4H9 (IV) [78682-44-7], i-C4H9 (V) [78682-45-8], and C5H11 (VI) [78682-46-9]] and of d,l-3,4-bis(3'-hydroxyphenyl)hexane [71953-71-4] are described. In vitro these compds. inhibited the 3H-labeled estradiol [50-28-2] receptor interaction competitively, exhibiting Ka values of 0.20 * 109-0.11 * 106 M-1. In vivo the meso compds. reduced the estrone [53-16-7]-stimulated mouse uterine growth; the most effective compds. were II, III and IV (48, 50, and 45% inhibition, resp.). Compds., II-V showed weak estrogenic activity in the mouse uterine wt. test and in the vaginal cornification test. Compds. I, II, and III exhibited a dose-dependent growth inhibition on the MCF-7 human breast tumor cell line (10-9-10-6 M). These compds. also showed a marked dose-dependent inhibition on the DMBA-induced, hormone-dependent mammary carcinoma of the Sprague-Dawley rat corresponding to their assocn. consts