Certain steroid N-bis-(haloethyl)-carbamates

Abstract

.Iadd.Antitumor active mono and poly N-Bis-(B-haloethyl)-carbamic acid esters of certain estrogenic steroid hormones, especially estradiol; such compounds wherein all hydroxyl groups of the steroid molecule are not thus esterified; and organic and inorganic acid esters of such latter compounds. .Iaddend.

What we claim is: 
     
       1. Mono- and polyesters of estrogenic steroid hormones selected from the group consisting of .[.estra-1,3,5(10)-triene-17β-ol,.]. estra-1,3,5(10)-triene-3,17β-diol, estra-1,3,5(10)-triene-3,17α-diol, .[.estra-1,3,5(10)-triene-3,17β-diol-16-one,.]. estra-1,3,5(10)-triene-3,16α,17β -triol, 17α-ethynyl-estra-1,3,5(10)-triene-3,17β-diol, .[.estra-1,3,5 (10)-triene-3,17β-diol-3-methyl-ether, and estra-1,3,5 (10)-triene-3,17β-diol-17-methylether,.]. with N-bis-(β-haloethyl)-carbamic acid of the formula: ##STR5## wherein X is selected from the group consisting of chlorine and bromine, one or more remaining hydroxyl groups when present in the steroid nucleus being selected from the group consisting of free hydroxyl groups and hydroxyl groups esterified with an acid selected from the group consisting of aliphatic, cycloaliphatic and aromatic carboxylic acids, and inorganic polybasic acids. 
     
     
       2. The esters of claim 1, in which the sole acid moiety is N-bis-(β-haloethyl)-carbamic acid (compound I). 
     
     
       3. The esters of claim 1, in which the hormone is estradiol. 
     
     
       4. Estradiol-3-N-bis-(β-chloroethyl)-carbamate. 
     
     
       5. Estradiol-3,17-bis-N-bis-(β-chloroethyl)-carbamate. 
     
     
       6. Estradiol-17-phosphate-3-N-bis-(β-chloroethyl)-carbamate. 
     
     
       7. Estradiol-3-phosphate-17-N-bis-(β-chloroethyl)-carbamate. 
     
     
       8. Estradiol-3-N-bis-(β-chloroethyl)-carbamate-17-propionate. .[.9. Mono- and polyesters of androgenic steroid hormones selected from the group consisting of androstane-3α,17β-diol, androstane-3α-ol-17-one, androstane-3β-ol-17-one, androst-5-ene-3β-ol-17-one, and etiocholane-3α-ol-17-one, with N-bis-(β-haloethyl)-carbamic acid of the formula: ##STR6## wherein X is selected from the group consisting of chlorine and bromine, one or more remaining hydroxyl groups when present in the steroid nucleus being selected from the group consisting of free hydroxyl groups and hydroxyl groups esterified with an acid selected from the group consisting of aliphatic, cycloaliphatic and aromatic carboxylic acids, and inorganic 
     
     
        polybasic acids..]. .[.10.  Mono- and polyesters of corticoid steroid hormones selected from the group consisting of pregnane-3α,20α-diol, pregn-5-ene-3β-ol-20-one, pregn-4-ene-17α, 21-diol-3,11-20-trione, pregn-4-ene-11β,17α,21-triol-3,20-dione, pregn-4-ene-11β, 21-diol-3,20-dione, pregn-4-ene-21-ol-3,11-20-trione, pregn-4-ene-21-ol-3,20-dione, pregn-1,4-diene-17α21-diol-3,11,20-trione, pregna-1,4-diene-11β,17α,21-triol-3,20-dione, 6α-methyl-pregna-1,4-diene-11β,17α,21-triol-3,20-dione, 9α-fluoro-pregn-4-ene-11β,17α,21-triol-3,20-dione, 6α9α-difluoro-pregn-1,4-diene-11β,16α,17α,21-tetrol-3,20-dione and 16α-methyl-9α-fluoro-pregna-1,4-diene-11β,17α,21-triol-3,20-dione with N-bis(β-haloethyl)-carbamic acid of the formula: ##STR7## wherein X is selected from the group consisting of chlorine and bromine, one or more remaining hydroxyl groups when present in the steroid nucleus being selected from the group consisting of free hydroxyl groups and hydroxyl groups esterified with an acid selected from the group consisting of aliphatic, cycloaliphatic and aromatic carboxylic acids, and inorganic 
     
     
        polybasic acids..]. 11. Estradiol-3-N-bis-(β-chloroethyl)-carbamate-17-lower-alkanoate. 
     
     
          . Estradiol-17β-N-bis-(β-chloroethyl)-carbamate. 
     
     
        13. Estradiol-17-N-bis-(β-bromoethyl)-carbamate. 
     
     
        14. Estradiol-3-acetate-17-N-bis-(β-chloroethyl)-carbamate. 15. Estradiol-3-lower-alkanoate-17-N-bis-(β-chloroethyl)-carbamate. 
     
     
          . Estradiol-3-acetate-17-N-bis-(β-bromoethyl)-carbamate. 17. Estradiol-3-lower-alkanoate-17-N-bis-(β-bromoethyl)-carbamate. 
     
     
            Estradiol-3-N-bis-(β-chloroethyl)-carbamate-17-trimethyl-acetate. 
     
     
        9. Estradiol-3-N-bis-(β-chloroethyl)-carbamate-17-acetate.