US3452061A - Steroidal nitrate esters - Google Patents

Steroidal nitrate esters Download PDF

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US3452061A
US3452061A US701054A US3452061DA US3452061A US 3452061 A US3452061 A US 3452061A US 701054 A US701054 A US 701054A US 3452061D A US3452061D A US 3452061DA US 3452061 A US3452061 A US 3452061A
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triene
dinitrate
allyloxy
ethyl
methoxyestra
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Gerhard R Wendt
Kurt W Ledig
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Wyeth LLC
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American Home Products Corp
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
    • C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
    • C07J41/0072—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the A ring of the steroid being aromatic

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  • This invention relates to and has for its objects the provision of new physiologically active compounds, novel processes for their production and new intermediates useful in the preparation thereof.
  • R is selected from the group consisting of lower alkyl of less than eight carbon atoms (e.g., methyl, ethyl, n-propyl, isopropyl, butyl, etc.) acyl and monocyclic cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.); R is a lower alkyl group of less than eight carbon atoms (e.g., methyl, ethyl, propyl, butyl, etc.) but preferably from 1 to 4 carbon atoms; R is selected from the group consisting of hydrogen and lower alkyl of less than 5 carbon atoms (e.g., methyl, ethyl, propyl, butyl) but preferably hydrogen; and n is 1, 2 or 3, preferably 1.
  • R is selected from the group consisting of lower alkyl of less than eight carbon atoms (e.g.,
  • the acyl radical of a hydrocarbon carboxylic acid of less than 12 carbon atoms as exemplified by the lower alkanoic acids (e.g., acetic, propionic, butyric, hexanoic and enanthic acid), the cycloalkane carboxylic acids (e.g., cyclobutane carboxylic acid), the monocyclic aromatic carboxylic acids (e.g., benzoic) and the monocyclic aryl lower alkanoic acids (e.g., phenacetic and fi-phenylpropionic acid).
  • the lower alkanoic acids e.g., acetic, propionic, butyric, hexanoic and enanthic acid
  • the cycloalkane carboxylic acids e.g., cyclobutane carboxylic acid
  • the monocyclic aromatic carboxylic acids e.g., benzoic
  • the monocyclic aryl lower alkanoic acids
  • the final products of this invention are physiologically active substances having blood pressure lowering activity and which may be used as vasodilators in experimental pharmacology or for veterinary or human use.
  • compositions containing active ingredients may be made up in standard dosage forms, generally with an inert excipient or carrier.
  • the blood pressure lowering effect was noted in the standard test animal (cat) within the dosage range of 5 to 10 mg./kg. of body weight.
  • a test procedure to elicit 7 blood pressure effects may be described as follows.
  • Cats are anesthetized with a standard agent, for example, Dial-urethane (Ciba). Blood pressure and heart rate are recorded. The test drug is injected intravenously (in most cases) in doses of 0.1, 1, 5, and 10 mg./kg. at intervals of 30 to 60 minutes depending on the time when blood pressure has been returned to the control level. Maximal changes in blood pressure are noted.
  • a standard agent for example, Dial-urethane (Ciba).
  • Blood pressure and heart rate are recorded.
  • the test drug is injected intravenously (in most cases) in doses of 0.1, 1, 5, and 10 mg./kg. at intervals of 30 to 60 minutes depending on the time when blood pressure has been returned to the control level. Maximal changes in blood pressure are noted.
  • the initial dose is best kept at the lowest portion of the indicated dosage range and then adjusted to the requirements of the animal or person treated. This is generally the case with vasodilators since the proper dose can only be determined on an individual basis.
  • R, R R and n are as hereinbefore defined as starting material.
  • the starting material of this invention may be prepared in accordance with the procedures set forth in co-pending application, Ser. No. 228,384, filed Oct. 4, 1962 in the names of Gordon A. Hughes and Herchel Smith, and in co-pending application, Ser. No. 319,484, filed Sept. 20, 1963 in the names of Kurt W. Ledig and Gerhard R. Wendt, now abandoned.
  • the final products may be prepared by introducing a nitrate ester group in the compounds of Formula II, as by treatment with silver nitrate in an inert organic medium (e.g., acetonitrile), in the presence of iodine.
  • an inert organic medium e.g., acetonitrile
  • EXAMPLE 2 175- (2,3-dihydroxypropoxy) -3-ethoxyestra- 1,3,5( 10) -triene, dinitrate Following the procedure of Example 1 but substituting 17 3 allyloxy 3 ethoxyestra 1,3,5(10) triene for 17p allyloxy 3 methoxyestra 1,3,5(l) triene there is obtained 175-(2,3-dihydroxypropoxy)-3-ethoxyestra-1,3,5 (10)-triene, dinitrate.
  • EXAMPLE 3 3-acetoxy-17B-(2,3-dihydroxypropoxy) -estra- 1,3,5(10)-triene, dinitrate Following the procedure of Example 1 but substituting 17/3 allyloxy 3 hydroxyestra 1,3,5(10) triene- 3-acetate for 17B-allyloxy-3-methoxyestra-1,3,5(10)-triene there is obtained 3-acetoxy-17fi-(2,3-dihydroxypropoxy) estra 1,3,5(10) triene, dinitrate.
  • EXAMPLE 5 3-acetoxy-17 3-(3,4-dihydroxypentoxy) -estra- 1,3,5 -triene, dinitrate Following the procedure of Example 1 but substituting 17 9 (3 penten 1 oxy) 3 hydroxyestra 1,3,5 (10)-triene 3 acetate for 1713 allyloxy 3 methoxyestra-1,3,5(10)-triene there is obtained 3-acetoxy-17p-(3, 4 dihydroxypentoxy) estra 1,3,5(10) triene, dinitrate.
  • EXAMPLE 6 13-ethyl-17fi- (2,3-dihydroxypropoxy) -3-methoxygona-1,3 (10)-triene, dinitrate Following the procedure of Example 1 but substituting 17/8 allyloxy 13 ethyl 3 methoxygona- 1,3,5(10)- triene for 17fi-allyloxy-3-methoxyestra-l,3,5(10)-triene there is obtained 13-ethyl-17fi-(2,3-dihydroxypropoxy)- 3-methoxygona-1,3 ,5 10) -triene, dinitrate.
  • EXAMPLE 7 13-ethyl-17fl-(2,3-dihydroxypropoxy)-3-ethoxygona- 1,3,5(10)-tn'ene, dinitrate Following the procedure of Example 1 but substituting 13 ethyl 17p allyloxy 3 ethoxygona 1,3,5(10)- 4 triene for 17/3 allyloxy -3-- methoxyestra --1,3,5(10)- triene there is obtained 13-ethyl-l7fi-(2,3-dihydroxypropoxy -3-ethoxygona- 1,3,5 10) -triene, dinitrate.
  • EXAMPLE 8 3-acetoxy-1 3-ethyl- 17 (2,3-dihydroxy propoxy) gona-1,3,5 10 -triene, dinitrate Following the procedure of Example 1 but substituting 13 ethyl 17 3 allyloxy 3 hydroxygona 1,3,5(10)- trien 3 acetate for 17,8 allyloxy 3 methoxyestra- 1,3,5(10)-triene there is obtained 3-acetoxy-13-ethyl- 17B (2,3 dihydroxypropoxy) gona. 1,3,5(10)- triene, dinitrate.
  • EXAMPLE 9 3-acetoxy-13-propy1-17fi-(2,3-dihydroxypropoxy)- gona-1,3,5 10 -triene, dinitrate Following the procedure of Example 1 but substituting 13 propyl allyloxy 3 hydroxygona 1,3,5(10)- triene 3 acetate for 17p allyloxy 3 methoxyestra- 1,3,5(10)-triene there is obtained 3-acetoxy-13-propyl- 17 9' (2,3 dihydroxypropoxy) gona 1,3,5(10)-triene, dinitrate.
  • EXAMPLE 11 3-acetoxy-13 -propyl- 1 75- (2, S-dihydroxypentoxy) gona-1,3,5 10) -triene, dinitrate Following the procedure of Example 1 but substituting 13 propyl 17g (2 penten 1 oxy) 3 hydroxygona 1,3,5(10 3 acetate for 1719 allyloxy 3 methoxyestra-1,3,5(10)-triene there is obtained 3-acetoxy-13- propyl 17,8 (2,3 dihydroxypentoxy) gona 1,3,5 (10)-triene, dinitrate.
  • EXAMPLE 12 3-acetoxy-1 3-butyl- 17 B-( 3,4-dihydroxypentoxy gona-1,3,5 10) -triene, dinitrate Following the procedure of Example 1 but substituting 13 butyl 17p (3 penten 1 oxy) 3 hydroxygona 1,3,5(10) trien 3 acetate for 17;? allyloxy- 3 methoxyestra 1,3,5(10) triene there is obtained 3 acetoxy 13 butyl 17p (3,4 dihydroxypentoxy)- gona-1,3,5 (10)-triene, dinitrate.
  • EXAMPLE 13 3-cyc1opentoxy-17,8-(2,3-dihydroxypropoxy)estra- 1,3,5(10)-triene, dinitrate Following the procedure of Example 1 but substituting 3 cyclopentoxy 17 3 allyloxy estra 1,3,5(10)- triene for 1718 allyloxy 3 methoxyestra 1,3,5(l0)- triene there is obtained 3-cyclopentoxy-17B-(2,3-dihydroxypropoxy) -estra-1,3,5 (10)-triene, dinitrate.
  • EXAMPLE 14 3-cyclohexyloxy-13-ethyl-17B- (2,3 -dihydr0xybutyloxy gona-1,3,5(10)-triene, dinitrate Following the procedure of Example 1 but substituting 3 cyclohexyloxy 13 ethyl 17B (2 buten 1 oxy)- gona 1,3,5(10) triene for 17p allyloxy 3 methoxyestra-1,3,5 (10)-triene there is obtained 3-cyclohexyloxy- 13 ethyl 17,8 (2,3 dihydroxybutyloxy-gona-1,3,5 (10)-triene, dinitrate.
  • R is a lower alkyl of 1 to 2 carbon atoms, acetyl or cyclopentyl and R is a lower alkyl of 1 to 4 carbon atoms.
  • R is methyl; R is ethyl; R is hydrogen and n is l.
  • R is cyclohexyl; R is ethyl; R is methyl and n is 1.
  • R is cyclopentyl; R is ethyl; R is hydrogen and n is 1.
  • R is acetyl; R is methyl; R is hydrogen and n is l.
  • R is acetyl; R is ethyl; R is hydrogen and n is 1.
  • R is acetyl; R is ethyl; R is methyl and n is 1.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Description

United States Patent US. Cl. 260397.5 9 Claims ABSTRACT OF THE DISCLOSURE The disclosure deals with 17-dihydroxy-(lower) alkoxyestratriene dinitrates which have been found to possess pharmacological activity, particularly as blood pressure lowering agents.
This is a continuation-in-part of our application, Ser. No. 538,982, filed Mar. 31, 1966, now abandoned.
This invention relates to and has for its objects the provision of new physiologically active compounds, novel processes for their production and new intermediates useful in the preparation thereof.
More particularly this invention relates to compounds of the Formula I:
wherein R is selected from the group consisting of lower alkyl of less than eight carbon atoms (e.g., methyl, ethyl, n-propyl, isopropyl, butyl, etc.) acyl and monocyclic cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.); R is a lower alkyl group of less than eight carbon atoms (e.g., methyl, ethyl, propyl, butyl, etc.) but preferably from 1 to 4 carbon atoms; R is selected from the group consisting of hydrogen and lower alkyl of less than 5 carbon atoms (e.g., methyl, ethyl, propyl, butyl) but preferably hydrogen; and n is 1, 2 or 3, preferably 1.
Among the suitable acyls may be mentioned the acyl radical of a hydrocarbon carboxylic acid of less than 12 carbon atoms, as exemplified by the lower alkanoic acids (e.g., acetic, propionic, butyric, hexanoic and enanthic acid), the cycloalkane carboxylic acids (e.g., cyclobutane carboxylic acid), the monocyclic aromatic carboxylic acids (e.g., benzoic) and the monocyclic aryl lower alkanoic acids (e.g., phenacetic and fi-phenylpropionic acid).
The final products of this invention are physiologically active substances having blood pressure lowering activity and which may be used as vasodilators in experimental pharmacology or for veterinary or human use.
In pharmacology, the compounds are preferably used intravenously although it is contemplated that they may also be used orally or parenterally (e.g., subcutaneously) in veterinary or human medicine. Compositions containing active ingredients may be made up in standard dosage forms, generally with an inert excipient or carrier.
The blood pressure lowering effect was noted in the standard test animal (cat) within the dosage range of 5 to 10 mg./kg. of body weight. A test procedure to elicit 7 blood pressure effects may be described as follows.
3,452,061 Patented June 24, 1969 Cats are anesthetized with a standard agent, for example, Dial-urethane (Ciba). Blood pressure and heart rate are recorded. The test drug is injected intravenously (in most cases) in doses of 0.1, 1, 5, and 10 mg./kg. at intervals of 30 to 60 minutes depending on the time when blood pressure has been returned to the control level. Maximal changes in blood pressure are noted.
It may be pointed out that if the compounds are to be used for other than experimental purposes, the initial dose is best kept at the lowest portion of the indicated dosage range and then adjusted to the requirements of the animal or person treated. This is generally the case with vasodilators since the proper dose can only be determined on an individual basis.
The compounds of this invention can be prepared by employing the novel processes of this invention beginning with the compounds of the Formula II:
wherein R, R R and n are as hereinbefore defined as starting material. The starting material of this invention may be prepared in accordance with the procedures set forth in co-pending application, Ser. No. 228,384, filed Oct. 4, 1962 in the names of Gordon A. Hughes and Herchel Smith, and in co-pending application, Ser. No. 319,484, filed Sept. 20, 1963 in the names of Kurt W. Ledig and Gerhard R. Wendt, now abandoned.
According to a feature of this invention, the final products (compounds of Formula I) may be prepared by introducing a nitrate ester group in the compounds of Formula II, as by treatment with silver nitrate in an inert organic medium (e.g., acetonitrile), in the presence of iodine.
Among the suitable starting steriods that are utilizable in the process of the invention may be mentioned 1 3-lower alkyl-17B-lower alkenyloxy-3-alkoxygona-1,3,
5 10) -triene (e.g.,
13-methyl-17B-(3-buten-1-oxy)-3-methoxygona-1,3,
5(10)-triene,
1 3-ethyl-17,8-ally1oxy-3-methoxygona- 1,3 ,5 10) -triene,
1 3-ethyl- 17/3-allyloxy3-ethoxygona- 1,3,5 10) -triene,
1 3-propyl-17B-(2-buten-1-0Xy) -3-ethoXygona-1,3,5 10 triene,
13-propyl-17,8-allyloxy-3-methoxygona-1,3 ,5 10) -triene,
13-butyl-17/3-(Z-penten-l-oxy) -3-propoXygona-1, 3,5 l 0) triene) l7 8-lower alkenyloXy-3-alkoxyestra-1,3,5 (10)-triene e. g.,
1713- Z-buten-l -oxy) -3-methoxyestral ,3 ,5 10) -triene,
17,9-allyloxy-3-methoxyestra-1,3 ,5 10) -triene,
17,8-allyloxy-3-ethoxyestra-1,3,5 10 -triene,
17 3-(3-buten-1-oxy)-3-methoxyestra-1,3,5(10)-triene,
17B-(2-penten-1-oxy) -3-butoxyestra-1,3 ,5 10 triene) 17B-alkenyloxy-3acyloxyestra-1,3,5 10)-triene (e. g.,
17fi-(2-buten-l-oxy)-3-hydroxyestra-1,3,5(10)-triene-3- acetate,
17 3-allyloxy-3-hydroxyestra-1,3,5 (10)-triene-3-acetate) 17 8-lower alkenyloxy-13-lower alkyl-3-acyloxygona1,3
5 (10) -triene (e.g.,
17/8-(2-buten-1-oxy) -1 3-ethyl-3-hydroxygona-1,3,5 10
triene-3-acetate,
17/8-al1yloxy-13-ethyl-3-hydroxygona-1,3,5 10 -triene-3- acetate), and the like.
The following examples illustrate the invention (all temperatures being in centigrade).
EXAMPLE 1 17 (2,3-dihydroxypropoxy) -3 -methoxyestra- 1,3,5 (10) -triene, dinitrate To 1.1 gm. of 17fl-allyloxy-3-methoxyestra-1,3,5(l0)- triene in 25 ml. of acetonitrile is added 1.2 gm. of silver nitrate. The mixture is then stirred and refluxed while 0.5 gm. of iodine is added over a period of 15 minutes. The mixture is refluxed additionally for one hour. The reaction mixture is cooled, filtered and the filtrate is diluted with water. The filtrate is then extracted with ether. The organic layer is washed with an aqueous sodium bisulfite solution and the solvent is evaporated in vacuo. The residue is chromatographed in a benzene-hexane (3:7) solution over Florex. The elution with benzene yielded 17 8-(2,3-dihydroxypropoxy)-3-methoxyestra-1,3, 5(10)-triene, dinitrate.
Analysis.Calcd. for C H N O C, 58.65; H, 6.71; N, 6.22. Found: C, 58.40; H, 6.62; N, 6.23.
EXAMPLE 2 175- (2,3-dihydroxypropoxy) -3-ethoxyestra- 1,3,5( 10) -triene, dinitrate Following the procedure of Example 1 but substituting 17 3 allyloxy 3 ethoxyestra 1,3,5(10) triene for 17p allyloxy 3 methoxyestra 1,3,5(l) triene there is obtained 175-(2,3-dihydroxypropoxy)-3-ethoxyestra-1,3,5 (10)-triene, dinitrate.
EXAMPLE 3 3-acetoxy-17B-(2,3-dihydroxypropoxy) -estra- 1,3,5(10)-triene, dinitrate Following the procedure of Example 1 but substituting 17/3 allyloxy 3 hydroxyestra 1,3,5(10) triene- 3-acetate for 17B-allyloxy-3-methoxyestra-1,3,5(10)-triene there is obtained 3-acetoxy-17fi-(2,3-dihydroxypropoxy) estra 1,3,5(10) triene, dinitrate.
EXAMPLE 4 17B- (2,3-dihydroxybutoxy) -3-methoxyestra- 1,3,5 10) -triene, dinitrate Following the procedure of Example 1 but substituting 175 (2 buten 1 oxy) 3 methoxyestra 1,3,5(l0)- triene for 176 allyloxy 3 methoxyestra 1,3,5(10)- triene there is obtained 17B-(2,3-dihydroXybutoxy)-3- methoxyestra-1,3,5 10) -triene, dinitrate.
EXAMPLE 5 3-acetoxy-17 3-(3,4-dihydroxypentoxy) -estra- 1,3,5 -triene, dinitrate Following the procedure of Example 1 but substituting 17 9 (3 penten 1 oxy) 3 hydroxyestra 1,3,5 (10)-triene 3 acetate for 1713 allyloxy 3 methoxyestra-1,3,5(10)-triene there is obtained 3-acetoxy-17p-(3, 4 dihydroxypentoxy) estra 1,3,5(10) triene, dinitrate.
EXAMPLE 6' 13-ethyl-17fi- (2,3-dihydroxypropoxy) -3-methoxygona-1,3 (10)-triene, dinitrate Following the procedure of Example 1 but substituting 17/8 allyloxy 13 ethyl 3 methoxygona- 1,3,5(10)- triene for 17fi-allyloxy-3-methoxyestra-l,3,5(10)-triene there is obtained 13-ethyl-17fi-(2,3-dihydroxypropoxy)- 3-methoxygona-1,3 ,5 10) -triene, dinitrate.
EXAMPLE 7 13-ethyl-17fl-(2,3-dihydroxypropoxy)-3-ethoxygona- 1,3,5(10)-tn'ene, dinitrate Following the procedure of Example 1 but substituting 13 ethyl 17p allyloxy 3 ethoxygona 1,3,5(10)- 4 triene for 17/3 allyloxy -3-- methoxyestra --1,3,5(10)- triene there is obtained 13-ethyl-l7fi-(2,3-dihydroxypropoxy -3-ethoxygona- 1,3,5 10) -triene, dinitrate.
EXAMPLE 8 3-acetoxy-1 3-ethyl- 17 (2,3-dihydroxy propoxy) gona-1,3,5 10 -triene, dinitrate Following the procedure of Example 1 but substituting 13 ethyl 17 3 allyloxy 3 hydroxygona 1,3,5(10)- trien 3 acetate for 17,8 allyloxy 3 methoxyestra- 1,3,5(10)-triene there is obtained 3-acetoxy-13-ethyl- 17B (2,3 dihydroxypropoxy) gona. 1,3,5(10)- triene, dinitrate.
EXAMPLE 9 3-acetoxy-13-propy1-17fi-(2,3-dihydroxypropoxy)- gona-1,3,5 10 -triene, dinitrate Following the procedure of Example 1 but substituting 13 propyl allyloxy 3 hydroxygona 1,3,5(10)- triene 3 acetate for 17p allyloxy 3 methoxyestra- 1,3,5(10)-triene there is obtained 3-acetoxy-13-propyl- 17 9' (2,3 dihydroxypropoxy) gona 1,3,5(10)-triene, dinitrate.
EXAMPLE 1O 3-acetoxy-13-butyl-17p-(2,3-dihydroxypropoxy) gona-1,3,5 10) -triene, dinitrate Following the procedure of Example 1 but substituting 13 butyl 17B allyloxy 3 hydroxygona 1,3,5(10)- triene 3 acetate for 175 allyloxy 3 methoxyestra- 1,3,5(l0)-triene there is obtained 3-acetoxy-l3-butyl- 17B (2,3 dihydroxypropoxy) gona 1,3,5(10)- triene, dinitrate.
EXAMPLE 11 3-acetoxy-13 -propyl- 1 75- (2, S-dihydroxypentoxy) gona-1,3,5 10) -triene, dinitrate Following the procedure of Example 1 but substituting 13 propyl 17g (2 penten 1 oxy) 3 hydroxygona 1,3,5(10 3 acetate for 1719 allyloxy 3 methoxyestra-1,3,5(10)-triene there is obtained 3-acetoxy-13- propyl 17,8 (2,3 dihydroxypentoxy) gona 1,3,5 (10)-triene, dinitrate.
EXAMPLE 12 3-acetoxy-1 3-butyl- 17 B-( 3,4-dihydroxypentoxy gona-1,3,5 10) -triene, dinitrate Following the procedure of Example 1 but substituting 13 butyl 17p (3 penten 1 oxy) 3 hydroxygona 1,3,5(10) trien 3 acetate for 17;? allyloxy- 3 methoxyestra 1,3,5(10) triene there is obtained 3 acetoxy 13 butyl 17p (3,4 dihydroxypentoxy)- gona-1,3,5 (10)-triene, dinitrate.
EXAMPLE 13 3-cyc1opentoxy-17,8-(2,3-dihydroxypropoxy)estra- 1,3,5(10)-triene, dinitrate Following the procedure of Example 1 but substituting 3 cyclopentoxy 17 3 allyloxy estra 1,3,5(10)- triene for 1718 allyloxy 3 methoxyestra 1,3,5(l0)- triene there is obtained 3-cyclopentoxy-17B-(2,3-dihydroxypropoxy) -estra-1,3,5 (10)-triene, dinitrate.
EXAMPLE 14 3-cyclohexyloxy-13-ethyl-17B- (2,3 -dihydr0xybutyloxy gona-1,3,5(10)-triene, dinitrate Following the procedure of Example 1 but substituting 3 cyclohexyloxy 13 ethyl 17B (2 buten 1 oxy)- gona 1,3,5(10) triene for 17p allyloxy 3 methoxyestra-1,3,5 (10)-triene there is obtained 3-cyclohexyloxy- 13 ethyl 17,8 (2,3 dihydroxybutyloxy-gona-1,3,5 (10)-triene, dinitrate.
The invention may be variously otherwise embodied within the scope of the appended claims.
What is claimed is:
1. A compound of the formula:
ONOz
O-CHz-CH-CH:
ONOg
in which R is a lower alkyl of 1 to 2 carbon atoms, acetyl or cyclopentyl and R is a lower alkyl of 1 to 4 carbon atoms.
3. A compound according to claim 1 wherein R is methyl; R is methyl; R is hydrogen and n is 1.
4. A compound according to claim 1 wherein R is methyl; R is ethyl; R is hydrogen and n is l.
5. A compound according to claim 1 where R is cyclohexyl; R is ethyl; R is methyl and n is 1.
6. A compound according to claim 1 wherein R is cyclopentyl; R is ethyl; R is hydrogen and n is 1.
7. A compound according to claim 1 wherein R is acetyl; R is methyl; R is hydrogen and n is l.
8. A compound according to claim 1 wherein R is acetyl; R is ethyl; R is hydrogen and n is 1.
9. A compound according to claim 1 wherein R is acetyl; R is ethyl; R is methyl and n is 1.
References Cited UNITED STATES PATENTS 3,352,891 11/1964 Wendi: et a1. 260-3974 3,374,251 3/1968 Cross 260397.1
LEWIS GOTTS, Primary Examiner.
E. G. LOVE, Assistant Examiner.
US. Cl. X.R. 260-999
US701054A 1966-02-11 1968-01-29 Steroidal nitrate esters Expired - Lifetime US3452061A (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US526716A US3352891A (en) 1966-02-11 1966-02-11 19-norsteroidal-17-nitrates
US53898266A 1966-03-31 1966-03-31
US559741A US3394150A (en) 1966-02-11 1966-06-23 Polynitrates of steroidal alcohols
US58637866A 1966-10-13 1966-10-13
US70105468A 1968-01-29 1968-01-29

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004098538A2 (en) * 2003-03-13 2004-11-18 Nitromed, Inc. Nitrosated and nitrosylated compounds, compositions and methods of use

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3352891A (en) * 1966-02-11 1967-11-14 American Home Prod 19-norsteroidal-17-nitrates
US3374251A (en) * 1963-05-24 1968-03-19 Syntex Corp 17-(aliphatic hydrocarbonoxy) and 17-(substituted aliphatic hydrocarbonoxy) estrane derivatives

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3374251A (en) * 1963-05-24 1968-03-19 Syntex Corp 17-(aliphatic hydrocarbonoxy) and 17-(substituted aliphatic hydrocarbonoxy) estrane derivatives
US3352891A (en) * 1966-02-11 1967-11-14 American Home Prod 19-norsteroidal-17-nitrates

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004098538A2 (en) * 2003-03-13 2004-11-18 Nitromed, Inc. Nitrosated and nitrosylated compounds, compositions and methods of use
WO2004098538A3 (en) * 2003-03-13 2005-03-31 Nitromed Inc Nitrosated and nitrosylated compounds, compositions and methods of use
US20060009431A1 (en) * 2003-03-13 2006-01-12 Nitromed, Inc. Nitrosated and nitrosylated compounds, compositions and methods use

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