American Home Products Corporation

Wake Forest University

Wyeth

Nanophagix LLC

Other

Steven Jay Adelman

Thomas B Clarkson

Scott A Washburn

J Koudy Williams

Michael R Adams

J Mark Cline

Janice D Wagner

Thomas C Register

Frederick O Gemmill, Jr

Chester E Orzech

William Alvin Kinney

H Donlon Skerrett

Dorothy H Prozialeck

Michael S Dey

Kurt E Steiner

Neal I Azrolan

Surendra N Sehgal

The present invention relates to compounds, and methods of use thereof, capable of entering macrophages. The invention further relates to compounds capable of modulating (for example inhibiting) the activity of the mammalian target of rapamycin (mTor), treating mTor-associated diseases, in particular, but not limited to, related to mTor in macrophages. The invention also relates to compounds capable of imaging mTor in a subject, in particular, but not limited to, mTor in macrophages.

Drug delivery and imaging chemical conjugate, formulations and methods of use thereof

The present invention relates to compounds of Formula 1, and methods of use thereof, capable of entering macrophages. The invention further relates to compounds capable of modulating (for example inhibiting) the activity of the mammalian target of rapamycin (mTor), treating mTor-associated diseases, in particular, but not limited to, related to mTor in macrophages. The invention also relates to compounds capable of imaging mTor in a subject, in particular, but not limited to, mTor in macrophages.  wherein Q is, in one embodiment, 

This invention provides a method of using 17&#x3b2;-dihydroequilenin or a pharmaceutically acceptable salt of 17&#x3b2;-dihydroequilenin-3-sulfate ester as an antioxidant.

Use of 17&#x3b2;-dihydroequilenin as an antioxidant

This invention provides a method of treating or inhibiting cardiovascular, cerebral vascular, or peripheral vascular disease in a mammal in need thereof, which comprises providing said mammal with an effective amount of a rapamycin.

Method of treating cardiovascular disease

This invention provides a method of using equilenin or a pharmaceutically acceptable salt of equilenin-3-sulfate ester as an antioxidant.

Use of equilenin as an antioxidant

The present invention relates to a method of using 17&agr;-dihydroequilenin and metabolic conjugates thereof to prevent and reduce atherogenesis in males and females without causing endometrial proliferation in females and without producing feminizing changes in males. 17&agr;-dihydroequilenin was evaluated for its effects on plasma lipid and lipoprotein, glucose, insulin concentrations, coronary artery vasomotor function, and reproductive organ and mammary gland proliferation in atherosclerotic mammals. 17&agr;-dihydroequilenin was found to prevent endothelium-dependent vasoconstriction in males (p<0.05) and ovariectomized females (p<0.08). 17&agr;-dihydroequilenin treatment increased plasma apolipoprotein A-1 concentrations (p<0.05) and lowered fasting insulin concentrations (p<0.05) without changing fasting plasma glucose concentrations in males. 17&agr;-dihydroequilenin had no other effects on plasma lipid and lipoprotein concentrations in either males or females. Also, 17&agr;-dihydroequilenin exhibited no trophic effects on the uterus, endometrium, or breast, and no effect on either prostatic or testicular weight. Thus, 17&agr;-dihydroequilenin may prevent breast and prostatic hyperplasia and neoplasia, and has no feminizing effects on the male urogenital system or mammary gland.

Effects of 17 &agr;-dihydroequilenin on plasma lipid and lipoprotein, glucose, insulin concentrations, coronary artery vasomotor function, and reproductive organ and mammary gland proliferation in atherosclerotic mammals

The present invention relates to a method of using 17.alpha.-dihydroequilenin and metabolic conjugates thereof to prevent and reduce atherogenesis in males and females without causing endometrial proliferation in females and without producing feminizing changes in males. 17.alpha.-dihydroequilenin was evaluated for its effects on plasma lipid and lipoprotein, glucose, insulin concentrations, coronary artery vasomotor function, and reproductive organ and mammary gland proliferation in atherosclerotic mammals. 17.alpha.-dihydroequilenin was found to prevent endothelium-dependent vasoconstriction in males (p&lt;0.05) and ovariectomized females (p&lt;0.08). 17.alpha.-dihydroequilenin treatment increased plasma apolipoprotein A-1 concentrations (p&lt;0.05) and lowered fasting insulin concentrations (p&lt;0.05) without changing fasting plasma glucose concentrations in males. 17.alpha.-dihydroequilenin had no other effects on plasma lipid and lipoprotein concentrations in either males or females. Also, 17.alpha.-dihydroequilenin exhibited no trophic effects on the uterus, endometrium, or breast, and no effect on either prostatic or testicular weight. Thus, 17.alpha.-dihydroequilenin may prevent breast and prostatic hyperplasia and neoplasia, and has no feminizing effects on the male urogenital system or mammary gland.

Effects of 17.alpha.-dihydroequilenin on plasma lipid and lipoprotein,

The present invention relates to a method of using 17.alpha.-dihydroequilenin and metabolic conjugates thereof to prevent and reduce atherogenesis in males and females without causing endometrial proliferation in females and without producing feminizing changes in males. 17.alpha.-dihydroequilenin was evaluated for its effects on plasma lipid and lipoprotein, glucose, insulin concentrations, coronary artery vasomotor function, and reproductive organ and mammary gland proliferation in atherosclerotic mammals. 17.alpha.-dihydroequilenin was found to prevent endothelium-dependent vasoconstriction in males (p&lt;0.05) and ovariectomized females (p&lt;0.08). 17.alpha.-dihydroequilenin treatment increased plasma apolipoprotein A-l concentrations (p&lt;0.05) and lowered fasting insulin concentrations (p&lt;0.05) without changing fasting plasma glucose concentrations in males. 17.alpha.-dihydroequilenin had no other effects on plasma lipid and lipoprotein concentrations in either males or females. Also, 17.alpha.-dihydroequilenin exhibited no trophic effects on the uterus, endometrium, or breast, and no effect on either prostatic or testicular weight. Thus, 17.alpha.-dihydroequilenin may prevent breast and prostatic hyperplasia and neoplasia, and has no feminizing effects on the male urogenital system or mammary gland.

This invention relates to treating Alzheimer's disease with 8.alpha.-3-hydroxyestra-1,3,5(10),9(11)tetraen-17-one (.DELTA.9(11)-dehydro-8-isoestrone) (VI), ##STR1## or a pharmaceutically acceptable salt thereof.

.DELTA.9(11)-dehydro-8-isoestrone used to treat alzheimer's disease

This invention provides a method of lowering cholesterol and blood lipid levels, preventing hypercholesterolemia, hyperlipidemia, cardiovascular disease, atherosclerosis, and peripheral vascular disease comprising administering an effective amount of 17.alpha.-dihydroequilenin or a mammalian metabolic conjugate thereof to a mammal in need thereof.

Method of lowering cholesterol

This invention relates to 8.alpha.-3-hydroxyestra-1,3,5(10),9(11)tetraen-17-one (.DELTA.9(11)-dehydro-8-isoestrone) (VI), ##STR1## to the process for its preparation, to pharmaceutical compositions containing said 8.alpha.-3-hydroxyestra-1,3,5(10),9(11)tetraen-17-one (.DELTA.9(11)-dehydro-8-isoestrone) (VI) and to the use of said 8.alpha.-3-hydroxyestra-1,3,5(10),9(11)tetraen-17-one (.DELTA.9(11)-dehydro-8-isoestrone) (VI) for modifying the balance between bone production and bone resorption, and as an antioxidant in a host animal, including man.

Method of modifying bone resorption with

A method for the treatment of atherosclerosis by administering to a patient in need of anti-atherosclerotic treatment, an effective amount of 17 alpha-dihydroequilin, a C.sub.2 -C.sub.6 alkanoyloxy ester thereof or a pharmaceutically acceptable salt of it's sulfate or phosphate ester, in the absence of naturally occurring estrogenic sreroids. A pharmaceutical composition containing 17 alpha-dihydroequilin, a C.sub.2 -C.sub.6 alkanoyloxy ester thereof or a pharmaceutically acceptable salt of it's sulfate or phosphate ester, in the absence of naturally occurring estrogenic sreroids, and a pharmaceutically acceptable carrier therefor.

Anti-atherosclerotic use of 17 alpha-dihydroequilin

This invention relates to 8.alpha.-3-hydroxyestra- 1,3,5( 10),9( 11 )tetraen-17-one (.DELTA.9( 11 )-dehydro-8-isoestrone) (VI), ##STR1## to the process for its preparation, to pharmaceutical compositions containing said 8.alpha.-3-hydroxyestra- 1,3,5(10), 9(11)tetraen-17-one (.DELTA.9(11)-dehydro-8-isoestrone) (VI) and to the use of said 8.alpha.-3-hydroxyestra-1,3,5(10),9(11 )tetraen-17-one (A9( 11 )-dehydro-8-isoestrone) (VI) for modifying the balance between bone production and bone resorption, and as an antioxidant in a host animal, including man.

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Doylestown, PA, United States of America

Steven Jay Adelman