Med Chem II Reproductive Hormones

Estradiol: estrane nucleus c18: "diol" C3 and C17

metabolized by CYP c17 OH into ketone: less active metabolite: estrone

phase II conjugation with sulfate group: HIGH FBM low bioavailability

Estrone: estrane C18: ketone version of estradiol: less active

Estriol: estrane C18: inactive product formed by hydration of estrone: tri-ol = 3 OH.. one at C3, C16 and C17

Ethinyl estradiol: estrane C18: estradiol with ethinyl group at C17 to prevent the oxidation of the OH on C17: but same estrogenic activity of estradiol... now a tertiary OH instead of a secondary: most commonly used in oral contraceptives

Mestranol: estrane C18: same structure as ethinyl estradiol but with ether on C3 so resistant to phase II metabolism... O-demethylation to ethinyl estradiol

Estropipate: Ogen: C18 estrane: estrogenic substance: IV or oral

sulfate conjugate of estrone stabilized by piperazine salt... PIP= piperazine

Estradiol Valerate: valeric acid: IM depot: injected into the muscle released over a prolonged period of time: pro drugs: once a week

esterified C17 hydroxyl with fatty acid

Estradiol Enanthate: enanthic acid: IM depot: injected into the muscle released over a prolonged period of time: pro drugs: once a week

esterified C17 hydroxyl with fatty acid

Estradiol Cypionate: cyclopenty-propionic acid: IM depot: injected into the muscle released over a prolonged period of time: pro drugs: once a week

esterified C17 hydroxyl with fatty acid

Chlortriansene: SERM: double bond surrounded by 3 aromatic rings, 3 ethers, chloro off of double bond: partial agonist

Tamoxifen: SERM: pure antagonist: double bond surrounded by 3 aromatic rings, tertiary amine; used in breast cancer by blocking estradiol receptors and stimulates transcription of estradiol receptors in bones for osteoporosis

Raloxifene: SERM: newer drug used mostly for osteoporosis by stimulating transcription of estradiol receptors in bones

Progesterone: pregnane (c21) produced by ovaries to prepare uterus for fertilized ovum to grow. if NO fertilization than it acts on the uterus to shed and induce menses (period). if pregnancy occurs it is produced by placenta.

Hydroxyprogesterone: pregnane C21 (progestin): active form of progesterone with an OH (hydroxyl) off of C17 but it is quickly metabolized to an inactive form by reducing C20 carbonyl into an alcohol

Hydroxyprogesterone acetate: (progestin): pregnane (c21): for oral use

Hydroxyprogesterone caproate (progestin) pregnane (c21): oil product: hydroxyl group at C17 of hydroxy progesterone allows for fatty acid ester formation: IM use

Ethisterone (acetate): hydroxyprogesterone with C20 and C21 replaced by ethinyl group C19 backbone similar to androgenic hormone testosterone so unwanted effects in females

Norethindrone: C18 estrane nucleus but progestin: NO androgenic effects: preferred oral progestin for oral contraceptives: no methyl coming off of C10

Norethisterone acetate: same as norethindrone but instead of a OH it is an ester coming off of C17

Mifepristone: induce abortion: Anti-progesterone

similarity to hydroxyprogesterone: aromatic ring off of C11: more lipophilic more affinity so acts as antagonist

Testosterone: Androgen: produced by the testes under control of HPA

2 major functions: male sex characteristics before puberty, sperm maturation sexual function and anabolic stimulates protein synthesis/ muscle build up: metabolism at C17 hydroxyl into ketone much less active

DHT (dihydrotestosterone): saturated form of testosterone at C4-C5 bond: more active metabolite as androgenic but not anabolic

Methyltestosterone: testosterone but with an extra methyl on C17: tertiary alcohol suppresses FPM 20-50x more potent: used for sexual impetus, breast cancer, muscle build up

Fluoxymestrone: testosterone but with an extra methyl on C17: tertiary alcohol suppresses FPM: also, extra Fluro on C9 and OH on C11: 20-50x more potent: used for sexual impetus, breast cancer, muscle build up

testosterone decanoate: by pass FBM fatty acid ester for IM use long acting drug: 10 carbons 'deca'

Finasteride: Anti-androgen: inhibits di-hydro testosterone reductase (inhibits conversion of testosterone to DHT) orally

Cyproterone acetate: competitive inhibitors at androgenic receptors: used orally and IM

Flutamide: competitive inhibitors at androgenic receptors: used orally: no steroid nucleus: but strng affinity

Methandrostenolone: anabolic steroid: higher anabloic activity: orally for anemia and body building illegally: increase number of double bonds go towards anabolic receptors

Testolactone: anabolic steroid

Danazol: ring A in a fused system to reduce char formation so more towards anabolic receptors

Nandrolone decanoate (IM fatty acid ester): anabolic steroid: maximize anabolic over androgenic remove the methyl group of C10 of testosterone: enhance protein synthesis