Med Chem II Steroidal Hormones

Steroid Nucleus (c17)

Androstane nucleus (c19)

Estrane Nucleus (c18)

Pregnane Nucleus (C21)

Cholestane nucleus (c27) cholesterol

Corticosterone (c21) pregnane nucleus

ketone: C3 and C20, double bond C4-C5, hydroxyl C11 and C21, methyl coming out of C10 and C13 which makes C19 and C18 respectively

Aldosterone (c21) - Major Mineralocorticoid

oxidized at c18 into an aldehyde

used for treatment of adrenal insufficiency (Addison's Disease)

Hydrocortisone (c21) Major glucocorticoid

oxidation of c17 of corticosterone into a hydroxyl

Cortisone (c21) same as hydrocortisone but C11 oxidized into a ketone

slightly more lipophilic

Fludrocortisone (c21) hydrocortisone with Fluorine at position 9 (alpha)

increased lipophilicity, 10x more glucocorticoid effect but 300x more mineralocorticoid effect; better drug for adrenal sufficiency Addison's disease; more potent less dosage

Prednisolone (c21) hydrocortisone with a double bond at C1-C2

high gluco/mineral ratio 10:1.. may lead to elevated BB: anti-inflammatory

Prednisone (C21) ketone version of prednisolone at C11 oxidized

same activity as Prednisolone

Triamcinolone: (c21) 3 modifications of HC to get this pure glucocorticoid activity: C1-C2 double bond, Fluro at C9, extra OH at C16: 4 OH groups so highly polar issue with bioavailability

Triamcinolone Acetonide: more lipophilic formation of acetonide by the 2 hydroxyl on C17 and C16; enhances the absorption and increases number of carbons

Dexamethasone: bioisostereic of triamcinolone with methyl (alpha) on C16 instead of OH; more lipophilic than triamcinolone

Betamethasone: SAME as dexamethasone but methyl on C16 in the beta position

Beclomethasone dipropionate: Beclo think Chloro on C9 instead of fluro; results in more lipophilic product; PRO DRUG: esters off of C17 makes it volatile used for inhalation (asthma)

Fluocinolone acetonide: same as triamcinolone with an additional fluro on C6 which enhances the lipophilicity

Clobetasol: triamcinolone with ester off of c17 and Cl on C21 instead of OH bioisosteres... makes it more lipophilic to penetrate skin

Mometasone: chloro on C9 and C21; furoic acid off of C17

used as aerosol for asthma due to furoate ester

Disodium Hydrocortisone phosphate: HC with phosphoric acid off of C21 to make water soluble forms for injection

Sodium hydrocortisone succinate: HC with succinate acid off of C21 to make water soluble forms for injection