medicinal chemistry test 2

steroid group: two methyl groups - one at C10 and one at C13 and an 8 carbon side chain at C17.  27 carbons.

steroid group: two methyl groups - one at C10 and one at C13.  no C17 side chain.  19 carbons.

steroid group: two methyl groups - one at C10 and one at C13 and a two carbon side chain at C17.  21 carbons.

steroid group: unsubstituted steroid nucleus.  17 carbons.

steroid group: single methyl group at C13, no C17 side chain. 'A' ring is usually aromatic.

a steroid substituent below the molecular plane is denoted by _____

steroid stereochemistry at carbon _____ is always noted because it determines the overall shape of the ring

steroid biosynthesis enzymes: stimulated by ACTH, rate limiting step in steroid synthesis.

steroid biosynthesis enzymes: isomerizes 5-6 double bond to 4-5 of beta-hydroxy-steroids.  turns the 3-beta-OH into a ketone

steroid biosynthesis enzymes: inserts a 17-OH.  converts corticosterone into cortisol

steroid biosynthesis enzymes: inserts an alpha-OH at C21.  converts progesterone to deoxycorticosterone

steroid biosynthesis enzymes: inserts a beta-OH at C11

steroid biosynthesis enzymes: converts corticosterone to aldosterone

steroid biosynthesis enzymes: removes acetone and OH from C17 and inserts a ketone at C17

steroid biosynthesis enzymes: reduces ketone at C17 to an OH

steroid biosynthesis enzymes: reduces 4-5 double bond, inserts a 5-alpha H, converts testosterone to dihydrotestosterone

steroid biosynthesis enzymes: converts androstenedione to estrone, and testosterone to estradiol

endocrine stimulation: ACTH

endocrine stimulation: renin/angiotensin

endocrine stimulation: LH

endocrine stimulation: FSH

endocrine stimulation: HCG

cortisol is bound to an alpha globulin called _____.  synthetic steroids are highly bound by _____.

general steroid receptor hypothesis: step 1

general steroid receptor hypothesis: step 2

general steroid receptor hypothesis: step 3

general steroid receptor hypothesis: step 4

major routes of metabolism for steroids

stress can compromise the immune response via cortisol's inhibition of _____

the dexamethasone suppression test: measures _____

the dexamethasone suppression test: cortisol levels should _____ in response to administration of dexamethasone

the dexamethasone suppression test: results indicative of Cushing's Disease

the dexamethasone suppression test: diagnosis if low/high dose dexamethasone has no effect on cortisol levels

disease in which there are higher levels of ACTH and lower levels of cortisol

steroids _____ gluconeogenesis, _____ serum glucose

steroids stimulate both _____ and _____, resulting in abnormal distribution of _____

steroids should be used cautiously in infective cases because they inhibit _____

macrophages and monocytes which need prostaglandins and leukotrienes are _____ by glucocorticoid induction of a protein (lipocortin) that inhibits _____

steroids decrease COX-2, IL-2, IL-3, and the inflammatory cytokine _____

steroids inhibit the basophil IgE-mediated release of _____

steroids can lead to DM because cortisol is an _____

disease in which patients 'bronze'

the structural difference between cortisol and cortisone is an OH or ketone, respectively, at carbon _____

cortisol is _____ at MRs and GRs, while cortisone is _____

11β-HSD2 converts cortisol to cortisone and is located mostly in the _____

11β-HSD1 is bidirectional, but mostly forms cortisol from cortisone, and is located mostly in _____

the effects of 11β-HSD2 help protect the MR from high circulating levels of _____

lack of 11β-HSD2 can lead to hypertension and hyopkalemia from over stimulation of _____

the only therapeutic mineralcorticoid of note

betamethasone and dexamethasone are _____

methylprednisolone's methyl substitution in the _____ position is uncommon

common hydrocortisone dose

short acting steroids (2)

intermediate-acting steroids (4)

long-acting steroids (2)

dexamethasone and betamethasone have no _____ activity

glucocorticoid SAR: C21 hydroxyl groups is present on most synthetic steroids, but is an absolute requirement for _____

glucocorticoid SAR: 17 hydroxyl group is present on all currently used glucocorticoids and confers _____

glucocorticoid SAR: _____ substitution eliminates mineralocorticoid activity.  when combine with a 1-2 double bond, the _____ have marked glucocorticoid activity

glucocorticoid SAR: _____ at the 9 position enhances both MC and GC activity, possibly related to electron-withdrawing effect on the nearby _____ group

glucocorticoid SAR: both of these ring A features are essential for both MC and GC activity

glucocorticoid SAR: C ring feature required for GC activity but not for MC activity

glucocorticoid SAR: ring A feature that slows metabolism and selectively increases GC to MC potency ratio.  they are called Δ¹-corticoids

topical steroid class: flurandrenolide

topical steroid class: halcinonide

topical steroid class: desonide

topical steroid class: clobetasol propionate

a carbothioate group makes fluticasone an _____ not a pregnane

inhaled steroids: if a compound has a free C21 OH, it tends to get _____ in the lungs, which extends its DOA. the two exceptions to this rule are _____ and _____

the most severe complication of steroid withdrawal, _____, results from long-term suppression of the HPA axis

blocks conversion of cholesterol to pregnenolone.  used in Cushing's.  also blocks aromatase and estrogen production

non-selective inhibitor of adrenal/gonadal synthesis.  inhibit cholesterol side chain cleavage.  used for Cushing's

inhibits GCR activation.  used in adrenal carcinoma and Chushing's.  also used as an anti-progestational agent

for adrenal cancers and Cushing's.  inhibits by binding specifically to zona reticularis and fasciculata mitochondrial proteins and disrupts steroid synthesis

biosynthesis of reproductive hormones takes place in the _____ of the adrenal cortex (androgens)

cells in the testes that produce mainly testosterone and mostly estrogens in the ovaries

cells in the ovaries that produce mainly estrogens

leydig cells in the placenta produce _____

main source of estrogen biosynthesis in men and post-menopausal women

converts estrone to 17β-estradiol (rapid)

LH, FSH, and E2 (estradiol) levels peak at the start of the _____

high levels of _____ are present during the secretory phase (menses)

____ from granulosa cells inhibits FSH secretion

regulates thecal cells

granulosa cells are regulated by _____ and _____

pregnancy tests measure _____

ovulation tests measure _____

major production occurs via placenta during pregnancy

DES was linked to _____

prevents rapid inactivation to estrone, creates postency 15-20X that of estradiol.

estrogen SAR: small groups are tolerated at 2 and 4, substitution at 1 _____

estrogen SAR: 11 substitution is _____

estrogen SAR: 17β-OH is essential for _____

estrogen SAR: alpha OH at 17 or a ketone decreases activity because a _____ molecule is best

estrogen SAR: 17α and 16 lipophilic substitution _____

estrogen SAR: intact _____ ring is not essential

estrogen SAR: aromatic A ring and _____ are essential for activity

estrogen SAR: unsaturation of the _____ decreases activity

estriol has about 10% of the activity of _____

tamoxifen and clomiphene

partial estrogen receptor agonist with tissue-specific inhibition.  used for post-menopausal treatment of osteoporosis

triazole aromatase inhibitors used for breast cancer

reversible steroidal inhibitor of aromatase

pure estrogen receptor antagonist.  first in a new class of estrogen receptor downregulators.  also degrades receptors.  potent inhibitor of breast cancer cells

estrogens are used to treat _____ in males