medicinal chemistry test 2

  1. steroid group: two methyl groups - one at C10 and one at C13 and an 8 carbon side chain at C17.  27 carbons.
  2. steroid group: two methyl groups - one at C10 and one at C13.  no C17 side chain.  19 carbons.
  3. steroid group: two methyl groups - one at C10 and one at C13 and a two carbon side chain at C17.  21 carbons.
  4. steroid group: unsubstituted steroid nucleus.  17 carbons.
  5. steroid group: single methyl group at C13, no C17 side chain. 'A' ring is usually aromatic.
  6. a steroid substituent below the molecular plane is denoted by _____
  7. steroid stereochemistry at carbon _____ is always noted because it determines the overall shape of the ring
  8. steroid biosynthesis enzymes: stimulated by ACTH, rate limiting step in steroid synthesis.
    cholesterol side-chain cleavage enzyme
  9. steroid biosynthesis enzymes: isomerizes 5-6 double bond to 4-5 of beta-hydroxy-steroids.  turns the 3-beta-OH into a ketone
    3-β-hydroxysteroid dehydrogenase
  10. steroid biosynthesis enzymes: inserts a 17-OH.  converts corticosterone into cortisol
  11. steroid biosynthesis enzymes: inserts an alpha-OH at C21.  converts progesterone to deoxycorticosterone
  12. steroid biosynthesis enzymes: inserts a beta-OH at C11
  13. steroid biosynthesis enzymes: converts corticosterone to aldosterone
    aldosterone synthase
  14. steroid biosynthesis enzymes: removes acetone and OH from C17 and inserts a ketone at C17
    17,20 lyase
  15. steroid biosynthesis enzymes: reduces ketone at C17 to an OH
    17-β-hydroxysteroid dehydrogenase
  16. steroid biosynthesis enzymes: reduces 4-5 double bond, inserts a 5-alpha H, converts testosterone to dihydrotestosterone
  17. steroid biosynthesis enzymes: converts androstenedione to estrone, and testosterone to estradiol
  18. endocrine stimulation: ACTH
  19. endocrine stimulation: renin/angiotensin
  20. endocrine stimulation: LH
    androgens and progestins
  21. endocrine stimulation: FSH
  22. endocrine stimulation: HCG
  23. cortisol is bound to an alpha globulin called _____.  synthetic steroids are highly bound by _____.
    transcortin (corticosteroid binding globulin [CBG]); albumin
  24. general steroid receptor hypothesis: step 1
    cytoplasmic receptor activation
  25. general steroid receptor hypothesis: step 2
    translocation of steroid-receptor complex into nucleus
  26. general steroid receptor hypothesis: step 3
    binding of steroid-receptor complex to DNA sites
  27. general steroid receptor hypothesis: step 4
    activation of transcription influencing protein synthesis
  28. major routes of metabolism for steroids
    oxidation, glucuronidation, and some sulfation at C21
  29. stress can compromise the immune response via cortisol's inhibition of _____
    IL-1, 2 and 6, and TNF-α
  30. the dexamethasone suppression test: measures _____
    the response of the adrenal glands to ACTH
  31. the dexamethasone suppression test: cortisol levels should _____ in response to administration of dexamethasone
  32. the dexamethasone suppression test: results indicative of Cushing's Disease
    no change in cortisol on low level dexamethasone, but inhibition of cortisol on high levels of dexamethasone.
  33. the dexamethasone suppression test: diagnosis if low/high dose dexamethasone has no effect on cortisol levels
    adrenocortical tumor or ectopic ACTH syndrome
  34. disease in which there are higher levels of ACTH and lower levels of cortisol
    Addison's Disease
  35. steroids _____ gluconeogenesis, _____ serum glucose
    stimulate; increasing
  36. steroids stimulate both _____ and _____, resulting in abnormal distribution of _____
    lipolysis; lipogenesis; fat
  37. steroids should be used cautiously in infective cases because they inhibit _____
  38. macrophages and monocytes which need prostaglandins and leukotrienes are _____ by glucocorticoid induction of a protein (lipocortin) that inhibits _____
    inhibited; phospholipase A2
  39. steroids decrease COX-2, IL-2, IL-3, and the inflammatory cytokine _____
    platelet activating factor (PAF)
  40. steroids inhibit the basophil IgE-mediated release of _____
  41. steroids can lead to DM because cortisol is an _____
    insulin antagonist
  42. disease in which patients 'bronze'
    Addison's Disease
  43. the structural difference between cortisol and cortisone is an OH or ketone, respectively, at carbon _____
  44. cortisol is _____ at MRs and GRs, while cortisone is _____
    active; inactive
  45. 11β-HSD2 converts cortisol to cortisone and is located mostly in the _____
  46. 11β-HSD1 is bidirectional, but mostly forms cortisol from cortisone, and is located mostly in _____
    the liver and adipose tissue
  47. the effects of 11β-HSD2 help protect the MR from high circulating levels of _____
  48. lack of 11β-HSD2 can lead to hypertension and hyopkalemia from over stimulation of _____
    mineralcorticoid receptors
  49. the only therapeutic mineralcorticoid of note
  50. betamethasone and dexamethasone are _____
    epimers at C16
  51. methylprednisolone's methyl substitution in the _____ position is uncommon
  52. common hydrocortisone dose
  53. short acting steroids (2)
    cortisone, hydrocortisone
  54. intermediate-acting steroids (4)
    prednisone, prednisolone, methylprednisolone, triamcinolone
  55. long-acting steroids (2)
    dexamethasone, betamethasone
  56. dexamethasone and betamethasone have no _____ activity
  57. glucocorticoid SAR: C21 hydroxyl groups is present on most synthetic steroids, but is an absolute requirement for _____
    mineralocorticoid activity
  58. glucocorticoid SAR: 17 hydroxyl group is present on all currently used glucocorticoids and confers _____
    optimal potency
  59. glucocorticoid SAR: _____ substitution eliminates mineralocorticoid activity.  when combine with a 1-2 double bond, the _____ have marked glucocorticoid activity
    C16; 9-fluoro derivatives
  60. glucocorticoid SAR: _____ at the 9 position enhances both MC and GC activity, possibly related to electron-withdrawing effect on the nearby _____ group
    fluorination; 11-β-hydroxyl
  61. glucocorticoid SAR: both of these ring A features are essential for both MC and GC activity
    4-5 double-bond and 3-keto
  62. glucocorticoid SAR: C ring feature required for GC activity but not for MC activity
  63. glucocorticoid SAR: ring A feature that slows metabolism and selectively increases GC to MC potency ratio.  they are called Δ1-corticoids
    1-2 double-bond
  64. topical steroid class: flurandrenolide
  65. topical steroid class: halcinonide
  66. topical steroid class: desonide
  67. topical steroid class: clobetasol propionate
  68. a carbothioate group makes fluticasone an _____ not a pregnane
  69. 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 _____
    lipid-conjugated; fluticasone; mometasone
  70. the most severe complication of steroid withdrawal, _____, results from long-term suppression of the HPA axis
    acute adrenal insufficiency
  71. blocks conversion of cholesterol to pregnenolone.  used in Cushing's.  also blocks aromatase and estrogen production
    aminoglutethimide (Cytadren)
  72. non-selective inhibitor of adrenal/gonadal synthesis.  inhibit cholesterol side chain cleavage.  used for Cushing's
  73. inhibits GCR activation.  used in adrenal carcinoma and Chushing's.  also used as an anti-progestational agent
  74. for adrenal cancers and Cushing's.  inhibits by binding specifically to zona reticularis and fasciculata mitochondrial proteins and disrupts steroid synthesis
    mitotane (lysodren)
  75. biosynthesis of reproductive hormones takes place in the _____ of the adrenal cortex (androgens)
    zona reticularis
  76. cells in the testes that produce mainly testosterone and mostly estrogens in the ovaries
  77. cells in the ovaries that produce mainly estrogens
  78. leydig cells in the placenta produce _____
    estrogens and progestins
  79. main source of estrogen biosynthesis in men and post-menopausal women
    adipose tissue
  80. converts estrone to 17β-estradiol (rapid)
    estradiol dehydrogenase
  81. LH, FSH, and E2 (estradiol) levels peak at the start of the _____
    luteal phase
  82. high levels of _____ are present during the secretory phase (menses)
  83. ____ from granulosa cells inhibits FSH secretion
  84. regulates thecal cells
  85. granulosa cells are regulated by _____ and _____
    LH, FSH
  86. pregnancy tests measure _____
  87. ovulation tests measure _____
    'surge' of LH
  88. major production occurs via placenta during pregnancy
  89. DES was linked to _____
    cancers in female offspring
  90. prevents rapid inactivation to estrone, creates postency 15-20X that of estradiol.
    20 ethinyl
  91. estrogen SAR: small groups are tolerated at 2 and 4, substitution at 1 _____
    largely decreases activity
  92. estrogen SAR: 11 substitution is _____
  93. estrogen SAR: 17β-OH is essential for _____
    maximum activity
  94. estrogen SAR: alpha OH at 17 or a ketone decreases activity because a _____ molecule is best
    flat, planar
  95. estrogen SAR: 17α and 16 lipophilic substitution _____
    may increase activity
  96. estrogen SAR: intact _____ ring is not essential
  97. estrogen SAR: aromatic A ring and _____ are essential for activity
  98. estrogen SAR: unsaturation of the _____ decreases activity
    B ring
  99. estriol has about 10% of the activity of _____
  100. tamoxifen and clomiphene
    selective estrogen receptor modulators
  101. partial estrogen receptor agonist with tissue-specific inhibition.  used for post-menopausal treatment of osteoporosis
  102. triazole aromatase inhibitors used for breast cancer
    letrozole and anastrazole
  103. reversible steroidal inhibitor of aromatase
  104. pure estrogen receptor antagonist.  first in a new class of estrogen receptor downregulators.  also degrades receptors.  potent inhibitor of breast cancer cells
  105. estrogens are used to treat _____ in males
    prostatic carcinoma and sexual problems
Card Set
medicinal chemistry test 2
medchem test 2