Exam 3 - Medical Chemistry Opioids

active for pain properties

inactive for pain properties

5

Substituted by 4 different groups

4 six member rings, 1 aromatic ring 1 five member ring

2 OH at 3,6 carbon 1 N + CH3 14 position carbon

converted by CYP2D6 enzyme 12% of US pop has version that doesn’t allow this conversion to occur

95% found in body is in protonated form

Removing 3rd position OH will cause decrease in analgesic potency Turning into CH3-O- will reduce analgesic potency but not as much as removing OH

Analgesic activity decreases 6-Acetylmorphine will be active but 3-Acetylmorphine will not (shows importance of 3-OH group)

removal, etherification and esterification of 6-OH will give consistent increase in analgesic potency compared to morphine 6-OH group not essential for analgesic effects

turning Tertiary amine into quaternary salt inactive when admin peripherally but equi-active to morphine when admin directly into CNS

A,B,C,D ring plus N-CH3….Missing E (5 member w/ O)

A,B,D ring plus N-CH3

A and D ring plus N-CH3

Just A ring plus long chain and NH-CH3

Just A ring plus long chain and NH-CH3

More potent than thebaine due to OH at 3, instead of CH3-O Etorphine and buprenorphine

Used for big animals, not humans added bulk group with OH to 7 carbon

Partial agonist at mu receptor more potent than morphine Also has an added bulky group with OH to 7 carbon, has tert-butyl

Morphine-6-glucuronidide (M6G) is 2-4 times more potent than morphine Morphine-3-glucuronidide (M3G) is not active codeine can be turned into morphine and then M3G, or M6G Morphine can also do OND to Normorphine which has decreased analgesic activity (Take CH3 off NH, turn into NH2+)

removing E ring, along with 6-OH and double bond will give you Levorphanol (L) or Dextromethorphan (D)

Amide bond is what gives it the “Anili” name.

L form 8 times more potent than morphine as analgesic Lipophilic and better oral/parenteral potency ration 2:1