Exam 3 - Medical Chemistry Opioids Flashcards
Levo (-)
active for pain properties
Dextro (+)
inactive for pain properties
Number of Chiral centers morphine
5
How to tell Chiral center?
Substituted by 4 different groups
Rings of Morphine structure
4 six member rings, 1 aromatic ring
1 five member ring
Important groups for pharmacological activities
2 OH at 3,6 carbon
1 N + CH3
14 position carbon
Codeine into morphine
converted by CYP2D6 enzyme
12% of US pop has version that doesn’t allow this conversion to occur
Which form is Morphine usually in?
95% found in body is in protonated form
Ring “A” modification
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
Esterification and Etherification of OH (3 position)
Analgesic activity decreases
6-Acetylmorphine will be active but 3-Acetylmorphine will not (shows importance of 3-OH group)
Ring “C” modification
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
Ring “D” modification, tertiary to quaternary
turning Tertiary amine into quaternary salt
inactive when admin peripherally but equi-active to morphine when admin directly into CNS
Morphinans structure
A,B,C,D ring plus N-CH3….Missing E (5 member w/ O)
Benzomorphans structure
A,B,D ring plus N-CH3
Piperidine structure
A and D ring plus N-CH3
