Lecture 15 - Beta Adrenergic Antagonists

aryloxypropanolamines SAR

• Aryloxypropanolamine

• NO substituent para to the oxygen on the aryl ring (keeps B1 = B2)

• Large branched alkyl group on the basic nitrogen (isopropyl or t-butyl)

• Basic nitrogen is required for binding; ionized form binds to receptor

• NO H-bond donor/acceptors directly attached to the aryl ring

• presence of beta -OH group

• bulk on side of aryl ring

non-selective (beta 1 and beta 2) antagonists list

aryloxypropanolamines, non-selectives with intrinsic sympathomimetic activity (ISA)s

Non-selective beta antagonists with Intrinsic Sympathomimetic Activity (ISA)

partial agonists that are technically antagonists; will have H-bonding group (N-H) directly attached to aromatic ring

beta 1-Selective Antagonists (Cardioselective) SAR

• Aryloxypropanolamine

• lipophilic substituent para to the oxygen on the aryl ring. The nature of this para substituent also dictates the relative duration of the drug.

• Large branched alkyl group on the basic nitrogen (e.g., isopropyl)

• Basic nitrogen is required for binding; ionized form binds to receptor

• NO H-bond donor/acceptors directly attached to the aryl ring (except acebutolol)

Combination alpha and beta Antagonists

Labetalol and Carvedilol

Combination alpha and beta Antagonists universal SAR

1. beta OH group

2. bulk on amine side (increases alpha 1 receptor affinity)

3. ionizable amine present