MK-7622

MK-7622

Clinical data
Drug class	positive allosteric modulator of M1 muscarinic receptor
Identifiers
IUPAC name 3-[(1S,2S)-2-hydroxycyclohexyl]-6-[(6-methyl-3-pyridinyl)methyl]benzo[h]quinazolin-4-one
CAS Number	1227923-29-6
PubChem CID	46207733
DrugBank	DB12897
UNII	57R7D1Q49R
ChEMBL	ChEMBL4078588
ECHA InfoCard	100.209.716
Chemical and physical data
Formula	C25H25N3O2
Molar mass	399.494 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC1=NC=C(C=C1)CC2=CC3=C(C4=CC=CC=C42)N=CN(C3=O)[C@H]5CCCC[C@@H]5O
InChI InChI=1S/C25H25N3O2/c1-16-10-11-17(14-26-16)12-18-13-21-24(20-7-3-2-6-19(18)20)27-15-28(25(21)30)22-8-4-5-9-23(22)29/h2-3,6-7,10-11,13-15,22-23,29H,4-5,8-9,12H2,1H3/t22-,23-/m0/s1 Key:JUVQLZBJFOGEEO-GOTSBHOMSA-N

The MK-7622 is the first-of-its-kind oral positive allosteric modulator of M₁ muscarinic receptors, developed by Merck for the treatment of Alzheimer’s disease, with a structure comprising a benzoquinazolinone bearing additional complex substituents at positions 3 and 6. MK-7622 failed to pass Phase II clinical trials for the treatment of Alzheimer's disease (as an adjunctive therapy) and has been withdrawn from production.

Pharmacology

Pharmacodynamics

MK-7622 acts as a highly selective positive allosteric modulator of the M₁ muscarinic receptor; it exhibits the properties of an allosteric agonist and is characterised by a predominant enhancement of beta-arrestin-associated signalling rather than balanced modulation, which is the cause of some of its cholinergic side effects.

Side effects

Side effects included behavioural seizures and cognitive impairment.