VU6028418

• CAT Number: I043453
• CAS Number: 2649803-05-2
• Molecular Formula: C23H27F3N4O
• Molecular Weight: 432.48
• Purity: ≥95%
• Synonyms: (3aR,6aS)-2-(oxan-4-ylmethyl)-N-[6-(2,3,5-trifluorophenyl)pyridazin-3-yl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrol-5-amine
• InChI: InChI=1S/C23H27F3N4O/c24-17-9-19(23(26)20(25)10-17)21-1-2-22(29-28-21)27-18-7-15-12-30(13-16(15)8-18)11-14-3-5-31-6-4-14/h1-2,9-10,14-16,18H,3-8,11-13H2,(H,27,29)/t15-,16+,18?
• InChIKey: ITSKPCHXUYILTR-BYICEURKSA-N
• SMILES: C1COCCC1CN2CC3CC(CC3C2)NC4=NN=C(C=C4)C5=C(C(=CC(=C5)F)F)F

VU6028418 is a potent, highly selective and orally bioavailable M4 mAChR antagonist with an IC50 of 4.1 nM against hM4[1].
VU6028418 is orally bioavailable[1].
In Vivo PK Parameters for VU6028418[1]

parameter
rat(SD)a
mouse(CD-1)a
dog(beagle)a

dose (mg/kg) iv/po
1/10
1/3
1/3

CLp (mL/min/kg)
6.1
17
43

Vss (L/kg)
6.7
10.6
8.5

elimination t1/2 (h)
13
NC
15

Cmax (ng/mL) po
17 000
181
70

Tmax (h) po
1.5
6.67
17

AUC0-inf (ng/mL•h) po
30 000
NC
1100

F (%) po
≥100
≥100
86

total brain/total plasma (Kp)
6.4
ND
ND

unbound brain/unbound plasma (Kp,uu)
0.61
ND
ND

CSF/plasma unbound (Kp,u)
0.24
ND
ND

a Values represent means from two to three animals. ND = not determined. NC = not calculated; there was insufficient data to define the elimination phase (i.e., Cmax was one of the last three time points).

Reference

[1]. Spock M, et al. Discovery of VU6028418: A Highly Selective and Orally Bioavailable M4 Muscarinic Acetylcholine Receptor Antagonist. ACS Med Chem Lett. 2021 Aug 2;12(8):1342-1349.
 [Content Brief]