For research use only. Not for therapeutic Use.
VU0467485 (Cat.No:I010056), also known as AZ13713945, is a potent, selective, and orally bioavailable muscarinic acetylcholine receptor 4 (M4) positive allosteric modulators (PAMs). VU0467485 represents a major advance in the field, as the first potent M4 PAM to overcome major species differences in potency while maintaining high selectivity versus M2 (rat, dog, cyno, and human EC50s > 30 μM), CNS penetration, and in vivo efficacy. VU0467485 showed robust efficacy in behavioral models that was evaluated as a preclinical candidate.
| Catalog Number | I010056 |
| CAS Number | 1451994-10-7 |
| Synonyms | VU 0467485; VU-0467485; VU0467485; AZ13713945; AZ-13713945; AZ 13713945.;5-amino-N-(3-fluoro-4-methoxybenzyl)-3,4-dimethylthieno[2,3-c]pyridazine-6-carboxamide |
| Molecular Formula | C17H17FN4O2S |
| Purity | ≥95% |
| Target | Neuronal Signaling |
| Solubility | Soluble in DMSO |
| Storage | 0 - 4 °C for short term, or -20 °C for long term |
| InChI | InChI=1S/C17H17FN4O2S/c1-8-9(2)21-22-17-13(8)14(19)15(25-17)16(23)20-7-10-4-5-12(24-3)11(18)6-10/h4-6H,7,19H2,1-3H3,(H,20,23) |
| InChIKey | VFNHDIWHQGVWLL-UHFFFAOYSA-N |
| SMILES | O=C(C1=C(N)C2=C(C)C(C)=NN=C2S1)NCC3=CC=C(OC)C(F)=C3 |
| Reference | 1:ACS Med Chem Lett. 2016 Dec 16;8(2):233-238. doi: 10.1021/acsmedchemlett.6b00461. eCollection 2017 Feb 9. Discovery of VU0467485/AZ13713945: An M4 PAM Evaluated as a Preclinical Candidate for the Treatment of Schizophrenia.Wood MR,Noetzel MJ,Melancon BJ,Poslusney MS,Nance KD,Hurtado MA,Luscombe VB,Weiner RL,Rodriguez AL,Lamsal A,Chang S,Bubser M,Blobaum AL,Engers DW,Niswender CM,Jones CK,Brandon NJ,Wood MW,Duggan ME,Conn PJ,Bridges TM,Lindsley CW, PMID: 28197318 PMCID: PMC5304297 [Available on 2018-02-09] DOI: 10.1021/acsmedchemlett.6b00461 </br><span>Abstract:</span> Herein, we report the structure-activity relationships within a series of potent, selective, and orally bioavailable muscarinic acetylcholine receptor 4 (M4) positive allosteric modulators (PAMs). Compound 6c (VU0467485) possesses robust in vitro M4 PAM potency across species and in vivo efficacy in preclinical models of schizophrenia. Coupled with an attractive DMPK profile and suitable predicted human PK, 6c (VU0467485) was evaluated as a preclinical development candidate. |
