Benzamide, 4-(cyclopropylmethoxy)-3-methoxy-N-[2-(1H-1,2,4-triazol-1-yl)-5-(trifluoromethoxy)phenyl]-
- Product Name
- Benzamide, 4-(cyclopropylmethoxy)-3-methoxy-N-[2-(1H-1,2,4-triazol-1-yl)-5-(trifluoromethoxy)phenyl]-
- CAS No.
- 2313526-86-0
- Chemical Name
- Benzamide, 4-(cyclopropylmethoxy)-3-methoxy-N-[2-(1H-1,2,4-triazol-1-yl)-5-(trifluoromethoxy)phenyl]-
- Synonyms
- VU6012962, 10 mM in DMSO;VU 6012962,Inhibitor,Metabotropic glutamate receptors,inhibit,mGluR,VU-6012962,VU6012962;N-(2-(1H-1,2,4-Triazol-1-yl)-5-(trifluoromethoxy)phenyl)-4-(cyclopropylmethoxy)-3-methoxybenzamide;Benzamide, 4-(cyclopropylmethoxy)-3-methoxy-N-[2-(1H-1,2,4-triazol-1-yl)-5-(trifluoromethoxy)phenyl]-
- CBNumber
- CB58095522
- Molecular Formula
- C21H19F3N4O4
- Formula Weight
- 448.4
- MOL File
- 2313526-86-0.mol
Benzamide, 4-(cyclopropylmethoxy)-3-methoxy-N-[2-(1H-1,2,4-triazol-1-yl)-5-(trifluoromethoxy)phenyl]- Property
- Density
- 1.44±0.1 g/cm3(Predicted)
- solubility
- DMSO:125.0(Max Conc. mg/mL);278.77(Max Conc. mM)
- form
- Solid
- pka
- 11.79±0.70(Predicted)
- color
- White to light yellow
N-Bromosuccinimide Price
- Product number
- CS-0084972
- Product name
- VU6012962
- Purity
- 99.92%
- Packaging
- 5mg
- Price
- $150
- Updated
- 2021/12/16
- Product number
- CS-0084972
- Product name
- VU6012962
- Purity
- 99.92%
- Packaging
- 10mg
- Price
- $250
- Updated
- 2021/12/16
- Product number
- CS-0084972
- Product name
- VU6012962
- Purity
- 99.92%
- Packaging
- 50mg
- Price
- $650
- Updated
- 2021/12/16
- Product number
- CS-0084972
- Product name
- VU6012962
- Purity
- 99.92%
- Packaging
- 100mg
- Price
- $950
- Updated
- 2021/12/16
- Product number
- CSN23892
- Product name
- VU6012962
- Packaging
- 50mg
- Price
- $600
- Updated
- 2021/12/16
Benzamide, 4-(cyclopropylmethoxy)-3-methoxy-N-[2-(1H-1,2,4-triazol-1-yl)-5-(trifluoromethoxy)phenyl]- Chemical Properties,Usage,Production
Description
VU6012962 is an orally bioavailable and CNS-penetrant metabotropic glutamate receptor 7 (mGlu7) negative allosteric modulator (NAM) that achieves exposure in cerebral spinal fluid (CSF) 2.5x above the in vitro IC50 at minimum effective doses (MEDs) of 3 mg/kg in preclinical anxiety models.
Uses
VU6012962 is an orally bioavailable and CNS-penetrant metabotropic glutamate receptor 7 negative allosteric modulator (mGlu7 NAM) with an IC50 of 347 nM[1].
in vitro
As many mGlu allosteric ligands engage induced-fit pockets, SAR can be challenging, and the “right” fit may only be “found” by exploring libraries of analogs via an exercise in strategic serendipity. VU6012962 (7d) proved optimal (IC50 = 350 nM, pIC50 = 6.46 ± 0.10, 12.6 ± 1.5% L-AP4 min) and the most potent within this chemotype to date. Beyond an enhancement in mGlu7 NAM potency, 7d also showed a significant improvement in predicted hepatic clearance (rat CLhep = 15.9 mL min–1 kg–1), generating enthusiasm for the further profiling of 7d. 7d was selective for mGlu7 versus the other seven mGlu receptors (>10 μM versus mGlu1–6,8) and largely devoid of ancillary pharmacology (compound activity at only one target, 5-HT2B receptor, that was greater than 50% at 10 μM) in a Eurofins lead profiling panel of 68 GPCRs, ion channels, and transporters. A 30 mg/kg (ip) tissue distribution study in rat was performed to assess levels of 7d in plasma, brain, and CSF. Here, it was noted that a brain:plasma Kp of 1.24 (([plasma]tot = 598 nM), [brain]tot = 745 nM) and a Kp,uu of 0.38 ([plasma]Unbound = 16.7 nM, [brain]unbound = 6.4 nM); however, the CSF:plasma Kp was 2.15, with levels of 7d in CSF of 1.3 μM, or ~3.8-fold above the in vitro IC50._x000D_ _x000D_ Reference: J Med Chem. 2019 Feb 14;62(3):1690-1695. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/30608678/
in vivo
VU6012962 (1-10 mg/kg; i.p. injection; 60 minutes prior to testing) decreases anxiety in the elevated zero maze (EZM) assay in mice[1].
| Animal Model: | C57Bl/6J male mice (8 weeks old)[1] |
| Dosage: | 1, 3, and 10 mg/kg |
| Administration: | I.p. injections; 60 minutes prior to testing |
| Result: | Increased total time spent in the open arms at a dose of 3 mg/kg. 10 mg/kg did cause a decrease in overall locomotion. |
target
VU6012962 is an orally bioavailable and CNS-penetrant metabotropic glutamate receptor 7 negative allosteric modulator (mGlu7 NAM) with an IC50 of 347 nM.
IC 50
mGlu7: 347 nM (IC50)
References
[1] Reed CW, et al. Discovery of an orally bioavailable and Central Nervous System (CNS) penetrant mGlu7 NegativeAllosteric Modulator (NAM) in vivo tool compound: N-(2-(1H-1,2,4-triazol-1-yl)-5-(trifluoromethoxy)phenyl)-4-(cyclopropylmethoxy)-3-methoxybenzamide (VU6012962). J Med Chem. 2019 Jan 4. DOI:10.1021/acs.jmedchem.8b01810
Benzamide, 4-(cyclopropylmethoxy)-3-methoxy-N-[2-(1H-1,2,4-triazol-1-yl)-5-(trifluoromethoxy)phenyl]- Preparation Products And Raw materials
Raw materials
Preparation Products
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