CPPHA
CPPHA is a positive allosteric modulator of metabotropic glutamate receptor 5 (mGluR5) that potentiates human and rat mGluR5 activation by glutamate, 3,5-DHPG and quisqualate.
For research use only. We do not sell to patients.
Chemical Information
| Name | CPPHA |
|---|---|
| Iupac Chemical Name | N-[4-chloro-2-[(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)methyl]phenyl]-2-hydroxy-benzamide |
| Synonyms | CPPHA |
| Molecular Formula | C22H15ClN2O4 |
| Molecular Weight | 406.82 |
| Smile | O=C(NC1=CC=C(Cl)C=C1CN(C(C2=C3C=CC=C2)=O)C3=O)C4=CC=CC=C4O |
| InChiKey | UFOUABRZSDGGAZ-UHFFFAOYSA-N |
| InChi | InChI=1S/C22H15ClN2O4/c23-14-9-10-18(24-20(27)17-7-3-4-8-19(17)26)13(11-14)12-25-21(28)15-5-1-2-6-16(15)22(25)29/h1-11,26H,12H2,(H,24,27) |
| CAS Number | 693288-97-0 |
| Related CAS |
Ordering Information
| Packaging | Price | Availability | Purity | Shipping Time |
|---|---|---|---|---|
| Bulk | Enquiry | Enquiry | Enquiry |
| Formulation | Solid powder |
|---|---|
| Purity | 98% Min. |
| Storage | Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years). |
| Solubility | Soluble in DMSO |
| Handling | |
| Shipping Condition | Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs. |
| HS Code |
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| Mechanism | |
| Cell study | |
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| Clinical study |
1: Li S, Rizvi MH, Lynch BB, Tracy JB, Ford E. Flexible Cyclic- Poly(phthalaldehyde)/Poly(ε-caprolactone) Blend Fibers with Fast Daylight- Triggered Transience. Macromol Rapid Commun. 2021 Apr;42(7):e2000657. doi: 10.1002/marc.202000657. Epub 2020 Dec 28. PMID: 33368746.
2: Butkiewicz M, Rodriguez AL, Rainey SE, Wieting J, Luscombe VB, Stauffer SR, Lindsley CW, Conn PJ, Meiler J. Identification of Novel Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5 Acting at Site Distinct from 2-Methyl-6-(phenylethynyl)-pyridine Binding. ACS Chem Neurosci. 2019 Aug 21;10(8):3427-3436. doi: 10.1021/acschemneuro.8b00227. Epub 2019 Jun 17. PMID: 31132237; PMCID: PMC6986193.
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4: Garcia-Barrantes PM, Cho HP, Starr TM, Blobaum AL, Niswender CM, Conn PJ, Lindsley CW. Re-exploration of the mGlu₁ PAM Ro 07-11401 scaffold: Discovery of analogs with improved CNS penetration despite steep SAR. Bioorg Med Chem Lett. 2016 May 1;26(9):2289-92. doi: 10.1016/j.bmcl.2016.03.044. Epub 2016 Mar 14. PMID: 27013388; PMCID: PMC4833523.
5: Nickols HH, Conn PJ. Development of allosteric modulators of GPCRs for treatment of CNS disorders. Neurobiol Dis. 2014 Jan;61:55-71. doi: 10.1016/j.nbd.2013.09.013. Epub 2013 Sep 27. PMID: 24076101; PMCID: PMC3875303.
6: Rodriguez AL, Tarr JC, Zhou Y, Williams R, Gregory KJ, Bridges TM, Daniels JS, Niswender CM, Conn PJ, Lindsley CW, Stauffer SR. Identification of a glycine sulfonamide based non-MPEP site positive allosteric potentiator (PAM) of mGlu5. 2012 Dec 17 [updated 2013 Mar 22]. In: Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010–. PMID: 24027804.
7: Noetzel MJ, Gregory KJ, Vinson PN, Manka JT, Stauffer SR, Lindsley CW, Niswender CM, Xiang Z, Conn PJ. A novel metabotropic glutamate receptor 5 positive allosteric modulator acts at a unique site and confers stimulus bias to mGlu5 signaling. Mol Pharmacol. 2013 Apr;83(4):835-47. doi: 10.1124/mol.112.082891. Epub 2013 Jan 24. Erratum in: Mol Pharmacol. 2013 Oct;84(4):654. PMID: 23348500; PMCID: PMC3608436.
8: Stauffer SR. Progress toward positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5). ACS Chem Neurosci. 2011 Aug 17;2(8):450-70. doi: 10.1021/cn2000519. Epub 2011 Jun 27. PMID: 22860171; PMCID: PMC3369763.
9: Hammond AS, Rodriguez AL, Townsend SD, Niswender CM, Gregory KJ, Lindsley CW, Conn PJ. Discovery of a Novel Chemical Class of mGlu(5) Allosteric Ligands with Distinct Modes of Pharmacology. ACS Chem Neurosci. 2010 Oct 20;1(10):702-716. doi: 10.1021/cn100051m. Epub 2010 Aug 19. PMID: 20981342; PMCID: PMC2957851.
10: Bradley SJ, Watson JM, Challiss RA. Effects of positive allosteric modulators on single-cell oscillatory Ca2+ signaling initiated by the type 5 metabotropic glutamate receptor. Mol Pharmacol. 2009 Dec;76(6):1302-13. doi: 10.1124/mol.109.059170. Epub 2009 Sep 8. PMID: 19737913; PMCID: PMC2784724.
11: Kozlov IA, Kubyshkin VA, Iashina NI, Vinokurova LV, Pashovkin IT. [Substantiation of the selection of tactics for the surgical treatment of chronic pancreatitis]. Eksp Klin Gastroenterol. 2008;(7):63-8. Russian. PMID: 19334447.
12: Chen Y, Goudet C, Pin JP, Conn PJ. N-{4-Chloro-2-[(1,3-dioxo-1,3-dihydro-2H- isoindol-2-yl)methyl]phenyl}-2-hydroxybenzamide (CPPHA) acts through a novel site as a positive allosteric modulator of group 1 metabotropic glutamate receptors. Mol Pharmacol. 2008 Mar;73(3):909-18. doi: 10.1124/mol.107.040097. Epub 2007 Dec 4. PMID: 18056795.
13: Zhao Z, Wisnoski DD, O'Brien JA, Lemaire W, Williams DL Jr, Jacobson MA, Wittman M, Ha SN, Schaffhauser H, Sur C, Pettibone DJ, Duggan ME, Conn PJ, Hartman GD, Lindsley CW. Challenges in the development of mGluR5 positive allosteric modulators: the discovery of CPPHA. Bioorg Med Chem Lett. 2007 Mar 1;17(5):1386-91. doi: 10.1016/j.bmcl.2006.11.081. Epub 2006 Dec 3. PMID: 17210250.
14: Liu F, Zhang G, Hornby G, Vasylyev D, Bowlby M, Park K, Gilbert A, Marquis K, Andree TH. The effect of mGlu5 receptor positive allosteric modulators on signaling molecules in brain slices. Eur J Pharmacol. 2006 May 1;536(3):262-8. doi: 10.1016/j.ejphar.2006.02.003. Epub 2006 Apr 5. PMID: 16600209.
15: Zhang Y, Rodriguez AL, Conn PJ. Allosteric potentiators of metabotropic glutamate receptor subtype 5 have differential effects on different signaling pathways in cortical astrocytes. J Pharmacol Exp Ther. 2005 Dec;315(3):1212-9. doi: 10.1124/jpet.105.090308. Epub 2005 Aug 31. PMID: 16135701.
16: O'Brien JA, Lemaire W, Wittmann M, Jacobson MA, Ha SN, Wisnoski DD, Lindsley CW, Schaffhauser HJ, Rowe B, Sur C, Duggan ME, Pettibone DJ, Conn PJ, Williams DL Jr. A novel selective allosteric modulator potentiates the activity of native metabotropic glutamate receptor subtype 5 in rat forebrain. J Pharmacol Exp Ther. 2004 May;309(2):568-77. doi: 10.1124/jpet.103.061747. Epub 2004 Jan 27. PMID: 14747613.
Chemical Structure
