Cipralisant

Cipralisant

Systematic (IUPAC) name
5-[(1S,2S)-2-(5,5-dimethylhex-1-ynyl)cyclopropyl]-1H-imidazole
Identifiers
CAS Number	213027-19-1
ATC code	None
PubChem	CID 10512919
ChemSpider	8688320 N
UNII	309713XSKW N
ChEMBL	CHEMBL278462 N
Chemical data
Formula	C14H20N2
Molar mass	216.32 g/mol
SMILES C(#CCCC(C)(C)C)[C@H]2C[C@@H]2c1cncn1
InChI InChI=1S/C14H20N2/c1-14(2,3)7-5-4-6-11-8-12(11)13-9-15-10-16-13/h9-12H,5,7-8H2,1-3H3,(H,15,16)/t11-,12-/m0/s1 N Key:CVKJAXCQPFOAIN-RYUDHWBXSA-N N
NY (what is this?)  (verify)

Cipralisant (GT-2331, tentative trade name Perceptin) is an extremely potent Histamine H₃ receptor ligand originally developed by Gliatech.^[1] Cipralisant was initially classified as a selective H₃ antagonist,^[2] but newer research (2005) suggests also agonist properties, i. e. functional selectivity.^[3] Cipralisant seemed to be well tolerated during early testing, entering Phase II trials for ADHD in 2000.^[4]

The relatively recent cloning of human H₃ receptor, as well as the discovery of its constitutive activity provided the ability to better assess the activity of H₃ receptor ligands. Consequently, cipralisant was reassessed as an H₃ receptor agonist in human and rat recombinant systems, showing functional selectivity and stimulating one type of G-protein coupled pathway while failing to activate other intracellular pathways.^[3]

Gliatech filed for bankruptcy in 2002, and its intellectual property was inherited by Merck. The development of cipralisant seems to have been suspended since 2003 but research is ongoing, and recently it has been shown that it is the 1S,2S enantiomer which is the biologically active one.^[5]

References

1. ↑ Detailed pharmacological characterization of GT-2331 for the rat histamine H3 receptor
2. ↑ Tedford CE, Hoffmann M, Seyedi N; et al. (June 1998). "High antagonist potency of GT-2227 and GT-2331, new histamine H3 receptor antagonists, in two functional models". Eur. J. Pharmacol. 351 (3): 307–311. doi:10.1016/S0014-2999(98)00396-3. PMID 9721022. 
3. 1 2 Krueger, KM; Witte, DG; Ireland-Denny, L; Miller, TR; Baranowski, JL; Buckner, S; Milicic, I; Esbenshade, TA; Hancock, AA (2005). "G protein-dependent pharmacology of histamine H3 receptor ligands: evidence for heterogeneous active state receptor conformations". The Journal of Pharmacology and Experimental Therapeutics 314 (1): 271–81. doi:10.1124/jpet.104.078865. PMID 15821027. 
4. ↑ Evaluate group: Gliatech Announces Initiation of Perceptin Phase II Clinical Trial.
5. ↑ An Efficient Multigram Synthesis of the Potent Histamine H3 Antagonist GT-2331 and the Reassessment of the Absolute Configuration