Cipralisant

Cipralisant
Clinical data
ATC code	none;
Identifiers
	IUPAC name 5-[(1S,2S)-2-(5,5-dimethylhex-1-ynyl)cyclopropyl]-1H-imidazole;
CAS Number	213027-19-1 ;
PubChem CID	10512919;
ChemSpider	8688320 ;
UNII	309713XSKW;
ChEMBL	ChEMBL278462 ;
CompTox Dashboard (EPA)	DTXSID201167209 ;
Chemical and physical data
Formula	C14H20N2
Molar mass	216.328 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC(C)(C)CCC#C[C@H]1C[C@@H]1c2cnc[nH]2;
	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 ; Key:CVKJAXCQPFOAIN-RYUDHWBXSA-N ;
	(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

^ Ito, Sayaka; Yoshimoto, Ryo; Miyamoto, Yasuhisa; Mitobe, Yuko; Nakamura, Takao; Ishihara, Akane; MacNeil, Douglas J.; Kanatani, Akio; Tokita, Shigeru (2006). "Detailed pharmacological characterization of GT-2331 for the rat histamine H3 receptor". European Journal of Pharmacology. 529 (1–3): 40–46. doi:10.1016/j.ejphar.2005.10.066. PMID 16316645.
^ 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.
^ ^a ^b 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. S2CID 20470970.
^ Evaluate group: Gliatech Announces Initiation of Perceptin Phase II Clinical Trial.
^ Liu, Huaqing; Kerdesky, Francis A.; Black, Lawrence A.; Fitzgerald, Michael; Henry, Rodger; Esbenshade, Timothy A.; Hancock, Arthur A.; Bennani, Youssef L. (2003). "An Efficient Multigram Synthesis of the Potent Histamine H3 Antagonist GT-2331 and the Reassessment of the Absolute Configuration". The Journal of Organic Chemistry. 69 (1): 192–194. doi:10.1021/jo035264t. ISSN 0022-3263. PMID 14703397.

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[1] Ito, Sayaka; Yoshimoto, Ryo; Miyamoto, Yasuhisa; Mitobe, Yuko; Nakamura, Takao; Ishihara, Akane; MacNeil, Douglas J.; Kanatani, Akio; Tokita, Shigeru (2006). "Detailed pharmacological characterization of GT-2331 for the rat histamine H3 receptor". European Journal of Pharmacology. 529 (1–3): 40–46. doi:10.1016/j.ejphar.2005.10.066. PMID 16316645.

[pmid9721022-2] 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.

[pmid15821027-3] 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. S2CID 20470970.

[4] Evaluate group: Gliatech Announces Initiation of Perceptin Phase II Clinical Trial.

[LiuKerdesky2003-5] Liu, Huaqing; Kerdesky, Francis A.; Black, Lawrence A.; Fitzgerald, Michael; Henry, Rodger; Esbenshade, Timothy A.; Hancock, Arthur A.; Bennani, Youssef L. (2003). "An Efficient Multigram Synthesis of the Potent Histamine H3 Antagonist GT-2331 and the Reassessment of the Absolute Configuration". The Journal of Organic Chemistry. 69 (1): 192–194. doi:10.1021/jo035264t. ISSN 0022-3263. PMID 14703397.

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