Cipralisant maleate

• CAT Number: I006140
• CAS Number: 223420-20-0
• Molecular Formula: C18H24N2O4
• Molecular Weight: 332.39
• Purity: ≥95%
• Synonyms: (Z)-but-2-enedioic acid;5-[(1R,2R)-2-(5,5-dimethylhex-1-ynyl)cyclopropyl]-1H-imidazole
• InChI: InChI=1S/C14H20N2.C4H4O4/c1-14(2,3)7-5-4-6-11-8-12(11)13-9-15-10-16-13;5-3(6)1-2-4(7)8/h9-12H,5,7-8H2,1-3H3,(H,15,16);1-2H,(H,5,6)(H,7,8)/b;2-1-/t11-,12-;/m1./s1
• InChIKey: QIQWRCNAPQJQLL-COALEZEGSA-N
• SMILES: CC(C)(C)CCC#CC1CC1C2=CN=CN2.C(=CC(=O)O)C(=O)O

Cipralisant (GT-2331) (maleate) is an orally active, low-toxicity, potent, selective, high affinity histamine H3 receptor full antagonist in vivo, and an agonist in vitro, with a pKi of 9.9 for histamine H3 receptor and a Ki of 0.47 nM for rat histamine H3 receptor. Cipralisant (maleate) has the potential for attention-deficit hyperactivity disorder research[1][2][3][4]. Cipralisant (maleate) is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
Cipralisant (maleate) behaves as a full agonist on adenylyl cyclase inhibition. Cipralisant (maleate) (HEK cells) potently inhibits forskolin-induced cAMP accumulation, showing that Cipralisant (maleate) works as a potent full histamine H3 receptor agonist. Cipralisant (maleate) increases the basal [35S]GTPγS binding activities in membranes from HEK cells expressing the rat histamine H3 receptor (EC50, 5.6 nM)[3].
Cipralisant (maleate) (0.3~30 mg/kg; s.c.) enhances acquisition over five trials, reaching significance at 1 mg/kg[2].
Cipralisant (maleate) (10 mg/kg; p.o.) completely blocks R-α-methylhistamine-induced drinking[3].
Cipralisant (maleate) promotes wakefulness in the rat. Cipralisant (maleate) potently and significantly improves performance in the repeated acquisition model, in line with its high affinity for the rat H3 receptor and good CNS penetration. Cipralisant (maleate) does not appear to be as efficacious as 3 mg/kg ciproxifan at its maximally effective dose [2]. Cipralisant (maleate) behaves as a partial agonist in a rat brain synaptosome model[3].

Reference

[1]. Raddatz R, et al. Histamine H3 antagonists for treatment of cognitive deficits in CNS diseases. Curr Top Med Chem. 2010;10(2):153-169.
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[2]. Fox GB, et al. Effects of histamine H(3) receptor ligands GT-2331 and ciproxifan in a repeated acquisition avoidance response in the spontaneously hypertensive rat pup. Behav Brain Res. 2002;131(1-2):151-161.
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[3]. Ito S, et al. Detailed pharmacological characterization of GT-2331 for the rat histamine H3 receptor. Eur J Pharmacol. 2006;529(1-3):40-46.
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[4]. Tedford CE, et al. High antagonist potency of GT-2227 and GT-2331, new histamine H3 receptor antagonists, in two functional models. Eur J Pharmacol. 1998;351(3):307-311.
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