5-HT7/5-HT2A receptor antagonist 1 

5-HT7/5-HT2A receptor antagonist 1 is a high-affinity, orally active, brain-penetrant 5-HT7 and 5-HT2A receptor ligand having a pK_i = 8.1 at both receptors. 5-HT7/5-HT2A receptor antagonist 1 behaves as an antagonist in an in vitro functional assay for 5-HT2A and as an inverse agonist in an in vitro functional assay for 5-HT7. 5-HT7/5-HT2A receptor antagonist 1 blockade of 5-Carboxamidotryptamine (5-CT) (HY-135555) induced hypothermia in rats, and blockade of 2,5-dimethoxy-4-iodoamphetamine (DOI) induced head-twitches in mice. 5-HT7/5-HT2A receptor antagonist 1 occupied 5-HT2A receptor binding sites in the frontal cortex of the rat brain. 5-HT7/5-HT2A receptor antagonist 1 can be used for the study of Neurological diseases^[1].

5-HT7/5-HT2A receptor antagonist 1 (Compound 4j) behaves as an antagonist at 5-HT2A with a pK_B = 8.1 based on an in vitro functional assay using calcium mobilization^[1].
5-HT7/5-HT2A receptor antagonist 1 is also an inverse agonist at 5-HT7 in a functional assay for 5-HT7 (cAMP, pIC50 = 7.0) 5-HT7/5-HT2A receptor antagonist 1 shows >50-fold selectivity over a panel of 50 mono-amine and peptide hormone receptors, ion channels, and neurotransmitter uptake sites^[1].
5-HT7/5-HT2A receptor antagonist 1 shows in vitro affinity for the h5-HT2B and 5-HT2C receptors with pKi 7.6 and 7.3, respectively^[1].
5-HT7/5-HT2A receptor antagonist 1 binds to plasma proteins was found to be below to moderate, with unbound fractions determined to be 30%fu and 20%fu in human and rat plasma, respectively^[1].
The metabolic stability of 5-HT7/5-HT2A receptor antagonist 1 is high in both rat and human liver microsomes (t1/2 > 60 min)^[1].
5-HT7/5-HT2A receptor antagonist 1 (10 μM) shows no inhibition of cytochrome P450 enzymes, suggesting that the potential liability for any drug-drug interactions are minimal^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

5-HT7/5-HT2A receptor antagonist 1 is found to be highly orally bioavailable in all species tested: rat (100%), mouse, dog (98%), monkey (72%)^[1].
5-HT7/5-HT2A receptor antagonist 1 (0.03-1 mg/kg, p.o., once) is a potent central 5-HT7 receptor antagonist that blocks 5-CT-induced hypothermia in rats^[1].
4J (0.001-10 mg/kg, p.o., s.c., 20min, 40 min) is an effective central 5-HT2A receptor antagonist with high oral bioavailability, exerting functional inhibitory effects in the central nervous system in mice^[1].
5-HT7/5-HT2A receptor antagonist 1 (0.01-10 mg/kg, p.o., 1 h) occupies 5-HT2A receptor binding sites found in the frontal cortex area of the rat brain with an ED₅₀ in good agreement with the ED50 value for central functional effect mediated by 5-HT2A receptor in rats (ED₅₀ = 0.8 mg/kg)^[1].
5-HT7/5-HT2A receptor antagonist 1 shows only weak activity in the blockade of phenylephrine-induced mydriasis in rats^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

273.35

C₁₆H₂₀FN₃

851375-22-9

CC(C)N1C(C2=CC=C(F)C=C2)=C3C(CCNCC3)=N1

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Curt A, et al. Discovery and SAR studies of 2-alkyl-3-phenyl-2,4,5,6,7,8-hexahydropyrazolo[3,4-d]azepines as 5-HT7/2 inhibitors leading to the identification of a clinical candidate, Bioorganic & Medicinal Chemistry Letters, Volume 31,2021,127669, ISSN 0960-894X.