Iloperidone metabolite Hydroxy Iloperidone (P88; Hydroxy Iloperidone) is the metabolite of Iloperidone.

Physicochemical Properties

Molecular Formula	C24H29FN2O4
Molecular Weight	428.50
Exact Mass	428.211
Elemental Analysis	C, 67.27; H, 6.82; F, 4.43; N, 6.54; O, 14.93
CAS #	133454-55-4
Related CAS #	Iloperidone;133454-47-4;Iloperidone hydrochloride;1299470-39-5;Iloperidone metabolite Hydroxy Iloperidone-d3;1504554-02-2
PubChem CID	9823904
Appearance	White to off-white solid powder
LogP	4.615
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	8
Heavy Atom Count	31
Complexity	548
Defined Atom Stereocenter Count	0
SMILES	FC1=CC=C2C(ON=C2C3CCN(CCCOC4=C(OC)C=C(C(C)O)C=C4)CC3)=C1
InChi Key	SBKZGLWZGZQVHA-UHFFFAOYSA-N
InChi Code	InChI=1S/C24H29FN2O4/c1-16(28)18-4-7-21(23(14-18)29-2)30-13-3-10-27-11-8-17(9-12-27)24-20-6-5-19(25)15-22(20)31-26-24/h4-7,14-17,28H,3,8-13H2,1-2H3
Chemical Name	1-[4-[3-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]propoxy]-3-methoxyphenyl]ethanol
Synonyms	133454-55-4; UNII-ARO6P38EJS; ARO6P38EJS; P 88-8991; P-88-8991; Benzenemethanol, 4-(3-(4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl)propoxy)-3-methoxy-alpha-methyl-; BENZENEMETHANOL, 4-(3-(4-(6-FLUORO-1,2-BENZISOXAZOL-3-YL)-1-PIPERIDINYL)PROPOXY)-3-METHOXY-.ALPHA.-METHYL-; BENZENEMETHANOL, 4-[3-[4-(6-FLUORO-1,2-BENZISOXAZOL-3-YL)-1-PIPERIDINYL]PROPOXY]-3-METHOXY-ALPHA-METHYL-;
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Metabolite of Iloperidone
ln Vitro	A series of 3-[[(aryloxy)alkyl]piperidinyl]-1,2-benzisoxazoles was synthesized and evaluated as potential antipsychotic D2/5-HT2 antagonists. Most of these compounds showed potent antipsychotic-like activity in an apomorphine-induced climbing mouse paradigm, with many also showing preferential mesolimbic activity, as indicated by their weaker effects in an apomorphine-induced stereotypy model. In receptor binding assays, many displayed a moderate affinity for the D2 receptor coupled with a significantly greater affinity for the 5-HT2 receptor: a property that has been suggested as necessary for atypicality. From this series, compound 45, 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1- piperidinyl]propoxy]-3-methoxyphenyl]ethanone (iloperidone, HP 873), was further evaluated in a battery of in vivo and in vitro assays. This compound showed a 300-fold greater potency in inhibition of climbing than in inhibition of stereotypy or induction of catalepsy, and when evaluated chronically in an electrophysiological model, 45 caused a depolarization blockade of dopamine neurons in the A10 area of the rat brain but not in the A9 area. Additionally, it showed positive activity in a social interaction paradigm, suggesting potential efficacy against asociality, a component of the negative symptoms of schizophrenia. In chronic ex vivo studies, 45, similar to clozapine, caused a down regulation of 5-HT2 receptors but had no effect on the number of D2 receptors. Compound 45 is currently undergoing clinical evaluation [1].
ADME/Pharmacokinetics	Metabolism / Metabolites 4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxy-a-methylbenzene methanol is a known human metabolite of iloperidone.
References	[1]. 3-[[(Aryloxy)alkyl]piperidinyl]-1,2-benzisoxazoles as D2/5-HT2 antagonists with potential atypical antipsychotic activity: antipsychotic profile of iloperidone (HP 873). J Med Chem. 1995 Mar 31;38(7):1119-31.

Solubility Data

Solubility (In Vitro)

DMSO: 25 mg/mL (58.34 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.83 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.83 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.3337 mL	11.6686 mL	23.3372 mL
	5 mM	0.4667 mL	2.3337 mL	4.6674 mL
	10 mM	0.2334 mL	1.1669 mL	2.3337 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.