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Details

Stereochemistry RACEMIC
Molecular Formula C24H29FN2O4
Molecular Weight 428.4965
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of P-88-8991

SMILES

COC1=CC(=CC=C1OCCCN2CCC(CC2)C3=NOC4=C3C=CC(F)=C4)C(C)O

InChI

InChIKey=SBKZGLWZGZQVHA-UHFFFAOYSA-N
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

HIDE SMILES / InChI

Molecular Formula C24H29FN2O4
Molecular Weight 428.4965
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Description

P-88-8991 (Hydroxy Iloperidone, 4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] propoxy]- 3-methoxy-methylbenzenemethanol) is the major active metabolite of Iloperidone an atypical antipsychotic that used for the acute treatment of schizophrenia in adults. Metabolic reduction of Iloperidone carbonyl group leads to P-88-8991 in rats, dogs, and humans. The receptor affinity profile of P-88-8991 is comparable to that of iloperidone: this metabolite binds to the serotonin 5-HT2A receptors, adrenergic alpha1 and alpha2C receptors, and D2A receptors and with lower affinity to other monoamine (dopamine, serotonin, and histamine H1 ) receptors. The comparable receptor binding profile of P-88-8991 indicates that it is likely to contribute to the clinical profile of iloperidone. Preclinical experiments, such as the mouse apomorphine climbing test, the rat self-stimulation, and the pole climb avoidance task, indicate antipsychotic activity of P88-8991 and confirm that this metabolite crosses the blood–brain barrier

CNS Activity

Originator

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
PubMed

PubMed

TitleDatePubMed
Receptor profile of P88-8991 and P95-12113, metabolites of the novel antipsychotic iloperidone.
2002 Apr
Patents

Patents

Sample Use Guides

In Vivo Use Guide
Male Wistar rats (150-250 g) were dosed ip with compound 57 at 2-20mk/kg
Route of Administration: Intraperitoneal
In Vitro Use Guide
Membranes from Chinese hamster ovary CHO cells expressing human recombinant 5-HT2A receptors were used for activity evaluation. The binding studies were performed in 96-well plates (Dynatech, Billinghurst, UK) in a total volume of 250 mkl, consisting of the radioligand [3H] Ketanserin (0.5 nM), drug (P-88-8991) and CHO membrane preparation diluted in 50 mM Tris buffer with pH 7.7. The plates were incubated for 15 min at 22 C Nonspecific binding was determined in the presence of ketanserin (10 mkM). Reactions were terminated by flash filtration and inverse transfer to 96-well filter plates [Perkin Elmer/Packard Bioscience, Mericlen, CT, USA 96-well cell harvester, filter plates GFC, coated with plasminogen activator inhibitor (PAI) as necessary]. The plates were dried for 30 min at 56 C and sealed at the bottom with an adhesive sheet (Topseal; Perkin Elmer/Packard Bioscience). Subsequently, 50 mkl of scintillation fluid (Microscint-20; Perkin Elmer/Packard Bioscience) was added to each well, the plates sealed on top and the radioactivity counted in a 96-well plate counter (Topcount; Perkin Elmer/Packard Bioscience).
Substance Class Chemical
Created
by admin
on Mon Oct 21 20:17:52 UTC 2019
Edited
by admin
on Mon Oct 21 20:17:52 UTC 2019
Record UNII
ARO6P38EJS
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
P-88-8991
Common Name English
BENZENEMETHANOL, 4-(3-(4-(6-FLUORO-1,2-BENZISOXAZOL-3-YL)-1-PIPERIDINYL)PROPOXY)-3-METHOXY-.ALPHA.-METHYL-
Systematic Name English
P 88-8991
Code English
P-88
Code English
Code System Code Type Description
PUBCHEM
9823904
Created by admin on Mon Oct 21 20:17:52 UTC 2019 , Edited by admin on Mon Oct 21 20:17:52 UTC 2019
PRIMARY
CAS
133454-55-4
Created by admin on Mon Oct 21 20:17:52 UTC 2019 , Edited by admin on Mon Oct 21 20:17:52 UTC 2019
PRIMARY
EPA CompTox
133454-55-4
Created by admin on Mon Oct 21 20:17:52 UTC 2019 , Edited by admin on Mon Oct 21 20:17:52 UTC 2019
PRIMARY
Related Record Type Details
PARENT -> METABOLITE ACTIVE
The active metabolite P88 accounts for 19.5% and 34.0% of total plasma exposure in EM and PM, respectively.
MAJOR
PLASMA; URINE