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Details

Stereochemistry RACEMIC
Molecular Formula C24H29FN2O4
Molecular Weight 428.4974
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of P-88-8991

SMILES

CC(c1ccc(c(c1)OC)OCCCN2CCC(CC2)c3c4ccc(cc4on3)F)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 428.4974
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Description
Curator's Comment:: The description was created based on several sources, including https://goo.gl/ntDHH8 | https://www.ncbi.nlm.nih.gov/pubmed/23618742 | https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022192s000_ClinPharmR.pdf | https://www.ncbi.nlm.nih.gov/pubmed/7707315

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

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Patents

Patents

Sample Use Guides

Male Wistar rats (150-250 g) were dosed ip with compound 57 at 2-20mk/kg
Route of Administration: Intraperitoneal
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 Sat Jun 26 03:38:42 UTC 2021
Edited
by admin
on Sat Jun 26 03:38:42 UTC 2021
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 Sat Jun 26 03:38:42 UTC 2021 , Edited by admin on Sat Jun 26 03:38:42 UTC 2021
PRIMARY
CAS
133454-55-4
Created by admin on Sat Jun 26 03:38:42 UTC 2021 , Edited by admin on Sat Jun 26 03:38:42 UTC 2021
PRIMARY
EPA CompTox
133454-55-4
Created by admin on Sat Jun 26 03:38:42 UTC 2021 , Edited by admin on Sat Jun 26 03:38:42 UTC 2021
PRIMARY
FDA UNII
ARO6P38EJS
Created by admin on Sat Jun 26 03:38:42 UTC 2021 , Edited by admin on Sat Jun 26 03:38:42 UTC 2021
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