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Details

Stereochemistry ABSOLUTE
Molecular Formula C21H19ClFNO4S
Molecular Weight 435.896
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LAROPIPRANT

SMILES

CS(=O)(=O)C1=CC(F)=CC2=C1N(CC3=CC=C(Cl)C=C3)C4=C2CC[C@@H]4CC(O)=O

InChI

InChIKey=NXFFJDQHYLNEJK-CYBMUJFWSA-N
InChI=1S/C21H19ClFNO4S/c1-29(27,28)18-10-15(23)9-17-16-7-4-13(8-19(25)26)20(16)24(21(17)18)11-12-2-5-14(22)6-3-12/h2-3,5-6,9-10,13H,4,7-8,11H2,1H3,(H,25,26)/t13-/m1/s1

HIDE SMILES / InChI

Molecular Formula C21H19ClFNO4S
Molecular Weight 435.896
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Laropiprant is a drug, which was used in combination with nicotinic acid (also known as niacin) and was known under tradename: tredaptive. Tredaptive was indicated as adjunctive therapy to diet for use in patients with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia. The marketing authorisation for Tredaptive has been withdrawn at the request of the marketing-authorisation holder due to increases in side effects with no cardiovascular benefit. Laropiprant is a selective antagonist of the prostaglandin D(2) (PGD(2)) receptor subtype 1 (DP1). It also has the affinity to interact with thromboxane A2 receptor (TP), although it is approximately 190-fold less potent when compared to DP1. Activation of TP has been shown to induce platelet aggregation in vitro, whereas activation of human platelet DP1 inhibits platelet aggregation. These in vitro data indicate that laropiprant may alter platelet function either by enhancement of platelet reactivity through DP1 antagonism or by inhibition of platelet aggregation through TP antagonism. Also were clinical trials phase II for the laropiprant alone, there were shown, that drug did not demonstrate efficacy in asthmatic patients or patients with allergic rhinitis.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
0.57 nM [Ki]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
Tredaptive
Palliative
Tredaptive
Primary
Unknown
Primary
Unknown

Cmax

ValueDoseCo-administeredAnalytePopulation
2.34 μM
40 mg single, oral
LAROPIPRANT plasma
Homo sapiens
3 μM
40 mg single, oral
LAROPIPRANT plasma
Homo sapiens
2.06 μM
40 mg single, oral
LAROPIPRANT plasma
Homo sapiens
2.4 μM
40 mg single, oral
LAROPIPRANT plasma
Homo sapiens
2.35 μM
40 mg single, oral
LAROPIPRANT plasma
Homo sapiens
4.73 μM
40 mg single, oral
LAROPIPRANT plasma
Homo sapiens
2.18 μM
40 mg single, oral
LAROPIPRANT plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
10.8 μM × h
40 mg single, oral
LAROPIPRANT plasma
Homo sapiens
19.4 μM × h
40 mg single, oral
LAROPIPRANT plasma
Homo sapiens
14 μM × h
40 mg single, oral
LAROPIPRANT plasma
Homo sapiens
19.69 μM × h
40 mg single, oral
LAROPIPRANT plasma
Homo sapiens
12.46 μM × h
40 mg single, oral
LAROPIPRANT plasma
Homo sapiens
33.3 μM × h
40 mg single, oral
LAROPIPRANT plasma
Homo sapiens
12 μM × h
40 mg single, oral
LAROPIPRANT plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
15.8 h
40 mg single, oral
LAROPIPRANT plasma
Homo sapiens
18 h
40 mg single, oral
LAROPIPRANT plasma
Homo sapiens
26 h
40 mg single, oral
LAROPIPRANT plasma
Homo sapiens
14.8 h
40 mg single, oral
LAROPIPRANT plasma
Homo sapiens
14.5 h
40 mg single, oral
LAROPIPRANT plasma
Homo sapiens
16.7 h
40 mg single, oral
LAROPIPRANT plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
1%
LAROPIPRANT plasma
Homo sapiens

Doses

PubMed

Sample Use Guides

In Vivo Use Guide
niacin/laropiprant 1 g/20 mg daily. After 4 weeks, niacin/laropiprant will be increased to 2 g/40 mg for remainder of study.
Route of Administration: Oral
In Vitro Use Guide
In vitro treatment of platelets with laropiprant (1 µmol/L) prevented the inhibitory effects of PGD(2) on platelet function, i.e. platelet aggregation, Ca(2+) flux, P-selectin expression, activation of glycoprotein IIb/IIIa and thrombus formation. At higher concentrations, 10 µmol/L laropiprant by itself attenuated platelet activation induced by thromboxane (TP) and E-type prostanoid (EP)-3 receptor stimulation, as demonstrated in assays of platelet aggregation, Ca(2+) flux, P-selectin expression, and activation of glycoprotein IIb/IIIa.
Substance Class Chemical
Record UNII
G7N11T8O78
Record Status Validated (UNII)
Record Version