| Stereochemistry | ACHIRAL |
| Molecular Formula | C28H22FN5O2 |
| Molecular Weight | 479.505 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CN(C)C(=O)N1C=C(C(=O)C2=CC=C(CN3C(C)=NC4=C3C=CN=C4)C(F)=C2)C5=C1C=CC=C5C#C
InChI
InChIKey=GDLNHSUSOZEAOR-UHFFFAOYSA-N
InChI=1S/C28H22FN5O2/c1-5-18-7-6-8-25-26(18)21(16-34(25)28(36)32(3)4)27(35)19-9-10-20(22(29)13-19)15-33-17(2)31-23-14-30-12-11-24(23)33/h1,6-14,16H,15H2,2-4H3
| Molecular Formula | C28H22FN5O2 |
| Molecular Weight | 479.505 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
ABT-491 is highly potent, selective and orally active platelet-activating factor (PAF) receptor antagonist, developed by Abbott Laboratories for allergic rhinitis treatment. ABT-491 is a potent antagonist of responses linked to the PAF receptor at the cellular level, especially platelets and neutrophils. ABT-491 was also effective in blocking platelet activation in blood, indicating that the presence of high concentrations of protein and other serum factors slightly alters the ability of ABT-491 to interact with PAF receptor. ABT-491 effectively antagonizes PAF-induced platelet and neutrophil responses at submicromolar concentrations in vitro and exhibits in vivo efficacy in alleviating PAF-mediated inflammatory and pathological processes in various animals, including guinea pigs, mice, and rats, via either i.v., i.p. or p.o. routes.
CNS Activity
Originator
Approval Year
PubMed
Sample Use Guides
The rat pups were administered intraperitoneally 0.4 mg/kg ABT-491 which was dissolved in saline, either immediately before or after hypoxia.
Route of Administration:
Intraperitoneal
Platelet activation and platelet–leukocyte interaction were assessed with the use of flow cytometry. Aliquots of blood were added to microcentrifuge tubes containing HEPES-Tyrodes buffer (5 mM HEPES, 137 mM NaCl, 2.7 mM NaHCO3, 0.36 mM NaH2PO4, 2 mM CaCl2, 4 mM MgCl2, and 5 mM glucose, pH 7.4) and fluorochrome-labeled ligands. A phycoerythrin (PE) Cc5 conjugated antibody to CD42 was used as an activation-independent marker of platelets. FITC-conjugated fibrinogen was added to permit assessment of activation of GP IIb-IIIa. When thrombin was used as an agonist, FITC-conjugated PAC-1 was used instead of FITC-fibrinogen, and the peptide GPRP was added to block polymerization of endogenous fibrinogen. A PE-conjugated antibody to CD62 was used to identify platelet surface expression of P-selectin. For assessment of platelet–leukocyte aggregates, a PE-conjugated antibody to CD14 was used to identify monocytes, and a FITC-conjugated antibody to CD61 was used as an activationindependent marker of platelets. For experiments with the receptor antagonists to PAF (ABT-491, 2.5 mkM), to P2Y12 (cangrelor, 10–1000 nM), and to P2Y1 (MRS-2179, 10–1000 mkM), whole blood anticoagulated with CTI (32 mkg/ml) was incubated at room temperature for 15 minutes in the presence of antagonist or control (vehicle) before addition of aliquots of blood to assay tubes.
