Masanao Inagaki

A novel oxidative azidation of aromatic compounds with hypervalent iodine reagent, phenyliodine(III) bis(trifluoroacetate) (PIFA) and trimethylsilyl azide

Abstract A novel and useful method for the azidation of aromatic compounds by the reaction of hypervalent iodine reagent, phenyliodine(III) bis(trifluoroacetate) (PIFA) in 1,1,1,3,3,3-hexafluoro-2-propanol followed by treatment of trimethylsilyl azide (TMSA) was developed. The possible mechanism is also discussed.

Synthesis and Biological Activity of Various Derivatives of a Novel Class of Potent, Selective, and Orally Active Prostaglandin D2 Receptor Antagonists. 2. 6,6-Dimethylbicyclo[3.1.1]heptane Derivatives

In an earlier paper, we reported that novel prostaglandin D(2) (PGD(2)) receptor antagonists having the bicyclo[2.2.1]heptane ring system as a prostaglandin skeleton were a potent new class of antiallergic agents and suppressed various allergic inflammatory responses such as those observed in conjunctivitis and asthma models. In the present study, we synthesized PGD(2) receptor antagonists having the 6,6-dimethylbicyclo[3.1.1]heptane ring system. These derivatives have the amide moiety, in contrast to those with the bicyclo[2.2.1]heptane ring system, which have the sulfonamide group. The derivatives having the 6,6-dimethylbicyclo[3.1.1]heptane ring also exhibited strong activity in PGD(2) receptor binding and cAMP formation assays. In in vivo assays such as allergic rhinitis, conjunctivitis, and asthma models, these series of derivatives showed excellent pharmacological profiles. In particular, compound 45 also effectively suppressed eosinophil infiltration in allergic rhinitis and asthma models. This compound (45, S-5751) is now being developed as a promising alternative antiallergic drug candidate.

Hypervalent iodine oxidation of O-silylated phenol derivatives to azacarbocyclic spirodienones ; synthetic approach to the anticancer marine alkaloid, discorhabdin C

Abstract Hypervalent iodine oxidation of O-silyated phenols bearing various types of aminoquinones at the p-position in 2,2,2-trifluoroethanol gave azacarbocyclic spirodienones in good yields and application of this reaction to the synthetic approach to discorhabdin C was also described.

Discovery of S-777469: an orally available CB2 agonist as an antipruritic agent.

The discovery of novel CB2 ligands based on the 3-carbamoyl-2-pyridone derivatives by adjusting the size of side chain at 1-, 5- and 6-position is reported. The structure-activity relationship around this template lead to the identification of S-777469 as a selective CB2 receptor agonist, which exhibited the significant inhibition of scratching induced by Compound 48/80 at 1.0 mg/kg po and 10 mg/kg po (55% and 61%, respectively).

A general formation of quinone imines and quinone imine acetals : an efficient synthesis of 5-oxygenated indoles

A general and high-yield synthesis of benzoquinone imines and benzoquinone imine monoacetals leading to 5-oxygenated indoles was developed

Hypervalent iodine induced cyclisation of α-(aryl)alkyl β-dicarbonyl derivatives

A novel and efficient intramolecular aromatic alkylation of α-(aryl)alkyl β-dicarbonyl derivatives using the hypervalent iodine reagent, phenyliodine(III) bis(trifluoroacetate)(PIFA), is described.

Discovery of S-444823, a potent CB1/CB2 dual agonist as an antipruritic agent.

The optimization of a series of 3-carbamoyl 2-pyridone derivatives as CB agonists is reported. These efforts resulted in the discovery of 3-(2-(1-(cyclohexylmethyl)-2-oxo-1,2,5,6,7,8,9,10-octahydrocycloocta[b]pyridine-3-carboxamido)thiazol-4-yl)propanoic acid (21), a potent dual CB1/CB2 agonist without CNS side effects induced by CB1 receptor activation. It exhibited strong inhibition of scratching as a 1.0% acetone solution in the pruritic model.

Totalsynthese von Terprenin, einem hochwirksamen Immunglobulin-E-Suppressivum

Regioselektive Halogenierungen und Suzuki-Reaktionen ermoglichen die richtige Verknupfung der aromatischen Ringe in zwei Totalsynthesen von Terprenin 1. Durch beide Reaktionswege kann 1 effizient und in groserer Menge erhalten werden.

CB 1/2 dual agonists with 3-carbamoyl 2-pyridone derivatives as antipruritics: reduction of CNS side effects by introducing polar functional groups.

Our lead compound 1 showed high affinity for both CB1 and CB2 receptors, suggesting the possibility of inducing psychoactive side effects through the CB1 receptor in the brain. To solve this issue, polar functional groups were introduced at the 3-position of the pyridone core of compound 1 to find CB1/2 dual agonists such as 17 and 20 which did not show any CNS side effects.

Synthesis and activities of oxidative metabolites of the anti-arthritic drug candidate S-2474

We have synthesized and characterized some oxidative metabolites of S-2474. In this study, we discovered a novel skeleton, the 2,3-dihydrobenzofuran derivative, which inhibited PGE(2) production at a very low concentration and was effective in the anti-carrageenin footpad edema assay.