Yasuhiko Sakamoto

Modafinil increases histamine release in the anterior hypothalamus of rats

Modafinil, (RS)-2-(Diphenylmethylsulfinyl)acetamide, is a well known wake promoting drug used for the treatment of narcolepsy. We investigated the effect of modafinil on the hypothalamic histamine release in the anesthetized rat using in vivo microdialysis. Modafinil (150 mg/kg, i.p.) increased histamine release by 150% of the basal release. The intracerebroventricular (i.c.v.) injection of modafinil (1 nmol) also increased histamine release, however, when modafinil (1 nmol) was injected directly into the tuberomammillary nucleus, a limited region where cell bodies of the histaminergic neurons are located, histamine release was not altered. These observations suggest that modafinil may promote waking via the activation of the histaminergic system, although it does not appear to be a direct pharmacological target of modafinil.

An Efficient Synthesis of Magallanesine Using [1,2]-Meisenheimer Rearrangement and Heck Cyclization

Abstract A straightforward total synthesis of magallanesine 1 was accomplished from readily available isoquinolineacetate 14 . This synthesis is emphasized by the following two points; i. the [1,2]-Meisenheimer rearrangement of the azetidine N-oxide 22 for the preparation of azocine ring, ii. the Pd-catalyzed intramolecular Heck reaction of N-benzoylenaminone 38 for the construction of isoindoloazocine skeleton.

A total synthesis of magallanesine via [1,2]-Meisenheimer rearrangement

Abstract A straightforward synthesis of magallanesine 1 from azetoisoquinoline 4 has been accomplished via [1,2]-Meisenheimer rearrangement and an intramolecular Heck cyclization as the key reactions.

Efficient approaches to S-alkyl-N-alkylisothioureas: syntheses of histamine H3 antagonist clobenpropit and its analogues.

S-Alkyl-N-alkylisothioureas were efficiently synthesized via synthetic approach (A) using 3-phenylpropionyl isothiocyanate (PPI). The utility of the approach was proved by the syntheses of clobenpropit, a potent histamine H(3) antagonist, and its analogues. Alternatively, clobenpropit could be prepared via intramolecular amide cleavage (B) with use of 2-nitrophenylacetyl isothiocyanate (NPAI).