Studies on the Pharmacokinetics of Arsenic Compound in the Chicken : I. Distribution, Excretion and Transference to the Eggs of Arsenic Administered Orally to Chickens.

1.3酸化ヒ素30mg/㎏を産卵鶏に経口投与して,1,2,4,8,16および32日めの各臓器,組織及び卵中のヒ素濃度をしらべた. 又雄鶏に人工肛門手術を施し,3酸化ヒ素30mg/㎏を経口投与して,以後排泄される尿と糞のヒ素量をしらべた. 2.検査した諸臓器のうちヒ素移行率の高かったのは肝,腎,心筋であった. 血漿と脾では中程度の分布率であり,赤血球,浅胸筋および脳組織の移行率は低かった. 又ヒ素のリテンションの長かったのは肝,腎,脾,浅胸筋であり,特に肝では32日めにも対照の水準に復しなかった. 3.卵ではヒ素は主として卵黄に移行し,卵白には極めて低濃度にしか移行しなかった. 4.人工肛門手術を受けたニワトリの尿中には投与後6時間めまでにヒ素が出現し始め,3日めまで急増して最高値となり,以後は一定の率で漸減した,一方糞中には投与後6～18時間でヒ素が出現し始め,36～48時間めまで急増して最高値となり,以後11日めまで緩やかに減少し,それ以後は急減した. 17日めまでに排泄されたヒ素の総量は尿中に投与量の15%,糞中に20%であった

O-N intramolecular alkoxycarbonyl migration of typical protective groups in hydroxyamino acids

O-N Intramolecular alkoxycarbonyl (carbonate-carbamate) migration was found to occur as a common reaction of hydroxyamino acids under mild basic aqueous conditions with no formation of side products. Carbonate protective groups migrate to produce amino-protected carbamate derivatives of hydroxyamino acids with high efficiency and purity

Development of novel water-soluble photocleavable protective group and its application for design of photoresponsive paclitaxel prodrugs

A novel coumarin-based highly water-soluble photocleavable protective group was designed and synthesized, and then this photosensitive protecting group was used to design paclitaxel prodrugs. These novel paclitaxel conjugates demonstrated excellent water solubility, over 100 mg mL(-1). Thus, the use of a detergent in the formulation can be omitted completely, even at high doses. Phototaxel 11 released the parent drug, paclitaxel, quickly and efficiently by minimal tissue-damaging 365 nm UV light irradiation at low power, while laser activation at 355 nm led to extensive decomposition of the prodrug. The carbamate-type prodrug, phototaxel 11, was stable in the dark prior to activation, whereas carbonate-type phototaxel 9 demonstrated poor stability under aqueous conditions. For such prodrugs, tumor-tissue targeting after administration could be achieved by selective light delivery, similar to that used in photodynamic therapy. In addition, newly designed coumarin derivative 8 can be applied in organic chemistry as a photosensitive protective group and for the design of caged compounds. (C) 2008 Elsevier Ltd. All rights reserved

Development of first photoresponsive prodrug of paclitaxel

A prodrug of paclitaxel which has a coumarin derivative conjugated to the amino acid moiety of isotaxel (O-acyl isoform of paclitaxel) has been synthesized. The prodrug was selectively converted to isotaxel by visible light irradiation (430 nm) with the cleavage of coumarin. Finally, paclitaxel was released by subsequent spontaneous O-N intramolecular acyl migration. (c) 2006 Elsevier Ltd. All rights reserved

No auxiliary, no byproduct strategy for water-soluble prodrugs of taxoids: Scope and limitation of O-N intramolecular acyl and acyloxy migration reactions

Since numerous new taxoids active against multidrug resistant (MDR) tumors have been developed and their poor water-solubility is a very real problem in intravenous administration, we have designed and synthesized a series of novel water-soluble taxoid prodrugs (isotaxoids). These prodrugs, a 2'-O-isoform of taxoids, showed promising results with higher water solubility (0.8- 1.1 mg/mL) and proper kinetics for parent drug release by a simple pH-dependent chemical mechanism via O-N intramolecular acyl migration. No additional functional auxiliaries are released during the conversion to parent drugs, which would be an advantage in toxicology and general pharmacology, and the cost for the evaluations of auxiliary units in these fields could be saved in prodrug development. In addition, we demonstrate for the first time the successful application of the O-N intramolecular acyloxy migration reaction in the prodrug design, with the exception of the tert-butyloxycarbonyl group, and that this reaction can be provided with no organic solvent and no side products