| Budget Amount *help |
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 2003: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 2002: ¥7,100,000 (Direct Cost: ¥7,100,000)
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| Research Abstract |
In the course of studies on molecular design, syntheses, and utilization of thiazole-related compounds, we have developed several new heterocyclic compounds involving intramolecular nonbonded S【triple bond】X (X = O, N, S, halogens) interactions and new syntheses of pharmaceutically interesting compounds. In each X-ray crystallographic structure of 2-(furan or thiophen-2-yl)1, 3 thiazole, chemospecific nonbonded O 【triple bond】 S or S 【triple bond】 N interaction was observed. We have synthesized a model compound of firefly luciferin and mono-, bi-, and tri-thiazole derivatives, in which the existence of each nonbonded S 【triple bond】 N interaction was confirmed by their X-ray crystallographic analyses. The DFT calculation of their model molecules could support that the molecule bearing such an S【triple bond】N interaction was most stable in relative energy among several ones. The first nonbonded S【triple bond】X(X = F, Cl, Br, I ) interactions in four kinds of 2-(2-halophenyl)-1, 3thiazole derivatives have been demonstrated in a same manner as described above. Interestingly, a tri-thiazole derivative exhibited considerable anticancer activities against some human cancer cells in vitro. The nonbonded S 【triple bond】 O interaction in the crystalline structures of diuretic acetazolamide and stromelysin-inhibitors, thiadiazolinethiones, was similarly observed even in their complex structures with carbonic anhydrase I and II and stromelysin. The pendant molecule (mercaptoazetidinyl thiazoline) of a new oral carbapenem antibiotic was efficiently synthesized by using azabicyclobutane. The antibody labeled with a new infrared fluorescent-labeling agent (indocyanine-green-acylthiazolidinethione ) was utilized for diagnosing microcancers
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