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KMID : 0370220080520060488
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Yakhak Hoeji
2008 Volume.52 No. 6 p.488 ~ p.493
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Synthesis of (±)-cis-8-amino-l-2,3,4,4a,5,10b-hexahydrothiazolo[4,5-f]indeno[1,2-b][1,4]oxazine
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Ma Eun-Sook
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Abstract
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2-Aminothiazole ring as a bioisoster of catechol in dopamine has provided with good oral availability and lipophilic property. 2-Aminoindan, is a rigid form of dopamine, was evaluated as a dopamine D3 agonist with low neurotoxicity. Dopamine D3 agonist was evaluated as selective for the treatment of Parkinson’s disease. In order to develop a novel dopamine D3 agonist, we tried to synthesize the aminothiazoloindenoxazine derivative that is a hybrid structure of aminoindenoxazine and thiazole ring. cis-2-Amino-1-indanol (2) was synthesized from 1,2-indandione-2-oxime by catalytic hydrogenation and it was treated with chloroacetyl chloride and NaH in benzene solution to give (±)-cis-4,4a,5,9b-tetrahydroindeno[1,2-b][1,4]oxazin-3(2H)-one (6). Nitration of 6 by the mixed acid gave 8-nitro compound (7) and the carbonyl group of 7 was reduced with LiAlH4 to afford compound (8). 8 was reduced to form (±)-cis-8-amino-2,3,4,4a,5,9b-hexahydroindeno[1,2-b][1,4]oxazine (9) and finally it was cyclized with KSCN in glacial acetic acid to yield (±)-cis-8-amino-2,3,4,4a,5,10b-hexahydrothiazolo[4,5-f]indeno[1,2-b][1,4]oxazine (10).
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KEYWORD
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Parkinson’s Disease, Dopamine D3 receptor agonist, Aminothiazoloindenooxazine
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