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公开(公告)号:US20050203145A1
公开(公告)日:2005-09-15
申请号:US10970046
申请日:2004-10-20
申请人: Young-Dae Gong , Hyae-Gyeong Cheon , Young-Sik Cho , Jin-Soo Seo , Jong-Yeon Hwang , Ji-Yeon Park , Sung-eun Yoo
发明人: Young-Dae Gong , Hyae-Gyeong Cheon , Young-Sik Cho , Jin-Soo Seo , Jong-Yeon Hwang , Ji-Yeon Park , Sung-eun Yoo
IPC分类号: C07D311/70 , A61K31/352 , A61K31/353 , A61K31/36 , A61K31/381 , A61K31/4045 , A61K31/4433 , A61P1/00 , A61P11/06 , A61P17/06 , A61P19/02 , A61P29/00 , A61P43/00 , C07B61/00 , C07D311/76 , C07D405/12 , C07D407/12 , C07D409/12 , C07D49/02 , C07D45/02
CPC分类号: C07D311/70 , C07D405/12 , C07D407/12 , C07D409/12
摘要: When a multi-step process reaction is carried out in a solution, it generally requires several treatments and purification procedures to go through with after the reaction, however, the inventive method for preparing 2,2′-disubstituted-3,4-dihydro-7,8-disubstituted-6-amino benzopyran derivative using a solid-phased synthetic method simplifies the treatment and purification procedures after the reaction, which makes possible to efficiently construct numerous drug-like libraries. In particular, since the inventive method of the present invention comprises the steps of introducing a carbonate linker of formula 2 into Wang resin used as a common solid support (Step 1); synthesizing various benzopyran in a carbamate form of formula 3 as a key intermediate by reacting various amino benzopyran derivatives with the carbamate resin of formula 2 (Step 2); synthesizing 2,2′-disubstituted-3,4-2H-6-substituted benzopyran resin of formula 4 (Step 3); and synthesizing 2,2′-disubstituted-3,4-2H-6-alkylamino benzopyran derivative of formula 1 using a dichloromethane solution containing TFA or an organic solvent containing an organic acid, the inventive method is capable of efficiently synthesizing various 2,2′-disubstituted-3,4-2H-6-alkylamino benzopyran derivatives. Consequently, the present invention has developed a new technique for constructing 2,2′-disubstituted-3,4-2H-6-alkylamino benzopyran library using a solid-phase parallel synthetic method and makes increased the applicability of combinatorial chemical synthetic method. Further, 2,2′-disubstituted-3,4-2H-6-alkylamino benzopyran derivative prepared by the inventive method has a high inhibitory effect to 5-lipoxygenase (5-LO) activity, and therefore, can be effectively used for developing a new propylactic or therapeutic drug for leukotriene activation-related diseases such as chronic inflammation, rheumatic arthritis, colitis, asthma and psoriasis.
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公开(公告)号:US07368575B2
公开(公告)日:2008-05-06
申请号:US10970046
申请日:2004-10-20
申请人: Young-Dae Gong , Hyae-Gyeong Cheon , Young-Sik Cho , Jin-Soo Seo , Jong-Yeon Hwang , Ji-Yeon Park , Sung-Eun Yoo
发明人: Young-Dae Gong , Hyae-Gyeong Cheon , Young-Sik Cho , Jin-Soo Seo , Jong-Yeon Hwang , Ji-Yeon Park , Sung-Eun Yoo
IPC分类号: C07D311/00 , C07D405/00
CPC分类号: C07D311/70 , C07D405/12 , C07D407/12 , C07D409/12
摘要: When a multi-step process reaction is carried out in a solution, it generally requires several treatments and purification procedures to go through with after the reaction, however, the inventive method for preparing 2,2′-disubstituted-3,4-dihydro-7,8-disubstituted-6-amino benzopyran derivative using a solid-phased synthetic method simplifies the treatment and purification procedures after the reaction, which makes possible to efficiently construct numerous drug-like libraries. In particular, since the inventive method of the present invention comprises the steps of introducing a carbonate linker of formula 2 into Wang resin used as a common solid support (Step 1); synthesizing various benzopyran in a carbamate form of formula 3 as a key intermediate by reacting various amino benzopyran derivatives with the carbamate resin of formula 2 (Step 2); synthesizing 2,2′-disubstituted-3,4-2H-6-substituted benzopyran resin of formula 4 (Step 3); and synthesizing 2,2′-disubstituted-3,4-2H-6-alkylamino benzopyran derivative of formula 1 using a dichloromethane solution containing TFA or an organic solvent containing an organic acid, the inventive method is capable of efficiently synthesizing various 2,2′-disubstituted-3,4-2H-6-alkylamino benzopyran derivatives.Consequently, the present invention has developed a new technique for constructing 2,2′-disubstituted-3,4-2H-6-alkylamino benzopyran library using a solid-phase parallel synthetic method and makes increased the applicability of combinatorial chemical synthetic method. Further, 2,2′-disubstituted-3,4-2H-6-alkylamino benzopyran derivative prepared by the inventive method has a high inhibitory effect to 5-lipoxygenase (5-LO) activity, and therefore, can be effectively used for developing a new propylactic or therapeutic drug for leukotriene activation-related diseases such as chronic inflammation, rheumatic arthritis, colitis, asthma and psoriasis.
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