2-Hydroxy-5-(4-(trifluoromethyl)phenethylamino)benzoic acid 유사체의 합성 및 약리효과 연구

Author(s)
이재우
Advisor
윤성화
Department
일반대학원 분자과학기술학과
Publisher
The Graduate School, Ajou University
Publication Year
2007-02
Language
eng
Abstract
Sulfasalazine의 유사체로 도안된 2-hydroxy-5-(4-(trifluoromethyl)- phenethyl amino)benzoic acid는 뛰어난 항산화 효과와 항염증 효과를 동시에 발현하였다. 그러나 물에 대한 물질의 용해도가 낮아 혈액 내에서 약효가 잘 발현되지 않는다는 단점이 있었다. 따라서 hetero ring과 phenol ring을 도입하여 용해도를 높이고 약효를 증가시키고자 하였다. 2-Hydroxy-5-(4-(trifluoromethyl)phenethylamino)benzoic acid의 유사체는 일반적인 유기화학합성을 통해 합성하였으며, 합성된 물질들은 DPPH 라디칼 소거 활성을 측정하기 위하여 알려진 Blosis 방법을 이용하여 항산화 효과를 측정하였다. 측정 결과, 유사체들의 항산화 효과는 2-hydroxy-5-(4-(trifluoromethyl) phenethylamino)benzoic acid에 미치지 못하는 것으로 나타났으며, phenol ring이 도입되었을 때 보다 항산화 효과가 뛰어난 것으로 확인되었다. 2-Hydroxy-5-(4-(trifluoromethyl)phenethylamino)benzoic acid의 유사체를 통한 약효개선에 실패했기 때문에, 이 물질을 신약후보물질로 선정한 후 대량생산에 필요한 공정을 개발하였다. 기존의 합성방식으로 합성하면 step수가 많아 비효율적이고, 고가의 시약들을 사용하기 때문에 생산단가가 높은 단점이 있었다. 따라서 protection-deprotection step을 제거함으로써 step수를 줄이고 생산단가를 낮추는 데 성공하였다.
Alternative Abstract
After we found that 2-hydroxy-5-(4-(trifluoromethyl)phenethylamino) benzoic acid, one of 5-aminosalicylic acid derivatives, showed strong anti-oxidant activity as well as potent anti-inflammatory effect, we needed to improve the poor solubility of compound in water for expanding the therapeutic effect of the compound in blood. For the purpose of improving the solubility, we modified the phenyl moiety in the structure of compound by introduction of either the hetero cyclic ring or phenol moieties. The designed analogues of 2-hydroxy-5-(4-(trifluoromethyl) phenethylamino)benzoic acid were synthesized by general organic methods, and tested their neuroprotective activities by Blosis method using DPPH free radical scavenging activity. Although all of analogues showed weaker antioxidant activities than as 2-hydroxy-5-(4-(trifluoromethyl)phenethylamino)benzoic acid, compounds containing phenol moiety showed moderate antioxidant effect while analogues with phenol moiety exhibited better anti-oxidant effect than those with hetero moiety. After we selected 2-hydroxy-5-[2-(4-(trifluoromethylphenyl)ethylamino)] benzoic acid as a new neuroprotective agent, we need to develop new synthetic method for the scale-up production of the compound. Since previous synthetic method was inefficient and high-cost method, new synthetic method reduced 2 reaction steps and replaced high cost reagents with cheaper reagents. As a result, the cost was lowered and the yield was improved.
URI
https://dspace.ajou.ac.kr/handle/2018.oak/5728
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Graduate School of Ajou University > Department of Molecular Science and Technology > 3. Theses(Master)
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