公开(公告)号：KR100868959B1

公开(公告)日：2008-11-17

申请号：KR1020060139200

申请日：2006-12-30

Applicant: 재단법인서울대학교산학협력재단

Inventor： 강창율 ,  김상희 ,  윤현준 ,  이윤숙 ,  이규아 ,  이태호 ,  백동재 ,  조민재

IPC: C07H15/00 ,  C07H15/10

CPC classification number: C07H15/00 ,  Y02P20/55

Abstract: 본 발명은 알파-갈락토실세라마이드 유도체, 이의 약학적으로 허용 가능한 염, 이의 제조방법 및 이를 유효성분으로 함유하는 면역보조용 약학적 조성물에 관한 것이다. 본 발명의 α-GalCer 아마이드 부분을 생물학적 등입체성을 가진 트리아졸로 변경한 화합물의 경우, 싸이토카인 IL-4와 IFN-
γ 중 한쪽으로 분비를 유도함으로써, IL-4에 의해 조절되는 제1형 당뇨병과 다발성 경화증과 같은 자가 면역 질환의 유용한 치료제로 사용될 수 있다.
[화학식 1]

(상기 식에서, A 및 R은 명세서에 정의한 바와 같다.)

알파-갈락토실세라마이드 유도체, α-GalCer, 자연살해 T 세포, NKT, 면역보조

公开(公告)号：KR1020080062973A

公开(公告)日：2008-07-03

申请号：KR1020060139200

申请日：2006-12-30

Applicant: 재단법인서울대학교산학협력재단

Inventor： 강창율 ,  김상희 ,  윤현준 ,  이윤숙 ,  이규아 ,  이태호 ,  백동재 ,  조민재

IPC: C07H15/00 ,  C07H15/10

CPC classification number: C07H15/00 ,  Y02P20/55

Abstract: An alpha-galactosylceramide derivative is provided to induce secretion of cytokine IL-4 or IFN-gamma by modifying an alpha-GalCer amide portion by a triazole having biological isosterism, thereby being used as a useful therapeutic agent of auto-immune diseases such as a type I diabetes and multiple sclerosis. An alpha-galactosylceramide derivative is represented by a formula(1a), wherein A is triazole or amide; and if the A is triazole, R is C1-35 alkyl which may be substituted or unsubstituted by at least one substituent selected from the group consisting of halogen, hydroxy, amino, amino substituted by at least one C1-20 alkyl, thiol, cyano, nitro, sulfonyl, phenyl, C1-30 alkoxy, C1-30 alkyl, C1-30 haloalkyl, C1-30 hydroxyalkyl, C1-30 alkoxyalkyl, C5-10 aryl, C5-10 heteroaryl, C5-10 arylalkyl and C5-10 heteroarylalkyl, and if the A is amide, R is C1-35 alkyl which is substituted by at least one substituent selected from the group consisting of halogen, hydroxy, amino, amino substituted by at least one C1-20 alkyl, thiol, cyano, nitro, sulfonyl, phenyl, C1-30 alkoxy, C1-30 alkyl, C1-30 haloalkyl, C1-30 hydroxyalkyl, C1-30 alkoxyalkyl, C5-10 aryl, C5-10 heteroaryl, C5-10 arylalkyl and C5-10 heteroarylalkyl. A method for preparing the alpha-galactosylceramide derivative comprises the steps of: (a) reacting a compound represented by a formula(2) with an alkyne compound to prepare an intermediate represented by a formula(4); and (b) reacting the intermediate of the formula(4) with Pd(OH)2 to remove a protecting group therefrom, wherein A is triazole, R1 is at least one of substituent R, which is defined above, and each Bn and PMB is benzyl or p-methoxybenzyl. A pharmaceutical composition for immunity adjuvant comprises the alpha-galactosylceramide derivative or a pharmaceutically acceptable salt thereof as an effective ingredient.

Abstract translation: 提供α-半乳糖神经酰胺衍生物以通过用具有生物等排阻的三唑修饰α-GalCer酰胺部分来诱导细胞因子IL-4或IFN-γ的分泌，从而用作自身免疫疾病的有用治疗剂，例如 I型糖尿病和多发性硬化症。 α-半乳糖神经酰胺衍生物由式（1a）表示，其中A是三唑或酰胺; 并且如果A是三唑，R是可被至少一个选自卤素，羟基，氨基，被至少一个C 1-20烷基，硫醇，氰基取代的氨基的取代基取代或未取代的C1-35烷基 ，硝基，磺酰基，苯基，C30-30烷氧基，C1-30烷基，C1-30卤代烷基，C1-30羟基烷基，C1-30烷氧基烷基，C5-10芳基，C5-10杂芳基，C5-10芳烷基和C5-10 杂芳基烷基，并且如果A是酰胺，则R是被至少一个选自卤素，羟基，氨基，被至少一个C 1-20烷基取代的氨基，硫醇，氰基， 硝基，磺酰基，苯基，C30-30烷氧基，C1-30烷基，C1-30卤代烷基，C1-30羟基烷基，C1-30烷氧基烷基，C5-10芳基，C5-10杂芳基，C5-10芳烷基和C5-10杂芳基烷基 。 制备α-半乳糖神经酰胺衍生物的方法包括以下步骤：（a）使由式（2）表示的化合物与炔化合物反应以制备由式（4）表示的中间体; 和（b）使式（4）的中间体与Pd（OH）2反应以除去其中的保护基，其中A是三唑，R 1是上述定义的R中的至少一个，每个Bn和PMB 是苄基或对甲氧基苄基。 用于免疫佐剂的药物组合物包含α-半乳糖神经酰胺衍生物或其药学上可接受的盐作为有效成分。