KR20080035378A - Composition for inhibiting the activity of glucose-6-phosphate dehydrogenase - Google Patents

Composition for inhibiting the activity of glucose-6-phosphate dehydrogenase Download PDF

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KR20080035378A
KR20080035378A KR1020060102010A KR20060102010A KR20080035378A KR 20080035378 A KR20080035378 A KR 20080035378A KR 1020060102010 A KR1020060102010 A KR 1020060102010A KR 20060102010 A KR20060102010 A KR 20060102010A KR 20080035378 A KR20080035378 A KR 20080035378A
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gallate
activity
glucose
phosphate dehydrogenase
inhibiting
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신의석
이태룡
조시영
신동욱
김재범
박지영
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(주)아모레퍼시픽
재단법인서울대학교산학협력재단
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin

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Abstract

A composition for inhibiting the activity of glucose-6-phosphate dehydrogenase is provided to inhibit production of NADPH(nicotinamide adenine dinucleotide phosphate) and fat biosynthesis, so that the composition is useful for prevention and treatment of fat metabolism disorders including obesity, hyperlipidemia and diabetes. A composition for inhibiting the activity of glucose-6-phosphate dehydrogenase comprises the compounds represented by the formula(1) selected from epigallocatechin gallate, gallocatechin gallate, epicatechin gallate, catechin gallate, octyl gallate and lauryl gallate, wherein R^1 is H or OH, R^2 is a structural formula 1 or 2, R^3 is C3-C20 alkyl, X is a structural formula 3 or 4, and R^4 is H or a structural formula 5; and the compounds represented by the formula(1) is quercetin or myricetin.

Description

글루코오스-6-인산 탈수소 효소의 활성 지방 합성 억제용 조성물{COMPOSITION FOR INHIBITING THE ACTIVITY OF GLUCOSE-6-PHOSPHATE DEHYDROGENASE}Composition for inhibiting the active fat synthesis of glucose-6-phosphate dehydrogenase {COMPOSITION FOR INHIBITING THE ACTIVITY OF GLUCOSE-6-PHOSPHATE DEHYDROGENASE}

도 1은 갈레이트(gallate) 기를 갖는 화합물과 갖지 않는 화합물의 활성 억제 효능을 비교한 것이다.1 compares the activity inhibitory effect of a compound with and without a gallate group.

도 2는 갈로카테친 갈레이트를 ob/ob 생쥐에 2주간 투여한 후 혈당을 측정하여 무투여 대조군과 비교한 결과이다. Figure 2 is the result of the administration of gallocatechin gallate to ob / ob mice for two weeks, the blood glucose was measured and compared with the non-administered control group.

도 3은 갈로카테친 갈레이트를 ob/ob 생쥐에 2주간 투여한 후 부고환 지방 조직 내의 트리글리세라이드(triglyceride) 양을 측정하여 비교한 결과이다. Figure 3 is a result of comparing the amount of triglyceride (triglyceride) in the epididymal adipose tissue after administering gallocatechin gallate to ob / ob mice for two weeks.

본 발명은 글루코오스-6-인산 탈수소 효소(glucose-6-phosphate dehydrogenase)의 활성을 억제하는 화합물을 유효성분으로 함유하는 지방합성 억제용 조성물에 관한 것이다. The present invention relates to a composition for inhibiting fat synthesis containing a compound that inhibits the activity of glucose-6-phosphate dehydrogenase as an active ingredient.

지방산과 콜레스테롤 합성에 필수적으로 요구되는 NADPH는 지방 합성에 필요한 환원능(reducing power)을 제공하는 역할을 하며, 말산 효소(malic enzyme), 글루코오스-6-인산 탈수소 효소(glucose-6-phosphate dehydrogenase), 6-인글루콘산염 탈수소 효소(6-phosphogluconate dehydrogenase) 등에 의해 생성된다. 따라서, NADPH 생성에 관여하는 효소들은 고지혈증이나 비만, 당뇨병과 같은 지방대사 이상 질환에 관여할 가능성이 매우 높다.NADPH, which is essential for the synthesis of fatty acids and cholesterol, provides the reducing power required for fat synthesis, malic enzyme, and glucose-6-phosphate dehydrogenase. And 6-phosphogluconate dehydrogenase. Therefore, the enzymes involved in NADPH production are very likely to be involved in diseases such as hyperlipidemia, obesity, and diabetes metabolism disorders.

상기 효소들 중 글루코오스-6-인산 탈수소 효소[glucose-6-phosphate dehydrogenase(이하, 'G6PDH'라 함)]는 글루코오스-6-인산을 탈수소화시켜 NADP+를 NADPH로 환원시키는 반응에 관여하는 효소로서, 백색 지방 조직에서 주로 발현되며 유전적인 결함으로 비만이 유도된 ob/ob 및 db/db 생쥐의 부고환 지방 조직에서 발현이 증가된다. 또한, 지방 세포에서 G6PDH 발현을 억제시켰을 때 지방 합성과 관련된 효소들의 발현이 억제되며 지방 조직의 분화와 지방 축적이 억제된다(Park et al., Molecular and cellular biology, 25, 5146-5157 ,2005]. 또한, G6PDH의 활성 저해제로 알려진 디하이드로에피안드로스테론[dehydroepiandrosterone(DHEA)]을 Avy 생쥐에 투여했을 경우 지방 합성이 감소하며 트리아실글리세라이드(triacylglyceride)의 축적이 감소되어 체중이 감소한다(Yen et al, Lipids., 12(5), 409-13, May, 1977).Among the enzymes, glucose-6-phosphate dehydrogenase (hereinafter referred to as 'G6PDH') is an enzyme that is involved in the reaction of dehydrogenating glucose-6-phosphate to reduce NADP + to NADPH. This is mainly expressed in white adipose tissue and is increased in epididymal adipose tissue of ob / ob and db / db mice induced by obesity due to genetic defects. In addition, inhibiting G6PDH expression in adipocytes inhibits the expression of enzymes related to fat synthesis and inhibits the differentiation and fat accumulation of adipose tissue (Park et al ., Molecular and cellular biology , 25, 5146-5157, 2005). In addition, administration of dehydroepiandrosterone (DHEA), known as an inhibitor of G6PDH, to Avy mice decreases fat synthesis and decreases the accumulation of triacylglycerides, resulting in weight loss (Yen). et al, Lipids ., 12 (5), 409-13, May, 1977).

이에 본 발명자들은 G6PDH의 활성을 억제하면 지방 합성에 필요한 NADPH의 생성이 저해됨으로써 지방 합성이 억제되고, 이에 따라 비만, 고지혈증, 당뇨병 등과 같은 지방대사 이상질환에 대한 예방 및 치료 효능이 나타날 것으로 예상하고, G6PDH의 활성을 억제하는 물질을 찾고자 수백 종의 화합물들을 탐색한 결과, 갈레이트(gallate) 기를 갖는 화합물 및 일부 플라보노이드(flavonoid)계 화합물이 G6PDH의 활성을 억제한다는 것을 확인하고 본 발명을 완성하였다.  Accordingly, the present inventors anticipate that inhibiting the activity of G6PDH inhibits the production of NADPH necessary for fat synthesis, thereby inhibiting the synthesis of fat, and thus will prevent and treat the effects of fat metabolism abnormalities such as obesity, hyperlipidemia and diabetes. In search of hundreds of compounds to find a substance that inhibits the activity of G6PDH, the present invention was confirmed that compounds having gallate groups and some flavonoid compounds inhibit the activity of G6PDH. .

따라서, 본 발명의 목적은 G6PDH의 활성 억제를 제공하는 것이다.Accordingly, it is an object of the present invention to provide inhibition of activity of G6PDH.

또한, 본 발명의 다른 목적은 G6PDH의 활성을 억제하는 화합물을 활성 성분으로 포함하는 약학 조성물을 제공하는 것이다.It is another object of the present invention to provide a pharmaceutical composition comprising as an active ingredient a compound that inhibits the activity of G6PDH.

상기 목적에 따라, 본 발명은 하기 화학식 1로 표시되는 글루코오스-6-인산 탈수소 효소(G6PDH)의 활성 억제제를 제공한다.In accordance with the above object, the present invention provides an activity inhibitor of glucose-6-phosphate dehydrogenase (G6PDH) represented by the following formula (1).

Figure 112006075615217-PAT00008
Figure 112006075615217-PAT00008

상기 식에서, Where

R1은 H 또는 OH이고;R 1 is H or OH;

R2는

Figure 112006075615217-PAT00009
또는
Figure 112006075615217-PAT00010
이고;R 2 is
Figure 112006075615217-PAT00009
or
Figure 112006075615217-PAT00010
ego;

R3는 C3~C20 알킬이고;R 3 is C 3 -C 20 alkyl;

X는

Figure 112006075615217-PAT00011
또는
Figure 112006075615217-PAT00012
이고;X is
Figure 112006075615217-PAT00011
or
Figure 112006075615217-PAT00012
ego;

R4는 H 또는

Figure 112006075615217-PAT00013
이고;R 4 is H or
Figure 112006075615217-PAT00013
ego;

Figure 112006075615217-PAT00014
는 단일결합 또는 이중결합이다.
Figure 112006075615217-PAT00014
Is a single bond or a double bond.

또한, 본 발명은 활성 성분으로서 상기 화합물을 포함하는 G6PDH의 활성 억제용 조성물을 제공한다. The present invention also provides a composition for inhibiting activity of G6PDH containing the compound as an active ingredient.

이하, 본 발명을 보다 상세히 설명한다.Hereinafter, the present invention will be described in more detail.

본 발명의 조성물은 생체 내에서 G6PDH의 활성을 억제함으로써 지방 합성을 억제하는 것을 특징으로 한다.The composition of the present invention is characterized by inhibiting fat synthesis by inhibiting the activity of G6PDH in vivo.

본 발명의 조성물의 활성 성분인 화학식 1의 화합물로서 바람직한 화합물로는, 에피갈로카테친 갈레이트[epigallocatechin gallate(EGCG)], 갈로카테친 갈레이트[gallocatechin gallate(GCG)], 에피카테친 갈레이트[epicatechin gallate(ECG)], 카테친 갈레이트[catechin gallate(CG)], 옥틸 갈레이트(octyl gallate), 라우릴 갈레이트(lauryl gallate), 케르세틴(quercetin) 및 미리세틴(myricetin)을 예시할 수 있다. Preferred compounds of the formula (I) as the active ingredient of the composition of the present invention include epigallocatechin gallate (EGCG), gallocatechin gallate (GCG), epicatechin gallate (epicatechin) gallate (ECG)], catechin gallate (CG), octyl gallate, lauryl gallate, quercetin and myricetin.

상기 화합물들은 공지의 합성방법에 의해 합성하거나 시판되는 것을 구입하여 사용할 수 있다. The compounds can be used by purchasing a synthetic or commercially available by a known synthesis method.

본 발명의 화합물들은 통상적인 방법에 따라 약제학적으로 허용되는 적절한 담체 또는 부형제와 혼합하거나 희석제로 희석하여 상기한 기능을 갖는 약학 조성물을 제조할 수 있다. 적합한 담체, 부형제 및 희석제의 예로는, 락토즈, 덱스트로즈, 수크로즈, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로즈, 폴리비닐피롤리돈, 물, 메틸하이드록시벤조에이트, 프로필하이드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다. 상기 약학 조성물은 충진제, 항응집제, 윤활제, 습윤제, 향료, 유화제, 방부제, 붕해제, 감미제, 활택제, 향미제 등을 추가로 포함할 수 있다. The compounds of the present invention can be mixed with a suitable pharmaceutically acceptable carrier or excipient or diluted with a diluent according to conventional methods to prepare a pharmaceutical composition having the above functions. Examples of suitable carriers, excipients and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, Microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. The pharmaceutical composition may further include fillers, anti-coagulants, lubricants, wetting agents, flavors, emulsifiers, preservatives, disintegrants, sweeteners, lubricants, flavoring agents and the like.

본 발명의 약학 조성물은 포유동물에 투여된 후 활성 성분의 신속, 지속 또는 지연된 방출을 제공할 수 있도록 당업계에 잘 알려진 방법을 사용하여 제형화될 수 있다. 제형은 정제, 알약, 분말, 새세이(sachet), 엘릭서(elixir), 현탁액, 에멀젼, 용액, 시럽, 에어로졸, 연질 또는 경질 젤라틴 캅셀, 멸균 주사용액, 멸균 분말 등의 형태일 수 있다. The pharmaceutical compositions of the invention may be formulated using methods well known in the art to provide rapid, sustained or delayed release of the active ingredient after administration to a mammal. The formulations may be in the form of tablets, pills, powders, sachets, elixirs, suspensions, emulsions, solutions, syrups, aerosols, soft or hard gelatin capsules, sterile injectable solutions, sterile powders and the like.

본 발명의 약학 조성물은 경구, 경피, 피하, 정맥 또는 근육을 포함한 여러 경로를 통해 투여될 수 있다. 본 발명의 활성 화합물들의 통상적인 1일 투여량은 0.1 내지 100 ㎎/㎏ 체중의 범위이고, 1회 또는 수회로 나누어 투여할 수 있다. 그러나, 활성 성분의 실제 투여량은 투여 경로, 환자의 연령, 성별 및 체중, 및 질환의 중증도 등 여러 관련 인자에 비추어 결정되어야 하는 것으로 이해되어야 하며, 따라서 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니 다. The pharmaceutical compositions of the invention can be administered via several routes including oral, transdermal, subcutaneous, intravenous or intramuscular. Typical daily dosages of the active compounds of the present invention range from 0.1 to 100 mg / kg body weight and may be administered once or in divided doses. However, it is to be understood that the actual dosage of the active ingredient should be determined in light of several relevant factors such as the route of administration, the age, sex and weight of the patient, and the severity of the disease, and therefore the dosage should in any way be within the scope of the invention. It is not intended to be limiting.

실시예 1: G6PDH 활성의 억제 효능Example 1 Inhibitory Efficacy of G6PDH Activity

G6PDH의 활성 측정에 필요한 시약은 모두 시그마 알드리치[Sigma Aldrich(St. Louis, USA)]에서 구입하였다. 먼저, 글루코오스-6-인산 100 mM, NADP+ 50 mM, NaCl 200 mM 및 MgCl2 6 mM 가 용해된 0.1M Tris (pH 7.5) 완충용액을 제조한 후, 에피갈로카테친 갈레이트(EGCG), 갈로카테친 갈레이트(GCG), 에피카테친 갈레이트(ECG), 카테친 갈레이트(CG), 옥틸 갈레이트, 라우릴 갈레이트, 에피갈로카테친(EGC), 카테친(C), 갈산(gallic acid), 에틸 갈레이트(ethyl gallate), 헤스페리틴(hesperitin) 및 나린게닌(naringenin)을 각각 0.064 mM, 0.32 mM, 1.6 mM, 8.0 mM, 40 mM, 200 mM 및 1000 mM의 농도가 되도록 반응 용액에 첨가하였다. 그 다음, G6PDH를 3.2M (NH4)2SO4, pH 7.0에 용해한 후 최종적으로 0.002 단위(unit)가 되도록 각 반응 용액에 첨가하였다. 반응이 진행되는 동안 340 nm 파장에서 흡광도를 측정함으로써 각 화합물 첨가에 따른 NADPH의 생성량을 정량하였으며, 상기 화합물을 첨가한 경우(시험군)와 첨가하지 않은 경우(대조군)의 NADPH 생성량을 비교함으로써 G6PDH 활성의 억제 정도를 확인하였다. 또한, 첨가된 각 화합물의 농도변화에 따른 NADPH 생성 반응 속도를 측정한 후(도 1), 시그마 플롯 프로그램(sigma plot program)을 이용하여 각 화합물의 IC50 값을 계산하였으며, 그 결과는 하기 표 1 및 표 2에 각각 표시하였다.Reagents for measuring the activity of G6PDH were all purchased from Sigma Aldrich (St. Louis, USA). First, 0.1M Tris (pH 7.5) buffer containing 100 mM glucose-6-phosphate, 50 mM NADP +, 200 mM NaCl, and 6 mM MgCl 2 was prepared, followed by epigallocatechin gallate (EGCG) and gallo. Catechin gallate (GCG), epicatechin gallate (ECG), catechin gallate (CG), octyl gallate, lauryl gallate, epigallocatechin (EGC), catechin (C), gallic acid, Ethyl gallate, hesperitin and naringenin were added to the reaction solution to concentrations of 0.064 mM, 0.32 mM, 1.6 mM, 8.0 mM, 40 mM, 200 mM and 1000 mM, respectively. . Then G6PDH was dissolved in 3.2M (NH 4 ) 2 SO 4 , pH 7.0 and added to each reaction solution to finally 0.002 units. During the reaction, the amount of NADPH produced according to the addition of each compound was measured by measuring the absorbance at the wavelength of 340 nm, and the amount of NADPH produced when the compound was added (test group) and no addition (control) was compared. The degree of inhibition of activity was confirmed. In addition, after measuring the reaction rate of NADPH production according to the concentration change of each compound added (Fig. 1), the IC 50 value of each compound was calculated using a sigma plot program, the results are shown in the following table 1 and Table 2, respectively.

Figure 112006075615217-PAT00015
Figure 112006075615217-PAT00015

Figure 112006075615217-PAT00016
Figure 112006075615217-PAT00016

상기 표 1 및 도 1의 결과에서 볼 수 있듯이, 에피갈로카테친 갈레이트(EGCG), 갈로카테친 갈레이트(GCG), 에피카테친 갈레이트(ECG), 카테친 갈레이트(CG), 옥틸 갈레이트, 라우릴 갈레이트와 같이 갈레이트(gallate) 기를 포함하는 화합물들은 G6PDH가 촉매로 작용하는 반응, 즉 글루코오스-6-인산을 탈수소화시켜 NADP+를 NADPH로 환원시키는 반응의 반응 속도를 저하시키므로 G6PDH의 활성을 억제함을 확인하였으며, 에피갈로카테친(EGC), 카테친(C)과 같이 갈레이트(gallate)기를 갖지 않는 화합물들과 갈레이트(gallic acid), 에틸 갈레이트(ethyl gallate)와 같이 갈레이트(gallate)기를 갖고 있더라도 곁사슬(side chain)이 없거나 길이가 짧은 화합물들은 G6PDH의 활성을 억제하지 않는다는 것을 확인하였다.As can be seen in the results of Table 1 and Figure 1, epigallocatechin gallate (EGCG), gallocatechin gallate (GCG), epicatechin gallate (ECG), catechin gallate (CG), octyl gallate, Compounds containing gallate groups, such as lauryl gallate, reduce the rate of reaction of G6PDH as a catalyst, ie, dehydrogenation of glucose-6-phosphate to reduce NADP + to NADPH. And gallates such as gallate and ethyl gallate, which do not have gallate groups such as epigallocatechin (EGC) and catechin (C). It was confirmed that compounds having no side chain or short lengths did not inhibit the activity of G6PDH even if they had a gallate group.

Figure 112006075615217-PAT00017
Figure 112006075615217-PAT00017

상기 표 2의 결과에서 볼 수 있듯이, 플라보노이드계 화합물 중 케르세틴(quercetin) 및 미리세틴(myricetin)이 G6PDH가 촉매로 작용하는 반응, 즉 글루코오스-6-인산을 탈수소화시켜 NADP+를 NADPH로 환원시키는 반응의 반응 속도를 저하시킴을 확인하였다. As can be seen from the results of Table 2, quercetin and myricetin of the flavonoid compounds react with G6PDH as a catalyst, ie, dehydrogenation of glucose-6-phosphate to reduce NADP + to NADPH. It was confirmed that the reaction rate of was lowered.

실시예 2: 갈로카테친 갈레이트(gallogatechin gallate)에 의한 혈당 억제 효과 및 트리글리세라이드(triglyceride) 생성 억제 효과Example 2 Inhibition of Blood Glucose and Inhibition of Triglyceride Formation by Gallogatechin Gallate

유전적으로 비만이 유도된 8주령의 수컷 ob/ob 생쥐(폴라스 인터내셔널, 한국)에 대하여, 갈로카테친 갈레이트(GCG)을 0.02 % 함유한 AIN93G 사료(한삶R&D, 한국)를 2주간 자유롭게 섭취하게 하였으며, 대조군으로는 갈로카테친 갈레이트가 포함되지 않은 AIN93G 사료를 역시 2주간 자유롭게 섭취하게 하였다. 2주 후 혈액을 채취하여 혈당을 측정하였으며(도 2), 부고환 지방조직을 분리하여 0.1 M Tris (pH 7.5) 완충용액에서 파쇄한 후 원심분리시켜 상층액을 분리하고 분리된 상층액에서 트리글리세라이드 측정 키트(Sigma, USA)를 이용하여 트리글리세라이드의 양을 측정하였다(도 3). 도 2 및 도 3의 결과에서 볼 수 있듯이, 갈로카테친 갈레이트(GCG) 처리군에서 혈당 및 부고환 지방 내의 트리글리세라이드의 양이 감소됨을 확인하였다. For 8-week-old male ob / ob mice (Polas International, Korea) that were genetically obese, freely consumed AIN93G feed (Hanlife R & D, Korea) containing 0.02% gallocatechin gallate (GCG) for 2 weeks. As a control, AIN93G feed without gallocatechin gallate was also freely consumed for 2 weeks. Two weeks later, blood was collected and blood glucose was measured (FIG. 2). The epididymal adipose tissue was separated, crushed in 0.1 M Tris (pH 7.5) buffer solution, centrifuged to separate the supernatant, and the triglycerides from the separated supernatant. The amount of triglycerides was measured using a measurement kit (Sigma, USA) (FIG. 3). As can be seen in the results of Figures 2 and 3, it was confirmed that the amount of triglycerides in the blood sugar and epididymal fat in the gallocatechin gallate (GCG) treatment group.

본 발명의 조성물은 글루코오스-6-인산 탈수소 효소의 활성을 억제함으로써 지방합성을 억제시키므로, 비만, 고지혈증, 당뇨병 등의 지방대사 이상질환에 대한 예방 또는 치료용 조성물로 유용하게 사용될 수 있다.Since the composition of the present invention inhibits the synthesis of glucose by inhibiting the activity of glucose-6-phosphate dehydrogenase, it may be usefully used as a composition for preventing or treating fat metabolism abnormal diseases such as obesity, hyperlipidemia and diabetes.

Claims (12)

하기 화학식 1로 표시되는 글루코오스-6-인산 탈수소 효소의 활성 억제제:Inhibitor of activity of glucose-6-phosphate dehydrogenase represented by Formula 1 below: [화학식][Formula]
Figure 112006075615217-PAT00018
Figure 112006075615217-PAT00018
 상기 식에서, Where R1은 H 또는 OH이고;R 1 is H or OH; R2는
Figure 112006075615217-PAT00019
또는
Figure 112006075615217-PAT00020
이고;R 2 is
Figure 112006075615217-PAT00019
or
Figure 112006075615217-PAT00020
ego; R3는 C3~C20 알킬이고;R 3 is C 3 -C 20 alkyl; X는
Figure 112006075615217-PAT00021
또는
Figure 112006075615217-PAT00022
이고;X is
Figure 112006075615217-PAT00021
or
Figure 112006075615217-PAT00022
ego; R4는 H 또는
Figure 112006075615217-PAT00023
이고;R 4 is H or
Figure 112006075615217-PAT00023
ego;
Figure 112006075615217-PAT00024
는 단일결합 또는 이중결합이다.
Figure 112006075615217-PAT00024
Is a single bond or a double bond. 제 1항에 있어서, The method of claim 1, 화학식 1의 화합물이 에피갈로카테친 갈레이트(epigallocatechin gallate), 갈로카 테친 갈레이트(gallocatechin gallate), 에피카테친 갈레이트(epicatechin gallate), 카테친 갈레이트(catechin gallate), 옥틸 갈레이트(octyl gallate) 및 라우릴 갈레이트(lauryl gallate)로 구성된 군으로부터 선택되는 것을 특징으로 하는 글루코오스-6-인산 탈수소 효소의 활성 억제제.Compounds of formula 1 are epigallocatechin gallate, gallocatechin gallate, epicatechin gallate, catechin gallate, octyl gallate And lauryl gallate. An inhibitor of activity of glucose-6-phosphate dehydrogenase, characterized in that it is selected from the group consisting of. 제 1항에 있어서, The method of claim 1, 화학식 1의 화합물이 케르세틴(quercetin) 또는 미리세틴(myricetin)인 것을 특징으로 하는 글루코오스-6-인산 탈수소 효소의 활성 억제제.An inhibitor of activity of glucose-6-phosphate dehydrogenase, characterized in that the compound of formula 1 is quercetin or myricetin. 제 1항에 있어서, The method of claim 1, 지방 합성을 억제하는 것을 특징으로 하는 글루코오스-6-인산 탈수소 효소의 활성 억제제.An inhibitor of activity of glucose-6-phosphate dehydrogenase, characterized by inhibiting fat synthesis. 제 1항에 있어서, The method of claim 1, 지방대사 이상질환에 대한 예방 또는 치료효능을 갖는 것을 특징으로 하는 글루코오스-6-인산 탈수소 효소의 활성 억제제.An activity inhibitor of glucose-6-phosphate dehydrogenase, characterized in that it has a prophylactic or therapeutic effect on adipose metabolic abnormal disease. 제 5항에 있어서, The method of claim 5, 지방대사 이상질환이 비만, 고지혈증 또는 당뇨병인 것을 특징으로 하는 글루코오스-6-인산 탈수소 효소의 활성 억제제.An activity inhibitor of glucose-6-phosphate dehydrogenase, characterized in that the fat metabolic disorder is obesity, hyperlipidemia or diabetes. 유효성분으로서 하기 화학식 1로 표시되는 화합물을 포함하는 글루코오스-6-인산 탈수소 효소의 활성을 억제하는 조성물:A composition for inhibiting the activity of glucose-6-phosphate dehydrogenase comprising the compound represented by the following formula (1) as an active ingredient: [화학식][Formula]
Figure 112006075615217-PAT00025
Figure 112006075615217-PAT00025
 상기 식에서, Where R1은 H 또는 OH이고;R 1 is H or OH; R2는
Figure 112006075615217-PAT00026
또는
Figure 112006075615217-PAT00027
이고;R 2 is
Figure 112006075615217-PAT00026
or
Figure 112006075615217-PAT00027
ego; R3는 C3~C20 알킬이고;R 3 is C 3 -C 20 alkyl; X는
Figure 112006075615217-PAT00028
또는
Figure 112006075615217-PAT00029
이고;X is
Figure 112006075615217-PAT00028
or
Figure 112006075615217-PAT00029
ego; R4는 H 또는
Figure 112006075615217-PAT00030
이고;R 4 is H or
Figure 112006075615217-PAT00030
ego;
Figure 112006075615217-PAT00031
는 단일결합 또는 이중결합이다.
Figure 112006075615217-PAT00031
Is a single bond or a double bond. 제 7항에 있어서, The method of claim 7, wherein 화학식 1의 화합물이 에피갈로카테친 갈레이트(epigallocatechin gallate), 갈로카 테친 갈레이트(gallocatechin gallate), 에피카테친 갈레이트(epicatechin gallate), 카테친 갈레이트(catechin gallate), 옥틸 갈레이트(octyl gallate) 및 라우릴 갈레이트(lauryl gallate)로 구성된 군으로부터 선택되는 것을 특징으로 하는 글루코오스-6-인산 탈수소 효소의 활성을 억제하는 조성물.Compounds of formula 1 are epigallocatechin gallate, gallocatechin gallate, epicatechin gallate, catechin gallate, octyl gallate And lauryl gallate (lauryl gallate) composition for inhibiting the activity of glucose-6-phosphate dehydrogenase, characterized in that selected from the group consisting of. 제 7항에 있어서, The method of claim 7, wherein 화학식 1의 화합물이 케르세틴(quercetin) 또는 미리세틴(myricetin)인 것을 특징으로 하는 글루코오스-6-인산 탈수소 효소의 활성을 억제하는 조성물.A composition for inhibiting the activity of glucose-6-phosphate dehydrogenase, characterized in that the compound of Formula 1 is quercetin or myricetin. 제 7항에 있어서, The method of claim 7, wherein 지방 합성을 억제하는 것을 특징으로 하는 글루코오스-6-인산 탈수소 효소의 활성을 억제하는 조성물.A composition for inhibiting the activity of glucose-6-phosphate dehydrogenase, characterized by inhibiting fat synthesis. 제 7항에 있어서, The method of claim 7, wherein 지방대사 이상질환에 대한 예방 또는 치료효능을 갖는 것을 특징으로 하는 글루코오스-6-인산 탈수소 효소의 활성을 억제하는 조성물.A composition for inhibiting the activity of glucose-6-phosphate dehydrogenase, characterized in that it has a prophylactic or therapeutic effect on adipose metabolic abnormal disease. 제 11항에 있어서, The method of claim 11, 지방대사 이상질환이 비만, 고지혈증 또는 당뇨병인 것을 특징으로 하는 글루코오스-6-인산 탈수소 효소의 활성을 억제하는 조성물.Composition for inhibiting the activity of glucose-6-phosphate dehydrogenase, characterized in that the fat metabolic disorder is obesity, hyperlipidemia or diabetes.
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014058160A1 (en) * 2012-10-11 2014-04-17 포항공과대학교 산학협력단 Composition comprising myricetin as active ingredient for enhancing exercise performance or fatigue recovery
KR101481041B1 (en) * 2007-11-30 2015-01-12 (주)아모레퍼시픽 Glucose-6-phosphate dehydrogenase inhibitor and a composition for inhibiting differentiation of adipocyte comprising same

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101481041B1 (en) * 2007-11-30 2015-01-12 (주)아모레퍼시픽 Glucose-6-phosphate dehydrogenase inhibitor and a composition for inhibiting differentiation of adipocyte comprising same
WO2014058160A1 (en) * 2012-10-11 2014-04-17 포항공과대학교 산학협력단 Composition comprising myricetin as active ingredient for enhancing exercise performance or fatigue recovery
KR101454425B1 (en) * 2012-10-11 2014-11-03 포항공과대학교 산학협력단 Composition for exercise performance improvement comprising myricetin as active ingredient
CN104755089A (en) * 2012-10-11 2015-07-01 浦项工科大学校产学协力团 Composition comprising myricetin as active ingredient for enhancing exercise performance or fatigue recovery
JP2015535218A (en) * 2012-10-11 2015-12-10 ポステック アカデミー‐インダストリー ファウンデーション Composition for enhancing exercise performance or recovering from fatigue comprising myricetin as an active ingredient
US9675580B2 (en) 2012-10-11 2017-06-13 Kyong-Tai Kim Method of treatment for enhancing exercise performance

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