公开(公告)号：KR1020130055391A

公开(公告)日：2013-05-28

申请号：KR1020110121111

申请日：2011-11-18

Applicant: 한올바이오파마주식회사

Inventor： 문애리 ,  고민수 ,  민창희 ,  이순임

IPC: C07C279/26 ,  C07C229/08 ,  A61K31/155 ,  A61P35/00

Abstract: PURPOSE: A metformin-gaba salt and the derivatives thereof are provided to have excellent treating effect for metabolic disease and diabetes and to suppress growth of cancer cells by having excellent AMPK activation effect. CONSTITUTION: A metformin-gaba salt and the derivatives thereof are represented by chemical formula 1. A manufacturing method thereof comprises a step of conduct a reaction of metformin hydrochloride represented by chemical formula 2, water, organic solvent, or a mixture solvent under the presence of a base, to manufacture a metformin glass base represented by chemical formula 3; and a step of conducting a reaction of the manufactured metformin glass base and gaba or a derivative thereof represented by chemical formula 4 or chemical formula 5, under the presence of water, organic solvent, or a mixture solvent thereof.

Abstract translation: 目的：提供二甲双胍加巴盐及其衍生物以对代谢疾病和糖尿病具有优异的治疗效果，并通过具有优异的AMPK活化作用抑制癌细胞的生长。 构成：二甲双胍盐酸盐及其衍生物由化学式1表示。其制造方法包括在存在下进行由化学式2表示的二甲双胍盐酸盐，水，有机溶剂或混合溶剂的反应的工序 的碱，制造由化学式3表示的二甲双胍玻璃碱; 以及在水，有机溶剂或其混合溶剂的存在下，通过化学式4或化学式5表示的制造的二甲双胍玻璃基和gaba或其衍生物进行反应的步骤。

公开(公告)号：KR1020130019351A

公开(公告)日：2013-02-26

申请号：KR1020120086999

申请日：2012-08-08

Applicant: 한올바이오파마주식회사

Inventor： 김성욱 ,  민창희 ,  박세환 ,  김용은 ,  김덕 ,  이지선 ,  오주훈

IPC: C07C279/26 ,  A61K31/155 ,  A61P35/00

CPC classification number: C07D211/14 ,  C07D205/04 ,  C07D207/04 ,  C07D207/06 ,  C07D211/06 ,  C07D223/04 ,  C07D257/04 ,  C07D295/14 ,  C07D295/215

Abstract: PURPOSE: A N1-cyclic-amine-N5-sbustituted phenyl bisguanide derivative is provided to have an excellent cancer cell growth by only the small amount and to have excellent blood sugar reducing effect and lipid reducing effect. CONSTITUTION: A N1-cyclic-amine-N5-sbustituted phenyl bisguanide derivative is indicated in chemical formula 1. In chemical formula 1, R1 and R2 form 3-8 membered heterocycloalkyl together with nitrogen connected thereto; n is an integer from 0-5; each of R3 is selected from hydrogen, halogen, hydroxy, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, amino, amide, sulfonamide, nitro, heteroaryl, cyano, sulfonic acid, and sulfamoyl; and R1, R2, or R3 is respectively substituted or unsubstituted by one or more substituents selected from halogen, hydroxy, and C1-6 alkyl.

Abstract translation: 目的：提供N1环状胺-N5取代苯基双胍衍生物，仅通过少量具有优异的癌细胞生长，并且具有优异的降血糖作用和降脂作用。 构成：化学式1中表示了N1环状胺-N5取代的苯基双胍衍生物。在化学式1中，R 1和R 2与连接的氮一起形成3-8元杂环烷基; n是0-5的整数; 每个R 3选自氢，卤素，羟基，C 1-6烷基，C 1-6烷氧基，C 1-6烷硫基，氨基，酰胺，磺酰胺，硝基，杂芳基，氰基，磺酸和氨磺酰基。 R1，R2或R3分别被一个或多个选自卤素，羟基和C 1-6烷基的取代基取代或未取代。

公开(公告)号：KR1020110117758A

公开(公告)日：2011-10-28

申请号：KR1020100037154

申请日：2010-04-22

Applicant: 한올바이오파마주식회사

Inventor： 김성욱 ,  전성수 ,  민창희 ,  구자성 ,  이상주 ,  이길호

IPC: A61K9/22 ,  A61K9/20 ,  A61K47/38 ,  A61K47/34

CPC classification number: A61K9/28 ,  A61K47/34 ,  A61K47/38

Abstract: 본 발명은 약리학적 활성성분으로 베타 아드레날린 차단제를 포함하는 선방출성 구획, 및 약리학적 활성성분으로 HMG-CoA 환원효소 억제제를 포함하는 지연방출성 구획을 포함하는 약제학적 제제를 제공한다. 본 발명의 약제학적 제제는 고지혈증, 관상 동맥 질환 등이 복합적으로 나타나는 고혈압 환자들의 치료와 합병증 예방에 유용하고, 약물간 상호작용에 따른 부작용 감소에 효과적이다.

公开(公告)号：KR1020110081095A

公开(公告)日：2011-07-13

申请号：KR1020110001442

申请日：2011-01-06

Applicant: 한올바이오파마주식회사

Inventor： 김성욱 ,  전성수 ,  민창희 ,  박세환 ,  김용은 ,  김덕 ,  이지선 ,  오주훈

IPC: C07C279/26 ,  C07C277/00 ,  A61K31/155 ,  A61P3/10

CPC classification number: A61K31/155 ,  A61K31/341 ,  A61K31/4406 ,  A61K31/472 ,  C07C277/04 ,  C07C279/04 ,  C07C279/06 ,  C07C279/08 ,  C07C279/16 ,  C07C279/18 ,  C07C279/26 ,  C07C2601/08 ,  C07C2601/14 ,  C07C2601/18 ,  C07C2603/74 ,  C07D213/38 ,  C07D307/52 ,  C07D317/58 ,  C07D333/20

Abstract: PURPOSE: Biguanide derivatives are provided to ensure an excellent AMPKa activation effect and inhibitory effect of cancer cell proliferation in a small amount and to enable the use for the treatment of diabetes, obesity, hyperlipidemia, hypercholesterolemia, fatty liver, coronary artery disease, osteoporosis, polycystic ovarian syndrome, metabolic syndrome, cancer and the like. CONSTITUTION: Biguanide derivatives are a compound of chemical formula 1 or pharmaceutically acceptable salts thereof. In chemical formula 1, R1, R2, and R3 represent hydrogen or non-halogen substituents selected from the group consisting of substituted or unsubstituted C1-12 alkyl, C1-12 alkoxy, C2-4 alkenyl, C3-10 cycloalkyl, hydroxyl, halogen, C5-12 aryl and C5-12 heteroaryl, wherein the C1-12 alkyl may be substituted with one or more nonhydrogen substituents selected from the group consisting of C5-12 aryl, C5-12 heteroaryl, C3-10 cycloalkyl, hydroxy and halogen.

Abstract translation: 目的：提供双胍衍生物，以确保少量的AMPKa活化作用和癌细胞增殖的抑制作用，并可用于治疗糖尿病，肥胖，高脂血症，高胆固醇血症，脂肪肝，冠状动脉疾病，骨质疏松症， 多囊卵巢综合征，代谢综合征，癌症等。 组分：双胍衍生物是化学式1的化合物或其药学上可接受的盐。 在化学式1中，R 1，R 2和R 3表示选自取代或未取代的C 1-12烷基，C 1-12烷氧基，C 2-4烯基，C 3-10环烷基，羟基，卤素 C 5-12芳基和C 5-12杂芳基，其中C 1-12烷基可以被一个或多个选自C 5-12芳基，C 5-12杂芳基，C 3-10环烷基，羟基和卤素的非氢取代基取代 。

公开(公告)号：KR1020110007985A

公开(公告)日：2011-01-25

申请号：KR1020100069244

申请日：2010-07-16

Applicant: 한올바이오파마주식회사

Inventor： 김성욱 ,  전성수 ,  민창희 ,  구자성 ,  강민석 ,  김용은

IPC: C07C279/26 ,  C07C277/00 ,  A61K31/155 ,  A61P3/10

CPC classification number: A61K31/155 ,  C07C53/124 ,  C07C279/26

Abstract: PURPOSE: N,N-dimethyl imidodicarbonimidic diamide butyrate is provided to ensure excellent physicochemical properties such as solubility, stability, hygroscopicity and adsorption preventing property, processibility of formulations. CONSTITUTION: A metformin butyrate is represented by chemical formula 1. The metformin butyrate has a crystal form. A melting point of the crystal form is 162°C. A method for preparing the metformin butyrate represented by chemical formula 1 comprises the steps of: reacting metformin hydrochloride represented by chemical formula 2 with base in an organic solvent to prepare metformin free base represented by chemical formula 3; and reacting the metformin free base with butyric acids.

Abstract translation: 目的：提供N，N-二甲基亚氨基二酰亚胺二酰胺丁酸酯，以确保优异的物理化学性质，如溶解度，稳定性，吸湿性和吸附防止性能，配方的加工性。 构成：二甲双胍丁酸酯由化学式1表示。二甲双胍丁酸酯具有晶体形式。 晶体的熔点为162℃。 由化学式1表示的制备丁酸二甲双胍的方法包括以下步骤：将由化学式2表示的二甲双胍盐酸盐与碱在有机溶剂中反应制备由化学式3表示的游离二甲双胍碱; 并使二甲双胍游离碱与丁酸反应。

公开(公告)号：KR101424667B1

公开(公告)日：2014-08-04

申请号：KR1020120086997

申请日：2012-08-08

Applicant: 한올바이오파마주식회사

Inventor： 김성욱 ,  민창희 ,  박세환 ,  김용은 ,  김덕 ,  이지선 ,  오주훈

IPC: C07C279/26 ,  A61K31/155 ,  A61P35/00

CPC classification number: C07D307/52 ,  C07D295/215 ,  C07D333/20

Abstract: 본 발명은 하기 화학식 1로 표시되는 N1-고리아민-N2-치환된 바이구아나이드 유도체 또는 그의 약학적으로 허용가능한 염, 이의 제조방법 및 이를 유효성분으로 하는 약학 조성물을 제공한다. 본 발명의 바이구아나이드 유도체는 기존 약물에 비해 적은 복용량으로도 에너지 대사 조절에 관여하는 AMPK가 우수한 활성화 효과를 나타냄으로써, 암세포 증식 억제 효과 및 암의 재발과 전이를 포함하는 항암 작용 효과를 나타낸다. 또한, AMPK 활성화는 우수한 혈당 강하 작용과 지질 저하 작용을 나타내어 당뇨, 비만, 고지혈증, 고콜레스테롤혈증, 지방간, 관상동맥질환, 골다공증, 다낭성 난소증후군 및 대사성 증후군 등의 치료를 위해 유용하게 이용될 수 있다.

[화학식 1]

公开(公告)号：KR101275258B1

公开(公告)日：2013-06-17

申请号：KR1020110057664

申请日：2011-06-14

Applicant: 한올바이오파마주식회사

Inventor： 김성욱 ,  전성수 ,  민창희 ,  구자성 ,  김진욱 ,  김용은 ,  선상욱

IPC: A61K31/155 ,  A61K31/70 ,  A61P3/10 ,  A61P35/00

CPC classification number: A61K31/7004 ,  A61K9/2031 ,  A61K9/2054 ,  A61K9/209 ,  A61K9/2866 ,  A61K9/4866 ,  A61K9/5084 ,  A61K31/155 ,  A61K31/506 ,  A61K45/06 ,  A61K2300/00

Abstract: 본 발명은 펜포르민 또는 그의 약제학적으로 허용 가능한 염과, 2-데옥시-D-글루코스를 활성 성분으로 포함하고, 항암 활성을 나타내는 약제학적 조성물에 관한 것이다. 이러한 약제학적 조성물은 각 활성 성분들간의 상승 작용을 통해 각각의 단일 활성 성분만을 사용하였을 경우에 비하여 훨씬 우수한 항암 효과를 나타냄과 동시에, 투여량이 감소되어 약물에 따른 부작용을 감소시킬 수 있다. 또한, 본 발명은 활성성분의 시간차 방출 또는 시간차 투여를 통해 펜포르민에 의한 유산산증과 같은 부작용을 현저히 감소시킬 수 있다. 특히 본 발명에 따른 약제학적 조성물은 환자의 복약 순응도 또한 상승하여, 각종 암을 치료하는데 매우 유용하게 사용될 수 있다.

公开(公告)号：KR1020130018623A

公开(公告)日：2013-02-25

申请号：KR1020120086997

申请日：2012-08-08

Applicant: 한올바이오파마주식회사

Inventor： 김성욱 ,  민창희 ,  박세환 ,  김용은 ,  김덕 ,  이지선 ,  오주훈

IPC: C07C279/26 ,  A61K31/155 ,  A61P35/00

CPC classification number: C07D307/52 ,  C07D295/215 ,  C07D333/20

Abstract: PURPOSE: An N1-cyclic amine-N5-substitued biguanide derivative is provided to have excellent cancer cell depressing effect by a smaller amount than conventional drugs and to have excellent lipid lower effect and excellent blood sugar reducing effect. CONSTITUTION: A compound indicated in chemical formula 1. In chemical formula 1, In chemical formula 1, R1 and R2 form a 3-8 membered heterocycloalkyl together with connected nitrogen thereto; R3 is a C3-7 cycloalkyl, C1-12 alkyl substituted or unsubstituted by C3-12 aryl or C3-12 heteroaryl, or C3-12 aryl. The 3-8 membered heterocycloalkyl, C3-12 aryl or C3-12 heteroaryl is substituted or unsubstituted by one or more non-hydrogen substituent which is selected from halogen, C1-4 alkyl, and C1-4 alkoxy.

Abstract translation: 目的：提供N1环胺-N5取代的双胍衍生物，其具有比常规药物更小量的优异的癌细胞抑制作用，并且具有优异的低脂效果和优异的降血糖作用。 化学式1中化学式1中，R1和R2与连接的氮一起形成3-8元杂环烷基; R 3是C 3-7环烷基，被C 3-12芳基或C 3-12杂芳基或C 3-12芳基取代或未取代的C 1-12烷基。 3-8元杂环烷基，C3-12芳基或C3-12杂芳基被一个或多个选自卤素，C 1-4烷基和C 1-4烷氧基的非氢取代基取代或未取代。

公开(公告)号：KR1020130018622A

公开(公告)日：2013-02-25

申请号：KR1020120086996

申请日：2012-08-08

Applicant: 한올바이오파마주식회사

Inventor： 김성욱 ,  민창희 ,  박세환 ,  김용은 ,  김덕 ,  이지선 ,  오주훈

IPC: C07C279/26 ,  A61K31/155 ,  A61P35/00

CPC classification number: C07D295/215 ,  C07D205/04 ,  C07D213/40 ,  C07D307/52 ,  C07D333/20

Abstract: PURPOSE: An N1-cyclic amine-N5-substitued biguanide derivative is provided to have excellent cancer cell depressing effect by a smaller amount than conventional drugs. CONSTITUTION: An N1-cyclic amine-N5-substitued biguanide derivative is indicated in chemical formula 1. In chemical formula 1, R1 and R2 form a 3-8 membered heterocycloalkyl together with connected nitrogen thereto; R3 is a C3-7 cycloalkyl or C1-12 alkyl substituted or unsubstituted by C3-12 aryl or C3-12 heteroaryl. The C3-7 cycloalkyl, 3-8 membered heterocycloalkyl, C3-12 aryl or C3-12 heteroaryl is substituted or unsubstituted by one or more non-hydrogen substituent which is selected from halogen, C1-4 alkyl, and C1-4 alkoxy. The non-hydrogen substituent is additionally substituted or unsubstituted by halogen.

Abstract translation: 目的：提供一种N1环胺-N5取代的双胍衍生物，具有比常规药物更小量的癌细胞抑制作用。 构成：化学式1中表示了N1环胺-N5取代的双胍衍生物。在化学式1中，R 1和R 2与连接的氮一起形成3-8元杂环烷基; R3是被C3-12芳基或C3-12杂芳基取代或未取代的C3-7环烷基或C1-12烷基。 C3-7环烷基，3-8元杂环烷基，C3-12芳基或C3-12杂芳基被一个或多个选自卤素，C 1-4烷基和C 1-4烷氧基的非氢取代基取代或未取代。 非氢取代基另外被卤素取代或未被取代。

公开(公告)号：KR1020120065308A

公开(公告)日：2012-06-20

申请号：KR1020120059607

申请日：2012-06-04

Applicant: 한올바이오파마주식회사

Inventor： 김성욱 ,  전성수 ,  민창희 ,  구자성 ,  강민석 ,  김용은

IPC: C07C279/26 ,  C07C309/02 ,  A61K31/145 ,  A61P3/08

CPC classification number: C07C309/04 ,  C07C279/26

Abstract: PURPOSE: A pharmaceutical composition containing metformin methanesulfonate salt is provided to have an excellent AMPKα activity and to increase pharmaceutical and physical advantages including solubility, stability, and non-hygroscopic property. CONSTITUTION: A pharmaceutical composition contains metformin methanesulfonate as an active ingredient. The metformin methanesulfonate has a structure represented by chemical formula 1. A melting point of the metformin methanesulfonate is 194.0-194.5 deg. Celsius. A pharmaceutical composition is effective for preventing or treating diabetes, metabolic syndrome, diabetic complication, menstrual irregularity, hypertension, fatty liver, coronary artery disease, osteoporosis, polycystic ovary syndrome, cancer, muscle pain, rhabdomyolysis, and/or menopausal syndrome.

Abstract translation: 目的：提供含有二甲双胍甲磺酸盐的药物组合物以具有优异的AMPKα活性并增加药物和物理优点，包括溶解性，稳定性和非吸湿性。 构成：药物组合物含有作为活性成分的甲磺酸二甲双胍。 二甲双胍甲磺酸盐具有由化学式1表示的结构。甲磺酸二甲双胍的熔点为194.0-194.5℃。 摄氏度。 药物组合物可有效预防或治疗糖尿病，代谢综合征，糖尿病并发症，月经不规则，高血压，脂肪肝，冠状动脉疾病，骨质疏松症，多囊卵巢综合症，癌症，肌肉疼痛，横纹肌溶解症和/或绝经综合征。