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    • 5. 发明公开
    • 오렉신 수용체 길항제로서의 모노아마이드 유도체
    • 单酰胺衍生物作为OREXIN受体拮抗剂
    • KR1020100039896A
    • 2010-04-16
    • KR1020107004514
    • 2008-07-24
    • 에프. 호프만-라 로슈 아게
    • 크누스트헨너네테코펜마티아스피나르드엠마누엘로슈올리비에로저스-에반스마크
    • C07C233/88C07C235/68A61K31/167A61P25/20
    • C07D405/12C07C233/29C07C235/38C07C235/80C07C237/20C07C237/22C07C251/48C07C255/58C07C255/60C07C271/22C07D205/04C07D207/12C07D209/44C07D211/46C07D213/56C07D231/56C07D235/06C07D235/08C07D235/10C07D235/16C07D235/26C07D277/62C07D305/02C07D305/08C07D307/14C07D307/52C07D307/79C07D317/28C07D317/46C07D317/66C07D319/20C07D333/24C07D471/04C07D487/04C07D491/107
    • The present invention relates to compounds of formula (I), wherein Ar is aryl or heteroaryl; Ris hydrogen, halogen, lower alkyl, lower alkyl substituted by halogen, lower alkoxy, lower alkoxy substituted by halogen, cyano, SO-lower alkyl or hydroxy; Ris hydrogen, halogen, lower alkyl, lower alkyl substituted by halogen, lower alkoxy, lower alkoxy substituted by halogen, cyano, S-lower alkyl, SO-lower alkyl, NOor hydroxy; Ris hydrogen, halogen, lower alkyl, lower alkyl substituted by halogen, lower alkoxy,-(CH)-O-lower alkyl, lower alkoxy substituted by halogen, 3-hydroxy-oxetan-3-yl, cyano or SO-lower alkyl; or if o is 2, Rmay form in 3 and 4 position together with the carbon atoms to which they are attached an addional ring with the groups-O-CH-O-,-O-CF-CF-O-,-N=CH-S-,-O-CF-O-,-(CH)-,-NH-C(O)-NH-,-O-(CH)-or _(CH)-O-; R/Rare independently from each other hydrogen,-(CR'')OH, lower alkyl, lower alkoxy,-NRR', or is-(CH)-heterocycloalkyl, optionally substituted by hydroxy, or Rand Rare together =O or =N-OH,; R/R' are independently from each other hydrogen, lower alkyl, C(O)H,-(CR'')m-OH,-(CR'')m-NR'',-(CR'')-NR''-C(O)-lower alkyl,-(CR'')-O-lower alkyl,-(CR'')-O-lower alkenyl,-C(O)O-lower alkyl,-C(O)-CR''-NH-C(O)O-lower alkyl,-C(O)-CR''-NR'', or is-(CH)-heterocycloalkyl or-(CH)-furan-2-yl; R'' are independently from each other hydrogen, lower alkoxy, phenyl or lower alkyl; n is 1, 2, 3 or 4; o is 1, 2 or 3; p is 1, 2 or 3; m is 1, 2 or 3; or to pharmaceutically suitable acid addition salts, optically pure enantiomers, racemates or diastereomeric mixtures thereof. The compounds of formula (I) may be used for example for the treatment of the sleep disorders, which are sleep apnea, narcolepsy, insomnia, parasomnia, jet lag syndrome, circadian rhythms disorder or sleep disorders associated with neurological diseases.
    • 本发明涉及式(I)化合物,其中Ar为芳基或杂芳基; R 1为氢,卤素,低级烷基,被卤素取代的低级烷基,低级烷氧基,被卤素取代的低级烷氧基,氰基,低级烷基或羟基; R 1为氢,卤素,低级烷基,被卤素取代的低级烷基,低级烷氧基,被卤素取代的低级烷氧基,氰基,S-低级烷基,低级烷基, 卤素,低级烷基,被卤素取代的低级烷基,低级烷氧基, - (CH)-O-低级烷基,被卤素取代的低级烷氧基,3-羟基 - 氧杂环丁烷-3-基,氰基或SO-低级烷基; 或如果o为2,则Rmay与它们所连接的碳原子一起形成3和4位,其中-O-CH-O - , - O-CF-CF-O - , - N = CH-S - , - O-CF-O - , - (CH) - , - NH-C(O)-NH - , - O-(CH) - 或_(CH) R / Rare彼此独立地为氢, - (CR“)OH,低级烷基,低级烷氧基,-NRR'或 - (CH) - 杂环烷基,任选被羟基取代,或者Rare R a一起= O或= N -哦,; R / R'彼此独立地是氢,低级烷基,C(O)H, - (CR“)m -OH, - (CR”)m -NR', - (CR“ -C(O) - 低级烷基, - (CR“)-O-低级烷基, - (CR”)-O-低级烯基,-C(O)O-低级烷基,-C(O) -CR“-NH-C(O)O-低级烷基,-C(O)-CR”-NR“或is-(CH) - 杂环烷基或 - (CH) - 呋喃-2-基; R“彼此独立地为氢,低级烷氧基,苯基或低级烷基; n为1,2,3或4; o是1,2或3; p为1,2或3; m为1,2或3; 或其药学上合适的酸加成盐,旋光纯对映异构体,外消旋体或非对映体混合物。 式(I)的化合物可用于例如睡眠呼吸暂停,发作性睡眠,失眠,睡眠睡眠,时差综合征,昼夜节律障碍或与神经疾病相关的睡眠障碍的睡眠障碍。
    • 7. 发明公开
    • 당뇨병 및 지질 장애의 치료에 사용되는 치환된 카르복시산유도체, 이의 제조 및 용도
    • 用于治疗糖尿病和脂肪障碍的替代性羧酸衍生物,其制备和使用
    • KR1020070119713A
    • 2007-12-20
    • KR1020077025029
    • 2006-03-29
    • 에스케이바이오팜 주식회사
    • 최용문신현우일란쿠마란파라니챠미
    • C07D235/10A61K31/4184A61P3/10
    • C07D235/10
    • A substituted carboxylic acid derivative is provided to reduce glucose, insulin, triglycerides, fatty acids and cholesterol in blood and elevate HDL, thereby being effective for treating and controlling diabetes, obesity, atherosclerosis, vascular inflammation and their related diseases. A carboxylic acid derivative is represented by the formula(1), wherein each R1, R2, R3 and R4 is independently selected from the group consisting of H, hydroxy, halogen, nitro, C1-7 alkyl, -O(C1-7 alkyl), C1-7 haloalkyl, -O(C1-7 haloalkyl), -SO2(C1-7 alkyl), SO2NRaRb, -SO2 phenyl, -SO2(C1-7 alkyl), -C(O)(C1-7 alkyl), -CO phenyl and phenyl; R5 is selected from the group consisting of H, C1-7 alkyl, -O(C1-7 alkyl), -O phenyl, -SO2(C1-7 alkyl), -SO2 phenyl, -C(O)(C1-3 alkyl), -C(O)phenyl, -C(O)O(C1-3 alkyl) and -C(O)NRaRb; each R6 and R6' is independently selected from the group consisting of H, halogen, C1-7 alkyl, C1-7 haloalkyl, -O(C1-7 alkyl), -O(C1-7 haloalkyl), and phenyl; R7 is selected from the group consisting of H, halogen, C1-7 alkyl, C1-7 haloalkyl and phenyl; R8 is selected from the group consisting of H, C1-7 alkyl, C1-7 haloalkyl and phenyl; Ar is a 6-10 membered monocyclic or bicyclic ring system divalent linking group which is unsubstituted or substituted with 1-5 substituents independently selected from the group consisting of halogen, C1-7 alkyl, C1-7 haloalkyl, -O(C1-7 alkyl), O(C1-7 haloalkyl) and phenyl; X is a divalent linking group selected from the group consisting of =O, =CRaRb, =NRa, =CO and =SO2; n is an integer from 1-6; W is selected from the group consisting of hydroxy, -ORc, -NRcRd and -NRcSO2Re; and the asterisk is an asymmetric carbon atom. A method for treating, controlling or preventing at least one diseases selected from the group consisting of non-insulin dependent diabetes mellitus(NIDDM), hyperglycemia, impaired glucose tolerance, insulin resistance, obesity, lipid disorders, dyslipidemia, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, low HDL levels, high LDL levels, atherosclerosis, retinopathy, neuropathy, nephropathy, and syndrome X comprises a step of administering an effective amount of the compound to a subject in need thereof.
    • 提供取代的羧酸衍生物以降低血液中的葡萄糖,胰岛素,甘油三酯,脂肪酸和胆固醇,提高HDL,从而有效治疗和控制糖尿病,肥胖,动脉粥样硬化,血管炎症及其相关疾病。 羧酸衍生物由式(1)表示,其中每个R 1,R 2,R 3和R 4独立地选自H,羟基,卤素,硝基,C 1-7烷基,-O(C 1-7烷基 ),C1-7卤代烷基,-O(C1-7卤代烷基),-SO2(C1-7烷基),SO2NRaRb,-SO2苯基,-SO2(C1-7烷基),-C(O) ),-CO苯基和苯基; R 5选自H,C 1-7烷基,-O(C 1-7烷基), - O苯基,-SO 2(C 1-7烷基),-SO 2苯基,-C(O) 烷基),-C(O)苯基,-C(O)O(C 1-3烷基)和-C(O)NR a R b; 每个R 6和R 6'独立地选自H,卤素,C 1-7烷基,C 1-7卤代烷基,-O(C 1-7烷基), - O(C 1-7卤代烷基)和苯基; R 7选自H,卤素,C 1-7烷基,C 1-7卤代烷基和苯基; R8选自H,C 1-7烷基,C 1-7卤代烷基和苯基; Ar是6-10元单环或双环环系二价连接基团,其未被取代或被1-5个独立地选自以下的取代基取代:卤素,C 1-7烷基,C 1-7卤代烷基,-O(C 1-7 烷基),O(C 1-7卤代烷基)和苯基; X是选自= O,= CRaRb,= NRa,= CO和= SO2的二价连接基团; n是1-6的整数; W选自羟基,-ORc,-NRcRd和-NRcSO2Re; 星号是不对称碳原子。 一种治疗,控制或预防选自非胰岛素依赖性糖尿病(NIDDM),高血糖,葡萄糖耐量异常,胰岛素抵抗,肥胖,脂质障碍,血脂异常,高脂血症,高甘油三酯血症,高胆固醇血症, 低HDL水平,高LDL水平,动脉粥样硬化,视网膜病变,神经病变,肾病和综合征X包括向有需要的受试者施用有效量的化合物的步骤。