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    • 11. 发明申请
    • ARYL SULFONIC ACIDS AND DERIVATIVES AS FSH ANTAGONISTS
    • ARYL SULFONIC酸和衍生物作为FSH拮抗剂
    • WO00058277A1
    • 2000-10-05
    • PCT/US2000/008365
    • 2000-03-29
    • A61P15/16A61P15/18C07C309/51C07C309/76C07C311/29C07C317/44C07C317/48C07D295/13C07D295/26A61K31/167C07D295/12C07D307/16C07D307/54
    • C07D295/26C07C309/51C07C309/76C07C311/29C07C317/44C07C317/48C07D295/13
    • This invention provides compounds of formula (I) having the structure wherein Q is hydrogen or -SO2R ; X is a bond, O, S(O)n, -CH=CH-, -CH2CH2-, -CC-, or -CH2S(O)nCH2-; R is OH, NH2, C1 to C6 alkoxy, C1 to C3 perfluoroalkoxy; Ar is (a) or (b); Ar' is (c) or (d); R and R are each, independently, hydrogen, OR , -S(O)mR , -NHR , -N(R )2, or -CH2SO2CH3; R and R are each, independently, hydrogen, -NO2, -NH2, -SO2R , or -CH2R ; R is hydrogen, C1 to C6 alkyl, C3 to C6 alkenyl, -CH2CH2Z, -CH2COR , -CH2CH=CHCOR , (e), (f) or (g); Y1 and Y are each, independently, N, or CH; Y and Y are each independently, O, S, or NR ; R is -OR , -NHR , -N(R )2, or -NHCH2CH2OR ; Z is -OR8, -OCH2CH2OR , -N(R )2, or (h); R8 is hydrogen or C1 to C3 alkyl; R is C1 to C6 alkyl, C3 to C6 alkenyl, OH, NHR , N(R )2, CH2COR , -CH2CH=CHCOR , or (i); R is C1 to C3 alkyl, C3 to C4 alkenyl, phenyl, -CH2CH2OCH3, or -(j); R is -OR , -NHR , -N(R )2, or -NHCH2CH2OR ; R is hydrogen, or C1 to C3 alkyl; R is hydrogen, or C1 to C3 alkyl; W is a bond, CH2, CH2CH2, O, S(O)q, NCHO, NCOCH3, or NR ; m is 0 - 2; n is 0 - 2; q is 0 - 2, with the proviso that R and R are not both hydrogen; or pharmaceutically acceptable salt thereof, which are useful as contraceptive agents.
    • 本发明提供具有其中Q为氢或-SO 2 R 1的结构的式(I)化合物; X是键,O,S(O)n,-CH = CH-,-CH 2 CH 2 - ,-CC-或-CH 2 S(O)n CH 2 - ; R 1是OH,NH 2,C 1至C 6烷氧基,C 1至C 3全氟烷氧基; Ar是(a)或(b); Ar'是(c)或(d); R 2和R 4各自独立地为氢,OR 6,-S(O)m R 6,-NHR 6,-N(R 6)2或-CH 2 SO 2 CH 3 ; R 3和R 5各自独立地为氢,-NO 2,-NH 2,-SO 2 R 9或-CH 2 R 9; R 6是氢,C 1至C 6烷基,C 3至C 6烯基,-CH 2 CH 2 Z,-CH 2 COR 7,-CH 2 CH = CHCOR 7,(e),(f)或(g) Y 1和Y 3各自独立地为N或CH; Y 2和Y 4各自独立地为O,S或NR 13; R 7是-OR 8,-NHR 8,-N(R 8)2或-NHCH 2 CH 2OR 8; Z是-OR 8,-OCH 2 CH 2OR 8,-N(R 8)2或(h); R8是氢或C1-C3烷基; 或(i); R 9是C 1 -C 6烷基,C 3至C 6烯基,OH,NHR 10,N(R 10)2,CH 2 COR 11,-CH 2 CH = CHCOR 11或。 R 10为C 1至C 3烷基,C 3至C 4烯基,苯基,-CH 2 CH 2 OCH 3或 - (j); R 11是-OR 12,-NHR 12,-N(R 12)2或-NHCH 2 CH 2OR 12; R 12是氢或C 1至C 3烷基; R 13是氢或C 1至C 3烷基; W是键,CH2,CH2CH2,O,S(O)q,NCHO,NCOCH3或NR12; m为0-2; n为0-2; q为0-2,条件是R 2和R 3不同时为氢; 或其药学上可接受的盐,其可用作避孕药。
    • 19. 发明申请
    • NAPHTHALENE UREAS AS GLUCOSE UPTAKE ENHANCERS
    • 作为葡萄糖摄取增强剂的海绵脲
    • WO0071506A9
    • 2001-09-20
    • PCT/US0014644
    • 2000-05-25
    • TELIK INC
    • SPEVAK WAYNELUM ROBERT TSHI SONGYUANMANCHEM PRASADKOZLOWSKI MICHAEL RSCHOW STEVEN R
    • C07D233/32A61K31/18A61K31/216A61K31/255A61K31/41A61K31/4166A61K31/4406A61K31/445A61K31/4965A61K31/505A61K31/662A61P3/10A61P43/00C07B59/00C07C273/00C07C275/42C07C303/22C07C303/30C07C303/38C07C309/51C07C309/58C07C309/76C07C309/88C07C311/21C07C311/47C07C335/16C07C335/18C07C335/32C07D211/60C07D211/96C07D213/76C07D233/36C07D239/42C07D241/20C07D257/04C07F9/40A61K31/395C07D335/18
    • C07D257/04C07C309/51C07C311/47C07C335/16C07C335/18C07C335/32C07D211/96C07D213/76C07D233/36C07D239/42C07D241/20C07F9/4021
    • Compounds of formula (I), wherein R and R are substituents on the A rings and are, independently, -SO2NR 2, -C(O)NR 2, -NR SO2R , -NR C(O)R , -SO2OR , -C(O)OR , -OSO2R , or -OC(O)R , R and R are, independently, hydrogen or lower alkyl, or R and R together are -(CH2)2-, -(CH2)3-, or -(CH2)4-, or R or R may be an electron pair, R and R are, independently, hydrogen, alkyl, substituted alkyl, cyano, halo, nitro, -SR , -C(O)R , -SO2OR , -OSO2R , -SO2NR 2, -NR SO2R , -OC(O)R , -C(O)OR , -C(O)NR 2, -NR C(O)R , -OR , or -NR 2, each R and R is, independently, hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, aryl(lower)alkyl, substituted aryl(lower)alkyl, heteroaryl(lower)alkyl, substituted heteroaryl(lower)alkyl, heterocyclyl, substituted heterocyclyl, heteroaryl, or substituted heteroaryl, each Y is, independently, a non-interfering substituent which is not linked to the naphthalene ring via an azo or amide linkage, each x is independently, 0, 1 or 2, and the linker connects a carbon designated as c to a carbon designated as d, or a pharmaceutically acceptable salt thereof, as a single stereoisomer or mixture of stereoisomers, are useful for treating conditions associated with hyperglycemia, especially Type II diabetes, with dinaphthylureas. These compounds are useful in stimulating the kinase activity of the insulin receptor, activating the insulin receptor, and stimulating the uptake of glucose. Pharmaceutical compositions comprising the antidiabetic compounds are also disclosed.
    • 式(I)化合物,其中R 1和R 2是A环上的取代基,并且独立地是-SO 2 NR 7,-C(O)NR 7,-NR 7 SO 2 R 7,-NR 7 C(O)R 7,-SO 2 OR 7,-C(O)OR 7,-OSO 2 R 7或-OC(O) R 3和R 4独立地是氢或低级烷基,或者R 3和R 4一起是 - (CH 2)2 - , - (CH 2)3 - 或 - ( CH 2)4 - 或R 3或R 4可以是电子对,R 5和R 6独立地是氢,烷基,取代的烷基,氰基,卤素,硝基,-SR 8,-C(O)R 8,-SO 2 OR 8,-OSO 2 R 8,-SO 2 NR 8,-NR 8 SO 2 R 8,-OC(O)R 8 ,-C(O)OR 8,-C(O)NR 8,-NR 8 C(O)R 8,-OR 8或-NR 8 2 ,每个R 7和R 8独立地是氢,烷基,取代的烷基,芳基,取代的芳基,芳基(低级)烷基,取代的芳基(低级)烷基,杂芳基(低级)烷基,取代的杂芳基 )烷基,杂环基,取代的杂环基,杂芳基或取代的杂芳基,每个Y独立地是通过偶氮偶联不与萘环连接的非干扰性取代基 r酰胺键,每个x独立地为0,1或2,并且连接体将指定为c的碳连接到指定为d的碳或其药学上可接受的盐作为单一立体异构体或立体异构体的混合物可用于 治疗与高血糖症相关的病症,特别是II型糖尿病,与二萘基脲。 这些化合物可用于刺激胰岛素受体的激酶活性,激活胰岛素受体,并刺激葡萄糖摄取。 还公开了包含抗糖尿病化合物的药物组合物。
    • 20. 发明申请
    • NOVEL NAPHTHALENE UREAS AS GLUCOSE UPTAKE ENHANCERS
    • 新的海参作为葡萄糖摄取增强剂
    • WO0071506A2
    • 2000-11-30
    • PCT/US0014644
    • 2000-05-25
    • TELIK INC
    • SPEVAK WAYNELUM ROBERT TSHI SONGYUANMANCHEM PRASADKOZLOWSKI MICHAEL RSCHOW STEVEN R
    • C07D233/32A61K31/18A61K31/216A61K31/255A61K31/41A61K31/4166A61K31/4406A61K31/445A61K31/4965A61K31/505A61K31/662A61P3/10A61P43/00C07B59/00C07C273/00C07C275/42C07C303/22C07C303/30C07C303/38C07C309/51C07C309/58C07C309/76C07C309/88C07C311/21C07C311/47C07C335/16C07C335/18C07C335/32C07D211/60C07D211/96C07D213/76C07D233/36C07D239/42C07D241/20C07D257/04C07F9/40C07C309/00
    • C07D257/04C07C309/51C07C311/47C07C335/16C07C335/18C07C335/32C07D211/96C07D213/76C07D233/36C07D239/42C07D241/20C07F9/4021
    • Compounds of formula (I), wherein R and R are substituents on the A rings and are, independently, -SO2NR 2, -C(O)NR 2, -NR SO2R , -NR C(O)R , -SO2OR , -C(O)OR , -OSO2R , or -OC(O)R , R and R are, independently, hydrogen or lower alkyl, or R and R together are -(CH2)2-, -(CH2)3-, or -(CH2)4-, or R or R may be an electron pair, R and R are, independently, hydrogen, alkyl, substituted alkyl, cyano, halo, nitro, -SR , -C(O)R , -SO2OR , -OSO2R , -SO2NR 2, -NR SO2R , -OC(O)R , -C(O)OR , -C(O)NR 2, -NR C(O)R , -OR , or -NR 2, each R and R is, independently, hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, aryl(lower)alkyl, substituted aryl(lower)alkyl, heteroaryl(lower)alkyl, substituted heteroaryl(lower)alkyl, heterocyclyl, substituted heterocyclyl, heteroaryl, or substituted heteroaryl, each Y is, independently, a non-interfering substituent which is not linked to the naphthalene ring via an azo or amide linkage, each x is independently, 0, 1 or 2, and the linker connects a carbon designated as c to a carbon designated as d, and is (a), where K is O, S, or NR*, and R* is H, cyano, or lower alkyl; or (b) or (c), where R* is H or lower alkyl; or (d) or (e), where R* is H, cyano, or lower alkyl; or (f), where R* is cyano or lower alkyl; and, where, if R and R are both -SO2OH, then: i) no Y is -SO2OH; ii) neither R nor R is -SO2OR or -OSO2R ; and iii) R and R are not both selected from the group consisting of hydroxy and hydrogen unless at least one (Y)x is (Y')x' wherein x' is 1 or 2 and Y' is a halo, or a pharmaceutically acceptable salt thereof, as a single stereoisomer or mixture of stereoisomers, are useful for treating conditions associated with hyperglycemia, especially Type II diabetes, with dinaphthylureas. These compounds are useful in stimulating the kinase activity of the insulin receptor, activating the insulin receptor, and stimulating the uptake of glucose. Pharmaceutical compositions comprising the antidiabetic compounds are also disclosed.
    • 式(I)化合物,其中R 1和R 2是A环上的取代基,并且独立地是-SO 2 NR 7,-C(O)NR 7,-NR 7 SO 2 R 7,-NR 7 C(O)R 7,-SO 2 OR 7,-C(O)OR 7,-OSO 2 R 7或-OC(O) R 3和R 4独立地是氢或低级烷基,或者R 3和R 4一起是 - (CH 2)2 - , - (CH 2)3 - 或 - ( CH 2)4 - 或R 3或R 4可以是电子对,R 5和R 6独立地是氢,烷基,取代的烷基,氰基,卤素,硝基,-SR 8,-C(O)R 8,-SO 2 OR 8,-OSO 2 R 8,-SO 2 NR 8,-NR 8 SO 2 R 8,-OC(O)R 8 ,-C(O)OR 8,-C(O)NR 8,-NR 8 C(O)R 8,-OR 8或-NR 8 2 ,每个R 7和R 8独立地是氢,烷基,取代的烷基,芳基,取代的芳基,芳基(低级)烷基,取代的芳基(低级)烷基,杂芳基(低级)烷基,取代的杂芳基 )烷基,杂环基,取代的杂环基,杂芳基或取代的杂芳基,每个Y独立地是通过偶氮偶联不与萘环连接的非干扰性取代基 r酰胺键,每个x独立地为0,1或2,并且连接体将指定为c的碳连接到指定为d的碳上,并且是(a),其中K是O,S或NR *,R *是H,氰基或低级烷基; 或(b)或(c),其中R *为H或低级烷基; 或(d)或(e),其中R *是H,氰基或低级烷基; 或(f),其中R *是氰基或低级烷基; 并且其中,如果R 1和R 2均为-SO 2 OH,则:i)不是Y是-SO 2 OH; ii)R 5和R 6都不是-SO 2 OR 8或-OSO 2 R 8; 和iii)R 5和R 6不均选自羟基和氢,除非至少一个(Y)x为(Y')x',其中x'为1或2,Y'为 作为单一立体异构体或立体异构体混合物的卤素或其药学上可接受的盐可用于治疗与高血糖症,特别是II型糖尿病相关的病症与二萘基脲。 这些化合物可用于刺激胰岛素受体的激酶活性,激活胰岛素受体,并刺激葡萄糖摄取。 还公开了包含抗糖尿病化合物的药物组合物。