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    • 1. 发明申请
    • CATECHOLAMINE SURROGATES USEFUL AS 'beta'3 AGONISTS
    • CATECHOLAMINE SURROGATES有用作β3激动剂
    • WO1997037646A1
    • 1997-10-16
    • PCT/US1997005324
    • 1997-04-01
    • BRISTOL-MYERS SQUIBB COMPANY
    • BRISTOL-MYERS SQUIBB COMPANYCHENG, Peter, T., W.BISACCHI, Gregory, S.GAVAI, Ashvinikumar, V.POSS, Kathleen, M.RYONO, Denis, E.SHER, Philip, M.SUN, Chong-QingWASHBURN, William, N.
    • A61K31/18
    • C07C311/46C07C311/08C07C311/39C07D263/32C07D277/28C07F9/4056
    • Compounds of formula (I) and pharmaceutically acceptable salts thereof. As used in formula (I), and throughout the specification, the symbols have the following meanings: R is lower alkyl, aryl or arylalkyl; R is hydrogen, hydroxyl, hydroxymethyl or halogen; R is hydrogen or alkyl; R and R are independently hydrogen, alkoxy, alkoxymethyl, hydroxyl, -CN, -CON(R )R 2 , -N(R )R , -NR COR , -NR SO2R ; or R and R may together with the carbon atoms to which they are bonded form a heterocycle; R , R and R are independently A or B, wherein A is hydrogen, alkyl, cylcoalkyl, halogen, hydroxyl, aryl, alkoxy, cyano, -SR , -SOR , -SO2R , -N(R )R , -NR COR , -OCH2CON(R )R , -OCH2CO2R , CON(R )R , -CO2R ; and B is -(CH2)nN(R )R , -(CH2)mPO(OR )OR , -(CH2)nNR COR , -O-aryl, -OCH2CH2N(R )R , -COR , -SO2N(R )R , -NR CO2R , -NR CO(N(R )R ), heterocycle or -R and R may together with the carbon atoms to which they are bonded form a heterocycle, provided that at least one of R , R and R is B; R and R are independently hydrogen or lower alkyl; R is lower alkyl; R is hydrogen, lower alkyl, aryl or arylalkyl; m is an integer of 0 to 6; and n is an integer of 1 to 6. These compounds are beta three adrenergic receptor agonists and are useful, therefore for example, in the treatment of diabetes, obesity and gastrointestinal diseases.
    • 式(I)化合物及其药学上可接受的盐。 在式(I)中使用,并且在整个说明书中,符号具有以下含义:R 1是低级烷基,芳基或芳基烷基; R 2是氢,羟基,羟甲基或卤素; R 3是氢或烷基; R 4和R 4独立地是氢,烷氧基,烷氧基甲基,羟基,-CN,-CON(R 6)R 6',-CO 2,R 6, R 6)R 6,-NR 6 COR 8,-NR 6 SO 2 R 1; 或R 4和R 4'可以与它们所键合的碳原子一起形成杂环; R 5,R 5和R 5独立地是A或B,其中A是氢,烷基,环烷基,卤素,羟基,芳基,烷氧基,氰基,-SR 7,-SOR -SO 2 R 7,-N(R 6)R 6',-NR 6 COR 8,-OCH 2 CON(R 6)R 6,-OCH 2 CO 2 R CON(R 6)R 6,-CO 2 R 6; 并且B是 - (CH 2)n N(R 6)R 6', - (CH 2)m PO(OR 6)OR 6, - (CH 2)n NR 6 COR 8, -O-芳基,-OCH 2 CH 2 N(R 6)R 6',-COR 7,-SO 2 N(R 6)R 6',-NR 6 CO 2 R 7, NR 6 CO(N(R 6)R 6'),杂环或-R 5和R 5可以与它们所键合的碳原子一起形成杂环,条件是 R 5,R 5'和R 5“中的至少一个是B; R 6和R 6独立地是氢或低级烷基; R 7是低级烷基; R 8是氢,低级烷基,芳基或芳基烷基; m为0〜6的整数。 并且n是1至6的整数。这些化合物是β三肾上腺素能受体激动剂,因此可用于例如糖尿病,肥胖症和胃肠道疾病的治疗。
    • 5. 发明授权
    • BENZAMIDE LIGANDS FOR THE THYROID RECEPTOR
    • 苯甲酰胺配体为甲状腺受体
    • EP1292568B1
    • 2007-08-15
    • EP01946036.9
    • 2001-06-01
    • Bristol-Myers Squibb Company
    • RYONO, Denis, E.
    • C07C235/52A61K31/166
    • A61K31/166C07C235/52C07C2601/02
    • New thyroid receptor ligands are provided which have the general formula (I) in which: X is -0-, -S-, -CH2-, -CO-, or -NH-; R1 is halogen, trifluoromethyl, or alkyl of 1 to 6 carbons or cycloalkyl of 3 to 7 carbons; R2 and R3 are the same or different and are hydrogen, halogen, alkyl of 1 to 4 carbons or cycloalkyl of 3 to 6 carbons, at least one of R2 and R3 being other than hydrogen; R4 is methyl, ethyl, n-propyl or trifluoromethyl; R5 is hydrogen or lower alkyl; R6 is carboxylic acid, or esters or prodrugs; R7 is hydrogen or an alkanoyl or an aroyl. In addition, a method is provided for preventing, inhibiting or treating a disease associated with metabolism dysfunction or which is dependent upon the expression of a T3 regulated gene, wherein a compound as described above is administered in a therapeutically effective amount. Examples of such diseases associated with metabolism dysfunction or are dependent upon the expression of a T3 regulated gene include obesity, hypercholesterolemia, atherosclerosis, cardiac arrhythmias, depression, osteoporosis, hypothyroidism, goiter, thyroid cancer as well as glaucoma, congestive heart failure and skin disorders.
    • 提供了具有通式(I)的新的甲状腺受体配体,其中:X是-O - , - S - , - CH 2 - , - CO-或-NH-; R1为卤素,三氟甲基或1-6个碳原子的烷基或3-7个碳原子的环烷基; R2和R3相同或不同,并且是氢,卤素,1至4个碳的烷基或3至6个碳的环烷基,R2和R3中的至少一个不是氢; R4是甲基,乙基,正丙基或三氟甲基; R5是氢或低级烷基; R6是羧酸,或酯或前药; R7是氢或烷酰基或芳酰基。 另外,提供了用于预防,抑制或治疗与代谢功能障碍相关的疾病或依赖于T3调节基因的表达的方法,其中如上所述的化合物以治疗有效量施用。 与代谢功能障碍相关或与T3调节基因的表达有关的这类疾病的例子包括肥胖症,高胆固醇血症,动脉粥样硬化,心律失常,抑郁症,骨质疏松症,甲状腺功能减退症,甲状腺肿,甲状腺癌以及青光眼,充血性心力衰竭和皮肤病 。