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1. 发明申请

US20100298276A1 THYROID RECEPTOR LIGANDS 失效
公开(公告)号：US20100298276A1
公开(公告)日：2010-11-25
申请号：US12469791
申请日：2009-05-21
申请人： Denis E. Ryono , Jon J. Hangeland , Todd J. Friends , Tamara Dejneka , Pratik Devasthale , Yolanda V. Caringal , Minsheng Zhang , Arthur M.P. Doweyko , Johan Malm , Andrei Sanin
发明人： Denis E. Ryono , Jon J. Hangeland , Todd J. Friends , Tamara Dejneka , Pratik Devasthale , Yolanda V. Caringal , Minsheng Zhang , Arthur M.P. Doweyko , Johan Malm , Andrei Sanin
IPC分类号： A61K31/662 , C07F9/02 , A61P3/10
CPC分类号： C07C311/46 , A61K31/4439 , A61K31/662 , A61K45/06 , C07C43/29 , C07C43/295 , C07C59/68 , C07C59/72 , C07C65/24 , C07C65/26 , C07C69/16 , C07C69/736 , C07C69/94 , C07C205/38 , C07C217/58 , C07C233/29 , C07C235/34 , C07C235/42 , C07C235/46 , C07C235/52 , C07C235/60 , C07C235/62 , C07C235/64 , C07C311/37 , C07C2601/02 , C07C2601/14 , C07C2602/08 , C07C2603/18 , C07D213/30 , C07D239/26 , C07D257/04 , C07D263/14 , C07D263/32 , C07D277/24 , C07D285/06 , C07D307/42 , C07D307/52 , C07D307/87 , C07D317/58 , C07D317/60 , C07D333/32 , C07F9/306 , C07F9/3241 , C07F9/4056 , A61K2300/00
摘要： Thyroid receptor ligands are provided which have the general formula I wherein: R1 is R2 and R3 are the same or different and are hydrogen, halogen, alkyl of 1 to 4 carbons or cycloalkyl of 3 to 5 carbons, provided that at least one of R2 and R3 is other than hydrogen; R4 is R5 and R6 are the same or different and are selected from hydrogen, aryl, heteroaryl, alkyl, cycloalkyl, aralkyl or heteroaralkyl. R7 is aryl, heteroaryl, alkyl, aralkyl, or heteroaralkyl; R8 is aryl, heteroaryl, or cycloalkyl; R9 is R7 or hydrogen; R10 is hydrogen, halogen, cyano or alkyl; R11 and R12 are each independently selected from the group consisting of hydrogen, halogen, alkoxy, hydroxy (—OH) cyano, and alkyl; R13 is carboxylic acid (COOH) or esters thereof, phosphonic and phosphinic acid or esters thereof, sulfonic acid, tetrazole, hydroxamic acid, thiazolidinedione, acylsulfonamide, or other carboxylic acid surrogates known in the art; R14 and R15 may be the same or different and are selected from hydrogen and alkyl, or R14 and R15 may be joined together forming a chain of 2 to 5 methylene groups [—(CH2)m-, m=2, 3, 4 or 5], thus forming 3- to 6-membered cycloalkyl rings; R16 is hydrogen or alkyl of 1 to 4 carbons; R17 and R18 are the same or different and selected from hydrogen, halogen and alkyl; n is 0 or an integer from 1 to 4; X is oxygen (—O—), sulfur (—S—), sulfonyl (—SO2—), sulfenyl (—SO—) selenium (—Se—), carbonyl (—CO—), amino (—NH—) or methylene (—CH2-); wherein the substituents are as described herein. In addition, a method is provided for preventing, inhibiting or treating diseases or disorders associated with metabolism dysfunction or which are dependent upon the expression of a T3 regulated gene, wherein a compound as described above is administered in a therapeutically effective amount.

2. 发明授权

US08263659B2 Thyroid receptor ligands 失效
标题翻译：甲状腺受体配体
公开(公告)号：US08263659B2
公开(公告)日：2012-09-11
申请号：US12469791
申请日：2009-05-21
申请人： Denis E. Ryono , Jon J. Hangeland , Todd J. Friends , Tamara Dejneka , Pratik Devasthale , Yolanda V. Caringal , Minsheng Zhang , Arthur M. P. Doweyko , Johan Malm , Andrei Sanin
发明人： Denis E. Ryono , Jon J. Hangeland , Todd J. Friends , Tamara Dejneka , Pratik Devasthale , Yolanda V. Caringal , Minsheng Zhang , Arthur M. P. Doweyko , Johan Malm , Andrei Sanin
IPC分类号： A61K31/19 , A61K31/165 , C07C321/00 , C07C229/00 , C07C59/00
CPC分类号： C07C311/46 , A61K31/4439 , A61K31/662 , A61K45/06 , C07C43/29 , C07C43/295 , C07C59/68 , C07C59/72 , C07C65/24 , C07C65/26 , C07C69/16 , C07C69/736 , C07C69/94 , C07C205/38 , C07C217/58 , C07C233/29 , C07C235/34 , C07C235/42 , C07C235/46 , C07C235/52 , C07C235/60 , C07C235/62 , C07C235/64 , C07C311/37 , C07C2601/02 , C07C2601/14 , C07C2602/08 , C07C2603/18 , C07D213/30 , C07D239/26 , C07D257/04 , C07D263/14 , C07D263/32 , C07D277/24 , C07D285/06 , C07D307/42 , C07D307/52 , C07D307/87 , C07D317/58 , C07D317/60 , C07D333/32 , C07F9/306 , C07F9/3241 , C07F9/4056 , A61K2300/00
摘要： A method is provided for preventing, inhibiting or treating diseases or disorders associated with metabolism dysfunction or which are dependent upon the expression of a T3 regulated gene, wherein a compound as described in the general formula I below is administered in a therapeutically effective amount:
摘要翻译：提供了一种用于预防，抑制或治疗与代谢功能障碍相关或与T3调节基因的表达有关的疾病或病症的方法，其中以治疗有效量施用下述通式I中所述的化合物：

3. 发明授权

US07557143B2 Thyroid receptor ligands 失效
标题翻译：甲状腺受体配体
公开(公告)号：US07557143B2
公开(公告)日：2009-07-07
申请号：US10826100
申请日：2004-04-15
申请人： Denis E. Ryono , Jon J. Hangeland , Todd J. Friends , Tamara Dejneka , Pratik Devasthale , Yolanda V. Caringal , Minsheng Zhang , Arthur M. P. Doweyko , Johan Malm , Andrei Sanin
发明人： Denis E. Ryono , Jon J. Hangeland , Todd J. Friends , Tamara Dejneka , Pratik Devasthale , Yolanda V. Caringal , Minsheng Zhang , Arthur M. P. Doweyko , Johan Malm , Andrei Sanin
IPC分类号： A61K31/165 , A61K31/19 , C07C239/00 , C07C325/00 , C07C229/00 , C07C59/00
CPC分类号： C07C311/46 , A61K31/4439 , A61K31/662 , A61K45/06 , C07C43/29 , C07C43/295 , C07C59/68 , C07C59/72 , C07C65/24 , C07C65/26 , C07C69/16 , C07C69/736 , C07C69/94 , C07C205/38 , C07C217/58 , C07C233/29 , C07C235/34 , C07C235/42 , C07C235/46 , C07C235/52 , C07C235/60 , C07C235/62 , C07C235/64 , C07C311/37 , C07C2601/02 , C07C2601/14 , C07C2602/08 , C07C2603/18 , C07D213/30 , C07D239/26 , C07D257/04 , C07D263/14 , C07D263/32 , C07D277/24 , C07D285/06 , C07D307/42 , C07D307/52 , C07D307/87 , C07D317/58 , C07D317/60 , C07D333/32 , C07F9/306 , C07F9/3241 , C07F9/4056 , A61K2300/00
摘要： Thyroid receptor ligands are provided which have the general formula I wherein: R1 is R2 and R3 are the same or different and are hydrogen, halogen, alkyl of 1 to 4 carbons or cycloalkyl of 3 to 5 carbons, provided that at least one of R2 and R3 is other than hydrogen; R4 is R5 and R6 are the same or different and are selected from hydrogen, aryl, heteroaryl, alkyl, cycloalkyl, aralkyl or heteroaralkyl. R7 is aryl, heteroaryl, alkyl, aralkyl, or heteroaralkyl; R8 is aryl, heteroaryl, or cycloalkyl; R9 is R7 or hydrogen; R10 is hydrogen, halogen, cyano or alkyl; R11 and R12 are each independently selected from the group consisting of hydrogen, halogen, alkoxy, hydroxy (—OH) cyano, and alkyl; R13 is carboxylic acid (COOH) or esters thereof, phosphonic and phosphinic acid or esters thereof, sulfonic acid, tetrazole, hydroxamic acid, thiazolidinedione, acylsulfonamide, or other carboxylic acid surrogates known in the art; R14 and R15 may be the same or different and are selected from hydrogen and alkyl, or R14 and R15 may be joined together forming a chain of 2 to 5 methylene groups [—(CH2)m-, m=2, 3, 4 or 5], thus forming 3- to 6-membered cycloalkyl rings; R16 is hydrogen or alkyl of 1 to 4 carbons; R17 and R18 are the same or different and selected from hydrogen, halogen and alkyl; n is 0 or an integer from 1 to 4; X is oxygen (—O—), sulfur (—S—), sulfonyl (—SO2—), sulfenyl (—SO—) selenium (—Se—), carbonyl (—CO—), amino (—NH—) or methylene (—CH2-); wherein the substituents are as described herein. In addition, a method is provided for preventing, inhibiting or treating diseases or disorders associated with metabolism dysfunction or which are dependent upon the expression of a T3 regulated gene, wherein a compound as described above is administered in a therapeutically effective amount.
摘要翻译：提供具有通式I的甲状腺受体配体，其中：R 1是R 2和R 3相同或不同，是氢，卤素，1至4个碳的烷基或3至5个碳原子的环烷基，条件是R2中的至少一个并且R 3不是氢; R 4是R 5和R 6相同或不同，并且选自氢，芳基，杂芳基，烷基，环烷基，芳烷基或杂芳烷基。 R7是芳基，杂芳基，烷基，芳烷基或杂芳烷基; R8是芳基，杂芳基或环烷基; R9为R7或氢; R 10是氢，卤素，氰基或烷基; R 11和R 12各自独立地选自氢，卤素，烷氧基，羟基（-OH）氰基和烷基; R13是羧酸（COOH）或其酯，膦酸和次膦酸或其酯，磺酸，四唑，异羟肟酸，噻唑烷二酮，酰基磺酰胺或本领域已知的其它羧酸替代物; R 14和R 15可以相同或不同，并且选自氢和烷基，或者R 14和R 15可以连接在一起形成2至5个亚甲基 - [ - （CH 2）m - ，m = 2,3,4或 5]，从而形成3-至6-元环烷基环; R16是氢或1至4个碳的烷基; R 17和R 18相同或不同，选自氢，卤素和烷基; n为0或1至4的整数; X是氧（-O-），硫（-S-），磺酰基（-SO 2 - ），亚磺酰基（-SO-），硒（-Se-），羰基（-CO-），氨基（-NH-）或亚甲基（-CH2-）; 其中取代基如本文所述。此外，提供了一种用于预防，抑制或治疗与代谢功能障碍相关或依赖于T3调节基因的表达的疾病或病症的方法，其中如上所述的化合物以治疗有效量施用。

4. 发明授权

US07109164B2 Aniline-derived ligands for the thyroid receptor 有权
标题翻译：苯胺衍生的甲状腺受体配体
公开(公告)号：US07109164B2
公开(公告)日：2006-09-19
申请号：US10930360
申请日：2004-08-30
申请人： Todd J. Friends , Denis E. Ryono , Minsheng Zhang
发明人： Todd J. Friends , Denis E. Ryono , Minsheng Zhang
IPC分类号： C07C37/00
CPC分类号： C07C233/27 , A61K31/167 , A61K45/06 , C07C233/25 , A61K2300/00
摘要： New thyroid receptor ligands are provided which have the general formula in which: X is —O—, —S—, —CH2—, —CO—, or —NH—; Y is —(CH2)n— where n is an integer from 1 to 5, or cis- or trans-ethylene; 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 hydrogen or lower alkyl; 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.
摘要翻译：提供了新的甲状腺受体配体，其具有以下通式：其中：X是-O - ， - S - ， - CH 2 - ， - CO-或-NH-; Y是 - （CH 2 CH 2）n - 其中n是1至5的整数，或顺式或反式 - 亚乙基; R 1是卤素，三氟甲基或1至6个碳的烷基或3至7个碳的环烷基; R 2和R 3相同或不同，为氢，卤素，1至4个碳的烷基或3至6个碳的环烷基，R 1， SUB 2和R 3不是氢; R 4是氢或低级烷基; R 5是氢或低级烷基; R 6是羧酸，或酯或前药; R 7是氢或烷酰基或芳酰基。此外，提供了一种用于预防，抑制或治疗与代谢功能障碍相关的疾病或依赖于T 3 N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。与代谢功能障碍相关或依赖于T 3受体基因表达的这种疾病的实例包括肥胖症，高胆固醇血症，动脉粥样硬化，心律失常，抑郁症，骨质疏松症，甲状腺机能减退，甲状腺肿，甲状腺癌以及青光眼，充血性心力衰竭和皮肤疾病。

5. 发明授权

US06800605B1 Aniline-derived ligands for the thyroid receptor 有权
标题翻译：苯胺衍生的甲状腺受体配体
公开(公告)号：US06800605B1
公开(公告)日：2004-10-05
申请号：US09761050
申请日：2001-01-16
申请人： Todd J. Friends , Denis E. Ryono , Minsheng Zhang
发明人： Todd J. Friends , Denis E. Ryono , Minsheng Zhang
IPC分类号： C07C3700
CPC分类号： C07C233/27 , A61K31/167 , A61K45/06 , C07C233/25 , A61K2300/00
摘要： New thyroid receptor ligands are provided which have the general formula in which: X is —O—, —S—, —CH2—, —CO—, or —NH—; Y is —(CH2)n— where n is an integer from 1 to 5, or cis- or trans-ethylene; 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 hydrogen or lower alkyl; 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.
摘要翻译：提供了新的甲状腺受体配体，其具有以下通式：X是-O-，-S-，-CH 2 - ， - CO-或-NH-; Y是 - （CH 2）n - ，其中n是 1至5，或顺式或反式 - 亚乙基; R 1为卤素，三氟甲基，或1至6个碳原子的烷基或3至7个碳的环烷基; R 2和R 3相同或不同，为氢，卤素，至4个碳或3至6个碳的环烷基，R2和R3中的至少一个不是氢; R4是氢或低级烷基; 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。此外，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取决于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。与代谢功能障碍相关或依赖于T3调节基因的表达的这种疾病的实例包括肥胖症，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，甲状腺癌，青光眼，充血性心力衰竭和皮肤病。

6. 发明授权

US07342127B2 Substituted anilide ligands for the thyroid receptor 有权
标题翻译：用于甲状腺受体的取代苯胺配体
公开(公告)号：US07342127B2
公开(公告)日：2008-03-11
申请号：US10763878
申请日：2004-01-23
申请人： William N. Washburn , Wei Meng , Denis E. Ryono , Bruce A. Ellsworth , Thomas Ericsson , Mahmoud Rahimi-Ghadim , Neeraj Garg , Johan Malm
发明人： William N. Washburn , Wei Meng , Denis E. Ryono , Bruce A. Ellsworth , Thomas Ericsson , Mahmoud Rahimi-Ghadim , Neeraj Garg , Johan Malm
IPC分类号： C07C54/00 , C07C315/00 , C07C229/00 , A01N37/12
CPC分类号： A61K45/06 , A61K31/195 , A61K31/277 , A61K31/44 , C07C233/25 , A61K2300/00
摘要： Novel thyroid receptor ligands are provided having the general formula I wherein X, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12 and R13 are as defined herein. In addition, a method is provided for preventing, inhibiting or treating diseases or disorders associated with metabolic dysfunction or which are dependent upon the expression of a T3 regulated gene, wherein a compound as described above is administered in a therapeutically effective amount.
摘要翻译：提供了具有通式I的新型甲状腺受体配体，其中X，R 1，R 2，R 3，R 4， R 5，R 6，R 7，R 8，R 9， R 11，R 11，R 12和R 13如本文所定义。此外，提供了一种用于预防，抑制或治疗与代谢功能障碍相关的疾病或病症或依赖于T 3 N调节基因的表达的方法，其中将如上所述的化合物施用于治疗有效量。

7. 发明申请

US20100324071A1 NOVEL GLUCOKINASE ACTIVATORS AND METHODS OF USING SAME 有权
标题翻译：新型GLUCOKINASE激活剂及其使用方法
公开(公告)号：US20100324071A1
公开(公告)日：2010-12-23
申请号：US12871226
申请日：2010-08-30
申请人： Yan Shi , Peter T. W. Cheng , Ying Wang , Denis E. Ryono
发明人： Yan Shi , Peter T. W. Cheng , Ying Wang , Denis E. Ryono
IPC分类号： A61K31/428 , C07D277/56 , C07D213/81 , C07D241/24 , C07D231/14 , C07D277/68 , C07D233/90 , C07D249/10 , A61K31/426 , A61K31/4402 , A61K31/4965 , A61K31/415 , A61K31/4164 , A61K31/4196 , A61P3/10 , A61P9/10 , A61P3/06 , A61P3/04 , A61P9/12 , A61P35/00 , A61P25/28 , A61P19/08 , A61P27/06
CPC分类号： C07D277/56 , C07C317/22 , C07D213/81 , C07D231/14 , C07D233/90 , C07D241/24 , C07D249/10 , C07D277/68 , C07D471/04 , C07D513/04
摘要： Compounds are provided which are activators of the enzyme glucokinase and thus are useful in treating diabetes and related diseases, which compounds have the structure where Q is and R1, R2, R3, R4, R5, R6, R7 and R8 are as defined herein or a pharmaceutically acceptable salt thereof. A method for treating diabetes and related diseases employing the above compounds is also provided.
摘要翻译：提供了作为葡糖激酶酶的激活剂的化合物，因此可用于治疗糖尿病和相关疾病，该化合物具有Q为结构，R 1，R 2，R 3，R 4，R 5，R 6，R 7和R 8如本文所定义或其药学上可接受的盐。还提供了使用上述化合物治疗糖尿病和相关疾病的方法。

8. 发明授权

US07812048B2 Glucokinase activators and methods of using same 有权
标题翻译：葡糖激酶活化剂及其使用方法
公开(公告)号：US07812048B2
公开(公告)日：2010-10-12
申请号：US12179648
申请日：2008-07-25
申请人： Yan Shi , Peter T. W. Cheng , Ying Wang , Denis E. Ryono
发明人： Yan Shi , Peter T. W. Cheng , Ying Wang , Denis E. Ryono
IPC分类号： C07D233/90 , A61K31/4164
CPC分类号： C07D277/56 , C07C317/22 , C07D213/81 , C07D231/14 , C07D233/90 , C07D241/24 , C07D249/10 , C07D277/68 , C07D471/04 , C07D513/04
摘要： Compounds are provided which are activators of the enzyme glucokinase and thus are useful in treating diabetes and related diseases, which compounds have the structure where Q is and R1, R2, R3, R4, R5, R6, R7 and R8 are as defined herein or a pharmaceutically acceptable salt thereof. A method for treating diabetes and related diseases employing the above compounds is also provided.
摘要翻译：提供了作为葡糖激酶酶的激活剂的化合物，因此可用于治疗糖尿病和相关疾病，该化合物具有Q为结构，R 1，R 2，R 3，R 4，R 5，R 6，R 7和R 8如本文所定义或其药学上可接受的盐。还提供了使用上述化合物治疗糖尿病和相关疾病的方法。

9. 发明授权

US4629724A Amino acid ester and amide renin inhibitors 失效
标题翻译：氨基酸酯和酰胺肾素抑制剂
公开(公告)号：US4629724A
公开(公告)日：1986-12-16
申请号：US677714
申请日：1984-12-03
申请人： Denis E. Ryono , Edward W. Petrillo, Jr.
发明人： Denis E. Ryono , Edward W. Petrillo, Jr.
IPC分类号： C07K14/81 , A61K38/00 , A61K38/55 , A61P9/12 , A61P43/00 , C07K5/02 , C07K5/06 , C07K5/062 , C07K5/065 , C07K5/068 , A61K37/43 , C07K5/08 , C07K7/02
CPC分类号： C07K5/0227 , Y10S530/86
摘要： Compounds of the formula ##STR1## wherein A is ##STR2## intervene in the conversion of angiotensinogen to angiotensin II by inhibiting renin and thus are useful as anti-hypertensive agents.
摘要翻译：其中A为“IMAGE”的化合物通过抑制肾素来介入血管紧张素原转化为血管紧张素II，因此可用作抗高血压药。

10. 发明授权

US08614332B2 Substituted pyrazolylamides useful as glucokinase activators 有权
标题翻译：用作葡糖激酶活化剂的取代的吡唑基酰胺
公开(公告)号：US08614332B2
公开(公告)日：2013-12-24
申请号：US13397123
申请日：2012-02-15
申请人： Denis E. Ryono , Peter T. W. Cheng , Scott A. Bolton , Sean Chen , Yan Shi , Wei Meng , Joseph A. Tino , Richard B. Sulsky
发明人： Denis E. Ryono , Peter T. W. Cheng , Scott A. Bolton , Sean Chen , Yan Shi , Wei Meng , Joseph A. Tino , Richard B. Sulsky
IPC分类号： C07D231/00
CPC分类号： C07F9/6539 , C07F9/58 , C07F9/65031 , C07F9/650952 , C07F9/6518
摘要： Compounds are provided which are phosphonate and phosphinate activators and thus are useful in treating diabetes and related diseases and have the structure is a heteroaryl ring; R4 is —(CH2)n—Z—(CH2)m—PO(OR7)(OR8), —(CH2)nZ—(CH2)m—PO(OR7)R9, —(CH2)n—Z—(CH2)m—OPO(OR7)R9, —(CH2)nZ—(CH2)m—OPO(R9)(R10), or —(CH2)nZ—(CH2)m—PO(R9)(R10); R5 and R6 are independently selected from H, alkyl and halogen; Y is R7(CH2)s or is absent; and X, n, Z, m, R4, R5, R6, R7, and s are as defined herein; or a pharmaceutically acceptable salt thereof. A method for treating diabetes and related diseases employing the above compounds is also provided.
摘要翻译：提供了膦酸酯和次膦酸酯活化剂的化合物，因此可用于治疗糖尿病和相关疾病，并且其结构是杂芳基环; R4是 - （CH2）nZ-（CH2）m-PO（OR7）（OR8）， - （CH2）nZ-（CH2）m-PO（OR7）R9， - （CH2）nZ-（CH2）（OR7）R9， - （CH2）nZ-（CH2）m-OPO（R9）（R10）或 - （CH2）nZ-（CH2）m-PO（R9）（R10） R5和R6独立地选自H，烷基和卤素; Y为R 7（CH 2）s或不存在; 并且X，n，Z，m，R 4，R 5，R 6，R 7和s如本文所定义; 或其药学上可接受的盐。还提供了使用上述化合物治疗糖尿病和相关疾病的方法。

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