公开(公告)号：US08501747B2

公开(公告)日：2013-08-06

申请号：US12525641

申请日：2008-02-11

申请人： Manuel de lera Ruiz ,  Kevin D. McCormick ,  Christopher W. Boyce ,  Robert G. Aslanian ,  Younong Yu ,  Pietro Mangiaracina ,  Junying Zheng ,  Michael Y. Berlin ,  Stephanie Louise Ciesla ,  Chia-Yu Huang ,  Bo Liang

发明人： Manuel de lera Ruiz ,  Kevin D. McCormick ,  Christopher W. Boyce ,  Robert G. Aslanian ,  Younong Yu ,  Pietro Mangiaracina ,  Junying Zheng ,  Michael Y. Berlin ,  Stephanie Louise Ciesla ,  Chia-Yu Huang ,  Bo Liang

IPC分类号： A61K31/404 ,  A61K31/4025 ,  A61K31/4178 ,  A61K31/4439 ,  A61K31/4709 ,  A61K31/506 ,  C07D401/04 ,  C07D401/14 ,  C07D403/02 ,  C07D403/14

CPC分类号： C07D403/14 ,  C07D233/10 ,  C07D401/14 ,  C07D403/06 ,  C07D403/10 ,  C07D405/14 ,  C07D407/14 ,  C07D409/14 ,  C07D413/14

摘要： In its many embodiments, the present invention provides a novel class of biaryl compounds as inhibitors of ÿ2C adrenergic receptor agonists, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more conditions associated with the ÿ2C adrenergic receptors using such compounds or pharmaceutical compositions.

摘要翻译： 在其许多实施方案中，本发明提供了一类新颖的联芳基化合物作为ÿ2C肾上腺素能受体激动剂的抑制剂，制备此类化合物的方法，含有一种或多种此类化合物的药物组合物，制备包含一种或多种此类化合物的药物制剂的方法， 以及使用这些化合物或药物组合物治疗，预防，抑制或改善与ÿ2C肾上腺素能受体相关的一种或多种病症的方法。

公开(公告)号：US20110166124A1

公开(公告)日：2011-07-07

申请号：US13054806

申请日：2009-07-21

申请人： Kevin D. McCormick ,  Robert G. Aslanian ,  Pietro Mangiaracina ,  Michael Y. Berlin ,  Manuel De Lera Ruiz ,  Christopher W. Boyce ,  Jianhua Chao ,  Pauline C. Ting ,  Junying Zheng ,  Stuart B. Rosenblum

发明人： Kevin D. McCormick ,  Robert G. Aslanian ,  Pietro Mangiaracina ,  Michael Y. Berlin ,  Manuel De Lera Ruiz ,  Christopher W. Boyce ,  Jianhua Chao ,  Pauline C. Ting ,  Junying Zheng ,  Stuart B. Rosenblum

IPC分类号： C07D471/10 ,  C07D491/107 ,  C07D495/10 ,  A61K31/438 ,  A61K31/501 ,  A61K31/553 ,  C07D498/10 ,  A61P37/08 ,  A61P9/00 ,  A61P29/00 ,  A61P1/00 ,  A61P27/00 ,  A61P3/00 ,  A61P3/06 ,  A61P3/10

CPC分类号： C07D471/10 ,  C07D401/06 ,  C07D401/14 ,  C07D405/14 ,  C07D417/14 ,  C07D491/107 ,  C07D491/20 ,  C07D495/20 ,  C07D498/10

摘要： The present invention relates to novel Tricyclic Spirocycle Derivatives, pharmaceutical compositions comprising the Tricyclic Spirocycle Derivatives and the use of these compounds for treating or preventing allergy, an allergy-induced airway response, congestion, a cardiovascular disease, an inflammatory disease, a gastrointestinal disorder, a neurological disorder, a metabolic disorder, obesity or an obesity-related disorder, diabetes, a diabetic complication, impaired glucose tolerance or aired fasting glucose.

摘要翻译： 本发明涉及新型三环螺环衍生物，包含三环螺环衍生物的药物组合物和这些化合物用于治疗或预防过敏，过敏诱发的气道反应，充血，心血管疾病，炎性疾病，胃肠道疾病， 糖尿病，糖尿病并发症，葡萄糖耐量降低或空腹血糖异常。

公开(公告)号：US07846946B2

公开(公告)日：2010-12-07

申请号：US12507563

申请日：2009-07-22

申请人： Robert G. Aslanian ,  Michael Y. Berlin ,  Christopher W. Boyce ,  Jianhua Chao ,  Manuel de Lera Ruiz ,  Pietro Mangiaracina ,  Kevin D. McCormick ,  Mwangi W. Mutahi ,  Stuart B. Rosenblum ,  Neng-Yang Shih ,  Daniel M. Solomon ,  Wing C. Tom ,  Henry A. Vaccaro ,  Junying Zheng ,  Xiaohong Zhu

发明人： Robert G. Aslanian ,  Michael Y. Berlin ,  Christopher W. Boyce ,  Jianhua Chao ,  Manuel de Lera Ruiz ,  Pietro Mangiaracina ,  Kevin D. McCormick ,  Mwangi W. Mutahi ,  Stuart B. Rosenblum ,  Neng-Yang Shih ,  Daniel M. Solomon ,  Wing C. Tom ,  Henry A. Vaccaro ,  Junying Zheng ,  Xiaohong Zhu

IPC分类号： A61K31/4545 ,  C07D401/14

CPC分类号： C07D295/185 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  Y02P20/582

摘要： Disclosed are novel compounds of the formula or a pharmaceutically acceptable salt thereof, wherein: M1 and M3 are CH or N; M2 is CH, CF or N; Y is —C(═O)—, —C(═S)—, —(CH2)q—, —C(═NOR7)— or —SO1-2—; Z is a bond or optionally substituted alkylene or alkenylene; R1 is H, or alkyl, cycloalkyl, aryl, heteroaryl, heterocycloalkyl, all optionally substituted, or a group of the formula: where ring A is a heteroaryl ring; R2 is optionally substituted alkyl, alkenyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl; R3 is H, —C(O)NH2, or alkyl, aryl, cycloalkyl, heterocycloalkyl or heteroaryl, all optionally substituted; and the remaining variables are as defined in the specification; compositions and methods of treating allergy-induced airway responses, congestion, obesity, metabolic syndrome, alcoholic fatty liver disease, hepatic steatosis, nonalcoholic steatohepatitis, cirrhosis, hepatacellular carcinoma and cognition deficit disorders using said compounds, alone or in combination with other agents.

摘要翻译： 公开了下式的新化合物或其药学上可接受的盐，其中：M1和M3是CH或N; M2是CH，CF或N; Y是-C（= O） - ， - C（= S） - ， - （CH 2）q - ， - C（= NOR 7） - 或-SO 1 2- Z是键或任选取代的亚烷基或亚烯基; R 1是H或烷基，环烷基，芳基，杂芳基，杂环烷基，全部被取代，或下式的基团：其中环A是杂芳基环; R 2是任选取代的烷基，烯基，芳基，杂芳基，环烷基或杂环烷基; R 3是H，-C（O）NH 2或烷基，芳基，环烷基，杂环烷基或杂芳基，全部被取代; 剩余的变量如规范中所定义; 使用所述化合物单独或与其它试剂组合治疗过敏引起的气道反应，充血，肥胖，代谢综合征，酒精性脂肪肝疾病，肝脂肪变性，非酒精性脂肪性肝炎，肝硬化，肝细胞癌和认知缺陷障碍的组合物和方法。

公开(公告)号：US07638531B2

公开(公告)日：2009-12-29

申请号：US11641175

申请日：2006-12-19

申请人： Mwangi W. Mutahi ,  Robert G. Aslanian ,  Michael Y. Berlin ,  Christopher W. Boyce ,  Manuel de Lera Ruiz ,  Kevin D. McCormick ,  Daniel M. Solomon ,  Henry A. Vaccaro ,  Junying Zheng ,  Purakkattle Biju ,  Younong Yu ,  Wei Zhou ,  Xiaohong Zhu

发明人： Mwangi W. Mutahi ,  Robert G. Aslanian ,  Michael Y. Berlin ,  Christopher W. Boyce ,  Manuel de Lera Ruiz ,  Kevin D. McCormick ,  Daniel M. Solomon ,  Henry A. Vaccaro ,  Junying Zheng ,  Purakkattle Biju ,  Younong Yu ,  Wei Zhou ,  Xiaohong Zhu

IPC分类号： A01N43/42 ,  A61K31/44 ,  A01N43/40 ,  C07D471/02 ,  C07D491/02 ,  C07D498/02 ,  C07D211/68 ,  C07D211/80 ,  C07D213/02

CPC分类号： C07D471/04 ,  C07D213/38 ,  C07D213/73 ,  C07D277/40 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D409/12 ,  C07D417/06 ,  C07D417/14 ,  C07D473/00

摘要： Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein: M is CH or N; U and W are each CH, or one of U and W is CH and the other is N; X is a bond, alkylene, —C(O)—, —C(N—OR5)—, —C(N—OR5)—CH(R6)—, —CH(R6)—C(N—OR5)—, —O—, —OCH2—, —CH2O— or —S(O)0-2—; Y is —O—, —(CH2)2—, —C(═O)—, —C(═NOR7)— or —SO0-2—; Z is a bond, optionally substituted alkylene or alkylene interrupted by a heteroatom or heterocyclic group; R1 is optionally substituted alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heterocycloalkyl, or benzimidazolyl or a derivative thereof; R2 is optionally substituted alkyl, alkenyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl or heterocycloalkyl; and the remaining variables are as defined in the specification; compositions and methods for treating an allergy-induced airway response, congestion, diabetes, obesity, an obesity-related disorder, metabolic syndrome and a cognition deficit disorder using said compounds, alone or in combination with other agents.

摘要翻译： 公开了下式的化合物或其药学上可接受的盐或溶剂化物，其中：M是CH或N; U和W各自为CH，或U和W中的一个为CH，另一个为N; X是键，亚烷基，-C（O） - ， - C（N-OR 5） - ， - C（N-OR 5）-CH（R 6） - ， - CH（R 6）-C（N-OR 5） ，-O - ， - OCH 2 - ， - CH 2 O-或-S（O）0-2-; Y是-O - ， - （CH 2）2 - ， - C（-O） - ， - C（-NOR 7） - 或-SOO 2 - ; Z是一个键，任选取代的被杂原子或杂环基中断的亚烷基或亚烷基; R1是任选取代的烷基，环烷基，芳基，芳烷基，杂芳基，杂环烷基或苯并咪唑基或其衍生物; R 2是任选取代的烷基，烯基，芳基，芳基烷基，杂芳基，杂芳基烷基，环烷基或杂环烷基; 剩余的变量如规范中所定义; 使用所述化合物单独或与其它试剂组合治疗过敏引起的气道反应，充血，糖尿病，肥胖，肥胖相关病症，代谢综合征和认知缺陷障碍的组合物和方法。

公开(公告)号：US07635705B2

公开(公告)日：2009-12-22

申请号：US11455625

申请日：2006-06-19

申请人： Robert G. Aslanian ,  Michael Y. Berlin ,  Christopher W. Boyce ,  Jianhua Chao ,  Manuel de Lera Ruiz ,  Pietro Mangiaracina ,  Kevin D. McCormick ,  Stuart B. Rosenblum ,  Neng-Yang Shih ,  Daniel M. Solomon ,  Wing C. Tom ,  Henry A. Vaccaro ,  Junying Zheng ,  Xiaohong Zhu ,  Mwangi W. Mutahi

发明人： Robert G. Aslanian ,  Michael Y. Berlin ,  Christopher W. Boyce ,  Jianhua Chao ,  Manuel de Lera Ruiz ,  Pietro Mangiaracina ,  Kevin D. McCormick ,  Stuart B. Rosenblum ,  Neng-Yang Shih ,  Daniel M. Solomon ,  Wing C. Tom ,  Henry A. Vaccaro ,  Junying Zheng ,  Xiaohong Zhu ,  Mwangi W. Mutahi

IPC分类号： A61K31/4545 ,  C07D401/14

CPC分类号： C07D295/185 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  Y02P20/582

摘要： Disclosed are novel compounds of the formula or a pharmaceutically acceptable salt thereof, wherein: M1 and M3 are CH or N; M2 is CH, CF or N; Y is —C(═O)—, —C(═S)—, —(CH2)q—, —C(═NOR7)— or —SO1-2—; Z is a bond or optionally substituted alkylene or alkenylene; R1 is H, or alkyl, cycloalkyl, aryl, heteroaryl, heterocycloalkyl, all optionally substituted, or a group of the formula: where ring A is a heteroaryl ring; R2 is optionally substituted alkyl, alkenyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl; R3 is H, —C(O)NH2, or alkyl, aryl, cycloalkyl, heterocycloalkyl or heteroaryl, all optionally substituted; and the remaining variables are as defined in the specification; compositions and methods of treating allergy-induced airway responses, congestion, obesity, metabolic syndrome, alcoholic fatty liver disease, hepatic steatosis, nonalcoholic steatohepatitis, cirrhosis, hepatacellular carcinoma and cognition deficit disorders using said compounds, alone or in combination with other agents.

摘要翻译： 公开了下式的新化合物或其药学上可接受的盐，其中：M1和M3是CH或N; M2是CH，CF或N; Y是-C（-O） - ， - C（-S） - ， - （CH 2）q - ， - C（-NOR 7） - 或-SO 1 - Z是键或任选取代的亚烷基或亚烯基; R 1是H或烷基，环烷基，芳基，杂芳基，杂环烷基，全部被取代，或下式的基团：其中环A是杂芳基环; R 2是任选取代的烷基，烯基，芳基，杂芳基，环烷基或杂环烷基; R 3是H，-C（O）NH 2或烷基，芳基，环烷基，杂环烷基或杂芳基，全部被取代; 剩余的变量如规范中所定义; 使用所述化合物单独或与其它试剂组合治疗过敏引起的气道反应，充血，肥胖，代谢综合征，酒精性脂肪肝疾病，肝脂肪变性，非酒精性脂肪性肝炎，肝硬化，肝细胞癌和认知缺陷障碍的组合物和方法。

公开(公告)号：US20090286830A1

公开(公告)日：2009-11-19

申请号：US12507563

申请日：2009-07-22

申请人： Robert G. Aslanian ,  Michael Y. Berlin ,  Christopher W. Boyce ,  Jianhua Chao ,  Manuel de Lera Ruiz ,  Pietro Mangiaracina ,  Kevin D. McCormick ,  Stuart B. Rosenblum ,  Neng-Yang Shih ,  Daniel M. Solomon ,  Wing C. Tom ,  Henry A. Vaccaro ,  Junying Zheng ,  Xiaohong Zhu ,  Mwangi W. Mutahi

发明人： Robert G. Aslanian ,  Michael Y. Berlin ,  Christopher W. Boyce ,  Jianhua Chao ,  Manuel de Lera Ruiz ,  Pietro Mangiaracina ,  Kevin D. McCormick ,  Stuart B. Rosenblum ,  Neng-Yang Shih ,  Daniel M. Solomon ,  Wing C. Tom ,  Henry A. Vaccaro ,  Junying Zheng ,  Xiaohong Zhu ,  Mwangi W. Mutahi

IPC分类号： A61K31/4545

CPC分类号： C07D295/185 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  Y02P20/582

摘要： Disclosed are novel compounds of the formula or a pharmaceutically acceptable salt thereof, wherein: M1 and M3 are CH or N; M2 is CH, CF or N; Y is —C(═O)—, —C(═S)—, —(CH2)q—, —C(═NOR7)— or —SO1-2—; Z is a bond or optionally substituted alkylene or alkenylene; R1 is H, or alkyl, cycloalkyl, aryl, heteroaryl, heterocycloalkyl, all optionally substituted, or a group of the formula: where ring A is a heteroaryl ring; R2 is optionally substituted alkyl, alkenyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl; R3 is H, —C(O)NH2, or alkyl, aryl, cycloalkyl, heterocycloalkyl or heteroaryl, all optionally substituted; and the remaining variables are as defined in the specification; compositions and methods of treating allergy-induced airway responses, congestion, obesity, metabolic syndrome, alcoholic fatty liver disease, hepatic steatosis, nonalcoholic steatohepatitis, cirrhosis, hepatacellular carcinoma and cognition deficit disorders using said compounds, alone or in combination with other agents.

摘要翻译： 公开了下式的新化合物或其药学上可接受的盐，其中：M1和M3是CH或N; M2是CH，CF或N; Y是-C（-O） - ， - C（-S） - ， - （CH 2）q - ， - C（-NOR 7） - 或-SO 1 - Z是键或任选取代的亚烷基或亚烯基; R 1是H或烷基，环烷基，芳基，杂芳基，杂环烷基，全部被取代，或下式的基团：其中环A是杂芳基环; R 2是任选取代的烷基，烯基，芳基，杂芳基，环烷基或杂环烷基; R 3是H，-C（O）NH 2或烷基，芳基，环烷基，杂环烷基或杂芳基，全部被取代; 剩余的变量如规范中所定义; 使用所述化合物单独或与其它试剂组合治疗过敏引起的气道反应，充血，肥胖，代谢综合征，酒精性脂肪肝疾病，肝脂肪变性，非酒精性脂肪性肝炎，肝硬化，肝细胞癌和认知缺陷障碍的组合物和方法。

公开(公告)号：US07531660B2

公开(公告)日：2009-05-12

申请号：US11837248

申请日：2007-08-10

申请人： Manuel de Lera Ruiz ,  Robert G. Aslanian ,  Michael Y. Berlin ,  Kevin D. McCormick ,  Chander S. Celly

发明人： Manuel de Lera Ruiz ,  Robert G. Aslanian ,  Michael Y. Berlin ,  Kevin D. McCormick ,  Chander S. Celly

IPC分类号： C07D498/02 ,  A01N43/42

CPC分类号： C07D471/04

摘要： The present invention discloses the compound of Formula I and pharmaceutically acceptable salts and solvates thereof. The invention also relates to pharmaceutical compositions comprising the Compound of Formula I and its use in treating obesity, metabolic syndrome, diabetes, hepatic lipidosis or nonalcoholic fatty liver disease. The invention also relates to the use of a combination of the Compound of Formula I with additional therapeutic agents for treating obesity, metabolic syndrome, diabetes, hepatic lipidosis or nonalcoholic fatty liver disease.

摘要翻译： 本发明公开了式I化合物及其药学上可接受的盐和溶剂化物。 本发明还涉及包含式I化合物及其在治疗肥胖，代谢综合征，糖尿病，肝脏脂质沉积或非酒精性脂肪性肝病中的用途的药物组合物。 本发明还涉及式I化合物与用于治疗肥胖，代谢综合征，糖尿病，肝脏脂质沉积或非酒精性脂肪性肝病的其它治疗剂的组合的用途。

公开(公告)号：US07332604B2

公开(公告)日：2008-02-19

申请号：US11523489

申请日：2006-09-19

申请人： Manuel de Lera Ruiz ,  Robert G. Aslanian ,  Michael Y. Berlin ,  Kevin D. McCormick

发明人： Manuel de Lera Ruiz ,  Robert G. Aslanian ,  Michael Y. Berlin ,  Kevin D. McCormick

IPC分类号： C07D498/02

CPC分类号： C07D471/04

摘要： The present invention discloses the compound of Formula I and pharmaceutically acceptable salts and solvates thereof. The invention also relates to pharmaceutical compositions comprising the Compound of Formula I and its use in treating obesity, metabolic syndrome, diabetes, hepatic lipidosis or nonalcoholic fatty liver disease. The invention also relates to the use of a combination of the Compound of Formula I with additional therapeutic agents for treating obesity, metabolic syndrome, diabetes, hepatic lipidosis or nonalcoholic fatty liver disease.

摘要翻译： 本发明公开了式I化合物及其药学上可接受的盐和溶剂化物。 本发明还涉及包含式I化合物及其在治疗肥胖，代谢综合征，糖尿病，肝脏脂质沉积或非酒精性脂肪性肝病中的用途的药物组合物。 本发明还涉及式I化合物与用于治疗肥胖，代谢综合征，糖尿病，肝脏脂质沉积或非酒精性脂肪性肝病的其它治疗剂的组合的用途。

公开(公告)号：US08524697B2

公开(公告)日：2013-09-03

申请号：US12736063

申请日：2008-12-18

申请人： John C. Anthes ,  Kevin D. McCormick ,  John A. Hey ,  Robert G. Aslanian ,  Purakkattle J. Biju ,  Michael Y. Berlin ,  Hongwu Yang ,  Yeon-Hee Lim ,  Yoon Joo Lee ,  Rema Danielle Bitar ,  Phillippa H. Solomon

发明人： John C. Anthes ,  Kevin D. McCormick ,  John A. Hey ,  Robert G. Aslanian ,  Purakkattle J. Biju ,  Michael Y. Berlin ,  Daniel M. Solomon ,  Hongwu Yang ,  Yeon-Hee Lim ,  Yoon Joo Lee ,  Rema Danielle Bitar

IPC分类号： A01N43/00 ,  A61K31/33 ,  C07D215/00 ,  C07D277/62

CPC分类号： C07J43/003

摘要： The present invention provides compounds of Formula (I), and pharmaceutically acceptable salts, solvates, esters, prodrugs, tautomers, or isomers of said compounds), having the general structure: wherein L, R1, R2, R3, R4, R5, and R6 are selected independently of each other and as defined herein. The present invention also provides compounds (and salts, solvates, esters, prodrugs, tautomers, and isomers) of Formulas II, III, IV, V, and VI, as defined herein. Also provided are pharmaceutical compositions, methods of preparing, and methods of using such compounds in the treatment and prophylaxis of a wide range of immune, autoimmune, and inflammatory diseases and conditions.

摘要翻译： 本发明提供具有以下通式结构的式（I）化合物及其药学上可接受的盐，溶剂合物，酯，前体药物，互变异构体或异构体）：其中L，R1，R2，R3，R4，R5和 R6彼此独立地选择并如本文所定义。 本发明还提供如本文定义的式II，III，IV，V和VI的化合物（和盐，溶剂合物，酯，前药，互变异构体和异构体）。 还提供了药物组合物，制备方法和使用这些化合物在治疗和预防广泛范围的免疫，自身免疫和炎性疾病和病症中的方法。

公开(公告)号：US20120171126A1

公开(公告)日：2012-07-05

申请号：US13378893

申请日：2010-06-15

申请人： Biju J. Purakkattle ,  Michael Y. Berlin ,  Yeon-Hee Lim ,  Rema D. Bitar ,  Kevin D. McCormick ,  Robert G. Aslanian ,  Yoon Joo Lee ,  Junying Zheng ,  Ying Huang ,  Walter Won

发明人： Biju J. Purakkattle ,  Michael Y. Berlin ,  Yeon-Hee Lim ,  Rema D. Bitar ,  Kevin D. McCormick ,  Robert G. Aslanian ,  Yoon Joo Lee ,  Junying Zheng ,  Ying Huang ,  Walter Won

IPC分类号： A61K31/58 ,  A61K9/12 ,  A61P37/00 ,  A61P29/00 ,  A61P17/00 ,  A61P17/06 ,  A61P17/04 ,  A61P11/06 ,  A61P11/02 ,  A61P11/08 ,  A61P11/00 ,  A61P1/00 ,  A61P1/04 ,  A61P25/00 ,  A61P27/02 ,  C07J71/00

CPC分类号： C07J71/0047 ,  C07J71/0063

摘要： The present invention provides compounds of Formula (I), and pharmaceutically acceptable salts, solvates, esters, prodrugs, tautomers, or isomers of said compounds), having the general structure: Formula (I) wherein L, R1, R2, R3, R4, R5, and R6 are selected independently of each other and as defined herein. The present invention also provides compounds (and salts, solvates, esters, prodrugs, tautomers, and isomers) of Formulas (H-A), (II-A1), (II-A2), (II-A2.1), (ll-A-2.2), (ll-A-2.3), (II-A4), (H-B), (H-C), (III), (IV), (V), (VI), as described herein. Also provided are pharmaceutical compositions, methods of preparing, and methods of using such compounds in the treatment and prophylaxis of a wide range of immune, autoimmune, and inflammatory diseases and conditions.

摘要翻译： 本发明提供具有以下通式结构的式（I）化合物及其药学上可接受的盐，溶剂合物，酯，前体药物，互变异构体或异构体：其中L，R1，R2，R3，R4 R 5和R 6彼此独立地选择并如本文所定义。 本发明还提供式（IIa），（Ⅱ-A1），（Ⅱ-A2），（Ⅱ-A2.1），（Ⅱ-A2）的化合物（和盐，溶剂合物，酯，前体药物，互变异构体和异构体） （II-A-2.3），（II-A4），（HB），（HC），（III），（IV），（V），（VI） 还提供了药物组合物，制备方法和使用这些化合物在治疗和预防广泛范围的免疫，自身免疫和炎性疾病和病症中的方法。