公开(公告)号：US08088776B2

公开(公告)日：2012-01-03

申请号：US12297349

申请日：2007-04-19

Applicant: Thomas Daniel Aicher ,  Zhaogen Chen ,  Ronald Jay Hinklin ,  Gary Alan Hite ,  Alexei Pavlovych Krasutsky ,  Renhua Li ,  Jefferson Ray McCowan ,  Ashraf Saeed ,  Nancy June Snyder ,  James Lee Toth ,  Owen Brendan Wallace ,  Leonard Larry Winneroski, Jr. ,  Yanping Xu ,  Jeremy Schulenburg York

Inventor： Thomas Daniel Aicher ,  Zhaogen Chen ,  Ronald Jay Hinklin ,  Gary Alan Hite ,  Alexei Pavlovych Krasutsky ,  Renhua Li ,  Jefferson Ray McCowan ,  Ashraf Saeed ,  Nancy June Snyder ,  James Lee Toth ,  Owen Brendan Wallace ,  Leonard Larry Winneroski, Jr. ,  Yanping Xu ,  Jeremy Schulenburg York

IPC: A61K31/496 ,  A61K31/453 ,  C07D403/02 ,  C07D405/14

CPC classification number: C07D207/12 ,  C07D401/10 ,  C07D401/12 ,  C07D403/10 ,  C07D405/14 ,  C07D413/10 ,  C07D417/10 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07D487/08 ,  C07D491/08 ,  C07D491/10

Abstract: The present invention discloses novel compounds of Formula I: possessing 11 β-HSD type 1 antagonist activity, as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising compounds of Formula I, as well as methods of using the compounds and compositions to treat diabetes, hyperglycemia, obesity, hypertension, hyperlipidemia, metabolic syndrome, cognitive disorders, and other conditions associated with 11 β-HSD type 1 activity.

Abstract translation: 本发明公开了具有11＆amp; b -HSD 1型拮抗剂活性的式I化合物，以及制备这些化合物的方法。 在另一个实施方案中，本发明公开了包含式I化合物的药物组合物，以及使用化合物和组合物治疗糖尿病，高血糖症，肥胖症，高血压，高脂血症，代谢综合征，认知障碍以及与其相关的其它病症的方法 ; -HSD 1型活动。

公开(公告)号：US07981918B2

公开(公告)日：2011-07-19

申请号：US12297375

申请日：2007-04-05

Applicant: Thomas Daniel Aicher ,  Peter Biagio Anzeveno ,  Renhua Li ,  Alexei Pavlovych Krasutsky ,  Thomas Edward Mabry ,  Ashraf Saeed ,  Nancy June Snyder ,  Hongqi Tian ,  Owen Brendan Wallace ,  Leonard Larry Winneroski ,  Yanping Xu

Inventor： Thomas Daniel Aicher ,  Peter Biagio Anzeveno ,  Renhua Li ,  Alexei Pavlovych Krasutsky ,  Thomas Edward Mabry ,  Ashraf Saeed ,  Nancy June Snyder ,  Hongqi Tian ,  Owen Brendan Wallace ,  Leonard Larry Winneroski ,  Yanping Xu

IPC: A61K31/416 ,  C07D231/56

CPC classification number: C07D403/04

Abstract: The present invention discloses novel compounds of Formula (I): having 11β-HSD type 1 antagonist activity, as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising compounds of Formula (I), as well as methods of using the compounds and compositions to treat diabetes, hyperglycemia, obesity, hypertension, hyperlipidemia, metabolic syndrome, and other conditions associated with 11β-HSD type 1 activity.

Abstract translation: 本发明公开了具有11＆amp; b -HSD 1拮抗剂活性的式（I）的新化合物，以及制备这些化合物的方法。 在另一个实施方案中，本发明公开了包含式（I）化合物的药物组合物，以及使用化合物和组合物治疗糖尿病，高血糖症，肥胖症，高血压，高脂血症，代谢综合征以及与其相关的其它病症的方法。 HSD 1型活动。

公开(公告)号：US07820659B2

公开(公告)日：2010-10-26

申请号：US12297361

申请日：2007-04-19

Applicant: Ashraf Saeed ,  Owen Brendan Wallace ,  Yanping Xu ,  Thomas Edward Mabry ,  Rebecca Lynn Rezac Guenther ,  Nancy June Snyder

Inventor： Ashraf Saeed ,  Owen Brendan Wallace ,  Yanping Xu ,  Thomas Edward Mabry ,  Rebecca Lynn Rezac Guenther ,  Nancy June Snyder

IPC: A61K31/41 ,  A61K31/42 ,  A61K31/44 ,  A61K31/445 ,  A61K31/497 ,  A61K31/505 ,  A61K31/535 ,  C07D211/32 ,  C07D403/02 ,  C07D413/14

CPC classification number: C07D405/14 ,  C07D207/12 ,  C07D401/10 ,  C07D401/12 ,  C07D403/10 ,  C07D413/10 ,  C07D417/10 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07D487/08 ,  C07D491/08 ,  C07D491/10

Abstract: The present invention discloses novel compounds of Formula I: (I) having 11β-HSD type 1 antagonist activity, as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising compounds of Formula I, as well as methods of using the compounds and compositions to treat diabetes, hyperglycemia, obesity, hypertension, hyperlipidemia, metabolic syndrome, and other conditions associated with 11β-HSD type 1 activity.

Abstract translation: 本发明公开了具有11bb -HSD 1型拮抗剂活性的式I的新化合物：（I），以及制备这些化合物的方法。 在另一个实施方案中，本发明公开了包含式I化合物的药物组合物，以及使用化合物和组合物治疗糖尿病，高血糖症，肥胖症，高血压，高脂血症，代谢综合征以及与其相关的其它病症的方法。 1活动。

公开(公告)号：US20090088428A1

公开(公告)日：2009-04-02

申请号：US12297361

申请日：2007-04-19

Applicant: Ashraf Saeed ,  Owen Brendan Wallace ,  Yanping Xu ,  Thomas Edward Mabry ,  Rebecca Lynn Rezac Guenther ,  Nancy June Snyder

Inventor： Ashraf Saeed ,  Owen Brendan Wallace ,  Yanping Xu ,  Thomas Edward Mabry ,  Rebecca Lynn Rezac Guenther ,  Nancy June Snyder

IPC: A61K31/4184 ,  C07D403/02 ,  C07D405/14 ,  C07D413/14 ,  C07D401/14 ,  C07D403/14 ,  A61K31/5377 ,  A61K31/496 ,  A61K31/454 ,  A61K31/506 ,  A61K31/437 ,  A61P3/10

CPC classification number: C07D405/14 ,  C07D207/12 ,  C07D401/10 ,  C07D401/12 ,  C07D403/10 ,  C07D413/10 ,  C07D417/10 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07D487/08 ,  C07D491/08 ,  C07D491/10

Abstract: The present invention discloses novel compounds of Formula I: (I) having 11β-HSD type 1 antagonist activity, as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising compounds of Formula I, as well as methods of using the compounds and compositions to treat diabetes, hyperglycemia, obesity, hypertension, hyperlipidemia, metabolic syndrome, and other conditions associated with 11β-HSD type 1 activity.

Abstract translation: 本发明公开了具有11β-HSD 1型拮抗剂活性的式I的新化合物：（I），以及制备这些化合物的方法。 在另一个实施方案中，本发明公开了包含式I化合物的药物组合物，以及使用化合物和组合物治疗糖尿病，高血糖症，肥胖症，高血压，高脂血症，代谢综合征和与11beta-HSD 1型相关的其它病症的方法 活动。

公开(公告)号：US20090062358A1

公开(公告)日：2009-03-05

申请号：US11828446

申请日：2007-07-26

Applicant: Ivan Collado Cano ,  Samuel James Dominianni ,  Garret Jay Etgen, JR. ,  Cristina Garcia-Paredes ,  Richard Duane Johnston ,  Michael Edward Letourneau ,  Nathan Bryan Mantlo ,  Michael John Martinelli ,  Daniel Ray Mayhugh ,  Ashraf Saeed ,  Richard Craig Thompson ,  Xiaodong Wang ,  David Scott Coffey ,  Christopher Randall Schmid ,  Jeffrey Thomas Vicenzi ,  Yanping Xu

Inventor： Ivan Collado Cano ,  Samuel James Dominianni ,  Garret Jay Etgen, JR. ,  Cristina Garcia-Paredes ,  Richard Duane Johnston ,  Michael Edward Letourneau ,  Nathan Bryan Mantlo ,  Michael John Martinelli ,  Daniel Ray Mayhugh ,  Ashraf Saeed ,  Richard Craig Thompson ,  Xiaodong Wang ,  David Scott Coffey ,  Christopher Randall Schmid ,  Jeffrey Thomas Vicenzi ,  Yanping Xu

IPC: A61K31/4196 ,  C07D249/12 ,  C07D405/02

CPC classification number: C07C281/06 ,  C07C257/22 ,  C07C281/04 ,  C07D249/12 ,  C07D401/06 ,  C07D405/06 ,  C07D409/06 ,  C07D409/12 ,  C07D413/06 ,  C07D417/12

Abstract: The present invention is directed to compounds represented by the following structural formula, and pharmaceutically acceptable salts, solvates and hydrates thereof, R1 is a substituted or unsubstituted group selected from C1-C8 alkyl, aryl-C0-2-alkyl, heteroaryl-C0-2-alkyl, C3-C6 cycloalkylaryl-C0-2-alkyl or phenyl. W is O or S. R2 is H or a substituted or unsubstituted group selected from C1-C6 alkyl, C3-C6 cycloalkyl and heteroaryl. X is a C2-C5 alkylene linker wherein one carbon atom of the linker may be replaced with O, NH or S. Y is C, O, S, NH or a single bond. Furthermore, E is (CH2)nCOOH, wherein n is 0, 1, 2 or 3, or C(R3)(R4)A, wherein A is an acidic functional group such as carboxyl, carboxamide substituted or unsubstituted sulfonamide, or substituted or unsubstituted tetrazole. R3 is H, saturated or unsaturated C1-C5 alkyl, C1-C5 alkoxy. Additionally, R4 is H, halo, a substituted or unsubstituted group selected from C1-C5 alkyl, C1-C5 alkoxy, C3-C6 cycloalkyl, arylC0-C4alkyl and phenyl, or R3 and R4 are combined to form a C3-C4 cycloalkyl.

Abstract translation: 本发明涉及由以下结构式表示的化合物及其药学上可接受的盐，溶剂合物和水合物，R 1是选自C 1 -C 8烷基，芳基-C 0-2 - 烷基，杂芳基-C 0 - C 3 -C 6环烷基芳基-C 0-2 - 烷基或苯基。 W是O或S.R 2是H或选自C 1 -C 6烷基，C 3 -C 6环烷基和杂芳基的取代或未取代的基团。 X是C2-C5亚烷基连接体，连接体的一个碳原子可被O，NH或S取代.Y是C，O，S，NH或单键。 此外，E是（CH 2）n COOH，其中n是0,1,2或3或C（R3）（R4）A，其中A是酸性官能团如羧基，甲酰胺取代或未取代的磺酰胺，或取代或未取代的 未取代的四唑。 R3是H，饱和或不饱和的C1-C5烷基，C1-C5烷氧基。 另外，R 4为H，卤素，取代或未取代的选自C 1 -C 5烷基，C 1 -C 5烷氧基，C 3 -C 6环烷基，芳基C 0 -C 4烷基和苯基，或R 3和R 4的基团，形成C 3 -C 4环烷基。

公开(公告)号：US06512100B1

公开(公告)日：2003-01-28

申请号：US09651622

申请日：2000-08-30

Applicant: Stephen C Johnson ,  Ashraf Saeed ,  Ming Luo

Inventor： Stephen C Johnson ,  Ashraf Saeed ,  Ming Luo

IPC: C07H1504

CPC classification number: C07H15/203 ,  C07H7/027 ,  C07H15/24 ,  C07H17/02 ,  C07H17/075

Abstract: The subject invention discloses materials and methods for the design, synthesis, and biochemical evaluation of chromogenic substrate compounds for sialidases of bacterial, viral, protozoa, and vertebrate (including humans) origin. In particular, this invention provides a novel class of effective compounds as chromogenic substrates of these sialidases which yield chromogenic products after reactions catalyzed by sialidase take place. Also provided are methods of making these substrate compounds, methods of diagnosis and prognosis of sialidase related diseases using these substrate compounds.

Abstract translation: 本发明公开了用于细菌，病毒，原生动物和脊椎动物（包括人）起源的唾液酸酶的显色底物化合物的设计，合成和生物化学评估的材料和方法。 特别地，本发明提供了一种新型的有效化合物作为这些唾液酸酶的显色底物，其在由唾液酸酶催化的反应发生后产生显色产物。 还提供了使用这些底物化合物制备这些底物化合物的方法，唾液酸酶相关疾病的诊断和预后的方法。

公开(公告)号：US20090111800A1

公开(公告)日：2009-04-30

申请号：US12297375

申请日：2007-04-05

Applicant: Thomas Daniel Aicher ,  Peter Biagio Anzeveno ,  Renhua Li ,  Alexei Pavlovych Krasutsky ,  Thomas Edward Mabry ,  Ashraf Saeed ,  Nancy June Snyder ,  Gregory Alan Stephenson ,  Hongqi Tian ,  Owen Brendan Wallace ,  Leonard Larry Winneroski, JR. ,  Yanping Xu

Inventor： Thomas Daniel Aicher ,  Peter Biagio Anzeveno ,  Renhua Li ,  Alexei Pavlovych Krasutsky ,  Thomas Edward Mabry ,  Ashraf Saeed ,  Nancy June Snyder ,  Gregory Alan Stephenson ,  Hongqi Tian ,  Owen Brendan Wallace ,  Leonard Larry Winneroski, JR. ,  Yanping Xu

IPC: A61K31/541 ,  C07D403/08 ,  A61K31/416 ,  A61K31/5377 ,  C07D307/20 ,  C07D413/14 ,  C07D417/14

CPC classification number: C07D403/04

Abstract: The present invention discloses novel compounds of Formula (I): having 11β-HSD type 1 antagonist activity, as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising compounds of Formula (I), as well as methods of using the compounds and compositions to treat diabetes, hyperglycemia, obesity, hypertension, hyperlipidemia, metabolic syndrome, and other conditions associated with 11β-HSD type 1 activity.

Abstract translation: 本发明公开了具有11β-HSD 1型拮抗剂活性的式（I）的新化合物，以及制备这些化合物的方法。 在另一个实施方案中，本发明公开了包含式（I）化合物的药物组合物，以及使用化合物和组合物治疗糖尿病，高血糖症，肥胖症，高血压，高脂血症，代谢综合征以及与11beta-HSD相关的其它病症的方法 类型1活动。

公开(公告)号：US07304062B2

公开(公告)日：2007-12-04

申请号：US10415673

申请日：2001-11-09

Applicant: Samuel James Dominianni ,  Garret Jay Etgen ,  Richard Duane Johnston ,  Nathan Bryan Mantlo ,  Daniel Ray Mayhugh ,  Ashraf Saeed ,  Richard Craig Thompson ,  Xiaodong Wang ,  Christopher Randall Schmid ,  Yanping Xu

Inventor： Samuel James Dominianni ,  Garret Jay Etgen ,  Richard Duane Johnston ,  Nathan Bryan Mantlo ,  Daniel Ray Mayhugh ,  Ashraf Saeed ,  Richard Craig Thompson ,  Xiaodong Wang ,  Christopher Randall Schmid ,  Yanping Xu

IPC: A61K31/5377 ,  A61K31/4709 ,  A61K31/4196 ,  C07D413/06 ,  C07D249/12 ,  C07D215/12

CPC classification number: C07C281/06 ,  C07C257/22 ,  C07C281/04 ,  C07D249/12 ,  C07D401/06 ,  C07D405/06 ,  C07D409/06 ,  C07D409/12 ,  C07D413/06 ,  C07D417/12

Abstract: The present invention is directed to compounds represented by the following structural formula, and pharmaceutically acceptable salts, solvates and hydrates thereof, R1 is a substituted or unsubstituted group selected from C1-C8 alkyl, aryl-C0-2-alkyl, heteroaryl-C0-2-alkyl, C3-C6 cycloalkylaryl-C0-2-alkyl or phenyl. W is O or S. R2 is H or a substituted or unsubstituted group selected from C1-C6 alkyl, C3-C6 cycloalkyl and heteroaryl. X is a C2-C5 alkylene linker wherein one carbon atom of the linker may be replaced with O, NH or S. Y is C, O, S, NH or a single bond. Furthermore, E is (CH2)nCOOH, wherein n is 0, 1, 2 or 3, or C(R3)(R4)A, wherein A is an acidic functional group such as carboxyl, carboxamide substituted or unsubstituted sulfonamide, or substituted or unsubstituted tetrazole. R3 is H, saturated or unsaturated C1-C5 alkyl, C1-C5 alkoxy. Additionally, R4 is H, halo, a substituted or unsubstituted group selected from C1-C5 alkyl, C1-C5 alkoxy, C3-C6 cycloalkyl, arylC0-C4alkyl and phenyl, or R3 and R4 are combined to form a C3-C4 cycloalkyl.

Abstract translation: 本发明涉及由以下结构式表示的化合物及其药学上可接受的盐，溶剂合物和水合物，R 1是选自C 1 -C 8烷基的取代或未取代的基团， 烷基，芳基-C 0-2 - - 烷基，杂芳基-C 0-2-2 - 烷基，C 3 -C 6环烷基芳基-C 0-2-2 - 烷基或苯基。 W是O或S.R 2是H或选自C 1 -C 6烷基，C 3 -C 3烷基的取代或未取代的基团， C 6环烷基和杂芳基。 X是连接子的一个碳原子可以被O，NH或S取代的C 2 -C 5亚烷基连接基，Y是C，O，S，NH 或单一债券。 此外，E是（CH 2 SO 2）n COOH，其中n是0,1,2或3，或C（R 3）（R 4）A，其中A是 酸性官能团如羧基，羧酰胺取代或未取代的磺酰胺，或取代或未取代的四唑。 R 3是H，饱和或不饱和的C 1 -C 5烷基，C 1 -C 5烷氧基。 另外，R 4是H，卤素，取代或未取代的选自C 1 -C 5烷基，C 1 -C 3烷基， 5个烷氧基，C 3 -C 6环烷基，芳基C 0 -C 4烷基和苯基 ，或R 3和R 4结合形成C 3 -C 4环烷基。

公开(公告)号：US20070112045A1

公开(公告)日：2007-05-17

申请号：US10580202

申请日：2004-12-21

Applicant: Nathan Mantlo ,  Antonio Navarro ,  Ashraf Saeed ,  Douglas Gernert ,  Tianwei Ma ,  Lance Pfeifer

Inventor： Nathan Mantlo ,  Antonio Navarro ,  Ashraf Saeed ,  Douglas Gernert ,  Tianwei Ma ,  Lance Pfeifer

IPC: A61K31/433 ,  A61K31/4245 ,  A61K31/4196 ,  C07D285/12 ,  C07D271/10 ,  C07D249/08

CPC classification number: A61K31/4196 ,  A61K31/4245 ,  A61K31/433 ,  C07D249/08 ,  C07D271/107 ,  C07D285/12

Abstract: The present invention is directed to compounds represented by the following structural formula, Formula (I): wherein: (a) X is selected from the group consisting of a single bond, O, S, S(O)2 and N; (b) U is an aliphatic linker; (c) Y is selected from the group consisting of O, C, S, NH and a single bond; (d) W is N, O or S; (e) E is C(R3)(R4)A or A and wherein; (f) A is selected from the group consisting of carboxyl, tetrazole, C1-C6 alkylnitrile, carboxamide, sulfonamide and acylsufonamide. The other substituents are defined in the claims; the compounds are modulators of peroxisome proleferator activated receptors (PPARs) and are useful for the treatment of diabetes and other metabolic disorders.

Abstract translation: 本发明涉及由下列结构式（I）表示的化合物：其中：（a）X选自单键，O，S，S（O）2， SUB>和N; （b）U是脂族连接体; （c）Y选自O，C，S，NH和单键; （d）W是N，O或S; （e）E是C（R3）（R4）A或A，其中; （f）A选自羧基，四唑，C 1 -C 6烷基腈，甲酰胺，磺酰胺和酰基磺酰胺。 其它取代基在权利要求书中定义; 该化合物是过氧化物酶体促进剂激活受体（PPAR）的调节剂，可用于治疗糖尿病和其他代谢紊乱。

公开(公告)号：US06844346B2

公开(公告)日：2005-01-18

申请号：US10328790

申请日：2002-12-24

Applicant: Stephen C. Johnson ,  Ashraf Saeed ,  Ming Luo

Inventor： Stephen C. Johnson ,  Ashraf Saeed ,  Ming Luo

IPC: C07H7/027 ,  C07H15/203 ,  C07H15/24 ,  C07H17/02 ,  C07H17/075 ,  C07H15/04 ,  C07H17/04

CPC classification number: C07H15/203 ,  C07H7/027 ,  C07H15/24 ,  C07H17/02 ,  C07H17/075

Abstract: The subject invention discloses materials and methods for the design, synthesis, and biochemical evaluation of chromogenic substrate compounds for sialidases of bacterial, viral, protozoa, and vertebrate (including humans) origin. These compounds are based upon N-acetylneuraminic acid glycosides. In particular, this invention provides a novel class of these compounds as chromogenic substrates of these sialidases which yield chromogenic products after reactions catalyzed by sialidase take place. Also provided are methods of making these substrate compounds, methods of diagnosis and prognosis of sialidase related diseases using these substrate compounds.

Abstract translation: 本发明公开了用于细菌，病毒，原生动物和脊椎动物（包括人）起源的唾液酸酶的显色底物化合物的设计，合成和生物化学评估的材料和方法。 这些化合物基于N-乙酰神经氨酸糖苷。 特别地，本发明提供了一类新颖的这些化合物作为这些唾液酸酶的显色底物，其在由唾液酸酶催化的反应后产生显色产物。 还提供了使用这些底物化合物制备这些底物化合物的方法，唾液酸酶相关疾病的诊断和预后的方法。