公开(公告)号：US20160214997A1

公开(公告)日：2016-07-28

申请号：US14914843

申请日：2014-08-25

Applicant: Amjad ALI ,  Gioconda V. GALLO ,  Timothy J. HENDERSON ,  Rongze KUANG ,  Yeon-Hee LIM ,  Michael Man-Chu LO ,  Edward METZGER ,  Manuel de Lera RUIZ ,  Andrew STAMFORD ,  Paul TEMPEST ,  Brent WHITEHEAD ,  Heping WU ,  MERCK SHARP & DOHME CORP.

Inventor： Ali Amjad ,  Gioconda V. Gallo ,  Timothy J. Henderson ,  Rongze Kuang ,  Yeon-Hee Lim ,  Michael Man-Chu Lo ,  Edward Metzger ,  Manuel de Lera Ruiz ,  Andrew Stamford ,  Paul Tempest ,  Brent Whitehead ,  Heping Wu

IPC: C07D519/00 ,  C07D491/147

CPC classification number: C07D519/00 ,  C07D491/147

Abstract: The present invention is directed to 2,2-difluorodioxolo compounds that are antagonists of A2A receptor. The present invention is also directed to uses of the 2,2-difluorodioxolo compounds described herein in the potential treatment or prevention of neurological disorders and diseases in which A2A receptor are involved. The present invention is also directed to pharmaceutical compositions comprising these compounds and to uses of these pharmaceutical compositions in the prevention or treatment of such diseases in which A2A receptors are involved.

Abstract translation: 本发明涉及作为A2A受体拮抗剂的2,2-二氟二氧代己基化合物。 本发明还涉及本文所述的2,2-二氟二氧代环戊基化合物在涉及A2A受体的神经障碍和疾病的潜在治疗或预防中的用途。 本发明还涉及包含这些化合物的药物组合物以及这些药物组合物用于预防或治疗其中涉及A2A受体的疾病的用途。

公开(公告)号：US20160009681A1

公开(公告)日：2016-01-14

申请号：US14772525

申请日：2014-02-27

Applicant: Michael MILLER ,  Kallol BASU ,  Duane MONG ,  Jack SCOTT ,  Hong LIU ,  Xing DAI ,  Andrew STAMFORD ,  Marc POIRIER ,  Paul TEMPEST ,  MERCK SHARP & DOHME CORP.

Inventor： Michael Miller ,  Kallol Basu ,  Duane DeMong ,  Jack Scott ,  Hong Liu ,  Xing Dai ,  Andrew Stamford ,  Marc Poirier ,  Paul Tempest

IPC: C07D401/04 ,  C07D498/08 ,  C07D401/14 ,  C07D495/08 ,  C07D498/04 ,  C07D487/04 ,  C07D413/14 ,  C07D405/14 ,  C07D417/14

CPC classification number: C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14 ,  C07D487/04 ,  C07D491/08 ,  C07D495/08 ,  C07D498/04 ,  C07D498/08

Abstract: The present invention is directed to indazole compounds which are potent inhibitors of LRRK2 kinase and useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which LRRK2 kinase is involved.

Abstract translation: 本发明涉及作为LRRK2激酶的有效抑制剂的吲唑化合物，可用于治疗或预防其中涉及LRRK2激酶的疾病，例如帕金森病。 本发明还涉及包含这些化合物的药物组合物以及这些化合物和组合物在预防或治疗涉及LRRK2激酶的疾病中的用途。

公开(公告)号：US08349825B2

公开(公告)日：2013-01-08

申请号：US12912094

申请日：2010-10-26

Applicant: Dawn M. Mampreian ,  Joey L. Methot ,  Thomas Miller ,  Paul Tempest ,  Anna A. Zabierek

Inventor： Dawn M. Mampreian ,  Joey L. Methot ,  Thomas Miller ,  Paul Tempest ,  Anna A. Zabierek

IPC: A61K31/00 ,  A61K31/445 ,  C07D221/00 ,  C07D205/00

CPC classification number: C07D471/10 ,  C07D487/10 ,  C07D491/10 ,  C07D491/107 ,  C07D498/10

Abstract: The present invention relates to a novel class of substituted spirocyclic compounds. These compounds can inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the compounds of the instant invention and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of these compounds in vivo.

公开(公告)号：US08158825B2

公开(公告)日：2012-04-17

申请号：US11922740

申请日：2006-06-21

Applicant: Jonathan Grimm ,  Paul Harrington ,  Richard Heidebrecht, Jr. ,  Thomas Miller ,  Karin Otte ,  Phieng Siliphaivanh ,  David Sloman ,  Matthew Stanton ,  Kevin Wilson ,  David Witter ,  Solomon Kattar ,  Paul Tempest

Inventor： Jonathan Grimm ,  Paul Harrington ,  Richard Heidebrecht, Jr. ,  Thomas Miller ,  Karin Otte ,  Phieng Siliphaivanh ,  David Sloman ,  Matthew Stanton ,  Kevin Wilson ,  David Witter ,  Solomon Kattar ,  Paul Tempest

IPC: C07C233/02 ,  C07C255/60 ,  C07C311/46 ,  C07C311/08 ,  C07C235/84 ,  A61K31/519 ,  A61K31/44 ,  C07D265/30 ,  C07D495/04 ,  C07D215/06 ,  C07D211/06 ,  C07D213/82

CPC classification number: C07C235/78 ,  C07C233/75 ,  C07C233/80 ,  C07C235/42 ,  C07C235/56 ,  C07C235/74 ,  C07C235/84 ,  C07C255/60 ,  C07C311/08 ,  C07C311/16 ,  C07C311/46 ,  C07C2602/08 ,  C07D207/06 ,  C07D207/327 ,  C07D209/14 ,  C07D209/20 ,  C07D211/06 ,  C07D213/40 ,  C07D213/56 ,  C07D213/82 ,  C07D215/06 ,  C07D215/12 ,  C07D215/40 ,  C07D231/40 ,  C07D249/08 ,  C07D261/14 ,  C07D265/30 ,  C07D277/28 ,  C07D277/46 ,  C07D277/56 ,  C07D295/135 ,  C07D295/155 ,  C07D295/185 ,  C07D307/68 ,  C07D319/16 ,  C07D319/18 ,  C07D333/20 ,  C07D333/38 ,  C07D333/70 ,  C07D413/14 ,  C07D495/04

Abstract: The present invention relates to a novel class of modified malonate derivatives. The modified malonate compounds can be used to treat cancer. The modified malonate compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the modified malonate derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the modified malonate derivatives in vivo.

Abstract translation: 本发明涉及一类新型改性丙二酸衍生物。 修饰的丙二酸酯化合物可用于治疗癌症。 修饰的丙二酸酯化合物还可以抑制组蛋白脱乙酰酶，并且适用于选择性诱导末端分化，并阻止肿瘤细胞的细胞生长和/或凋亡，从而抑制这些细胞的增殖。 因此，本发明的化合物可用于治疗具有以肿瘤细胞增殖为特征的肿瘤的患者。 本发明的化合物还可用于预防和治疗TRX介导的疾病，例如自身免疫性，过敏性和炎性疾病，以及预防和/或治疗中枢神经系统（CNS）的疾病，例如 神经退行性疾病 本发明还提供包含改性丙二酸酯衍生物和这些药物组合物的安全给药方案的药物组合物，其易于遵循，并且其在体内导致治疗有效量的修饰的丙二酸酯衍生物。

公开(公告)号：US08026260B2

公开(公告)日：2011-09-27

申请号：US12084268

申请日：2006-10-30

Applicant: Joshua Close ,  Richard W. Heidebrecht, Jr. ,  Solomon Kattar ,  Thomas A. Miller ,  David Sloman ,  Matthew G Stanton ,  Paul Tempest ,  David J. Witter

Inventor： Joshua Close ,  Richard W. Heidebrecht, Jr. ,  Solomon Kattar ,  Thomas A. Miller ,  David Sloman ,  Matthew G Stanton ,  Paul Tempest ,  David J. Witter

IPC: A61K31/4439 ,  A61K31/415 ,  A61K31/423 ,  A61K31/425 ,  A61K31/4245 ,  C07D401/02 ,  C07D271/10 ,  C07D277/20 ,  C07D231/10

CPC classification number: C07D401/12 ,  C07D231/40 ,  C07D409/04 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12

Abstract: The present invention relates to a novel class of histone deacetylase inhibitors with aryl-pyrazolyl motifs. The compounds of this invention can be used to treat cancer. The compounds of this invention are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The present invention further provides pharmaceutical compositions comprising the compounds of this invention and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the compounds of this invention in vivo.

Abstract translation: 本发明涉及新一类具有芳基 - 吡唑基基序的组蛋白脱乙酰酶抑制剂。 本发明的化合物可用于治疗癌症。 本发明的化合物适用于选择性诱导终末分化，阻止肿瘤细胞的细胞生长和/或凋亡，从而抑制这些细胞的增殖。 因此，本发明的化合物可用于治疗具有以肿瘤细胞增殖为特征的肿瘤的患者。 本发明进一步提供包含本发明化合物和这些药物组合物的安全给药方案的药物组合物，其易于遵循，并且其在体内导致治疗有效量的本发明化合物。

公开(公告)号：US20100160327A1

公开(公告)日：2010-06-24

申请号：US11922740

申请日：2006-06-21

Applicant: Jonathan Grimm ,  Paul Harrington ,  Richard Heidebrecht, JR. ,  Thomas Miller ,  Karin Otte ,  Phieng Siliphaivanh ,  David Sloman ,  Matthew Stanton ,  Kevin Wilson ,  David Witter ,  Solomon Kattar ,  Paul Tempest

Inventor： Jonathan Grimm ,  Paul Harrington ,  Richard Heidebrecht, JR. ,  Thomas Miller ,  Karin Otte ,  Phieng Siliphaivanh ,  David Sloman ,  Matthew Stanton ,  Kevin Wilson ,  David Witter ,  Solomon Kattar ,  Paul Tempest

IPC: A61K31/5375 ,  A61K31/519 ,  A61K31/47 ,  A61K31/4453 ,  A61K31/44 ,  A61K31/4409 ,  A61K31/426 ,  A61K31/42 ,  A61K31/4196 ,  A61K31/404 ,  A61K31/402 ,  A61K31/381 ,  A61K31/357 ,  A61K31/34 ,  A61K31/277 ,  A61K31/18 ,  A61K31/167 ,  C07D265/30 ,  C07D495/04 ,  C07D215/06 ,  C07D211/06 ,  C07D213/82 ,  C07D213/56 ,  C07D277/46 ,  C07D277/56 ,  C07D261/14 ,  C07D249/08 ,  C07D209/20 ,  C07D207/327 ,  C07D333/70 ,  C07D319/16 ,  C07D307/68 ,  C07C255/60 ,  C07C311/46 ,  C07C311/08 ,  C07C235/84 ,  A61P35/00

CPC classification number: C07C235/78 ,  C07C233/75 ,  C07C233/80 ,  C07C235/42 ,  C07C235/56 ,  C07C235/74 ,  C07C235/84 ,  C07C255/60 ,  C07C311/08 ,  C07C311/16 ,  C07C311/46 ,  C07C2602/08 ,  C07D207/06 ,  C07D207/327 ,  C07D209/14 ,  C07D209/20 ,  C07D211/06 ,  C07D213/40 ,  C07D213/56 ,  C07D213/82 ,  C07D215/06 ,  C07D215/12 ,  C07D215/40 ,  C07D231/40 ,  C07D249/08 ,  C07D261/14 ,  C07D265/30 ,  C07D277/28 ,  C07D277/46 ,  C07D277/56 ,  C07D295/135 ,  C07D295/155 ,  C07D295/185 ,  C07D307/68 ,  C07D319/16 ,  C07D319/18 ,  C07D333/20 ,  C07D333/38 ,  C07D333/70 ,  C07D413/14 ,  C07D495/04

Abstract: The present invention relates to a novel class of modified malonate derivatives. The modified malonate compounds can be used to treat cancer. The modified malonate compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the modified malonate derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the modified malonate derivatives in vivo.

Abstract translation: 本发明涉及一类新型改性丙二酸衍生物。 修饰的丙二酸酯化合物可用于治疗癌症。 修饰的丙二酸酯化合物还可以抑制组蛋白脱乙酰酶，并且适用于选择性诱导末端分化，并阻止肿瘤细胞的细胞生长和/或凋亡，从而抑制这些细胞的增殖。 因此，本发明的化合物可用于治疗具有以肿瘤细胞增殖为特征的肿瘤的患者。 本发明的化合物还可用于预防和治疗TRX介导的疾病，例如自身免疫性，过敏性和炎性疾病，以及预防和/或治疗中枢神经系统（CNS）的疾病，例如 神经退行性疾病 本发明还提供包含改性丙二酸酯衍生物和这些药物组合物的安全给药方案的药物组合物，其易于遵循，并且其在体内导致治疗有效量的修饰的丙二酸酯衍生物。

公开(公告)号：US07659276B2

公开(公告)日：2010-02-09

申请号：US12367083

申请日：2009-02-06

Applicant: Christopher Hulme ,  Paul Tempest ,  Vu Ma ,  Thomas Nixey ,  Guity Balow

Inventor： Christopher Hulme ,  Paul Tempest ,  Vu Ma ,  Thomas Nixey ,  Guity Balow

IPC: A61K31/41 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/496

CPC classification number: C07D257/04 ,  C07D401/06 ,  C07D403/06 ,  C07D403/10 ,  C07D403/12 ,  C07D405/06 ,  C07D405/12

Abstract: Novel compounds, or pharmaceutically-acceptable salts, tautomers or prodrugs thereof, of Formula I wherein A, W, X, Z, R1-R3, and R8 are as defined in the specification, are provided. Also provided are methods of treating or preventing a melanin concentrating hormone-mediated disorder in a subject, comprising administering to a subject in need of such treatment or prevention a compound of Formula I.

Abstract translation: 其中A，W，X，Z，R 1 -R 3和R 8如说明书中所定义的式I的新化合物或其药学上可接受的盐，互变异构体或前药。 还提供了治疗或预防受试者中黑色素浓缩激素介导的病症的方法，其包括向需要这种治疗或预​​防的受试者施用式I化合物。

公开(公告)号：US20090143405A1

公开(公告)日：2009-06-04

申请号：US12367083

申请日：2009-02-06

Applicant: Christopher Hulme ,  Paul Tempest ,  Vu Van Ma ,  Thomas Nixey ,  Guity Balow

Inventor： Christopher Hulme ,  Paul Tempest ,  Vu Van Ma ,  Thomas Nixey ,  Guity Balow

IPC: A61K31/497

CPC classification number: C07D257/04 ,  C07D401/06 ,  C07D403/06 ,  C07D403/10 ,  C07D403/12 ,  C07D405/06 ,  C07D405/12

Abstract: Novel compounds, or pharmaceutically-acceptable salts, tautomers or prodrugs thereof, of Formula I wherein A, W, X, Z, R1-R3, and R8 are as defined in the specification, are provided. Also provided are methods of treating or preventing a melanin concentrating hormone-mediated disorder in a subject, comprising administering to a subject in need of such treatment or prevention a compound of Formula I.

Abstract translation: 其中A，W，X，Z，R 1 -R 3和R 8如说明书中所定义的式I的新化合物或其药学上可接受的盐，互变异构体或前药。 还提供了治疗或预防受试者中黑色素浓缩激素介导的病症的方法，其包括向需要这种治疗或预​​防的受试者施用式I化合物。

公开(公告)号：US20050215526A1

公开(公告)日：2005-09-29

申请号：US10916011

申请日：2004-08-11

Applicant: Christopher Hulme ,  Paul Tempest ,  Vu Ma ,  Thomas Nixey ,  Guity Balow

Inventor： Christopher Hulme ,  Paul Tempest ,  Vu Ma ,  Thomas Nixey ,  Guity Balow

IPC: A61K31/4025 ,  A61K31/495 ,  A61K31/496 ,  A61K31/66 ,  A61K31/675 ,  C07D20060101 ,  C07D257/04 ,  C07D401/14 ,  C07D403/06 ,  C07D43/02

CPC classification number: C07D257/04 ,  C07D401/06 ,  C07D403/06 ,  C07D403/10 ,  C07D403/12 ,  C07D405/06 ,  C07D405/12

Abstract: Novel compounds, or pharmaceutically-acceptable salts, tautomers or prodrugs thereof, of Formula I wherein A, W, X, Z, R1-R3, and R8 are as defined in the specification, are provided. Also provided are methods of treating or preventing a melanin concentrating hormone-mediated disorder in a subject, comprising administering to a subject in need of such treatment or prevention a compound of Formula I.

Abstract translation: 式I的新型化合物或其药学上可接受的盐，互变异构体或前药，其中A，W，X，Z，R 1〜R 3，和R 0 > 8 如说明书中所定义。 还提供了治疗或预防受试者中黑色素浓缩激素介导的病症的方法，其包括向需要这种治疗或预​​防的受试者施用式I化合物。

公开(公告)号：US09676780B2

公开(公告)日：2017-06-13

申请号：US14655572

申请日：2013-12-20

Applicant: MERCK SHARP & DOHME CORP. ,  Amjad Ali ,  Michael Man-Chu Lo ,  Yeon-Hee Lim ,  Andrew Stamford ,  Rongze Kuang ,  Paul Tempest ,  Younong Yu ,  Michael Berlin ,  Pauline Ting ,  Gang Zhou ,  Tao Yu ,  Christopher Boyce ,  Joseph Michael Kelly ,  Jayaram R. Tagat ,  Junying Zheng ,  Xianhai Huang ,  Wei Zhou ,  Jae-Hun Kim ,  Nicolas Zorn ,  Dong Xiao ,  Gioconda V. Gallo ,  Walter Won ,  Heping Wu ,  Rajan Anand ,  Qiaolin Deng

Inventor： Amjad Ali ,  Michael Man-Chu Lo ,  Yeon-Hee Lim ,  Andrew Stamford ,  Rongze Kuang ,  Paul Tempest ,  Younong Yu ,  Michael Berlin ,  Pauline Ting ,  Gang Zhou ,  Tao Yu ,  Christopher Boyce ,  Joseph Michael Kelly ,  Jayaram R. Tagat ,  Junying Zheng ,  Xianhai Huang ,  Wei Zhou ,  Jae-Hun Kim ,  Nicolas Zorn ,  Dong Xiao ,  Gioconda V. Gallo ,  Walter Won ,  Heping Wu ,  Rajan Anand ,  Qiaolin Deng

IPC: C07D487/04 ,  A61K31/519 ,  C07D487/08 ,  C07D487/18 ,  C07D513/04

CPC classification number: C07D487/04 ,  C07D487/08 ,  C07D487/18 ,  C07D513/04

Abstract: Disclosed are compounds of Formula A: (structurally represented) where “RG1”, “RG2a”, “RG4”, “RG5”, “MG1”, “n” and “m” are defined herein which compounds are antagonists of A2A receptor. Disclosed herein also are uses of the compounds described herein as antagonists of the A2a receptor in the potential treatment or prevention of neurological disorders and diseases in which A2A receptors are involved. Disclosed herein also are pharmaceutical compositions comprising these compounds and uses of these pharmaceutical compositions.