公开(公告)号：US20170189441A1

公开(公告)日：2017-07-06

申请号：US15033715

申请日：2014-11-03

申请人： Steven L. COLLETTI ,  Thomas J. TUCKER ,  David M. TELLERS ,  Boyoung KIM ,  Rob BURKE ,  Kathleen B. CALATI ,  Matthew G. STANTON ,  Rubina G. PARMAR ,  Jeffrey G. AARONSON ,  Weimin WANG ,  MERCK SHARP & DOHME CORP.

发明人： Steven L. Colletti ,  Thomas J. Tucker ,  David M. Tellers ,  Boyoung Kim ,  Rob Burke ,  Kathleen B. Calati ,  Matthew G. Stanton ,  Rubina G. Parmar ,  Jeffery G. Aaronson ,  Weimin Wang

IPC分类号： A61K31/7125 ,  A61K38/10 ,  A61K38/16 ,  A61K31/713

CPC分类号： A61K31/7125 ,  A61K31/713 ,  A61K38/10 ,  A61K38/16 ,  C07K2319/10 ,  C12N15/111 ,  C12N15/113 ,  C12N15/87 ,  C12N2310/14 ,  C12N2310/351 ,  C12N2320/31

摘要： Disclosed herein is a method for inhibiting expression of a gene of a subject comprising administering (1) a composition comprising R-(L)a-(G)b; wherein R is an oligonucleotide selected from the group consisting of DNA, RNA, siRNA, and microRNA; L is a linker and each occurrence of L is independently selected from Table 3; G is a targeting ligand and each occurrence of G is independently selected from Table 4; each of a and b is independently 0, 1, 2, 3 or 4; and (2) a composition comprising (P)c-(L)d-(G)e; wherein P is a peptide and each occurrence of P is independently selected from Table 2; L is a linker and each occurrence of L is independently selected from Table 3; G is a targeting ligand and each occurrence of G is independently selected from Table 4; d is 0, 1, 2, 3, 4, 5 or 6; and each of c and e is independently 1, 2, 3, 4, 5 or 6. Compositions in (1) and (2) can be co-administered or sequentially administered.

公开(公告)号：US10010562B2

公开(公告)日：2018-07-03

申请号：US15033715

申请日：2014-11-03

申请人： Merck Sharp & Dohme Corp.

发明人： Steven L. Colletti ,  Thomas J. Tucker ,  David M. Tellers ,  Boyoung Kim ,  Rob Burke ,  Kathleen B. Calati ,  Matthew G. Stanton ,  Rubina G. Parmar ,  Jeffrey G. Aaronson ,  Weimin Wang

IPC分类号： A61K31/713 ,  C12N15/113 ,  C07H15/203 ,  A61K31/7125 ,  A61K38/10 ,  A61K38/16

CPC分类号： A61K31/7125 ,  A61K31/713 ,  A61K38/10 ,  A61K38/16 ,  C07K2319/10 ,  C12N15/111 ,  C12N15/113 ,  C12N15/87 ,  C12N2310/14 ,  C12N2310/351 ,  C12N2320/31

摘要： Disclosed herein is a method for inhibiting expression of a gene of a subject comprising administering (1) a composition comprising R-(L)a-(G)b; wherein R is an oligonucleotide selected from the group consisting of DNA, RNA, siRNA, and microRNA; L is a linker and each occurrence of L is independently selected from Table 3; G is a targeting ligand and each occurrence of G is independently selected from Table 4; each of a and b is independently 0, 1, 2, 3 or 4; and (2) a composition comprising (P)c-(L)d-(G)e; wherein P is a peptide and each occurrence of P is independently selected from Table 2; L is a linker and each occurrence of L is independently selected from Table 3; G is a targeting ligand and each occurrence of G is independently selected from Table 4; d is 0, 1, 2, 3, 4, 5 or 6; and each of c and e is independently 1, 2, 3, 4, 5 or 6. Compositions in (1) and (2) can be co-administered or sequentially administered.

公开(公告)号：US20190015442A1

公开(公告)日：2019-01-17

申请号：US15974135

申请日：2018-05-08

申请人： Merck Sharp & Dohme Corp.

发明人： Steven L. Colletti ,  Thomas J. Tucker ,  David M. Tellers ,  Boyoung Kim ,  Rob Burke ,  Kathleen B. Calati ,  Matthew G. Stanton ,  Rubina G. Parmar ,  Jeffrey G. Aaronson ,  Weimin Wang

IPC分类号： A61K31/7125 ,  C12N15/113 ,  C12N15/87 ,  A61K38/16 ,  A61K38/10 ,  A61K31/713 ,  C12N15/11

CPC分类号： A61K31/7125 ,  A61K31/713 ,  A61K38/10 ,  A61K38/16 ,  C07K2319/10 ,  C12N15/111 ,  C12N15/113 ,  C12N15/87 ,  C12N2310/14 ,  C12N2310/351 ,  C12N2320/31

摘要： Disclosed herein is a method for inhibiting expression of a gene of a subject comprising administering (1) a composition comprising R-(L)a-(G)b; wherein R is an oligonucleotide selected from the group consisting of DNA, RNA, siRNA, and microRNA; L is a linker and each occurance of L is independently selected from Table 3; G is a targeting ligand and each occurance of G is independently selected from Table 4; each of a and b is independently 0, 1, 2, 3 or 4; and (2) a composition comprising (P)c-(L)d-(G)e; wherein P is a peptide and each occurance of P is independently selected from Table 2; L is a linker and each occurance of L is independently selected from Table 3; G is a targeting ligand and each occurance of G is independently selected from Table 4; d is 0, 1, 2, 3, 4, 5 or 6; and each of c and e is independently 1, 2, 3, 4, 5 or 6. Compositions in (1) and (2) can be co-administered or sequentially administered.

公开(公告)号：US10239957B2

公开(公告)日：2019-03-26

申请号：US15033731

申请日：2014-11-03

申请人： Merck Sharp & Dohme Corp.

发明人： Steven L. Colletti ,  Thomas J. Tucker ,  David M. Tellers ,  Boyoung Kim ,  Rob Burke ,  Kathleen B. Calati ,  Matthew G. Stanton ,  Rubina G. Parmar ,  Jeffery G. Aaronson ,  Weimin Wang

IPC分类号： C07K19/00 ,  C12N15/62 ,  C12N15/113 ,  A61K38/14

摘要： Disclosed herein is a peptide containing conjugate comprising (P)c-(L)d-(G)e, wherein P is a peptide and each occurance of P is independently selected from Table 2; L is an optional linker and each occurance of L, if present, is independently selected from Table 3; G is a targeting ligand and each occurance of G is independently selected from Table 4; d is 0, 1, 2, 3, 4, 5 or 6; and each of c and e is independently 1, 2, 3, 4, 5 or 6. The conjugate can be administered to a subject either alone or in combination with a composition comprising R-(L)a-(G)b, wherein R is an oligonucleotide as defined herein, to inhibit expression of a gene of the subject.

公开(公告)号：US20170081425A1

公开(公告)日：2017-03-23

申请号：US15033731

申请日：2014-11-03

申请人： Merck Sharp & Dohme Corp.

发明人： Steven L. Colletti ,  Thomas J. Tucker ,  David M. Tellers ,  Boyoung Kim ,  Rob Burke ,  Kathleen B. Calati ,  Matthew G. Stanton ,  Rubina G. Parmar ,  Jeffery G. Aaronson ,  Weimin Wang

IPC分类号： C07K19/00 ,  C12N15/113

CPC分类号： C07K19/00 ,  A61K38/14 ,  C07K2319/00 ,  C07K2319/01 ,  C12N15/113 ,  C12N15/62 ,  C12N2310/14 ,  C12N2310/3513

摘要： Disclosed herein is a peptide containing conjugate comprising (P)c-(L)d-(G)e, wherein P is a peptide and each occurance of P is independently selected from Table 2; L is an optional linker and each occurance of L, if present, is independently selected from Table 3; G is a targeting ligand and each occurance of G is independently selected from Table 4; d is 0, 1, 2, 3, 4, 5 or 6; and each of c and e is independently 1, 2, 3, 4, 5 or 6. The conjugate can be administered to a subject either alone or in combination with a composition comprising R-(L)a-(G)b, wherein R is an oligonucleotide as defined herein, to inhibit expression of a gene of the subject.

公开(公告)号：US10532068B2

公开(公告)日：2020-01-14

申请号：US15974135

申请日：2018-05-08

申请人： Merck Sharp & Dohme Corp.

发明人： Steven L. Colletti ,  Thomas J. Tucker ,  David M. Tellers ,  Boyoung Kim ,  Rob Burke ,  Kathleen B. Calati ,  Matthew G. Stanton ,  Rubina G. Parmar ,  Jeffrey G. Aaronson ,  Weimin Wang

IPC分类号： C12N15/87 ,  A61K31/713 ,  A61K38/10 ,  A61K38/16 ,  C12N15/11 ,  C12N15/113 ,  A61K31/7125

摘要： Disclosed herein is a method for inhibiting expression of a gene of a subject comprising administering (1) a composition comprising R-(L)a-(G)b; wherein R is an oligonucleotide selected from the group consisting of DNA, RNA, siRNA, and microRNA; L is a linker and each occurrence of L is independently selected from Table 3; G is a targeting ligand and each occurrence of G is independently selected from Table 4; each of a and b is independently 0, 1, 2, 3 or 4; and (2) a composition comprising (P)c-(L)d-(G)e; wherein P is a peptide and each occurrence of P is independently selected from Table 2; L is a linker and each occurrence of L is independently selected from Table 3; G is a targeting ligand and each occurrence of G is independently selected from Table 4; d is 0, 1, 2, 3, 4, 5 or 6; and each of c and e is independently 1, 2, 3, 4, 5 or 6. Compositions in (1) and (2) can be co-administered or sequentially administered.

公开(公告)号：US07538112B2

公开(公告)日：2009-05-26

申请号：US11579772

申请日：2005-05-03

申请人： John S. Wai ,  Joseph P. Vacca ,  Linghang Zhuang ,  Boyoung Kim ,  Terry A. Lyle ,  Catherine M. Wiscount ,  Melissa S. Egbertson ,  Lou Anne Neilson ,  Mark Embrey ,  Thorsten E. Fisher ,  Donnette D. Staas

发明人： John S. Wai ,  Joseph P. Vacca ,  Linghang Zhuang ,  Boyoung Kim ,  Terry A. Lyle ,  Catherine M. Wiscount ,  Melissa S. Egbertson ,  Lou Anne Neilson ,  Mark Embrey ,  Thorsten E. Fisher ,  Donnette D. Staas

IPC分类号： C07D487/14 ,  A61K31/5025 ,  A61K31/4985

CPC分类号： A61K31/5025 ,  C07D487/14 ,  Y02A50/414

摘要： Hydroxy-substituted pyrazinopyrrolopyridazine dione compounds are inhibitors of HIV integrase and inhibitors of HIV replication. In one embodiment, the dione compounds are of Formula (I) wherein R1, R2, R3, R4, R5, R6 and R7 are defined herein. The compounds are useful in the prevention and treatment of infection by HIV and in the prevention, delay in the onset, and treatment of AIDS. The compounds are employed against HIV infection and AIDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.

摘要翻译： 羟基取代的吡嗪并吡咯并哒嗪二酮化合物是HIV整合酶和HIV复制抑制剂的抑制剂。 在一个实施方案中，二酮化合物具有式（I），其中R 1，R 2，R 3，R 4，R 5，R 6和R 7在本文中定义。 这些化合物可用于预防和治疗艾滋病毒感染以及预防，延迟艾滋病的发病和治疗。 这些化合物用作抗感染和艾滋病作为化合物本身或以药学上可接受的盐的形式。 化合物及其盐可以用作药物组合物中的成分，任选与其它抗病毒剂，免疫调节剂，抗生素或疫苗组合使用。

公开(公告)号：US20070179196A1

公开(公告)日：2007-08-02

申请号：US10587682

申请日：2005-03-09

申请人： Wei Han ,  Melissa Egbertson ,  John Wai ,  Linghang Zhuang ,  Rowena Ruzek ,  Debra Perlow ,  Richard Isaacs ,  Mark Cameron ,  Bruce Foster ,  Ulf Dolling ,  R. Hoermer ,  Vanessa Obligado ,  Lou Neilson ,  Boyoung Kim ,  Linda Payne ,  Matthew Morrissette ,  Peter Williams ,  Philip Pye ,  Remy Angelaud ,  Danny Mancheno ,  David Askin

发明人： Wei Han ,  Melissa Egbertson ,  John Wai ,  Linghang Zhuang ,  Rowena Ruzek ,  Debra Perlow ,  Richard Isaacs ,  Mark Cameron ,  Bruce Foster ,  Ulf Dolling ,  R. Hoermer ,  Vanessa Obligado ,  Lou Neilson ,  Boyoung Kim ,  Linda Payne ,  Matthew Morrissette ,  Peter Williams ,  Philip Pye ,  Remy Angelaud ,  Danny Mancheno ,  David Askin

IPC分类号： A01N37/08

CPC分类号： C07D471/04

摘要： Hydroxy (tetra- or hexa-)hydronaphthyridine dione compounds of Formula I are inhibitors of HIV integrase and inhibitors of HIV replication: (I) wherein a, R,1?, R,2?, R,3?, R,4? and R,5? are defined herein. The compounds are useful in the prevention and treatment of infection by HIV and in the prevention, delay in the onset, and treatment of AIDS. The compounds are employed against HIV infection and AIDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.

摘要翻译： 式I的羟基（四或六） - 氢化萘啶二酮化合物是HIV整合酶和HIV复制抑制剂的抑制剂：（I）其中a，R ，1？，R 2？R ，3？，R ，4？ 并且R ，5？ 在本文中定义。 这些化合物可用于预防和治疗艾滋病毒感染以及预防，延迟艾滋病的发病和治疗。 这些化合物用作抗感染和艾滋病作为化合物本身或以药学上可接受的盐的形式。 化合物及其盐可以用作药物组合物中的成分，任选与其它抗病毒剂，免疫调节剂，抗生素或疫苗组合使用。

公开(公告)号：US20070093496A1

公开(公告)日：2007-04-26

申请号：US10576328

申请日：2004-10-18

申请人： John Wai ,  Thorsten Fisher ,  Linghang Zhuang ,  Donnette Staas ,  Terry Lyle ,  Boyoung Kim ,  Mark Embrey ,  Catherine Wiscount ,  Lekhanh Tran ,  Melissa Egbertson ,  Kelly Savage

发明人： John Wai ,  Thorsten Fisher ,  Linghang Zhuang ,  Donnette Staas ,  Terry Lyle ,  Boyoung Kim ,  Mark Embrey ,  Catherine Wiscount ,  Lekhanh Tran ,  Melissa Egbertson ,  Kelly Savage

IPC分类号： A61K31/498 ,  C07D487/14

CPC分类号： C07D471/14

摘要： Hydroxy-substituted pyridopyrrolopyrazine dione compounds are inhibitors of HIV integrase and inhibitors of HIV replication. In one embodiment, the dione compounds are of Formula (I): (I) wherein a, b, A, B, R1, R2, R3, R4, R5, R6, R7 and R8 are defined herein. The compounds are useful in the prevention and treatment of infection by HIV and in the prevention, delay in the onset, and treatment of AIDS. The compounds are employed against HIV infection and AIDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.

摘要翻译： 羟基取代的吡啶并吡咯并吡嗪二酮化合物是HIV整合酶和HIV复制抑制剂的抑制剂。 在一个实施方案中，二酮化合物具有式（I）：（I）其中a，b，A，B，R 1，R 2， R 4，R 4，R 5，R 6，R 7和R 9， 这里定义了8。 这些化合物可用于预防和治疗艾滋病毒感染以及预防，延迟艾滋病的发病和治疗。 这些化合物用作抗感染和艾滋病作为化合物本身或以药学上可接受的盐的形式。 化合物及其盐可以用作药物组合物中的成分，任选与其它抗病毒剂，免疫调节剂，抗生素或疫苗组合使用。

公开(公告)号：US20130296317A1

公开(公告)日：2013-11-07

申请号：US13880992

申请日：2011-10-25

申请人： John A. McCauley ,  Hemaka A. Rajapakse ,  Thomas J. Greshock ,  John Sanders ,  Boyoung Kim ,  Vanessa L. Rada ,  Jonathan T. Kern ,  Heather H. Stevenson ,  Mark T. Bilodeau

发明人： John A. McCauley ,  Hemaka A. Rajapakse ,  Thomas J. Greshock ,  John Sanders ,  Boyoung Kim ,  Vanessa L. Rada ,  Jonathan T. Kern ,  Heather H. Stevenson ,  Mark T. Bilodeau

IPC分类号： C07D495/04 ,  C07D495/10

CPC分类号： C07D495/04 ,  C07D495/10

摘要： Disclosed are compounds of Formula (I): and the pharmaceutically acceptable salts thereof, wherein “A” is S—; —SO—, —SO2—, —O— or NRac—, wherein Rac is H, or C1-20 alkyl and R1 through R5 are defined herein. Also disclosed are pharmaceutical formulations comprising a compound of Formula I and methods of treating, managing, or ameliorating diseases amenable to treatment, management, or amelioration by inhibition of LRRK2 kinase activity, for example, Parkinson's disease.

摘要翻译： 公开了式（I）的化合物及其药学上可接受的盐，其中“A”为S-; -SO - ， - SO 2 - ， - O-或NRac-，其中Rac是H，或C 1-20烷基和R 1至R 5在本文中定义。 还公开了包含式I化合物的药物制剂以及通过抑制LRRK2激酶活性（例如帕金森病）治疗，治疗或改善易于治疗，治疗或改善的疾病的方法。