公开(公告)号：US11339156B2

公开(公告)日：2022-05-24

申请号：US16621953

申请日：2018-06-22

Applicant: Merck Sharp & Dohme Corp. ,  MSD R&D (China) Co., Ltd.

Inventor： John J. Acton, III ,  Jianming Bao ,  Qiaolin Deng ,  Melissa Egbertson ,  Ronald Ferguson, II ,  Xiaolei Gao ,  Scott Timothy Harrison ,  Timothy J. Henderson ,  Sandra L. Knowles ,  Chunsing Li ,  Michael Man-Chu Lo ,  Robert D. Mazzola, Jr. ,  Meng Na ,  Michael T. Rudd ,  Oleg B. Selyutin ,  David M. Tellers ,  Ling Tong ,  Fengqi Zhang ,  Takao Suzuki

IPC: C07D471/04 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  C07D487/04 ,  C07D417/14

Abstract: The present invention is directed to pyrazol-4-yl-pyridine compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which M4 muscarinic acetylcholine receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which M4 muscarinic acetylcholine receptors are involved.

公开(公告)号：US11149036B2

公开(公告)日：2021-10-19

申请号：US16621959

申请日：2018-06-22

Applicant: John J. Acton, III ,  Merck Sharp & Dohme Corp. ,  MSD R&D (China) Co., Ltd. ,  Jianming Bao ,  Qiaolin Deng ,  Melissa Egbertson ,  Ronald Ferguson, II ,  Xiaolei Gao ,  Scott Timothy Harrison ,  Sandra L. Knowles ,  Chunsing Li ,  Michael Man-Chu Lo ,  Robert D. Mazzola, Jr. ,  Zhaoyang Meng ,  Meng Na ,  Michael T. Rudd ,  Oleg Selyutin ,  David M. Tellers ,  Ling Tong ,  Fengqi Zhang

Inventor： John J. Acton, III ,  Jianming Bao ,  Qiaolin Deng ,  Melissa Egbertson ,  Ronald Ferguson, II ,  Xiaolei Gao ,  Scott Timothy Harrison ,  Sandra L. Knowles ,  Chunsing Li ,  Michael Man-Chu Lo ,  Robert D. Mazzola, Jr. ,  Zhaoyang Meng ,  Meng Na ,  Michael T. Rudd ,  Oleg Selyutin ,  David M. Tellers ,  Ling Tong ,  Fengqi Zhang

IPC: C07D471/04 ,  C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  C07D491/048 ,  C07D498/04

Abstract: The present invention is directed to pyrazol-4-yl-pyridine compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which M4 muscarinic acetylcholine receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which M4 muscarinic acetylcholine receptors are involved.

公开(公告)号：US10933056B2

公开(公告)日：2021-03-02

申请号：US16674546

申请日：2019-11-05

Applicant: Merck Sharp & Dohme Corp. ,  MSD R&D (CHINA) CO., LTD.

Inventor： John J. Acton, III ,  Jianming Bao ,  Melissa Egbertson ,  Xiaolei Gao ,  Scott T. Harrison ,  Sandra L. Knowles ,  Chunsing Li ,  Michael Man-Chu Lo ,  Robert D. Mazzola, Jr. ,  Zhaoyang Meng ,  Michael T. Rudd ,  Oleg B. Selyutin ,  David M. Tellers ,  Ling Tong ,  Jenny Miu-Chun Wai

IPC: C07D401/14 ,  C07D405/14 ,  C07D471/04 ,  A61K31/4439 ,  A61P25/28 ,  A61P25/18 ,  A61P25/16 ,  A61K31/437

Abstract: The present invention is directed to pyrazol-4-yl-pyridine compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which M4 muscarinic acetylcholine receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which M4 muscarinic acetylcholine receptors are involved.

公开(公告)号：US10239957B2

公开(公告)日：2019-03-26

申请号：US15033731

申请日：2014-11-03

Applicant: Merck Sharp & Dohme Corp.

Inventor： 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: C07K19/00 ,  C12N15/62 ,  C12N15/113 ,  A61K38/14

Abstract: 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：US20190000824A1

公开(公告)日：2019-01-03

申请号：US16062500

申请日：2016-12-19

Applicant: Merck Sharp & Dohme Corp.

Inventor： John J. Acton, III ,  Jianming Bao ,  Melissa Egbertson ,  Xiaolei Gao ,  Scott T. Harrison ,  Sandra L. Knowles ,  Chunsing Li ,  Michael Man-Chu Lo ,  Robert D. Mazzola, Jr. ,  Zhaoyang Meng ,  Michael T. Rudd ,  Oleg B. Selyutin ,  David M. Tellers ,  Ling Tong ,  Jenny Miu-Chun Wai

IPC: A61K31/4439 ,  A61K31/437 ,  A61P25/16 ,  A61P25/18 ,  A61P25/28

CPC classification number: A61K31/4439 ,  A61K31/437 ,  A61P25/16 ,  A61P25/18 ,  A61P25/28 ,  C07D401/14 ,  C07D405/14 ,  C07D471/04

Abstract: The present invention is directed to pyrazol-4-yl-pyridine compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which M4 muscarinic acetylcholine 5 receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which M4 muscarinic acetylcholine receptors are involved.

公开(公告)号：US20170081425A1

公开(公告)日：2017-03-23

申请号：US15033731

申请日：2014-11-03

Applicant: Merck Sharp & Dohme Corp.

Inventor： 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: C07K19/00 ,  C12N15/113

CPC classification number: C07K19/00 ,  A61K38/14 ,  C07K2319/00 ,  C07K2319/01 ,  C12N15/113 ,  C12N15/62 ,  C12N2310/14 ,  C12N2310/3513

Abstract: 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：US10981902B2

公开(公告)日：2021-04-20

申请号：US16621943

申请日：2018-06-22

Applicant: Merck Sharp & Dohme Corp. ,  MERCK R&D (CHINA) CO., LTD.

Inventor： Jianming Bao ,  Timothy J. Henderson ,  Chunsing Li ,  Michael Man-Chu Lo ,  Robert D. Mazzola, Jr. ,  Meng Na ,  Michael T. Rudd ,  David M. Tellers ,  Ling Tong

IPC: C07D413/14 ,  C07D471/04 ,  C07D487/04

Abstract: The present invention is directed to 5-(pyridine-3-yl)oxaxole compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which M4 muscarinic acetylcholine receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which M4 muscarinic acetylcholine receptors are involved.

公开(公告)号：US10010562B2

公开(公告)日：2018-07-03

申请号：US15033715

申请日：2014-11-03

Applicant: Merck Sharp & Dohme Corp.

Inventor： 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: A61K31/713 ,  C12N15/113 ,  C07H15/203 ,  A61K31/7125 ,  A61K38/10 ,  A61K38/16

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

Abstract: 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：US20170189441A1

公开(公告)日：2017-07-06

申请号：US15033715

申请日：2014-11-03

Applicant: 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.

Inventor： 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: A61K31/7125 ,  A61K38/10 ,  A61K38/16 ,  A61K31/713

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

Abstract: 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：US20210395224A1

公开(公告)日：2021-12-23

申请号：US17286591

申请日：2019-10-24

Applicant: Merck Sharp & Dohme Corp. ,  MSD R&D (China) Co. LTD.

Inventor： John J. Acton, III ,  Melissa Egbertson ,  Xiaolei Gao ,  Scott T. Harrison ,  Timothy J. Henderson ,  Michael Man-Chu Lo ,  Robert D. Mazzola, Jr. ,  Zhaoyang Meng ,  James Mulhearn ,  Vanessa L. Rada ,  Jeffrey W. Schubert ,  Oleg B. Selyutin ,  David M. Tellers ,  Ling Tong ,  Fengqi Zhang ,  Jianming Bao ,  Chunsing Li

IPC: C07D401/14 ,  C07D405/14

Abstract: The present invention is directed to cinnolinyl and quinolinyl pyrazol-4-yl-pyridine compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which M4 muscarinic acetylcholine receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which M4 muscarinic acetylcholine receptors are involved.