Abstract: The present invention is directed to compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.
Type:
Application
Filed:
March 11, 2009
Publication date:
February 24, 2011
Applicant:
Merck Sharp & Dohme Corp.
Inventors:
Scott D. Kuduk, Ronald K. Chang, Christina Ng Di Marco
Abstract: The present invention involves an interactive selection system for a consumer product that improves the consumer's ability to quickly sort through numerous criteria in a complex decision making process and determine whether that particular consumer product is appropriate for his or her purchase and use.
Abstract: Compounds of formula I: (wherein variables A1, A2, A3, A4, m, n, J, Q, R4, Ea, Eb, Ec, R6, R7, Re, Rf, RPG and Y are as described herein) which are antagonists of CGRP receptors and which are useful in the treatment or prevention of diseases in which the CGRP is involved, such as migraine. 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 CGRP is involved.
Type:
Grant
Filed:
November 9, 2009
Date of Patent:
February 22, 2011
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Michael R. Wood, Steven N. Gallicchio, Harold G. Selnick, C. Blair Zartman, Ian M. Bell, Craig A. Stump
Abstract: This invention concerns compositions for the treatment of urinary frequency, urinary urgency and urinary incontinence comprising (R)-N-[4-[2-[[2-hydroxy-2-(pyridin-3 -yl)ethyl]amino]ethyl]phenyl]-4-[4-(4-trifluoromethylphenyl)thiazol-2-yl]benzenesulfonamide and pharmaceutically acceptable salts thereof. In another aspect, this invention concerns combination therapy for urinary frequency, urinary urgency and urinary incontinence wherein one of the active agents is (R)-N-[4-[2-[[2-hydroxy-2-(pyridin-3-yl)ethyl]amino]ethyl]phenyl]-4-[4-(4-trifluoromethylphenyl)thiazol-2-yl]benzenesulfonamide and pharmaceutically acceptable salts thereof.
Type:
Grant
Filed:
September 29, 2006
Date of Patent:
February 22, 2011
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Keith M. Gottesdiener, Stuart A. Green, Euan MacIntyre
Abstract: Benzazepinone compounds represented by Formula (I), or pharmaceutically acceptable salts thereof. Pharmaceutical compositions comprise an effective amount of the instant compounds, either alone, or in combination with one or more other therapeutically active compounds, and a pharmaceutically acceptable carrier. Methods of treating conditions associated with, or caused by, sodium channel activity, including, for example, acute pain, chronic pain, visceral pain, inflammatory pain, neuropathic pain, epilepsy, irritable bowel syndrome, urinary incontinence, pruritis, itchiness, allergic dermatitis, depression, anxiety, multiple sclerosis, and bipolar disorder, comprise administering an effective amount of the present compounds, either alone, or in combination with one or more other therapeutically active compounds.
Type:
Grant
Filed:
June 5, 2007
Date of Patent:
February 15, 2011
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Scott B. Hoyt, Clare London, Dong Ok, William H. Parsons
Abstract: The present invention is directed to novel substituted aminopiperidines which are inhibitors of the dipeptidyl peptidase-IV enzyme (“DPP-IV inhibitors”) and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. 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 the dipeptidyl peptidase-IV enzyme is involved.
Type:
Grant
Filed:
September 27, 2005
Date of Patent:
February 8, 2011
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Jason M. Cox, Scott D. Edmondson, Bart Harper, Ann E. Weber
Abstract: The present invention relates to macrocyclic compounds of formula (I) that are useful as inhibitors of the hepatitis C virus (HCV) NS3 protease, their synthesis, and their use for treating or preventing HCV infections.
Type:
Grant
Filed:
April 28, 2006
Date of Patent:
February 1, 2011
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
M. Katharine Holloway, Nigel J. Liverton, Steven W. Ludmerer, John A. McCauley, David Olsen, Michael T. Rudd, Joseph P. Vacca
Abstract: The present application features the use of the somatostatin subtype 3 receptor (SST3) as a target for affecting insulin secretion and for diagnosing diabetes related disorders. Glucose stimulated insulin secretion was found to be stimulated by knocking down expression of SST3 and through the use of a SST3 selective antagonist.
Type:
Grant
Filed:
November 17, 2006
Date of Patent:
February 1, 2011
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Yun-Ping Zhou, Jing Li, Weizhen Wu, Jin Shang, John R. Thompson, Nancy A. Thornberry
Abstract: A compound having the structure wherein R is an angiotensin receptor antagonist active group, Y is -Y1-Y2-Y3-Y4-Y5-; Y1 is C(R1R2); R1 is selected from the group consisting of hydrogen and C1-4 alkyl; R2 is selected from the group consisting of hydrogen, C1-4 alkyl, and —OC(O)C1-4 alkyl; Y2 is O or CH2; Y3 is C(O) or CH2; Y4 is O or CH2; Y5 is —(CH2)1-2—(X)0-1—(CH2)0-1— or is absent; X is —O— or —CR3R4—; and R3 and R4 are independently selected from the group consisting of hydrogen and C1-C4 alkyl; or a pharmaceutically acceptable salt or hydrate thereof, which is useful for treating hypertension.
Type:
Grant
Filed:
December 11, 2007
Date of Patent:
February 1, 2011
Assignees:
Merck Sharp & Dohme Corp., NiCox S.A.
Inventors:
Iyassu K. Sebhat, Michael Man-chu Lo, Ravi P. Nargund, Amjad Ali, Chris Franklin, Nicoletta Almirante, Laura Storoni, Silvia Stefanini
Abstract: The present invention provides nucleoside aryl phosphoramidates of structural formula (I) which are precursors to inhibitors of RNA-dependent RNA viral polymerase. These compounds are precursors to inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as precursors to inhibitors of hepatitis C virus (HCV) NS5B polymerase, as precursors to inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside aryl phosphoramidates alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the nucleoside aryl phosphoramidates of the present invention.
Type:
Grant
Filed:
February 12, 2007
Date of Patent:
February 1, 2011
Assignees:
Merck Sharp & Dohme Corp., Istituto di Ricerche di Biologia Molecolare P. Angeletti S.p.A.
Inventors:
Malcolm MacCoss, David B. Olsen, Monica Donghi, Cristina Gardelli, Steven Harper, Malte Meppen, Frank Narjes, Barbara Pacini
Abstract: The identification of a unique series of compounds which possesses special advantages in terms of drug-like properties due to their possessing advantageous properties in terms of potency and/or pharmacokinetic and/or selectivity and/or in vivo receptor occupancy properties. Specifically, the selection of a 1,3-thiazol-2-yl ring member linked by an ethynylene to the 3 position of a pyridyl ring or the 5 position of a pyrimidinyl ring, wherein the ring is substituted with selected substituents, results in a compound having superior drug-like properties. The invention includes pharmaceutically acceptable salt forms of these heterocyclic compounds, in particular chloride salts and trifluoroacetate salts.
Type:
Grant
Filed:
October 6, 2005
Date of Patent:
February 1, 2011
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Nicholas D. Cosford, Thomas J. Seiders, Joseph E. Payne, Jeffrey R. Roppe, Dehua Huang, Nicholas D. Smith, Steve F. Poon, Chris King, Brian W. Eastman, Bowei Wang, Jeannie M. Arruda, Jean-Michel Vernier, Xiumin Zhao
Abstract: The present invention relates to compounds having the structure useful as potassium channel inhibitors to treat cardiac arrhythmias, and the like.
Type:
Grant
Filed:
July 27, 2005
Date of Patent:
February 1, 2011
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Christopher J. Dinsmore, Jeffrey M. Bergman, Douglas C. Beshore, B. Wesley Trotter, Kausik K. Nanda, Richard Isaacs, Linda S. Payne, Lou Anne Neilson, Zhicai Wu, Mark T. Bilodeau, Peter J. Manley, Adrienne E. Balitza
Abstract: The present invention is directed to pyridyl amide compounds which are antagonists of T-type calcium channels, and which are useful in the treatment or prevention of disorders and diseases in which T-type calcium channels are involved. 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 T-type calcium channels are involved.
Type:
Grant
Filed:
April 11, 2007
Date of Patent:
January 25, 2011
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
James C. Barrow, Thomas S. Reger, Zhi-Qiang Yang
Abstract: Novel crystalline salts of 3-[1-(4-chlorophenyl)-trans-3-fluorocyclobutyl]-4,5-dicyclopropyl-r-4H-1,2,4-triazole are potent inhibitors of 11?-hydroxysteroid dehydrogenase Type 1 and are useful for the treatment of conditions associated with Metabolic Syndrome as well as cognitive impairment. The invention also relates to pharmaceutical compositions containing these novel salts, processes to prepare these salts and their pharmaceutical compositions as well as uses thereof for the treatment of Type 2 diabetes, hyperglycemia, obesity, dyslipidemia, hypertension, and cognitive impairment.
Type:
Grant
Filed:
January 21, 2005
Date of Patent:
January 25, 2011
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Yuri Bereznitski, Mark A. Huffman, Joseph E. Lynch, Matthew Zhao
Abstract: The present invention relates to a novel class of hydroxamic acid derivatives carbamate, urea, amide and sulfonamide substitutions. The hydroxamic acid compounds can be used to treat cancer. The hydroxamic acid 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 are also 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.
Type:
Grant
Filed:
April 14, 2006
Date of Patent:
January 18, 2011
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Joey Methot, Thomas A. Miller, David J. Witter
Abstract: The present invention relates to novel enfumafungin derivatives of formula I and pharmaceutically acceptable salts thereof, their synthesis, and their use as inhibitors of (1,3)-?-D-glucan synthase. The present compounds and pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions comprising the present compounds and pharmaceutically acceptable salts thereof, are useful for treating or preventing antifungal infections and associated diseases and conditions.
Type:
Grant
Filed:
March 29, 2007
Date of Patent:
January 4, 2011
Assignees:
Merck Sharp & Dohme Corp., Scynexis, Inc.
Inventors:
James M. Balkovec, Frances Aileen Bouffard, Bruno Tse, James Dropinski, Dongfang Meng, Mark L. Greenlee, Michael Peel, Weiming Fan, Ahmed Mamai, Hao Liu, Keqaing Li
Abstract: The present invention relates to genetic markers whose expression is correlated with breast cancer. Specifically, the invention provides sets of markers whose expression patterns can be used to differentiate clinical conditions associated with breast cancer, such as the presence or absence of the estrogen receptor ESR1, and BRCA1 and sporadic tumors, and to provide information on the likelihood of tumor distant metastases within five years of initial diagnosis. The invention relates to methods of using these markers to distinguish these conditions. The invention also relates to kits containing ready-to-use microarrays and computer software for data analysis using the statistical methods disclosed herein.
Type:
Grant
Filed:
June 23, 2008
Date of Patent:
January 4, 2011
Assignees:
The Netherlands Cancer Institute, Merck Sharp & Dohme Corp.
Inventors:
HongYue Dai, Yudong He, Peter S. Linsley, Mao Mao, Christopher J. Roberts, Laura Johanna Van't Veer, Marc J. Van de Vijver, Rene Bernards, Augustinus A. M. Hart
Abstract: The present invention relates to compounds, compositions, and methods useful for modulating the expression of genes associated with respiratory and pulmonary disease, such as cholinergic muscarinic receptor genes, using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of cholinergic muscarinic receptor genes, or other genes involved in pathways of cholinergic muscarinic receptor gene expression and/or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of M3 muscarinic acetylcholine receptor or cholinergic receptor muscarinic 3 (CHRM3).
Abstract: Certain novel substituted imidazole 4-carboxamides are ligands of the human cholecystokinin receptor and, in particular, are selective ligands of the human cholecystokinin-1 receptor (CCK-1R). They are therefore useful for the treatment, control, or prevention of diseases and disorders responsive to the modulation of CCK-1R, such as obesity, and diabetes.
Type:
Grant
Filed:
April 10, 2007
Date of Patent:
December 28, 2010
Assignee:
Merck Sharp & Dohme Corp.
Inventors:
Richard Berger, Scott Edmondson, Alexa Hansen, Cheng Zhu
Abstract: Compounds of Formula I: I (where variables R1A, R1B, R2, R3, R4, A, and Z are as defined herein) useful as antagonists of CGRP receptors, and useful in the treatment or prevention of diseases in which CGRP receptors are involved, such as headache, and in particular migraine and cluster headache. 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 CGRP receptors are involved.