Patents Represented by Attorney Keith D. MacMillan
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Patent number: 8338614Abstract: The present invention is directed to tertiary carbinamine compounds having substituted heterocycles, which are inhibitors of the beta-secretase enzyme, and are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of such diseases in which the beta-secretase enzyme is involved.Type: GrantFiled: January 13, 2006Date of Patent: December 25, 2012Assignee: Merck, Sharp & Dohme Corp.Inventors: Georgia B. McGaughey, Philippe G. Nantermet, Hemaka A. Rajapakse, Shaun R. Stauffer
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Patent number: 8293759Abstract: The present invention is directed to spiropiperidine compounds of formula (I) which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of such diseases in which the beta-secretase enzyme is involved.Type: GrantFiled: October 29, 2007Date of Patent: October 23, 2012Assignee: Merck, Sharp & Dohme, Corp.Inventors: Shaun R. Stauffer, Ivory D. Hills, Ashley Nomland
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Patent number: 8278334Abstract: Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is R is —C(O)—N(R27)(R28) or and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease. Also disclosed are pharmaceutical compositions and methods of treating cognitive or neurodegenerative diseases comprising the compounds of formula I in combination with a ?-secretase inhibitor other than those of formula I, an HMG-CoA reductase inhibitor, a gamma-secretase inhibitor, a non-steroidal anti-inflammatory agent, an N-methyl-D-aspartate receptor antagonist, a cholinesterase inhibitor or an anti-amyloid antibody.Type: GrantFiled: December 18, 2009Date of Patent: October 2, 2012Assignee: Merck, Sharp & Dohme Corp.Inventors: Jared N. Cumming, Ulrich Iserloh, Andrew Stamford, Corey Strickland, Johannes H. Voigt, Yusheng Wu, Ying Huang, Yan Xia, Samuel Chackalamannil, Tao Guo, Douglas W. Hobbs, Thuy X. H. Le, Jeffrey F. Lowrie, Kurt W. Saionz, Suresh D. Babu
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Patent number: 8242112Abstract: Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, —C(?S)—, —S(O)—, —S(O)2—, —C(?O)—, —O—, —C(R6)(R7)—, —N(R5)— or —C(?N(R5))—; X is —O—, —N(R5)— or —C(R6)(R7)—; provided that when X is —O—, U is not —O—, —S(O)—, —S(O)2—, —C(?O)— or —C(?NR5)—; U is a bond, —S(O)—, —S(O)2—, —C(O)—, —O—, —P(O)(OR15)—, —C(?NR5)—, —(C(R6)(R7))b— or —N(R5)—; wherein b is 1 or 2; provided that when W is —S(O)—, —S(O)2—, —O—, or —N(R5)—, U is not —S(O)—, —S(O)2—, —O—, or —N(R5)—; provided that when X is —N(R5)— and W is —S(O)—, —S(O)2—, —O—, or —N(R5)—, then U is not a bond; and R1, R2, R3, R4, R5, R6, and R7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I.Type: GrantFiled: May 16, 2011Date of Patent: August 14, 2012Assignees: Schering Corporation, Pharmacopeia Drug Discovery, Inc.Inventors: Zhaoning Zhu, Brian McKittrick, Zhong-Yue Sun, Yuanzan C. Ye, Johannes H. Voigt, Corey Strickland, Elizabeth M. Smith, Andrew W. Stamford, William J. Greenlee, Robert D. Mazzola, Jr., John P. Caldwell, Jared N. Cumming, Lingyan Wang, Yusheng Wu, Ulrich Iserloh, Tao Guo, Thuy X. H. Le, Kurt W. Saionz, Suresh D. Babu, Rachael C. Hunter, Michelle L. Morris, Huizhong Gu, Gang Qian, Dawit Tadesse
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Patent number: 8211904Abstract: The present invention is directed to spiropiperidine compounds of formula (I) and tautomers thereof, which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of such diseases in which the beta-secretase enzyme is involved.Type: GrantFiled: July 14, 2006Date of Patent: July 3, 2012Assignees: Merck, Sharp & Dohme Corp., Sunesis Pharmaceuticals, Inc.Inventors: Craig A. Coburn, Melissa S. Egbertson, Samuel L. Graham, Georgia B. McGaughey, Shaun R. Stauffer, Hemaka A. Rajapakse, Philippe G. Nantermet, Shawn J. Stachel, Wenjin Yang, Wanli Lu, Bruce Fahr
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Patent number: 8202854Abstract: Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein Ar, R1, R2, R3, R4 and R5 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.Type: GrantFiled: July 27, 2011Date of Patent: June 19, 2012Assignee: Schering CorporationInventors: Zhaoning Zhu, Andrew W. Stamford, Brian McKittrick
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Patent number: 8183252Abstract: Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, —C(?S)—, —S(O)—, —S(O)2—, —C(?O)—, —O—, —C(R6)(R7)—, —N(R5)— or —C(?N(R5))—; X is —O—, —N(R5)— or —C(R6)(R7)—; provided that when X is —O—, U is not —O—, —S(O)—, —S(O)2—, —C(?O)— or —C(?NR5)—; U is a bond, —S(O)—, —S(O)2—, —C(O)—, —O—, —P(O)(OR15)—, —C(?NR5)—, —(C(R6)(R7))b— or —N(R5)—; wherein b is 1 or 2; provided that when W is —S(O)—, —S(O)2—, —O—, or —N(R5)—, U is not —S(O)—, —S(O)2—, —O—, or —N(R5)—; provided that when X is —N(R5)— and W is —S(O)—, —S(O)2—, —O—, or —N(R5)—, then U is not a bond; and R1, R2, R3, R4, R5, R6, and R7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I.Type: GrantFiled: January 26, 2010Date of Patent: May 22, 2012Assignees: Schering Corporation, Pharmacopeia Inc.Inventors: Zhaoning Zhu, Zhong-Yue Sun, Andrew Stamford, William J. Greenlee, Jared N. Cumming, Lingyan Wang, Ulrich Iserloh, Xiaoxiang Liu, Ying Huang, Guoqing Li, Jianping Pan
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Patent number: 8168641Abstract: Disclosed are compounds of formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, U, W, X, R1, R2, R6, R7, R30 and R31 are as described above in the specification. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.Type: GrantFiled: June 7, 2007Date of Patent: May 1, 2012Assignee: Schering CorporationInventors: Yusheng Wu, Ulrich Iserloh, Jared N. Cumming, Xiaoxiang Liu, Robert D. Mazzola, Zhong-Yue Sun, Ying Huang, Andrew Stamford, Brian McKittrick, Zhaoning Zhu
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Patent number: 8143405Abstract: The present invention is directed to compounds of formula (I) which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of such diseases in which the beta-secretase enzyme is involved.Type: GrantFiled: September 19, 2007Date of Patent: March 27, 2012Assignee: Merck, Sharp & Dohme CorpInventor: Shaun R. Stauffer
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Patent number: 8143246Abstract: The invention relates to 1-(4-(pyridin-2-yl)benzyl)imidazolidine-2,4-dione derivative having the general Formula I wherein R1 is H, (C1-6)alkyl (optionally substituted with oxo, (C1-3)alkyloxy, (C1-3)alkyloxycarbonyl, halogen or CN), (C3-6)cycloalkyl or (C3-6)cycloalkyl(C1-3)alkyl, each cycloalkyl ring optionally comprising a heteroatom selected from O and S; R2 and R3 are independently H or (C1-3)alkyl; or R2 and R3 form together with the carbon atom to which they are bound a (C3-5)cycloalkyl group; R4 is H or 1 to 3 F substituents; R5 is H or 1 to 4 F substituents; R6 and R7 are independently H or F; X represents R8, OR8, NR8R9, R8 is (C5-7)cycloalkyl optionally comprising a heteroatom selected from O, S, SO and SO2; R9 is H or (C1-4)alkyl; R10 represents 1-3 substituents independently selected from H, (C1-3)alkyl, halogen, oxo, CN and CF3; Y is CF2, O, S, SO or SO2; or a pharmaceutically acceptable salt thereof, to pharmaceutical compositions comprising the same, as well as to the use of said 1-(4Type: GrantFiled: February 15, 2010Date of Patent: March 27, 2012Assignee: MSD OSS B.V.Inventors: Marcelis van der Stelt, Joseph Maria Gerardus Barbara Cals, Johannes Petrus Gerardus Klomp
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Patent number: 8114887Abstract: The present invention is directed to spiropiperidine compounds of formula (I) which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of such diseases in which the beta-secretase enzyme is involved.Type: GrantFiled: October 12, 2005Date of Patent: February 14, 2012Assignees: Merck, Sharp & Dohme Corp., Sunesis Pharmaceuticals, Inc.Inventors: James C. Barrow, Craig A. Coburn, Melissa S. Egbertson, Georgia B. McGaughey, Melody A. McWherter, Lou Anne Neilson, Kenneth E. Rittle, Harold G. Selnick, Shaun R. Stauffer, Zhi-Qiang Yang, Wenjin Yang, Wanli Lu, Bruce Fahr
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Patent number: 8110682Abstract: Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein A is a bond, —C(O)—, or —C(R3?)(R4?)—; X is —N(R1)— or —C(R6)(R7)—; Y is —S(O)2—, —C(?O)—, —PO(OR9) or —C(R6?R7?)—; is a single or double bond and R, R1, R2, R3, R4, R3?, R4?, R5, R6, R6?, R7 and R7? are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic antagonist.Type: GrantFiled: June 12, 2006Date of Patent: February 7, 2012Assignee: Schering CorporationInventors: Brian McKittrick, Zhaoning Zhu, Andrew Stamford, Elizabeth M. Smith
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Patent number: 8093254Abstract: Disclosed are compounds of formula I (Chemical formula should be inserted here as it appears on abstract in paper form) Formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, R3, R4, R14, V, W, X, Y, Z, p, and ring A are as described in the specification. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.Type: GrantFiled: December 10, 2007Date of Patent: January 10, 2012Assignee: Schering CorporationInventors: Zhaoning Zhu, Andrew Stamford, Mihirbaran Mandal, Xiaoxiang Liu
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Patent number: 8012953Abstract: Disclosed are novel compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, R3, n and X are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease. Also disclosed are methods of treating a cognitive or neurodegenerative disease comprising administering to a patient I need of such treatment a combination of at least one compound of formula I and at least one compound selected from the group consisting of ?-secretase inhibitors other than those of formula I, HMG-CoA reductase inhibitors, gamma-secretase inhibitors, non-steroidal anti-inflammatory agents, N-methyl-D-aspartate receptor antagonists, cholinesterase inhibitors and anti-amyloid antibodies.Type: GrantFiled: October 1, 2009Date of Patent: September 6, 2011Assignee: Schering CorporationInventors: Andrew W. Stamford, Ying Huang, Guoqing Li, Corey O. Strickland, Johannes H. Voigt
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Patent number: 8008315Abstract: The present invention is directed to compounds which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of such diseases in which the beta-secretase enzyme is involved.Type: GrantFiled: May 3, 2010Date of Patent: August 30, 2011Assignee: Merck, Sharp & Dohme Corp.Inventors: Philippe G. Nantermet, Hemaka Anthony Rajapakse, Harold G. Selnick
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Patent number: 7973067Abstract: Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, —C(?S)—, —S(O)—, —S(O)2—, —C(?O)—, —O—, —C(R6)(R7)—, —N(R5)— or —C(?N(R5))—; X is —O—, —N(R5)— or —C(R6)(R7)—; provided that when X is —O—, U is not —O—, —S(O)—, —S(O)2—, —C(?O)— or —C(?NR5)—; U is a bond, —S(O)—, —S(O)2—, —C(O)—, —O—, —P(O)(OR15)—, —C(?NR5)—, —(C(R6)(R7))b— or —N(R5)—; wherein b is 1 or 2; provided that when W is —S(O)—, —S(O)2—, —O—, or —N(R5)—, U is not —S(O)—, —S(O)2—, —O—, or —N(R5)—; provided that when X is —N(R5)— and W is —S(O)—, —S(O)2—, —O—, or —N(R5)—, then U is not a bond; and R1, R2, R3, R4, R5, R6, and R7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I.Type: GrantFiled: December 10, 2008Date of Patent: July 5, 2011Assignee: Schering CorporationInventors: Zhaoning Zhu, Brian McKittrick, Zhong-Yue Sun, Yuanzan C. Ye, Johannes H. Voigt, Corey Strickland, Elizabeth M. Smith, Andrew Stamford, William J. Greenlee, Robert D. Mazzola, Jr., John P. Caldwell, Jared N. Cumming, Lingyan Wang, Yusheng Wu, Ulrich Iserloh, Tao Guo, Thuy X. H. Le, Kurt W. Saionz, Suresh D. Babu, Rachel C. Hunter, Michelle L. Morris, Huizhong Gu, Gang Qian, Dawit Tadesse
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Patent number: 7968571Abstract: The present invention is directed to 2,4,6-substituted pyridyl derivative compounds which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of such diseases in which the beta-secretase enzyme is involved.Type: GrantFiled: April 20, 2005Date of Patent: June 28, 2011Assignee: Merck, Sharp & Dohme, Corp.Inventors: James C. Barrow, Georgia B. McGaughey, Philippe G. Nantermet, Hemaka A. Rajapakse, Harold G. Selnick, Shaun R. Stauffer, Joseph P. Vacca, Shawn J. Stachel, Craig A. Coburn, Matthew G. Stanton
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Patent number: 7951949Abstract: The present invention is directed to macrocyclic aminopyridyl compounds represented by general formula (I), which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of such diseases in which the beta-secretase enzyme is involved.Type: GrantFiled: November 18, 2005Date of Patent: May 31, 2011Assignee: Merck, Sharp & Dohme, Corp.Inventors: Philippe G. Nantermet, Hemaka A. Rajapakse, Harold G. Selnick, Keith P. Moore
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Patent number: 7932275Abstract: The present invention is directed to 2-aminopyridine compounds which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of such diseases in which the beta-secretase enzyme is involved.Type: GrantFiled: October 25, 2005Date of Patent: April 26, 2011Assignee: Merck, Sharp & Dohme Corp.Inventors: Craig A. Coburn, M. Katharine Holloway, Shawn J. Stachel
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Patent number: 7910590Abstract: Disclosed are novel compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is X is —O—, —C(R 14)2— or —N(R)—; Z is —C(R14)2— or —N(R)—; t is 0, 1, 2 or 3; each R and R2 is independently H, alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, heterocycloalkylalkyl, alkenyl or alkynyl; each R14 is H, alkyl, alkenyl, alkynyl, halo, —CN, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, heterocycloalkylalkyl, —OR35, —N(R24)(R25) or —SR35; R41 is alkyl, cycloalkyl, —SO2(alkyl), —C(O)-alkyl, —C(O)-cycloalkyl or -alkyl-NH—C(O)CH3; and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I and methods of treating cognitive or neurodegenerative diseases with compounds of formula I.Type: GrantFiled: June 24, 2009Date of Patent: March 22, 2011Assignee: Schering CorporationInventors: Ying Huang, Guoqing Li, Ulrich Iserloh, Andrew Stamford, Corey Strickland, Johannes H. Voigt, Jianping Pan