Patents by Inventor Thomas H. Graham
Thomas H. Graham has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Publication number: 20240083913Abstract: The disclosure provides compounds of Formula (I) or a pharmaceutically acceptable salt thereof, wherein W1, W2, Y, Z, M, L, CY, Cz, R1, R2, R3, R4, R2a, Ry, Rz, and the subscripts m, n, q, and r are as described herein. The compounds or their pharmaceutically acceptable salts can inhibit the G12C mutant of Kirsten rat sarcoma (KRAS) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The disclosure also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The disclosure also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.Type: ApplicationFiled: May 3, 2023Publication date: March 14, 2024Inventors: Indu Bharathan, Symon Gathiaka, Yongxin Han, Xiaoshen Ma, Ryan D. Otte, David L. Sloman, Thomas H. Graham, Timothy Henderson, Elisabeth Hennessy, Anandan Palani
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Publication number: 20240076297Abstract: The present invention provides compounds of the structural Formula (I), and pharmaceutically acceptable salts thereof, wherein, are as defined herein, pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other therapeutically active agents), and methods for their preparation and use, alone and in combination with other therapeutic agents, as antagonists of A2a and/or A2b receptors, and in the treatment of a variety of diseases, conditions, or disorders that are mediated, at least in part, by the adenosine A2a receptor and/or the adenosine A2b receptor.Type: ApplicationFiled: July 22, 2021Publication date: March 7, 2024Applicant: Merck Sharp & Dohme LLCInventors: Amjad Ali, Jared N. Cumming, Manuel De Lera Ruiz, Duane DeMong, Thomas H. Graham, Elisabeth T. Hennessy, Joseph M. Kelly, Rongze Kuang, Michael Man-Chu Lo, Umar Faruk Mansoor, Jesus Moreno, Uma Swaminathan, Heping Wu, Yingchun Ye, Younong Yu
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Publication number: 20240043448Abstract: The disclosure provides compounds of Formula (I) or a pharmaceutically acceptable salt thereof, wherein W1, W2, Y, Z, M, L, Cy, Cz, R1, R2, R3, R4, R2a, Ry, Rz, and the subscripts m, n, q, and r are as described herein. The compounds or their pharmaceutically acceptable salts can inhibit the G12C mutant of Kirsten rat sarcoma (KRAS) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The disclosure also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The disclosure also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.Type: ApplicationFiled: May 3, 2023Publication date: February 8, 2024Inventors: Indu Bharathan, Symon Gathiaka, Yongxin Han, Xiaoshen Ma, Ryan D. Otte, David L. Sloman, Thomas H. Graham, Timothy Henderson, Elisabeth Hennessy, Anandan Palani
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Publication number: 20230322785Abstract: The present invention provides compounds of the structural Formula (I) and pharmaceutically acceptable salts thereof, wherein, are as defined herein, pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other therapeutically active agents), and methods for their preparation and use, alone and in combination with other therapeutic agents, as antagonists of A2a and/or A2b receptors, and in the treatment of a variety of diseases, conditions, or disorders that are mediated, at least in part, by the adenosine A2a receptor and/or the adenosine A2b receptor.Type: ApplicationFiled: July 21, 2022Publication date: October 12, 2023Applicant: Merck Sharp & Dohme LLCInventors: Amjad Ali, Christopher W. Boyce, Jared N. Cumming, Duane DeMong, Thomas H. Graham, Subrahmanyam Gudipati, Andrew J. Hoover, Xianhai Huang, Rongze Kuang, Jae-Hun Kim, Joseph M. Kelly, Yeon-Hee Lim, Michael Man-Chu Lo, Jesus Moreno, Jing Su, Heping Wu, Dong Xiao, Younong Yu, Xiaohong Zhu
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Patent number: 11697657Abstract: The disclosure provides compounds of Formula (I) or a pharmaceutically acceptable salt thereof, wherein W1, W2, Y, Z, M, L, Cy, Cz, R1, R2, R3, R4, R2a, Ry, Rz and the subscripts m, n, q, and r are as described herein. The compounds or their pharmaceutically acceptable salts can inhibit the G12C mutant of Kirsten rat sarcoma (KRAS) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The disclosure also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The disclosure also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.Type: GrantFiled: October 27, 2020Date of Patent: July 11, 2023Assignee: Merck Sharp & Dohme LLCInventors: Indu Bharathan, Symon Gathiaka, Yongxin Han, Xiaoshen Ma, Ryan D. Otte, David L. Sloman, Thomas H. Graham, Timothy Henderson, Elisabeth Hennessy, Anandan Palani
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Publication number: 20230054411Abstract: In its many embodiments, the present invention provides certain 7-, 8-, and 10-substituted amino triazolo quinazoline derivatives of Formula (I): or a pharmaceutically acceptable salt thereof, wherein ring A, R1, R2, and R4 are as defined herein, pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other therapeutic agents), and methods for their preparation and use, alone and in combination with other therapeutic agents, as antagonists of A2a and/or A2b receptors, and their use in the treatment of a variety of diseases, conditions, or disorders that are mediated, at least in part, by the adenosine A2a receptor and/or the adenosine A2b receptor.Type: ApplicationFiled: November 26, 2019Publication date: February 23, 2023Applicant: Merck Sharp & Dohme Corp.Inventors: Yonglian Zhang, Amjad Ali, Jared Cumming, Duane DeMong, Qiaolin Deng, Thomas H. Graham, Elisabeth Hennessy, Matthew A. Larsen, Kun Liu, Ping Liu, Umar Faruk Mansoor, Jianping Pan, Christopher W. Plummer, Aaron Sather, Uma Swaminathan, Huijun Wang
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Publication number: 20220402916Abstract: Provided are compounds of Formula (I) or a pharmaceutically acceptable salt thereof, wherein Y, CY, R1, R3, R4, R5, R6, R2a, R2b, RMa, RMb, and the subscripts m, n, and q are as described herein. The compounds or their pharmaceutically acceptable salts can inhibit the G12C mutant of Kirsten rat sarcoma (KRAS) protein and are expected to have utility as therapeutic agents, for example, for treatment of cancer. Also provided are pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. Also provided are methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.Type: ApplicationFiled: September 18, 2020Publication date: December 22, 2022Inventors: Andrew J. Hoover, Thomas H. Graham, Xiaoshen Ma, Zahid Hussain, Mihir Mandal, Symon Gathiaka, Yongxin Han, David L. Sloman
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Publication number: 20220220117Abstract: In its many embodiments, the present invention provides certain 9-substituted amino triazolo quinazoline compounds of the structural Formula (I): and pharmaceutically acceptable salts thereof, wherein, ring A, R1 and R2 are as defined herein, pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other therapeutically active agents), and methods for their preparation and use, alone and in combination with other therapeutic agents, as antagonists of A2a and/or A2b receptors, and in the treatment of a variety of diseases, conditions, or disorders that are mediated, at least in part, by the adenosine A2a receptor and/or the adenosine A2b receptor.Type: ApplicationFiled: March 31, 2022Publication date: July 14, 2022Applicant: Merck Sharp & Dohme Corp.Inventors: Matthew A. Larsen, Amjad Ali, Jared Cumming, Duane DeMong, Qiaolin Deng, Thomas H. Graham, Elisabeth Hennessy, Andrew J. Hoover, Ping Liu, Kun Liu, Umar Faruk Mansoor, Jianping Pan, Christopher W. Plummer, Aaron Sather, Uma Swaminathan, Huijun Wang, Yonglian Zhang
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Patent number: 11358711Abstract: The present invention relates to Tetracyclic Heterocycle Compounds of Formula and pharmaceutically acceptable salts or prodrug thereof, wherein A, X, R1, R2, R3 and Ware as defined herein. The present invention also relates to compositions comprising at least one Tetracyclic Heterocycle Compound, and methods of using the Tetracyclic Heterocycle Compounds for treating or preventing HIV infection in a subject.Type: GrantFiled: September 18, 2020Date of Patent: June 14, 2022Assignee: Merck Sharp & Dohme Corp.Inventors: Thomas H. Graham, Tao Yu, Yonglian Zhang, John A. McCauley
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Patent number: 11312719Abstract: In its many embodiments, the present invention provides certain 9-substituted amino triazolo quinazoline compounds of the structural Formula (I): and pharmaceutically acceptable salts thereof, wherein, ring A, R1 and R2 are as defined herein, pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other therapeutically active agents), and methods for their preparation and use, alone and in combination with other therapeutic agents, as antagonists of A2a and/or A2b receptors, and in the treatment of a variety of diseases, conditions, or disorders that are mediated, at least in part, by the adenosine A2a receptor and/or the adenosine A2b receptor.Type: GrantFiled: November 26, 2019Date of Patent: April 26, 2022Assignee: Merck Sharp & Dohme Corp.Inventors: Matthew A. Larsen, Amjad Ali, Jared Cumming, Duane DeMong, Qiaolin Deng, Thomas H. Graham, Elisabeth Hennessy, Andrew J. Hoover, Ping Liu, Kun Liu, Umar Faruk Mansoor, Jianping Pan, Christopher W. Plummer, Aaron Sather, Uma Swaminathan, Huijun Wang, Yonglian Zhang
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Publication number: 20220040184Abstract: In its many embodiments, the present invention provides certain substituted amino triazolopyrimidine and amino triazolopyrazine compounds of Formula (IA) and Formula (IB): and, and pharmaceutically acceptable salts thereof, wherein, R1, n, R2, and R3 are as defined herein, pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other therapeutically active agents), and methods for their preparation and use, alone and in combination with other therapeutic agents, as antagonists of A2a and/or A2b receptors, and their use in the treatment of a variety of diseases, conditions, or disorders that are mediated, at least in part, by the adenosine A2a receptor and/or the adenosine A2b receptor.Type: ApplicationFiled: November 15, 2019Publication date: February 10, 2022Applicant: Merck Sharp Dohme Corp.Inventors: Zachary G. Brill, Amjad Ali, Jared Cumming, Duane DeMong, Qiaolin Deng, Gioconda V. Gallo-Etienne, Thomas H. Graham, Rongze Kuang, Matthew A. Larsen, Yeon-Hee Lim, Kun Liu, Umar Faruk Mansoor, Jesus Moreno, Brandon A. Vara, Huijun Wang, Yonglian Zhang
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Publication number: 20210395255Abstract: In its many embodiments, the present invention provides certain substituted amino triazolopyrimidine and amino triazolopyrazine compounds of Formula (IA) and Formula (IB): or and pharmaceutically acceptable salts thereof, wherein, R1, R2, and R3 are as defined herein, pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other therapeutically active agents), and methods for their preparation and use, alone and in combination with other therapeutic agents, as antagonists of A2a and/or A2b receptors, and their use in the treatment of a variety of diseases, conditions, or disorders that are mediated, at least in part, by the adenosine A2a receptor and/or the adenosine A2b receptor.Type: ApplicationFiled: November 15, 2019Publication date: December 23, 2021Applicant: Merck Sharp & Dohme Corp.Inventors: Zachary G. Brill, Amjad Ali, Jared Cumming, Duane DeMong, Qiaolin Deng, Thomas H. Graham, Rongze Kuang, Yeon-Hee Lim, Christopher W. Plummer, Jenny Lorena Rico Duque, Huijun Wang, Yonglian Zhang, Kake Zhao
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Patent number: 11161854Abstract: The present invention is directed to substituted certain reversed indazolyl-spiro[2.2]pentane-carbonitrile derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, X, Y, and Z are as defined herein, which are potent inhibitors of LRRK2 kinase and may be useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease and other diseases and disorders described herein. 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 LRRK-2 kinase is involved.Type: GrantFiled: October 8, 2018Date of Patent: November 2, 2021Assignee: Merck Sharp & Dohme Corp.Inventors: David Annunziato Candito, Thomas H. Graham, John Acton, Ryan Wing-Kun Chau, Joanna L. Chen, J. Michael Ellis, Peter H. Fuller, Anmol Gulati, Hakan Gunaydin, Solomon Kattar, Mitchell Henry Keylor, Blair T. Lapointe, Ping Liu, Weiguo Liu, Joey L. Methot, Santhosh F. Neelamkavil, Vladimir Simov, Ling Tong, Harold B. Wood
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Patent number: 11104690Abstract: The present invention relates to a compound represented by formula I?: and pharmaceutically acceptable salts thereof. The compounds of formula I are inhibitors of diacylglyceride O-acyltransferase 2 (“DGAT2”) and may be useful in the treatment, prevention and suppression of diseases mediated by DGAT2. The compounds of the present invention may be useful in the treatment of hepatic steatosis, diabetes mellitus, obesity, hyperlipidemia, hypercholesterolemia, atherosclerosis, cardiorenal diseases such as chronic kidney diseases and heart failure and related diseases and conditions.Type: GrantFiled: November 13, 2017Date of Patent: August 31, 2021Assignee: Merck Sharp & Dohme Corp.Inventors: Dong-Ming Shen, Thomas H. Graham, Wensheng Liu, Clare Tudge, Andreas Verras, Jinlong Jiang
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Publication number: 20210188863Abstract: The present invention is directed to substituted certain reversed indazolyl-spiro[2.2]pentane-carbonitrile derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, X, Y, and Z are as defined herein, which are potent inhibitors of LRRK2 kinase and may be useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease and other diseases and disorders described herein. 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 LRRK-2 kinase is involved.Type: ApplicationFiled: October 8, 2018Publication date: June 24, 2021Applicant: Merck Sharp & Dohme Corp.Inventors: David Annunziato Candito, Thomas H. Graham, John Acton, Ryan Wing-Kun Chau, Joanna L. Chen, J. Michael Ellis, Peter H. Fuller, Anmol Gulati, Hakan Gunaydin, Solomon Kattar, Mitchell Henry Keylor, Blair T. Lapointe, Ping Liu, Weiguo Liu, Joey L. Methot, Santhosh F. Neelamkavil, Vladimir Simov, Ling Tong, Harold B. Wood
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Publication number: 20210122764Abstract: The disclosure provides compounds of Formula (I) or a pharmaceutically acceptable salt thereof, wherein W1, W2, Y, Z, M, L, Cy, Cz, R1, R2, R3, R4, R2a, Ry, Rz and the subscripts m, n, q, and r are as described herein. The compounds or their pharmaceutically acceptable salts can inhibit the G12C mutant of Kirsten rat sarcoma (KRAS) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The disclosure also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The disclosure also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.Type: ApplicationFiled: October 27, 2020Publication date: April 29, 2021Inventors: Indu Bharathan, Symon Gathiaka, Yongxin Han, Xiaoshen Ma, Ryan D. Otte, David L. Sloman, Thomas H. Graham, Timothy Henderson, Elizabeth Hennessy, Anandan Palani
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Publication number: 20210107904Abstract: In its many embodiments, the present invention provides certain 9-substituted amino triazolo quinazoline compounds of the structural Formula (I): and pharmaceutically acceptable salts thereof, wherein, ring A, R1 and R2 are as defined herein, pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other therapeutically active agents), and methods for their preparation and use, alone and in combination with other therapeutic agents, as antagonists of A2a and/or A2b receptors, and in the treatment of a variety of diseases, conditions, or disorders that are mediated, at least in part, by the adenosine A2a receptor and/or the adenosine A2b receptor.Type: ApplicationFiled: November 26, 2019Publication date: April 15, 2021Applicant: Merck Sharp & Dohme Corp.Inventors: Matthew A. Larsen, Amjad Ali, Jared Cumming, Duane DeMong, Qiaolin Deng, Thomas H. Graham, Elisabeth Hennessy, Andrew J. Hoover, Ping Liu, Kun Liu, Umar Faruk Mansoor, Jianping Pan, Christopher W. Plummer, Aaron Sather, Uma Swaminathan, Huijun Wang, Yonglian Zhang
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Patent number: 10947222Abstract: The present invention relates to a compound represented by formula I: and pharmaceutically acceptable salts thereof. The compounds of formula I are inhibitors of diacylglyceride O-acyltransferase 2 (“DGAT2”) and may be useful in the treatment, prevention and suppression of diseases mediated by DGAT2. The compounds of the present invention may be useful in the treatment of hepatic steatosis, diabetes mellitus, obesity, hyperlipidemia, hypercholesterolemia, atherosclerosis, nonalcoholic steatohepatitis (NASH), cardiorenal diseases such as chronic kidney diseases and heart failure and related diseases and conditions.Type: GrantFiled: November 13, 2017Date of Patent: March 16, 2021Assignee: Merck Sharp & Dohme Corp.Inventors: Dong-Ming Shen, Thomas H. Graham, Jinlong Jiang, Fa-Xiang Ding, Clare Tudge
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Patent number: 10934312Abstract: The present invention relates to Tricyclic Heterocycle Compounds of Formula (I): and pharmaceutically acceptable salts or prodrug thereof, wherein A, X, Y, Z, R1, R7A, R7B and R8 are as defined herein. The present invention also relates to compositions comprising at least one Tricyclic Heterocycle Compound, and methods of using the Tricyclic Heterocycle Compounds for treating or preventing HIV infection in a subject.Type: GrantFiled: December 1, 2017Date of Patent: March 2, 2021Assignee: MERCK SHARP & DOHME CORP.Inventors: Thomas H. Graham, Tao Yu, Sherman T. Waddell, John A. McCauley
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Publication number: 20210040096Abstract: The present invention relates to Fused Tricyclic Heterocyclic Compounds of Formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2 and R3 are as defined herein. The present invention also relates to compositions comprising at least one Fused Tricyclic Heterocyclic Compound, and methods of using the Fused Tricyclic Heterocyclic Compounds for treating or preventing HIV infection in a subject.Type: ApplicationFiled: October 27, 2020Publication date: February 11, 2021Applicant: Merck Sharp & Dohme Corp.Inventors: Tao Yu, Sherman T. Waddell, Thomas H. Graham, Yonglian Zhang, John A. McCauley, Andrew W. Stamford, Jiaqiang Cai, Zhiqi Qi