- Development of a selective HDAC inhibitor aimed at reactivating the HIV latent reservoir
-
The synthesis and SAR development of a trisubstituted imidazole HDAC inhibitor is described. The compounds were synthesized with high diastereocontrol by leveraging Ellman sulfinyl imine chemistry. Structural elucidation provided insight into binding mode and supported design rational. Pharmacokinetic properties of lead compounds were determined.
- Barnard, Richard J. O.,Chung, Christine C.,Clausen, Dane J.,Duffy, Joseph L.,Fells, James,Holloway, Kate,Howell, Bonnie J.,Klein, Daniel J.,Kozlowski, Joseph,Liu, Jian,Myers, Robert W.,Wu, Guoxin,Wu, Jin,Yu, Wensheng
-
-
Read Online
- INHIBITORS OF HISTONE DEACETYLASE USEFUL FOR THE TREATMENT OR PREVENTION OF HIV INFECTION
-
The present invention relates to Compounds of Formula (I): Formula (I) and pharmaceutically acceptable salts or prodrug thereof, wherein R1, R2, R3, Ra, Rb, A and B are as defined herein. The present invention also relates to compositions comprising at least one compound of Formula (I), and methods of using the compounds of Formula (I) for treating or preventing HIV infection in a subject.
- -
-
Page/Page column 166; 167; 168
(2020/02/23)
-
- SUBSTITUTED PYRAZOLOPYRIMIDINES AND SUBSTITUTED PURINES AND THEIR USE AS UBIQUITIN-SPECIFIC-PROCESSING PROTEASE 1 (USP1) INHIBITORS
-
The present disclosure provides compounds having Formula I: and the pharmaceutically acceptable salts and solvates thereof, wherein X1, X2, X11, X12, R1, R3, R5, R5', R6, and R7 are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula I to inhibit a USP1 protein and/or to treat a disorder responsive to the inhibition of USP1 proteins and USP1 activity. Compounds of the present disclosure are especially useful for treating cancer.
- -
-
Paragraph 0692-0693
(2020/07/14)
-
- IMIDAZOLE DERIVATIVES AND THEIR USE IN THE TREATMENT OF AUTOIMMUNE OR INFLAMMATORY DISEASES OR CANCERS
-
Compounds of formula (I) and salts thereof: wherein R1, R2, R3, a, X1, X2, X3, X4, and X5 are as defined hereinbefore. Compounds of formula (I) and salts thereof have been found to inhibit the binding of the BET family of bromodomain containing proteins to, for example, acetylated lysine residues and thus may have use in therapy, for example in the treatment of autoimmune and inflammatory diseases, such as rheumatoid arthritis; and cancers.
- -
-
Page/Page column 53
(2018/03/25)
-
- Cyano-substituted 2-carboxyimidazoles: Synthesis of 4-cyano-1-{[2- (trimethylsilyl)ethoxy]methyl}-1H-imidazole-2-carboxylate potassium salt
-
The first example of a monocyano-substituted 2-carboxyimidazole is reported. A synthesis of potassium 4-cyano-1-{[2-(trimethylsilyl)ethoxy]methyl}- 1H-imidazole-2-carboxylate (2) is demonstrated where the carboxylate group is introduced via bromine-magnesium exchange on a SEM-protected cyanoimidazole followed by reaction with ethyl cyanoformate. The synthesis includes the equilibration of a regioisomeric mixture of SEM-protected imidazoles to give a single product. Georg Thieme Verlag Stuttgart.
- Wall, Mark J.,Schubert, Carsten,Illig, Carl R.
-
experimental part
p. 3377 - 3379
(2009/05/07)
-
- Structure-based optimization of a potent class of arylamide FMS inhibitors
-
An anti-inflammatory 1,2,4-phenylenetriamine-containing series of FMS inhibitors with a potential to form reactive metabolites was transformed into a series with equivalent potency by incorporation of carbon-based replacement groups. Structure-based modeling provided the framework to efficiently effect this transformation and restore potencies to previous levels. This optimization removed a risk factor for potential idiosyncratic drug reactions.
- Meegalla, Sanath K.,Wall, Mark J.,Chen, Jinsheng,Wilson, Kenneth J.,Ballentine, Shelley K.,DesJarlais, Renee L.,Schubert, Carsten,Crysler, Carl S.,Chen, Yanmin,Molloy, Christopher J.,Chaikin, Margery A.,Manthey, Carl L.,Player, Mark R.,Tomczuk, Bruce E.,Illig, Carl R.
-
scheme or table
p. 3632 - 3637
(2009/04/06)
-
- METHOD OF INHIBITING C-KIT KINASE
-
A method of reducing or inhibiting kinase activity of C-KIT in a cell or a subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and/or disorders related to C-KIT using a compound of the present invention: or a solvate, hydrate, tautomer or pharmaceutically acceptable salt thereof. The present invention is further directed to methods for treating conditions such as cancers and other cell proliferative disorders.
- -
-
Page/Page column 34
(2008/06/13)
-
- C-FMS KINASE INHIBITORS
-
The invention is directed to compounds of Formula II: wherein A, R1, R2, R3, R4, X, Y and W are set forth in the specification, as well as solvates, hydrates, tautomers or pharmaceutically acceptable salts thereof, that inhibit protein tyrosine kinases, especially c-fms kinase.
- -
-
-
- METHOD OF INHIBITING FLT3 KINASE
-
A method of reducing or inhibiting kinase activity of FLT3 in a cell or a subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and/or disorders related to FLT3 using a compound of the present invention (I), or a solvate, hydrate, tautomer or pharmaceutically acceptable salt thereof. The present invention is further directed to methods for treating conditions such as cancers and other cell proliferative disorders.
- -
-
Page/Page column 148-149
(2010/11/27)
-
- INHIBITORS OF C-FMS KINASE
-
The invention is directed to compounds of Formula I: wherein Z, X, J, R2 and W are set forth in the specification, as well as solvates, hydrates, tautomers and pharmaceutically acceptable salts thereof, that inhibit protein tyrosine kinases, es
- -
-
Page/Page column 23
(2008/06/13)
-
- INHIBITORS OF C-FMS KINASE
-
The invention is directed to compounds of Formula I: wherein Z, X, J, R2 and W are set forth in the specification, as well as solvates, hydrates, tautomers and pharmaceutically acceptable salts thereof, that inhibit protein tyrosine kinases, especially c-fms kinase. Methods of treating autoimmune diseases; and diseases with an inflammatory component; treating metastasis from ovarian cancer, uterine cancer, breast cancer, colon cancer, stomach cancer, hairy cell leukemia and non-small lung carcinoma; and treating pain, including skeletal pain caused by tumor metastasis or osteoarthritis, or visceral, inflammatory, and neurogenic pain; as well as osteoporosis, Paget's disease, and other diseases in which bone resorption mediates morbidity including arthritis, prosthesis failure, osteolytic sarcoma, myeloma, and tumor metastasis to bone with the compounds of Formula I, are also provided.
- -
-
Page/Page column 35
(2008/06/13)
-
- INHIBITORS OF C-FMS KINASE
-
The invention is directed to compounds of Formula I: wherein Z, X, J, R2 and W are set forth in the specification, as well as solvates, hydrates, tautomers and pharmaceutically acceptable salts thereof, that inhibit protein tyrosine kinases, es
- -
-
Page/Page column 24-25
(2008/06/13)
-
- AROMATIC AMIDES AS INHIBITORS OF C-FMS KINASE
-
The invention relates to compounds of Formula (I), wherein A, X, R2 and W are set forth in the specification, as well as solvates, hydrates, tautomers and pharmaceutically acceptable salts thereof, that inhibit protein tyrosine kinases, especially c-fms kinase. Methods of treating autoimmune diseases; and diseases with an inflammatory component; treating metastasis from ovarian cancer, uterine cancer, breast cancer, colon cancer, stomach cancer, hairy cell leukemia and non-small lung carcinoma; and treating pain, including skeletal pain caused by tumor metastasis or osteoarthritis, or visceral, inflammatory, and neurogenic pain; as well as osteoporosis, Paget's disease, and other diseases in which bone resorption mediates morbidity including arthritis, prosthesis failure, osteolytic sarcoma, myeloma, and tumor metastasis to bone with the compounds of Formula (I), are also provided.
- -
-
Page/Page column 148
(2008/06/13)
-
- SYNERGISTIC MODULATION OF FLT3 KINASE USING A FLT3 INHIBITOR AND A FARNESYL TRANSFERASE INHIBITOR
-
The invention is directed to a method of inhibiting FLT3 tyrosine kinase activity or expression or reducing FLT3 kinase activity or expression in a cell or a subject comprising the administration of a farnesyl transferase inhibitor and a FLT3 kinase inhibitor selected from compounds of Formula I′: Included within the present invention is both prophylactic and therapeutic methods for treating a subject at risk of (or susceptible to) developing a cell proliferative disorder or a disorder related to FLT3.
- -
-
Page/Page column 89
(2008/06/13)
-
- INHIBITORS OF C-FMS KINASE
-
The invention is directed to compounds of Formula (I): wherein A, X, R2 and W are set forth in the specification, as well as solvates, hydrates, tautomers and pharmaceutically acceptable salts thereof, that inhibit protein tyrosine kinases, especially c-fms kinase. Methods of treating autoimmune diseases; and diseases with an inflammatory component; treating metastasis from ovarian cancer, uterine cancer, breast cancer, colon cancer, stomach cancer, hairy cell leukemia and non-small lung carcinoma; and treating pain, including skeletal pain caused by tumor metastasis or osteoarthritis, or visceral, inflammatory, and neurogenic pain; as well as osteoporosis, Paget's disease, and other diseases in which bone resorption mediates morbidity including arthritis, prosthesis failure, osteolytic sarcoma, myeloma, and tumor metastasis to bone with the compounds of Formula (I), are also provided.
- -
-
Page/Page column 42
(2008/06/13)
-
- C-fms kinase inhibitors
-
The invention is directed to compounds of Formulae I: wherein A, R1, R2, R3, R4, X, and W are set forth in the specification, as well as solvates, hydrates, tautomers or pharmaceutically acceptable salts thereof, that inhibit protein tyrosine kinases, especially c-fms kinase.
- -
-
-