- WEE1 inhibitors as well as preparation and application thereof
-
The invention relates to WEE1 inhibitors as well as preparation and application thereof. The present invention relates to compounds of formula (I), or pharmaceutically acceptable salts, solvates, polymorphs or isomers thereof, and their use in the preparation of medicaments for the treatment of diseases associated with WEE1 activity.
- -
-
Paragraph 0955-0961
(2020/10/14)
-
- POSITRON EMISSION TOMOGRAPHY (PET) RADIOTRACERS FOR IMAGING MACROPHAGE COLONY-STIMULATING FACTOR 1 RECEPTOR (CSF1R) IN NEUROINFLAMMATION
-
Positron emission tomography (PET) radiotracers for imaging macrophage colony stimulating factor-1 receptors in a subject afflicted with or suspected of being afflicted with a neuroinflammatory or neurodegenerative disease or disorder are disclosed.
- -
-
Page/Page column 82
(2020/01/24)
-
- HETEROCYCLIC COMPOUNDS AND USES THEREOF
-
Heterocyclic compounds as Wee1 inhibitors are provided. The compounds may find use as therapeutic agents for the treatment of diseases and may find particular use in oncology.
- -
-
Paragraph 0284-0286
(2019/04/25)
-
- PYRIMIDOPYRIMIDINONES USEFUL AS WEE-1 KINASE INHIBITORS
-
The present invention relates to compounds that are useful as inhibitors of the activity of Wee-1 kinase. The present invention also relates to pharmaceutical compositions comprising these compounds and to methods of using these compounds in the treatment of cancer and methods of treating cancer.
- -
-
-
- 8-ETHYL-6-(ARYL)PYRIDO [2,3-D]PYRIMIDIN-7(8H) -ONES FOR THE TREATMENT OF NERVOUS SYSTEM DISORDERS AND CANCER
-
Provided herein are PAK inhibitors and methods of utilizing PAK inhibitors for the treatment of CNS disorders such as neuropsychiatric disorders or neurofibromatosis. Also described herein are methods of utilizing PAK inhibitors for the treatment of cancer.
- -
-
Paragraph 00590
(2013/04/10)
-
- NAMPT INHIBITORS
-
Disclosed are compounds which inhibit the activity of NAMPT, compositions containing the compounds and methods of treating diseases during which NAMPT is expressed.
- -
-
Page/Page column 167; 188
(2013/12/03)
-
- Optimization of a potent class of arylamide colony-stimulating factor-1 receptor inhibitors leading to anti-inflammatory clinical candidate 4-cyano-N -[2-(1-cyclohexen-1-yl)-4-[1-[(dimethylamino)acetyl]-4-piperidinyl]phenyl]-1 H -imidazole-2-carboxamide (JNJ-28312141)
-
A class of potent inhibitors of colony-stimulating factor-1 receptor (CSF-1R or FMS), as exemplified by 8 and 21, was optimized to improve pharmacokinetic and pharmacodynamic properties and potential toxicological liabilities. Early stage absorption, distribution, metabolism, and excretion assays were employed to ensure the incorporation of druglike properties resulting in the selection of several compounds with good activity in a pharmacodynamic screening assay in mice. Further investigation, utilizing the type II collagen-induced arthritis model in mice, culminated in the selection of anti-inflammatory development candidate JNJ-28312141 (23, FMS IC50 = 0.69 nM, cell assay IC50 = 2.6 nM). Compound 23 also demonstrated efficacy in rat adjuvant and streptococcal cell wall-induced models of arthritis and has entered phase I clinical trials.
- Illig, Carl R.,Manthey, Carl L.,Wall, Mark J.,Meegalla, Sanath K.,Chen, Jinsheng,Wilson, Kenneth J.,Ballentine, Shelley K.,Desjarlais, Renee L.,Schubert, Carsten,Crysler, Carl S.,Chen, Yanmin,Molloy, Christopher J.,Chaikin, Margery A.,Donatelli, Robert R.,Yurkow, Edward,Zhou, Zhao,Player, Mark R.,Tomczuk, Bruce E.
-
experimental part
p. 7860 - 7883
(2012/01/05)
-
- 5-OXO-5,8-DIHYDRO-PYRIDO-PYRIMIDINES AS INHIBITORS OF C-FMS KINASE
-
The invention addresses the current need for selective and potent protein tyrosine kinase inhibitors by providing potent inhibitors of c-fms kinase. The invention is directed to the novel compounds of Formula I: or a salt, stereoisomer, tautomer, crystalline, polymorph, amorphous, solvate, hydrate, ester, prodrug or metabolite form thereof, wherein A, Y, Z, R101 and R200 are described in the specification.
- -
-
Page/Page column 90
(2008/12/05)
-
- 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 41
(2008/06/13)
-
- 5-Oxo-5,8-dihydro-pyrido-pyrimidines as inhibitors of c-fms kinase
-
The invention addresses the current need for selective and potent protein tyrosine kinase inhibitors by providing potent inhibitors of c-fms kinase. The invention is directed to the novel compounds of Formula I: or a solvate, hydrate, tautomer or pharmaceutically acceptable salt thereof, wherein: W, A, Y, Z, R101 and R200 are described in the specification.
- -
-
Page/Page column 32; 52-53
(2010/11/26)
-
- 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 75-76; 94-95
(2010/11/27)
-
- 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 58
(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 55
(2008/06/13)
-