- Optimization of WZ4003 as NUAK inhibitors against human colorectal cancer
-
NUAK, the member of AMPK (AMP-activated protein kinase) family of protein kinases, is phosphorylated and activated by the LKB1 (liver kinase B1) tumor suppressor protein kinase. Recent work has indicated that NUAK1 is a key component of the antioxidant stress response pathway, and the inhibition of NUAK1 will suppress the growth and survival of colorectal tumors. As a promising target for anticancer drugs, few inhibitors of NUAK were developed. With this goal in mind, based on NUAK inhibitor WZ4003, a series of derivatives has been synthesized and evaluated for anticancer activity. Compound 9q, a derivative of WZ4003 by removing a methoxy group, was found to be the most potential one with stronger inhibitory against NUAK1/2 enzyme activity, tumor cell proliferation and inducing apoptosis of tumor cells. By in vivo efficacy evaluations of colorectal SW480 xenografts, 9q suppresses tumor growth more effectively with an excellent safety profile in vivo and is therefore seen as a suitable candidate for further investigation.
- Yang, Huali,Wang, Xiaobing,Wang, Cheng,Yin, Fucheng,Qu, Lailiang,Shi, Cunjian,Zhao, Jinhua,Li, Shang,Ji, Limei,Peng, Wan,Luo, Heng,Cheng, Maosheng,Kong, Lingyi
-
-
- PHENYLAMINOPYRIMIDINE AMIDE AUTOPHAGY INHIBITORS AND METHODS OF USE THEREOF
-
Described herein are compounds that are inhibitors of autophagy and their use in the treatment of disorders such as cancers.
- -
-
Paragraph 0225-0226; 0231
(2020/11/23)
-
- Pyrazolopyrimidines and related heterocycles as CK2 inhibitors
-
The invention provides compounds that inhibit protein kinase CK2 activity (CK2 activity), and compositions containing such compounds. These compounds and compositions are useful for treating proliferative disorders such as cancer, as well as other kinase-associated conditions including inflammation, pain, and certain immunological disorders, and have the following general formula:
- -
-
Page/Page column 500
(2016/05/02)
-
- Pyrazolopyrimidin CK2 and related heterocyclic compound as an inhibitor
-
The invention provides compounds that inhibit protein kinase CK2 activity (CK2 activity), and compositions containing such compounds. These compounds and compositions are useful for treating proliferative disorders such as cancer, as well as other kinase-associated conditions including inflammation, pain, and certain immunological disorders, and have the following general formula:
- -
-
Paragraph 0646
(2016/10/08)
-
- 2,7-Pyrrolo[2,1-f][1,2,4]triazines as JAK2 inhibitors: Modification of target structure to minimize reactive metabolite formation
-
The JAK2/STAT pathway has important roles in hematopoiesis. With the discovery of the JAK2 V617F mutation and its presence in many patients with myeloproliferative neoplasms, research in the JAK2 inhibitor arena has dramatically increased. We report a nov
- Weinberg, Linda R.,Albom, Mark S.,Angeles, Thelma S.,Breslin, Henry J.,Gingrich, Diane E.,Huang, Zeqi,Lisko, Joseph G.,Mason, Jennifer L.,Milkiewicz, Karen L.,Thieu, Tho V.,Underiner, Ted L.,Wells, Gregory J.,Wells-Knecht, Kevin J.,Dorsey, Bruce D.
-
scheme or table
p. 7325 - 7330
(2012/02/04)
-
- PROTEIN KINASE MODULATORS
-
The invention relates in part to molecules having certain biological activities that include, but are not limited to, inhibiting cell proliferation, modulating protein kinase activity and modulating polymerase activity. Molecules of the invention can modulate Pim kinase activity and/or FMS-like tyrosine kinase (Flt) activity. The invention also relates in part to methods for using such molecules.
- -
-
Page/Page column 353
(2009/10/01)
-
- 2-ANILINOPURIN-8-ONES AS INHIBITORS OF TTK/MPS1 FOR THE TREATMENT OF PROLIFERATIVE DISORDERS
-
The invention relates to chemical compounds of the formula (I), or a pharmaceutically acceptable salt thereof, which possess inhibitory activity against the spindle checkpoint kinase: Tyrosine Threonine Kinase (TTK)/monopolar spindle 1 (Mpsl) and are accordingly useful for their anti-cancer effect in a warm-blooded animal such as man. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them, and to their use in the manufacture of a medicament for the treatment of conditions mediated by TTK/Mpsl, for use either alone or in combination with other anti-pro liferative agents.
- -
-
Page/Page column 87
(2009/04/25)
-
- Applicability aspects of transition metal-catalyzed aromatic amination protocols in medicinal chemistry
-
The application of palladium- and coppercatalyzed reactions for the aromatic amination of pharmacologically relevant scaffolds is investigated. The focus is set on the scope of several protocols for the introduction of amines of broad structural diversity, allowing for the synthesis of numerous derivatives of one biological hit structure for screening in biological assay systems. Thus, attaining optimized yields and TONs had not a major priority, most important were practical aspects, that is no further purification and drying of reagents and solvents had to be envisaged, ideally only a few transition metalbased protocols had to be applied for synthesizing structurally diverse compounds in sufficient amounts (several milligrams) for screening without any finetuning of conditions and catalytic systems.
- Tasler, Stefan,Mies, Jan,Lang, Martin
-
p. 2286 - 2300
(2008/09/19)
-
- Nitro-substituted phenyl-piperazine compounds, their preparation and use in medicaments
-
The present invention relates to nitro-substituted phenyl-piperazine compounds of general formula I, a process for their preparation, medicaments comprising said nitro-substituted phenyl-piperazine compounds as well as the use of said nitre-substituted ph
- -
-
Page/Page column 67-68
(2008/06/13)
-
- SUBSTITUTED PHENYL-PIPERAZINE COMPOUNDS, THEIR PREPARATION AND USE IN MEDICAMENTS
-
The present invention relates to substituted phenyl-piperazine compounds of general formula (I), a process for their preparation, medicaments comprising said substituted phenyl-piperazine compounds as well as the use of said substituted phenyl-piperazine compounds for the preparation of medicaments, which are particularly suitable for the prophylaxis and/or treatment of disorders or diseases that are at least partially mediated via 5-HT6 receptors.
- -
-
Page/Page column 104
(2008/06/13)
-