- CK2 INHIBITORS, COMPOSITIONS AND METHODS THEREOF
-
The present invention provides synthesis, pharmaceutically acceptable formulations and uses of compounds in accordance with Formula (I), or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof. For Formula (I) compounds R1, R2, R3, Ar and Z are as defined in the specification. The inventive Formula (I) compounds are inhibitors of CK2 and find utility in any number of therapeutic applications, including but not limited to treatment of proliferative disorders such as cancer, inflammation and immunological disorders.
- -
-
Paragraph 0264; 0265
(2018/02/01)
-
- SUBSTITUTED PYRROLO[1,2-A]PYRIMIDINES AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS
-
The invention provides substituted pyrrolo[l,2-a]pyrimi dines and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted pyrrolo[1,2-a]pyrimidines compounds described herein include substituted 2,4-dimethyl-N-phenylpyrrolo[l,2-a]pyrimidine-8-carboxamide compounds and variants thereof.
- -
-
Paragraph 00227
(2016/06/28)
-
- SUBSTITUTED PYRAZOLO(1,5-A)PYRIMIDINES AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS
-
The invention provides substituted pyrazolo[l,5-a]pyrimidine and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted pyrazolo[l,5-a]pyrimidine compounds described herein include 5,7- dimethyl-N-phenylpyrazolo[l,5-a]pyrimidine-3-carboxamide compounds and variants thereof.
- -
-
Paragraph 00295
(2016/06/01)
-
- SUBSTITUTED IMIDAZO[1,5-A]PYRIMIDINES AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS
-
The invention provides substituted imidazo[1,5-a]pyrimidines and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted imidazo[1,5-a]pyrimidine compounds described herein include substituted 2,4-dimethyl-N-phenylimidazo[1,5-a]pyrimidine-8-carboxamide compounds and variants thereof.
- -
-
Paragraph 00252
(2016/06/01)
-
- THERAPEUTIC COMPOUNDS
-
The invention provides compounds of formula (I): wherein, A, C, D, X, and Y have any of the values defined in the specification, and salts thereof. The compounds are SIRT2 inhibitors and are useful for treating SIRT2 associated conditions.
- -
-
Paragraph 0395; 0403; 0405
(2017/01/23)
-
- Synthesis, antimalarial activity, and preclinical pharmacology of a novel series of 4'-fluoro and 4'-chloro analogues of amodiaquine. identification of a suitable "back-up" compound for N-tert-butyl isoquine
-
On the basis of a mechanistic understanding of the toxicity of the 4-aminoquinoline amodiaquine (1b), three series of amodiaquine analogues have been prepared where the 4-aminophenol "metabolic alert" has been modified by replacement of the 4'-hydroxy gro
- O'Neill, Paul M.,Shone, Alison E.,Stanford, Deborah,Nixon, Gemma,Asadollahy, Eghbaleh,Park, B. Kevin,Maggs, James L.,Roberts, Phil,Stocks, Paul A.,Biagini, Giancarlo,Bray, Patrick G.,Davies, Jill,Berry, Neil,Hall, Charlotte,Rimmer, Karen,Winstanley, Peter A.,Hindley, Stephen,Bambal, Ramesh B.,Davis, Charles B.,Bates, Martin,Gresham, Stephanie L.,Brigandi, Richard A.,Gomez-de-las-Heras, Federico M.,Gargallo, Domingo V.,Parapini, Silvia,Vivas, Livia,Lander, Hollie,Taramelli, Donatella,Ward, Stephen A.
-
supporting information; experimental part
p. 1828 - 1844
(2009/12/31)
-
- NOVEL BENZAMIDE DERIVATIVES AS MODULATORS OF THE FOLLICLE STIMULATING HORMONE
-
The present invention provides new compounds of formula I, wherein Q, R1, R2, R4, R5, R6, Xi, R7, R8, M and G1 nare defined as in formula I; invention compounds are modulators of follicle-stimulating hormone - ("FSH") which are useful for male and female contraception as well as other disorders modulated by FSH receptor.
- -
-
Page/Page column 150-151
(2008/12/04)
-
- 4-Phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione inhibitors of the checkpoint kinase Wee1. structure-activity relationships for chromophore modification and phenyl ring substitution
-
High-throughput screening has identified a novel class of inhibitors of the checkpoint kinase Wee1, which have potential for use in cancer chemotherapy. These inhibitors are based on a 4-phenylpyrrolo[3,4-c]-carbazole-1,3(2H,6H)- dione template and have been shown by X-ray crystallography to bind at the ATP site of the enzyme. An extensive study of the effects of substitution around this template has been carried out, which has identified substituents which lead to improvements in potency and selectivity for Wee1. While retention of the maleimide ring and pendant 4-phenyl group is necessary for potency, replacement of the carbazole nitrogen by oxygen is well tolerated and results in improved Wee1 selectivity against the related checkpoint kinase Chk1. Wee1 potency and selectivity are also enhanced by the incorporation of lipophilic functionality at the 2′-position of the 4-phenyl ring, and Wee1 selectivity against Chk1 is favored by C3-C5 alkyl substitution of the carbazole nitrogen. These studies provide a basis for the design of active analogues of the pyrrolocarbazole lead with improved physical properties.
- Palmer, Brian D.,Thompson, Andrew M.,Booth, R. John,Dobrusin, Ellen M.,Kraker, Alan J.,Lee, Ho H.,Lunney, Elizabeth A.,Mitchell, Lorna H.,Ortwine, Daniel F.,Smaill, Jeff B.,Swan, Leesa M.,Denny, William A.
-
p. 4896 - 4911
(2007/10/03)
-
- Identification of novel p38α MAP kinase inhibitors using fragment-based lead generation
-
We describe the structure-guided optimization of the molecular fragments 2-amino-3-benzyl-oxypyridine 1 (IC50 1.3 mM) and 3-(2-(4-pyridyl) ethyl)indole 2 (IC50 35 μM) identified using X-ray crystallographic screening of p38α MAP kinase. Using two separate case studies, the article focuses on the key compounds synthesized, the structure-activity relationships and the binding mode observations made during this optimization process, resulting in two potent lead series that demonstrate significant increases in activity. We describe the process of compound elaboration either through the growing out from fragments into adjacent pockets or through the conjoining of overlapping fragments and demonstrate that we have exploited the mobile conserved activation loop, consisting in part of Asp168-Phe169-Gly170 (DFG), to generate significant improvements in potency and kinase selectivity.
- Gill, Adrian L.,Frederickson, Martyn,Cleasby, Anne,Woodhead, Steven J.,Carr, Maria G.,Woodhead, Andrew J.,Walker, Margaret T.,Congreve, Miles S.,Devine, Lindsay A.,Tisi, Dominic,O'Reilly, Marc,Seavers, Lisa C. A.,Davis, Deborah J.,Curry, Jayne,Anthony, Eachel,Padova, Alessandro,Murray, Christopher W.,Carr, Robin A. E.,Jhoti, Harren
-
p. 414 - 426
(2007/10/03)
-
- ALPHA ARYL OR HETEROARYL METHYL BETA PIPERIDINO PROPANAMIDE COMPOUNDS AS ORL1-RECEPTOR ANTAGONIST
-
This invention provides the compounds of formula (I): or a pharmaceutically acceptable ester of such compound, or a pharmaceutically acceptable salt thereof, wherein Ri and R2 independently represent a hydrogen atom or the like; R3 represents a hydrogen atom, or the like; R4 represents a hydrogen atom or the like; (formula II) represents one of the following or the like; R5 represents an aryl group having from 6 to 10 ring atoms or the like; X represents an oxygen atom, or the like; Y represents an oxgen atom or the like and n represents an integer 0, 1 or 2. These compounds have ORL1-receptor antagonist activity; and therefore, are useful to treat diseases or conditions such as pain, various CNS diseases etc.
- -
-
Page/Page column 86
(2010/02/14)
-
- 3-`(HETERO) ARYLMETHOXY ! PYRIDINES AND THEIR ANALOGUES AS P38 MAP KINASE INHIBITORS
-
Compounds of the formula (I), wherein: -X=Y- is selected from -CR2=CR3- and -CR2=N-; R1 is selected from H, halo, NRR', NHC(=O)R, NHC(=O)NRR', NH2SO2R, and C(=O)NRR'; R2 and R3 (where present) are independently selected from H, optionally substituted C1-7 alkyl, optionally substituted C5-20 aryl, optionally substituted C3-20 heterocyclyl, halo, amino, amido, hydroxy, ether, thio, thioether, acylamido, ureido and sulfonamino; R4 is an optionally substituted C5-20 aryl or C5-20 heteroaryl group; and R5 is selected from R5’, halo, NHR5’, C(=O)NHR5’, OR5’, SR5’, NHC(=O)R5’, NHC(=O)NHR5’, NHS(=O)R5’, wherein R5’ is H or C1-3 alkyl (optionally substituted by halo, NH2, OH, SH) are disclosed for use in therapy and for treating diseases ameliorated by inhibiting p38 MAP kinase.
- -
-
Page/Page column 67
(2010/11/30)
-