- FUSED IMIDAZOLE AND PYRAZOLE DERIVATIVES AS MODULATORS OF TNF ACTIVITY
-
A series of substituted benzimidazole, imidazo[1,2-a]pyridine and pyrazolo[1,5-a]pyridine derivatives, and analogues thereof, being potent modulators of human TNFα activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders.
- -
-
Page/Page column 131
(2015/06/25)
-
- FUSED IMIDAZOLE AND PYRAZOLE DERIVATIVES AS MODULATORS OF TNF ACTIVITY
-
A series of substituted benzimidazole, imidazo[1,2-α]pyridine and pyrazolo[1,5- α]pyridine derivatives, and analogues thereof, being potent modulators of human TNFα activity, are accordingly of benefit in the treatment and/or prevention of various human a
- -
-
Page/Page column 102
(2015/06/25)
-
- FUSED TRICYCLIC IMIDAZOLE DERIVATIVES AS MODULATORS OF TNF ACTIVITY
-
A series of substituted fused tricyclic imidazole derivatives, in particular dihydro- 1H-pyrano[4',3':4,5]imidazo[1,2-a]pyridine, 1,2,3,4-tetrahydroimidazo[1,2-a:5,4- c']dipyridine, dihydro-1H-pyrano[3',4':4,5]imidazo[1,2-a]pyridine and tetrahydro-6H- cyc
- -
-
Page/Page column 114; 115
(2015/06/25)
-
- FUSED TRICYCLIC IMIDAZOLE DERIVATIVES AS MODULATORS OF TNF ACTIVITY
-
A series of fused tricyclic imidazole derivatives, in particular dihydro-1H-cyclopenta[4,5]imidazo[1,2-a]pyridine derivatives, and analogues thereof, being potent modulators of human TNFα activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders.
- -
-
Page/Page column 147
(2015/06/25)
-
- FUSED TRICYCLIC BENZIMIDAZOLES DERIVATIVES AS MODULATORS OF TNF ACTIVITY
-
A series of tricyclic benzimidazole derivatives, in particular dihydro-1H- imidazo [1,2-a]benzimidazo le, dihydro-1H-pyrrolo [1,2-a]benzimidazo le, dihydro-1H- pyrazino[1,2-a]benzimidazole, dihydro-1H-[1,4]oxazino[4,3-a]benzimidazole and dihydrothiazolo[3,4-a]benzimidazolem, and analogues thereof, being potent modulators of human TNFa activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders.
- -
-
Page/Page column 121; 122
(2015/06/25)
-
- PYRAZOLOPYRIDINE DERIVATIVES AS MODULATORS OF TNF ACTIVITY
-
A series of substituted pyrazolo[1,5-a]pyridine derivatives, being potent modulators of human TNFα activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders.
- -
-
Page/Page column 82; 83
(2015/06/25)
-
- TRIAZOLOPYRIDAZINE DERIVATIVES AS MODULATORS OF TNF ACTIVITY
-
A series of substituted [1,2,4]triazolo[4,3-b]pyridazine derivatives of formula (I), being potent modulators of human TNFa activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflamma
- -
-
Page/Page column 74; 75
(2015/06/25)
-
- IMIDAZOPYRIDAZINE DERIVATIVES AS MODULATORS OF TNF ACTIVITY
-
A series of substituted imidazo[1,2-b]pyridazine derivatives of formula (I), being potent modulators of human TNFa activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory dis
- -
-
Page/Page column 89
(2015/06/25)
-
- TRIAZOLOPYRIDINE DERIVATIVES AS MODULATORS OF TNF ACTIVITY
-
A series of substituted [l,2,4]triazolo[4,3-α]pyridine derivatives, being potent modulators of human TNFα activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; n
- -
-
Page/Page column 74
(2015/06/25)
-
- IMIDAZOPYRIDINE DERIVATIVES AS MODULATORS OF TNF ACTIVITY
-
A series of imidazo[l,2-a]pyridine derivatives of formula (I), being potent modulators of human TNFa activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders.
- -
-
Page/Page column 128; 129
(2014/02/15)
-
- Novel bisaryl substituted thiazoles and oxazoles as highly potent and selective peroxisome proliferator-activated receptor δ agonists
-
The discovery, synthesis, and optimization of compound 1 from a high-throughput screening hit to highly potent and selective peroxisome proliferator-activated receptor δ (PPARδ) agonists are reported. The synthesis and structure-activity relationship in this series are described in detail. On the basis of a general schematic PPAR pharmacophore model, scaffold 1 was divided into headgroup, linker, and tailgroup and successively optimized for PPAR activation using in vitro PPAR transactivation assays. A (2-methylphenoxy)acetic acid headgroup, a flexible linker, and a five-membered heteroaromatic center ring with two hydrophobic aryl substituents were required for efficient and selective PPARδ activation. The fine-tuning of these aryl substituents led to an array of highly potent and selective compounds such as compound 38c, displaying an excellent pharmacokinetic profile in mouse. In an in vivo acute dosing model, selected members of this array were shown to induce the expression of pyruvate dehydrogenase kinase-4 (PDK4) and uncoupling protein-3 (UCP3), genes that are known to be involved in energy homeostasis and regulated by PPARδ in skeletal muscle.
- Epple, Robert,Cow, Christopher,Xie, Yongping,Azimioara, Mihai,Russo, Ross,Wang, Xing,Wityak, John,Karanewsky, Donald S.,Tuntland, Tove,Nguyê?-Tran, Van T. B.,Ngo, Cara Cuc,Huang, David,Saez, Enrique,Spalding, Tracy,Gerken, Andrea,Iskandar, Maya,Seidel, H. Martin,Tian, Shin-Shay
-
experimental part
p. 77 - 105
(2010/04/30)
-
- COMPOUNDS AND COMPOSITIONS AS PPAR MODULATORS
-
The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with the activity of the Peroxisome Proliferator-Activated Receptor (PPAR) families, particularly the activity of PPAR.
- -
-
Page/Page column 53-54
(2010/02/14)
-