Abstract: A new, stable trimeric TNF? structure is disclosed with distorted symmetry which can bind to the TNFR1 receptor to attenuate signalling therefrom, which can be used in the treatment and/or prevention of diseases associated with the soluble TNF?/TNFR1 interaction. Membrane-bound TNF? is not affected in its ability to signal through TNFR2, and thus the new structure of TNF? may be used in therapies which do not significantly raise the risk of infection or malignancy.

Abstract: A series of fused pentacyclic imidazole derivatives, 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. In particular, the present invention is concerned with 6,7-dihydro-7,14-methanobenzimidazo[1,2-b][2,5]benzodiazocin-5(14H)-one derivatives and analogs thereof.

Abstract: A new, stable trimeric TNF? structure is disclosed with distorted symmetry which can bind to the TNFR1 receptor to attenuate signalling therefrom, which can be used in the treatment and/or prevention of diseases associated with the soluble TNF?/TNFR1 interaction. Membrane-bound TNF? is not affected in its ability to signal through TNFR2, and thus the new structure of TNF? may be used in therapies which do not significantly raise the risk of infection or malignancy.

Abstract: A series of fused pentacyclic imidazole derivatives, 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. In particular, the present invention is concerned with 6,7-dihydro-7,14-methanobenzimidazo[1,2-b][2,5]benzodiazocin-5(14H)-one derivatives and analogs thereof.

Abstract: A new, stable trimeric TNF? structure is disclosed with distorted symmetry which can bind to the TNFR1 receptor to attenuate signalling therefrom, which can be used in the treatment and/or prevention of diseases associated with the soluble TNF?/TNFR1 interaction. Membrane-bound TNF? is not affected in its ability to signal through TNFR2, and thus the new structure of TNF? may be used in therapies which do not significantly raise the risk of infection or malignancy.

Abstract: A series of fused pentacyclic imidazole derivatives, 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. In particular, the present invention is concerned with 6,7-dihydro-7,14-methanobenzimidazo[1,2-b][2,5]benzodiazocin-5(14H)-one derivatives and analogs thereof.

Abstract: A series of fused pentacyclic imidazole derivatives, 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. In particular, the present invention is concerned with 6,7-dihydro-7,14-methanobenzimidazo[1,2-b][2,5]benzodiazocin-5(14H)-one derivatives and analogs thereof.

Abstract: 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 TNF? 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.

Abstract: A new, stable trimeric TNF? structure is disclosed with distorted symmetry which can bind to the TNFR1 receptor to attenuate signalling therefrom, which can be used in the treatment and/or prevention of diseases associated with the soluble TNF?/TNFR1 interaction. Membrane-bound TNF? is not affected in its ability to signal through TNFR2, and thus the new structure of TNF? may be used in therapies which do not significantly raise the risk of infection or malignancy.

Abstract: A series of substituted benzimidazole, imidazo[1,2-?]pyridine and pyrazolo[1,5-?]pyridine derivatives, and analogs thereof, being potent modulators of human TNF? 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.

Abstract: A series of tricyclic benzimidazole derivatives, in particular dihydro-1H-imidazo [1,2-a]benzimidazole, dihydro-1H-pyrrolo [1,2-a]benzimidazole, dihydro-1H-pyrazino[1,2-a]benzimidazole, dihydro-1H-[1,4]oxazino[4,3-a]benzimidazole and dihydrothiazolo[3,4-a]benzimidazolem, and analogs 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.

Abstract: A series of fused pentacyclic imidazole derivatives, 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. In particular, the present invention is concerned with 6,7-dihydro-7,14-methanobenzimidazo[1,2-b][2,5]benzodiazocin-5(14H)-one derivatives and analogs thereof.

Abstract: A series of substituted benzimidazole, imidazo[1,2-?]pyridine and pyrazolo[1,5-?]pyridine derivatives, and analogues thereof, being potent modulators of human TNF? 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.

Abstract: A series of benzimidazole derivatives, being potent modulators of human TNF? 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.

Abstract: 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 TNF? 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.

Abstract: A series of tricyclic benzimidazole derivatives, in particular dihydro-1H-imidazo [1,2-a]benzimidazole, dihydro-1H-pyrrolo [1,2-a]benzimidazole, 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.

Abstract: A series of benzimidazole derivatives, being potent modulators of human TNF? 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.