Celltech Therapeutics Limited

Angiogene Pharmaceuticals Limited

Celltech R&d Limited

Astrazeneca Ab

Peter David Davis

David Festus Moffat

Martin Clive Hutchings

Jeremy Martin Davis

Mark James Batchelor

David Festus Charles Moffat

David Mark Parry

Francis Thomas Boyle

Jean-Claude Arnould

Graeme Dougherty

Vascular damaging agents composed of substituted 5(6)-substituted benzimidazole-2-carbamates are provided. These agents are useful in the preparation of medicaments for the treatment of diseases involving neovascularisation, particularly for the treatment of solid tumors, macular degeneration, diabetic retinopathy, rheumatoid arthritis, psoriasis, and atherosclerosis. Embodiments include a 5(6)-substituted benzimidazole-2-carbamate of formula I wherein A represents a multi-substituted alkyl group or aromatic ring.

Benzimidazole vascular damaging agents

A compound for use in inducing necrosis in vascular tissue of a tumor in an animal. The compound contains a first moiety which is a cis-stilbene moiety and a second moiety which is an inhibitor of the formation or action of nitric acid. Also, a method for inducing necrosis in vasculature of a tumor in an animal by administering to the animal the compound in an amount effective for inducing the necrosis.

Substituted stilbene compounds with vascular damaging activity

The invention relates to the use of compounds of formula (I): wherein X is &#x2014;C(O)&#x2014;, &#x2014;C(S)&#x2014;, &#x2014;C&#x2550;NOH, or &#x2014;CH(R)&#x2014; wherein Ris hydrogen, hydroxy, Calkoxy, &#x2014;ORor &#x2014;NRR(wherein Ris a group &#x2014;YR(wherein Yis a direct bond, &#x2014;C(O)&#x2014;, &#x2014;C(S)&#x2014;, &#x2014;S&#x2014;, &#x2014;C(O)O, &#x2014;C(O)NR&#x2014;, &#x2014;SO&#x2014; or &#x2014;SONR&#x2014; (wherein Rand R, which may be the same or different, each independently represents hydrogen, Calkyl or CalkoxyCalkyl) and Ris as defined herein, and Rincludes hydrogen; R, Rand Rare as defined herein and are preferably methyl; R, Rand Rare as defined herein with the proviso that Ris not hydroxy, alkoxy, substituted alkoxy, &#x2014;OPOH, &#x2014;O&#x2014;Calkanoyl or benzyloxy; and salts thereof in the manufacture of a medicament for use in the production of a vascular damaging effect in warm-blooded animals such as humans. The present invention further relates to compounds of the formula (I), pharmaceutical compositions containing them, processes for their preparation and to a method of treatment using the compounds to produce a vascular damaging effect in a warm-blooded animal such as a human. The compounds of formula (I) and the pharmaceutically acceptable salts thereof may be useful in the treatment of a number of disease states including cancer and rheumatoid arthritis. 

Colchinol derivatives as vascular damaging agents

Compositions for the inhibition of the formation of new vaculature by angiogenesis are provided as in compounds which are salts comprising as an acidic component a compound of formula (1) wherein: R, Rand Rare each independently alkyl, Ris alkoxy, haloalkoxy, alkyl, haloalkyl, alkenyl, alkynyl, alkylthio, alkylsulphinyl, alkylsulphonyl, hydroxy or halo, Ris hydrogen, alkoxy, alkyl, alkylthio, hydroxy, phosphate or halo, and, as the basic component, a compound selected from the group consisting of (2) a compound of formula (2) wherein Ris hydrogen or alkyl Ris alkyl, alkylamino, dialkylamino, nitroamino, hydrazine, mercapto or alkylthio X is CH, CHCH, CHS, CHCHS Y is NH or S or a compound of formula (3) wherein Ris alkyl or aminoalkyl Ris hydrogen, alkyl or optionally substituted phenyl or, a compound of formula (4) wherein Z is O, S, CH2, CHR13 or a bond R, R, Rand Rare each independently alkyl or hydrogen or, a compound of formula (5) wherein Ris alkyl and the pharmaceutically acceptable solvates and hydrates thereof.

Compositions with vascular damaging activity

Compositions for the inhibition of the formation of new vasculature by angiogenesis are provided comprising the combination of a vasculature damaging agent and an inhibitor of the formation or action of nitric oxide in mammalian systems. There are also provided the use of said combinations in medicaments and kits of said compounds and treatment employing said materials.

Combinations for the treatment of diseases involving angiogenesis

Fused bicyclic amines of formula (1) are described wherein Ar is an aryl or heteroaryl group; Y is a &#x2014;S(O)&#x2014; or &#x2014;C(O)&#x2014; group; Ris a hydrogen or halogen atom or an alkyl, haloalkyl, alkoxy, haloalkoxy or cyano group; X is a nitrogen atom or a C(R) group where Ris as defined for Rand may be the same or different; W and Z are each a carbon atom and together with U form an optionally substituted five- or six-membered monocyclic aromatic or heteroaromatic group; and the salts, solvates, hydrates and N-oxides thereof. The compounds are able to inhibit the activity of Class 1 receptor tyrosine kinases and are of use in the prophylaxis and treatment of hyperproliferative disorders such as cancer, psoriasis, restenosis, atherosclerosis and fibrosis.

Bicyclic amine derivatives as inhibitors of class 1 receptor tyrosine kinases

The invention relates to a method for the production of a vascular damaging effect in a warm-blooded animal such as a human, which comprises administering to said animal an effective amount of ZD6126 or a pharmaceutically acceptable salt thereof, before, after or simultaneously with an effective amount of one of the following therapies: i) ionizing radiation; ii) a platinum anti-tumor agent; and iii) a taxane. The invention also relates to the use of ZD6126 and one of the above therapies in the manufacture of a medicament for use in the production of a vascular damaging effect in a warm-blooded animal such as a human and to pharmaceutical compositions and kits each comprising ZD6126 and one of a platinum anti-tumor agent and a taxane

N-acetylcolchinol-O-phosphate combination therapies with vascular damaging activity

Fused polycyclic 2-aminopyrimidine derivatives

2-pyrimidineamine derivatives and processes for their preparation

Substituted 2-anilinopyrimidines useful as protein kinase inhibitors

Compounds of general formula (1) are described:

Fused polycyclic 2-aminopyrimidines of formula (1) are described: wherein

Compounds of general formula (1) ##STR1## are described wherein: Ar is an optionally substituted aromatic group;

Growing community of inventors

Oxford, United Kingdom

Peter David Davis