Astrazeneca Ab

Other

Angiogene Pharmaceuticals Limited

Jean-Claude Arnould

Francis Thomas Boyle

Gareth Morse Davies

Peter David Davis

James Michael Wardleworth

David Charles Blakey

Grigorios Nikitidis

Thomas Geoffrey Colerick Bird

Joakim Larsson

Thomas Geoffrey Bird

Peter Storm

John Peter Bailey

Edward Jolyon Griffen

Malena Bengtsson

Annie Antoinette Christiane Olivier

The invention provides thiazole derivatives of formula (I), or pharmaceutically acceptable salts thereof in which Ring A, R, Rand Rare as defined in the specification; a processes for their preparation; pharmaceutical compositions containing them; and their use in therapy, for example in the treatment of disease mediated by a PI3K enzyme and/or a mTOR kinase.

5-heteroaryl thiazoles and their use as PI3K inhibitors

This invention relates to the use of compounds of Formula (I) as vascular damaging agents: wherein X is selected from: &#x2014;O&#x2014;, &#x2014;S&#x2014;, &#x2014;S(O)&#x2014;, &#x2014;S(O)&#x2014;, &#x2014;N(R)&#x2014;, &#x2014;C(O)&#x2014;, &#x2014;C(O)N(R)&#x2014;, &#x2014;N(R)C(O)&#x2014;, &#x2014;S(O2)N(R)&#x2014;, or &#x2014;N(R)S(O)&#x2014;; Ris independently selected from: amino, halo, hydroxy, &#x2014;OPOH, Calkyl, or Calkoxy, wherein the amino group is optionally substituted by an amino acid residue and the hydroxy group is optionally esterified; Ris selected from: hydrogen or Calkyl; Ris selected from: hydrogen, halo, hydroxy, hydroxyCalkyl, cyano, cyanoCalkyl, carboxy, carboxyCalkyl, Calkanoyl, CalkanoylCalkyl, carbamoyl, carbamoylCalkyl, Calkoxy, Calkoxycarbonyl, CalkoxycarbonylCalkyl, Calkoxycarbonylamino, amino, N&#x2014;Calkylamino, NN-diCalkylamino, aminoCalkyl, N&#x2014;CalkylaminoCalkyl, NN-diCalkylaminoCalkyl, ureido, or Calkylureyleno; Ris independently selected from: Calkyl, Calkoxy or halo; Ris selected from: hydrogen or Calkyl; n is 0 or 1; p is 0, 1, 2 or 3; and q is 0, 1 or 2; or a salt, pro-drug or solvate thereof. The invention also relates to novel compounds of Formula (I) and to processes for the preparation of compounds of Formula (I). 

Indolone derivatives having 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

The invention relates to the use of a compound of Formula (I), for the manufacture of a medicament to inhibit and/or reverse and/or alleviate symptoms of angiogenesis and/or any disease state associated with angiogenesis: wherein: X, p, q, R, R, R, R, and Rare as defined in the description. The invention also related to use of compounds of Formula (I) as medicaments and also to novel compounds of Formula (I). The invention further provides pharmaceutical compositions of compounds of Formula (I) and processes for the synthesis of compounds of Formula (I).

Indole derivatives having anti-angiogenetic activity

The invention provides a compound of Formula (I).Wherein R1, R2, R3, R10 and R11 have the meanings given in the description. Such compounds are predicted to cause the selective destruction of tumour vasculature. They may therefore be used to inhibit and/or reverse, and/or alleviate symptoms of angiogenesis and/or any disease state associated with angiogenesis.

Indole derivatives with vascular damaging activity

This invention relates to compounds of formula (1), wherein substituents are defined in the description, that inhibit farnesylation of mutant ras gene products tough inhibition of the enzyme farnesyl-protein transferase (FPTase). The invention also relates to methods of manufacturing the compounds, pharmaceutical compositions and methods of treating diseases, especially cancer, which are mediated through farnesylation of ras.

Chemical compounds

Imidazolyl compounds as inhibitors of farnesyl-protein tranferase

The present invention relates to a compound of Formula (1) wherein Ar represent (A) or (B) or (C); R is hydrogen, C alkyl or C alkanoyl; R and R are independently hydrogen or C alkyl; Ar is phenyl or heteroaryl; p is 0 or 1; Ar is of formula (I) wherein W, X, Y and Z are independently CH or N, provided that at least two of W, X, Y and Z are CH and R and &mdash;(CH ) R are attached to ring carbon atoms; R is a group of Formula (II) or R represents a lactone of Formula (III) the group of Formula (II) or (III) having L or D configuration at the chiral alpha carbon in the corresponding free amino acid; n is 0, 1 or 2; R is phenyl or heteroaryl; provided that: when n is 0, Ar is substituted by R in the 4-position and &mdash;(CH ) R in the 3- or 5-position; and when n is 1 or 2, Ar is substituted by R in the 3- or 5-position and &mdash;(CH ) R in the -position; and R -R , m and n are as defined in the specification; or a pharmaceutically-acceptable salt, prodrug or solvate thereof. Processes for their preparation, their use as therapeutic agents and pharmaceutical compositions containing them. A particular use is in cancer therapy.

Growing community of inventors

Reims, France

Jean-Claude Arnould