Astrazeneca Ab

Zeneca Limited

Other

Genzyme Corporation

Astra Zeneca U.k. Limited

Zeneca Pharma S. A.

Elaine Sophie Elizabeth Stokes

Laurent Francois Andre Hennequin

Andrew Peter Thomas

Craig Johnstone

Michael James Waring

Jean-Jacques Marcel Lohmann

David Michael Andrews

Edward Clayton

Andrew Turner

George R Brown

David Waterson

Robin Wood

Nicholas John Newcombe

Zbigniew Stanley Matusiak

John Graham Cumming

Keith Hopkinson Gibson

William J Watkins

Mark Andrew Graham

Craig Anthony Roberts

The invention relates to quinazoline derivatives of formula (I), wherein m is an integer from 1 to 3; R' represents halogeno or Calkyl; Xrepresents &#x2014;O&#x2014;; Ris selected from one of the following three groups: 1) CalkylR(wherein Ris piperidin-4-yl which may bear one or two substituents selected from hydroxy, halogeno, Calkyl, Chydroxyalkyl and Calkoxy; 2) CalkenylR(wherein Ris as defined hereinbefore); 3) CalkynylR(wherein Ris as defined hereinbefore); and wherein any alkyl, alkenyl or alkynyl group may bear one or more substituents selected from hydroxy, halogeno and amino; and salts thereof; processes for their preparation, pharmaceutical compositions containing a compound of formula (I) or a pharmaceutically acceptable salt thereof as active ingredient. The compounds of formula (I) and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis. 

Quinazoline derivatives as VEGF inhibitors

The invention relates to quinazoline derivatives of formula (I), wherein m is an integer from 1 to 3; Rrepresents halogeno or Calkyl; Xrepresents &#x2014;O&#x2014;; Ris selected from one of the following three groups: 1) CalkylR, wherein Ris piperidinyl-4-yl which may bear one or two substituents selected from hydroxy, halogeno, Calkyl, Chydroxyalkyl and Calkoxy; 2) CalkenylR, wherein Ris as defined herein; 3) CalkynylR, wherein Ris as defined herein; and wherein any alkyl, alkenyl or alkynyl group may bear one or more substituents selected from hydroxy, halogeno and amino; and salts thereof; processes for their preparation; pharmaceutical compositions containing a compound of formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient.

The invention concerns benzamide compounds of formula (I): compound of formula (I): wherein Ris a C-linked pyrazole ring, which is optionally substituted by one or more groups selected from Calkyl, Ccycloalkyl, Calkoxy and Ccycloalkoxy;or a pharmaceutically acceptable salt or pro-drug form thereof. The invention also concerns processes for the preparation of such compounds, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an antiproliferative agent in the prevention or treatment of tumors or other proliferative conditions, which are sensitive to the inhibition of histone deacetylase (HDAC).

Benzamide compounds useful as histone deacetylase inhibitors

The invention relates to quinazoline derivatives of formula (I), wherein m is an integer from 1 to 3; Rrepresents halogeno or Calkyl; Xrepresents &#x2014;O&#x2014;; Ris selected from one of the following three groups: 1) C-5alkylR(wherein Ris piperidinyl-4-yl which may bear one or two substituents selected from hydroxy, halogeno, Calkyl, Chydroxyalkyl and Calkoxy; 2) CalkenylR(wherein Ris as defined hereinbefore); 3) CalkynylR(wherein Ris as defined hereinbefore); and wherein any alkyl, alkenyl or alkynyl group may bear one or more substituents selected from hydroxy, halogeno and amino; and salts thereof; processes for their preparation, pharmaceutical compositions containing a compound of formula (I) or a pharmaceutically acceptable salt thereof as active ingredient. The compounds of formula (I) and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis. 

The invention concerns a compound of the formula (I) wherein Ring A is heterocyclyl; m is 0-4 and each Ris a group such as hydroxy, halo, trifluoromethyl and cyano; Ris halo and n is 0-2; and each Ris a group such as hydroxy, halo, trifluoromethyl and cyano; p is 0-4; and Ris amino or hydroxy;or pharmaceutically-acceptable salts or in-vivo-hydrolysable ester or amide thereof;processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of diseases or medical conditions mediated by histone deacetylase.

Benzamide derivatives useful as histone deacetylase inhibitors

The invention concerns benzamide compounds of formula (I), wherein Ris a C-linked pyrazole ring, which is optionally substituted by one or more groups selected from Calkyl, Ccycloalkyl, Calkoxy and Ccycloalkoxy; or a pharmaceutically acceptable salt or pro-drug form thereof. The invention also concerns processes for the preparation of such compounds, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an antiproliferative agent in the prevention or treatment of tumors or other proliferative conditions, which are sensitive to the inhibition of histone deacetylase (HDAC). 

The invention relates to quinazoline derivatives of formula (1) wherein m is an integer from 1 to 2; Rrepresents hydrogen, hydroxy, halogeno, nitro, trifluoromethyl, cyano, Calkyl, Calkoxy, Calkylthio, or &#x2014;NRR(wherein Rand R, which may be the same or different, each represents hydrogen or Calkyl); Rrepresents hydrogen, hydroxy, halogeno, methoxy, amino or nitro; Rrepresents hydroxy, halogeno, Calkyl, Calkoxy, Calkanoyloxy, trifluoromethyl, cyano, amino or nitro; Xrepresents &#x2014;O&#x2014;, &#x2014;CH&#x2014;, &#x2014;S&#x2014;, &#x2014;SO&#x2014;, &#x2014;SO&#x2014;, &#x2014;NRCO&#x2014;, &#x2014;CONR&#x2014;, &#x2014;SONR&#x2014;, &#x2014;NRSO&#x2014; or &#x2014;NR&#x2014; (wherein R, R, R, Rand Reach independently represents hydrogen, Calkyl or CalkoxyCalkyl); Rrepresents an optionally substituted 5 or 6 membered saturated carbocyclic or heterocyclic group or a group which is alkenyl, alkynyl or optionally substituted alkyl, which alkyl group may contain a heteroatom linking group, which alkenyl, alkynyl or alkyl group may carry a terminal optionally substituted group selected from alkyl and a 5 or 6 membered saturated carbocyclic or heterocyclic group, and salts thereof; processes for their preparation, pharmaceutical compositions containing a compound of formula (I) or a pharmaceutically acceptable salt thereof as active ingredient. The compounds of formula (I) and pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.

Quinazoline derivatives and pharmaceutical compositions containing them

The invention concerns benzamide compounds of Formula (I), wherein R, R, R, R, R, R, m and n have any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an antiproliferative agent in the prevention or treatment of tumours or other proliferative conditions which are sensitive to the inhibition of histone deacetylase (HDAC).

Benzamide compounds

The invention relates to quinazoline derivatives of formula (I), wherein m is an integer from 1 to 3; Rrepresents halogeno or Calkyl; Xrepresents &#x2014;O&#x2014;; Ris selected from one of the following three groups: 1) CalkylR(wherein Ris piperidin-4-yl which may bear one or two substituents selected from hydroxy, halogeno, Chydroxyalkyl and Calkoxy; 2) CalkenylR(wherein Ris as defined hereinbefore); 3) CalkynylR(wherein Ris as defined hereinbefore); and wherein any alkyl, alkenyl or alkynyl group may bear one or more substituents selected from hydroxy, halogeno and amino; and salts thereof, processes for their preparation, pharmaceutical compositions containing a compound of formula (I) or a pharmaceutically acceptable salt thereof as a active ingredient. The compounds of formula (I) and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of number of disease states including cancer and rheumatoid arthritis.

The invention concerns quinazoline derivatives of Formula (I) wherein ring A is phenyl or a 5-or 6-membered heterocyclic ring which may be saturated, partially saturated or unsaturated and may be aromatic or non-aromatic and which contains 1, 2 or 3 ring heteroatoms selected from O, N and S; Z is &#x2014;O&#x2014;, &#x2014;NH&#x2014; or &#x2014;S&#x2014;; and X, R, R, R, m and Rhave any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in producing an antiangiogenic and/or vascular permeability reducing effect in warm-blooded animals, and in the treatment of disease states such as cancer, rheumatoid arthritis and psorlasis.

Quinazoline compounds

The invention relates to quinazoline derivatives of formula (I) wherein m is an integer from 1 to 2; Rrepresents hydrogen, hydroxy, halogeno, nitro, trifluoromethyl, cyano, Calkyl, Calkoxy, Calkylthio, or &#x2014;NRR(wherein Rand R, which may be the same or different, each represents hydrogen or Calkyl); Rrepresents hydrogen, hydroxy, halogeno, methoxy, amino or nitro; Rrepresents hydroxy, halogeno, Calkyl, Calkoxy, Calkanoyloxy, trifluoromethyl, cyano, amino or nitro; Xrepresents &#x2014;O&#x2014;, &#x2014;CH&#x2014;, &#x2014;S&#x2014;, &#x2014;SO&#x2014;, &#x2014;SO&#x2014;, &#x2014;NRCO&#x2014;, &#x2014;CONR&#x2014;, &#x2014;SONR&#x2014;, &#x2014;NRSO&#x2014; or &#x2014;NR&#x2014; (wherein R, R, R, Rand Reach independently represents hydrogen, Calkyl or CalkoxyCalkyl); Rrepresents an optionally substituted 5 or 6 membered saturated carbocyclic or heterocyclic group or a group which is alkenyl, alkynyl or optionally substituted alkyl, which alkyl group may contain a heteroatom linking group, which alkenyl, alkynyl or alkyl group may carry a terminal optionally substituted group selected from alkyl and a 5 or 6 membered saturated carbocyclic or heterocyclic group, and salts thereof; processes for their preparation, pharmaceutical compostions containing a compound of formula (I) or a pharmaceutically acceptable salt thereof as active ingredient. The compounds of formula (I) and the pharmaceutically acceptable salts thereof inhibit the effects of VEGP, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.

Growing community of inventors

Macclesfield, United Kingdom

Elaine Sophie Elizabeth Stokes