Astrazeneca Ab

Andrew Mortlock

Frederic H Jung

Nicola Murdoch Heron

Nicholas John Keen

Georges Rene Pasquet

Georges Pasquet

Andrew George Brewster

Quinazoline derivatives of formula (I): wherein A is 5-membered heteroaryl containing a nitrogen atom and one or two further nitrogen atoms; compositions containing them, processes for their preparation and their use in therapy.

Methods of treatment using N-(3-fluorophenyl)-2-{3-[(7-{3-[ethyl(2-hydroxyethyl)amino]propoxy}-quinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide

Phosphonoxy quinazoline derivatives and their pharmaceutical use

The use of a compound of formula (I) or a salt, ester, amide or prodrug thereof; where X is O, or S, S(O) or S(O), NH or NRwhere Ris hydrogen or Calkyl; Ris selected from a group NHC(O)OR, NHC(O)R, NHS(O)R, C(O)R, C(O)OR, S(O)R, S(O)OR, S(O)OR, C(O)NRR, S(O)NRRS(O)ONRR, where R, Ror Rare various specified organic groups; Ris hydrogen, optionally substituted hydrocarbyl or optionally substituted heterocyclyl; Rand Rare various specified organic groups, and R, R, R, Rare independently selected from halogeno, cyano, nitro, Calkylsulphanyl, &#x2014;N(OH)R&#x2014; (wherein Ris hydrogen, or Calkyl), or RX&#x2014; (wherein Xrepresents a direct bond, &#x2014;O&#x2014;, &#x2014;CH&#x2014;, &#x2014;OCO&#x2014;, carbonyl, &#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, Rand Reach independently represents hydrogen, Calkyl or Calkoxy Calkyl), and Ris hydrogen, optionally substituted hydrocarbyl, optionally substituted heterocyclyl or optionally substituted alkoxy; in the preparation of a medicament for use in the inhibition of aurora 2 kinase. 

Quinazoline derivatives and their use as pharmaceuticals

Quinazoline derivatives of formula (I); for use in the treatment of proliferative diseases such as cancer and in the preparation of medicaments for use in the treatment of proliferative diseases, and to process for their preparation, as well as pharmaceutical compositions containing them as active ingredient. 

Chemical compounds

Quinazoline derivatives of formula (I) wherein A is 5-membered heteroaryl containing a nitrogen atom and one or two further nitrogen atoms; compositions containing them, processes for their preparation and their use in therapy. 

Phosphonooxy quinazoline derivatives and their pharmaceutical use

Quinazoline derivatives of formula (I) wherein A is 5-membered heteroaryl containing a sulphur atom and optionally containing one or more nitrogen atoms; compositions containing them, processes for their preparation and their use in therapy. 

Quinazoline compounds

A compound of formula (I) or a salt, ester, amide or prodrug thereof; where X is O, or S, S(O), S(O)or NRwhere Ris hydrogen of Calkyl; Ris an optionally substituted 6-membered aromatic ring containing at least one nitrogen atom, and R, R, R, Rare independently selected from halogeno, cyano, nitro, Calkylsulphanyl, &#x2014;N(OH)R&#x2014; (wherein Ris hydrogen, or Calkyl), or RX&#x2014; (wherein Xrepresents a direct bond, &#x2014;O&#x2014;, &#x2014;CH&#x2014;, &#x2014;OC(O), &#x2014;C(O)&#x2014;, &#x2014;S&#x2014;, &#x2014;SO&#x2014;, &#x2014;SO&#x2014;, &#x2014;NRC(O)&#x2014;, &#x2014;C(O)NR&#x2014;, &#x2014;SONR&#x2014;, &#x2014;NRSO&#x2014; or NR&#x2014; (wherein R, R, R, Rand Reach independently represents hydrogen, Calkyl or CalkoxyCalkyl), and Ris hydrogen, optionally substituted hydrocarbyl, optionally substituted heterocyclyl or optionally substituted alkoxy; provided that at least one of Ror Ris other than hydrogen. These compounds inhibit aurora 2 kinase and are useful in the preparation of medicaments for the treatment of proliferative disease such as cancer.

Therapeutic quinazoline derivatives

A compound of formula (I) or a salt, ester or amide thereof; where X is O, or S, S(O) or S(O)or NRwhere Ris hydrogen or Calkyl, and R, R, R, R, R, R, R, Rand Rare various specified organic groups. These compounds are inhibitors of aurora 2 kinase, and are useful in the treatment of cancer. 

Quinazoline derivatives

The use of a compound of formula (I) or a salt, ester or amide thereof;where X is O, or S, S(O) or S(O), NH or NRwhere Ris hydrogen or Calkyl;Ris a 3-quinoline group or a group of sub-formula (i) where R, Rand Rare various specific organic groups, in the preparation of a medicament for use in the inhibtion of aurora 2 kinase. Novel compounds of formula (I) and pharmaceutical compositions useful in the treatment of cancer are also described and claimed.

Quinazoline compounds and pharmaceutical compositions containing them

A compound of formula (I)or a salt, ester, amide or prodrug thereof; Ris an optionally substituted 6-membered aromatic ring containing at least one nitrogen atom, and R, R, R, Rare independently selected from halogeno, cyano, nitro, Calkylsulphonyl, &#x2014;N(OH)R&#x2014; (wherein Ris hydrogen, or Calkyl), or RX&#x2014; (wherein Xrepresents a direct bond, &#x2014;O&#x2014;, &#x2014;CH&#x2014;, &#x2014;OC(O)&#x2014;, &#x2014;C(O)&#x2014;, &#x2014;S&#x2014;, &#x2014;SO&#x2014;, &#x2014;SO&#x2014;, &#x2014;NRC(O)&#x2014;, &#x2014;C(O)NR&#x2014;, &#x2014;SONR&#x2014;, &#x2014;NRSO&#x2014; or &#x2014;NR&#x2014; (wherein R, R, R, Rand Reach independently represents hydrogen, Calkyl or CalkoxyCalkyl), and Ris hydrogen, optionally substituted hydrocarbyl, optionally substituted heterocyclyl or optionally substituted alkoxy); provided that at least one of Ror Ris other than hydrogen. These compounds are inhibitors of aurora 2 kinase. Thus they, and pharmaceutical compositions containing them, are useful in methods of treatment of proliferative disease such as cancer and in particular cancers such as colorectal or breast cancer where aurora 2 is upregulated.

Quinoline derivatives and their use as aurora 2 kinase inhibitors

The use of a compound of formula (I)or a salt, ester or amide thereof;where X is O, or S, S(O) or S(O), or NRwhere Ris hydrogen or Calkyl; Certain compounds are novel and these, together with pharmaceutical compositions containing them are also described and claimed.

Growing community of inventors

Macclesfield, United Kingdom

Andrew Mortlock