Astrazeneca Ab

Nicholas John Keen

Andrew Mortlock

Frederic H Jung

Andrew David Bruce Pannifer

Andrew George Brewster

Richard Alexander Pauptit

Malcom Anderson

Sian Rowsell

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

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

The invention provides crystalline forms of a polypeptide corresponding to the catalytic domain of Aurora kinase. The active site ATP binding pocket is defined by its amino acid residues and their atomic coordinates. This structure may be used to select or design chemical modulators of Aurora kinase, particularly Aurora inhibitors. These modulators may be used to treat diseases of cell proliferation, e.g. cancer.

Crystal structure of aurora a kinase and uses thereof

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.

Growing community of inventors

Macclesfield, United Kingdom

Nicholas John Keen