Biota Europe Limited

Biota Scientific Management Pty Ltd

Taxis Pharmaceuticals, Inc.

Biota Scientific Pty Ltd

Prolysis Ltd.

Biots Scientific Management Pty Ltd

David John Haydon

Lloyd George Czaplewski

Ian Collins

John Atherall

Dale Mitchell

Nicholas Palmer

Tamara Ladduwahetty

Christopher Steele

Gary Robert William Pitt

James T Palmer

David Davies

David Ryall Brown

David Wyn Watson

Jeffrey Peter Mitchell

Dale Robert Mitchell

Laura Andrau

Lorraine Claire Axford

Edward Malcolm Tyndall

Nicholas John Palmer

Michael Blair

Daniel A Offermann

Christopher James Lunnis

Daniel Offermann

Neil Robert Stokes

Christopher Richard Steele

The present invention provides compounds of Formula (I): and salts, racemates, isomers, diastereoisomers, enantiomers, hydrates, solvates, N-oxides, pharmaceutically acceptable derivatives or prodrugs thereof. Also provided the use of these compounds as antibacterials, compositions comprising them and processes for their manufacture. 

Aromatic amides and uses thereof

The present invention provides a compound of the following formula and salts thereof: Also provided is the use of these compounds as antibacterials, compositions comprising them and processes for their manufacture.

Antibacterial compounds

Compounds of formula (I) have antibacterial activity: wherein R represents hydrogen or 1, 2 or 3 optional substituents; W is &#x2550;C(R)&#x2014;; Ris hydrogen and Ris hydrogen, methyl, or fluorine; or Rand Rtaken together are &#x2014;CH&#x2014;, &#x2014;CHCH, &#x2014;O&#x2014;, or, in either orientation, &#x2014;O&#x2014;CH&#x2014; or &#x2014;OCHCH&#x2014;; and Ris a radical of formula -(Alk)-(Z)-(Alk)-Q.

Antibacterial agents

Compounds of formula (IA) or (IB) have antibacterial activity: wherein W is &#x2550;CH&#x2014; or &#x2550;N&#x2014;; Ri and R2 are independently selected from hydrogen, fluoro and chloro, provided that Ri and R2 are not each hydrogen when W is &#x2550;CH&#x2014;; n is 0 or 1; X is &#x2014;O&#x2014;, &#x2014;S&#x2014;, or &#x2014;CH&#x2014;; and Q is (i) a phenyl radical, a naphthyl radical, a monocyclic carbocyclic or heteroaryl radical having 3 to 6 ring atoms, or a bicyclic heteroaryl radical having 5 to 10 ring atoms, any of which radicals being optionally substituted; or (ii) an optionally substituted C-Calkyl, C-Calkenyl, or C-Calkynyl radical, which may optionally be interrupted by &#x2014;O&#x2014;, &#x2014;S&#x2014;, &#x2014;S(O)&#x2014;, &#x2014;S(O)&#x2014;, &#x2014;NH&#x2014;, &#x2014;N(CH)&#x2014;, &#x2014;N(CHCH)&#x2014;, &#x2014;C&#x2014;K&#x2550;Oh or &#x2014;C(&#x2550;O)&#x2014;O&#x2014;. 

Compounds of formula (I) have antibacterial activity: wherein: m is 0 or 1; Q is hydrogen or cyclopropyl; Alk is an optionally substituted, divalent C-Calkylene, alkenylene or alkynylene radical which may contain an ether (&#x2014;O&#x2014;), thioether (&#x2014;S&#x2014;) or amino (&#x2014;NR)&#x2014; link, wherein R is hydrogen, &#x2014;CN or C-Calkyl; X is &#x2014;C(&#x2550;O)NR&#x2014;, &#x2014;S(O)NR&#x2014;, &#x2014;C(&#x2550;O)O&#x2014; or &#x2014;S(&#x2550;O)O&#x2014; wherein Ris hydrogen, optionally substituted C-Calkyl, C-Calkenyl, C-Calkynyl, -Cyc, or &#x2014;(C-Calkyl)-Cyc wherein Cyc is optionally substituted monocyclic carbocyclic or heterocyclic having 3-7 ring atoms; Z is N; Rand Rare as defined in the description.

Antibacterial compositions

Compounds of formula (IA) or (IB) have antibacterial activity: wherein W is &#x2550;C(H)&#x2014; or &#x2550;N&#x2014;; Ris a radical of formula -(Alk)-(Z)-(Alk)-Q wherein m, p and n are independently 0 or 1, provided that at least one of m, p and n is, Z1 is &#x2014;O&#x2014;, &#x2014;S&#x2014;, &#x2014;S(O)&#x2014;, &#x2014;S(O)&#x2014;, &#x2014;NH&#x2014;, &#x2014;N(CH)&#x2014;, &#x2014;N(CHCH)&#x2014;, &#x2014;C(&#x2014;O)&#x2014;, &#x2014;0&#x2014;(C&#x2550;O)&#x2014;, &#x2014;C(&#x2550;O)&#x2014;O&#x2014;, or an optionally substituted divalent monocyclic carbocyclic or heterocyclic radical having 3 to 6 ring atoms; or an optionally substituted divalent bicyclic carbocyclic or heterocyclic radical having 5 to 10 ring atoms; Alkand Alkare optionally substituted C-Calkylene, C-Calkenylene, or C-Calkynylene radicals, which may optionally terminate with or be interrupted by &#x2014;O&#x2014;, &#x2014;S&#x2014;, &#x2014;S(O)&#x2014;, &#x2014;S(O)&#x2014;, &#x2014;NH&#x2014;, &#x2014;N(CH)&#x2014;, Or &#x2014;N(CHCH)&#x2014;; and Q is hydrogen, halogen, nitrile, or hydroxyl, or an optionally substituted monocyclic carbocyclic or heterocyclic radical having 3 to 6 ring atoms; or an optionally substituted bicyclic carbocyclic or heterocyclic radical having 5 to 10 ring atoms; Rand Rare optional substituents; and R, Rand Rare independently hydrogen or a radical of formula -(Alk)-(Z)y-(Alk)-H wherein x, y and z are independently 0 or 1, Zis &#x2014;O&#x2014;, &#x2014;S&#x2014;, &#x2014;S(O)&#x2014;, &#x2014;S(O)&#x2014;, &#x2014;NH&#x2014;, &#x2014;N(CH)&#x2014;, &#x2014;N(CHCH)&#x2014;, &#x2014;C(&#x2014;O)&#x2014;, &#x2014;0&#x2014;(C&#x2550;O)&#x2014; or &#x2014;C(&#x2550;O)&#x2014;O&#x2014;; Alkand Alkare optionally substituted C-Calkylene, C-Calkenylene, or C-Calkynylene radicals, which may optionally terminate with or be interrupted by &#x2014;O&#x2014;, &#x2014;S&#x2014;, &#x2014;S(O)&#x2014;, &#x2014;S(O)&#x2014;, &#x2014;NH&#x2014;, &#x2014;N(CH)&#x2014;, or &#x2014;N(CHCH)&#x2014;. 

Substituted benzamidines as antibacterial agents

Compounds of formula (I) have antibacterial activity: wherein: m is 0 or 1; Q is hydrogen or cyclopropyl; Alk is an optionally substituted, divalent C-Calkylene, alkenylene or alkynylene radical which may contain an ether (&#x2014;O&#x2014;), thioether (&#x2014;S&#x2014;) or amino (&#x2014;NR)&#x2014; link, wherein R is hydrogen, &#x2014;CN or C-Calkyl; X is &#x2014;C(&#x2550;O)NR&#x2014;, &#x2014;S(O)NR&#x2014;, &#x2014;C(&#x2550;O)O&#x2014; or &#x2014;S(&#x2550;O)O&#x2014; wherein Ris hydrogen, optionally substituted C-Calkyl, C-Calkenyl, C-Calkynyl, -Cyc, or &#x2014;(C-Calkyl)-Cyc wherein Cyc is optionally substituted monocyclic carbocyclic or heterocyclic having 3-7 ring atoms; Z is N or CH, or CF; Rand Rare as defined in the description.

Compound of formula (I) have antibacterial activity: wherein: m is 0 or 1; Q is hydrogen or cyclopropyl; AIk is an optionally substituted, divalent C-Calkylene, alkenylene or alkynylene radical which may contain an ether (&#x2014;O&#x2014;), thioether (&#x2014;S&#x2014;) or amino (&#x2014;NR)&#x2014; link, wherein R is hydrogen, &#x2014;CN or C-Calkyl; X is &#x2014;C(&#x2550;O)NR&#x2014;, or &#x2014;C(&#x2550;O)O&#x2014; wherein Ris hydrogen, optionally substituted C-Calkyl, C-Calkenyl or C-Calkynyl; Zis &#x2014;N&#x2550; or &#x2014;CH&#x2550;Zis &#x2014;N&#x2550; or &#x2014;C(R)&#x2550;; Ris hydrogen, methyl, ethyl, ethenyl, ethynyl, methoxy, mercapto, mercaptomethyl, halo, fully or partially fluorinated (C-C)alkyl, (C-CJaIkoxy or (C-C)alkylthio, nitro, or nitrile (&#x2014;CN); Ris a group Q-[Alk]q-Q-, wherein q is 0 or 1; AIk1 is an optionally substituted, divalent, straight chain or branched C-Calkylene, or C-Calkenylene or C-Calkynylene radical which may contain or terminate in an ether (&#x2014;O&#x2014;), thioether (&#x2014;S&#x2014;) or amino (&#x2014;NR)&#x2014; link; Qis an optionally substituted divalent monocyclic carbocyclic or heterocyclic radical having 5 or 6 ring atoms or an optionally substituted divalent bicyclic carbocyclic or heterocyclic radical having 9 or 10 ring atoms; Qis hydrogen, an optional substituent, or an optionally substituted carbocyclic or heterocyclic radical having 3-7 ring atoms. 

Antibacterial condensed thiazoles

Compounds of formula (I) have antibacterial activity: wherein R represents hydrogen or 1, 2 or 3 optional substituents; W is &#x2550;C(R)&#x2014; or &#x2550;N&#x2014;; Ris hydrogen or an optional substituent and Ris hydrogen, methyl, or fluorine; or Rand Rtaken together are &#x2014;CH&#x2014;, &#x2014;CHCH&#x2014;, &#x2014;O&#x2014;, or, in either orientation, &#x2014;O&#x2014;CH&#x2014; or &#x2014;OCHCH&#x2014;; Ris a radical of formula -(Alk)-(Z)-(Alk)-Q wherein m, p and n are independently 0 or 1, provided that at least one of m, p and n is 1, Z is &#x2014;O&#x2014;, &#x2014;S&#x2014;, &#x2014;S(O)&#x2014;, &#x2014;S(O)&#x2014;, &#x2014;NH&#x2014;, &#x2014;N(CH)&#x2014;, &#x2014;N(CHCH)&#x2014;, &#x2014;C(&#x2550;O)&#x2014;, &#x2014;O&#x2014;(C&#x2550;O)&#x2014;, &#x2014;C(&#x2550;O)&#x2014;O&#x2014;, or an optionally substituted divalent monocyclic carbocyclic or heterocyclic radical having 3 to 6 ring atoms; or an optionally substituted divalent bicyclic heterocyclic radical having 5 to 10 ring atoms; Alkand Alkare optionally substituted C-Calkylene, C-Calkenylene, or C-Calkynylene radicals, which may optionally terminate with or be interrupted by &#x2014;O&#x2014;, &#x2014;S&#x2014;, &#x2014;S(O)&#x2014;, &#x2014;S(O)&#x2014;, &#x2014;NH&#x2014;, &#x2014;N(CH)&#x2014;, or &#x2014;N(CHCH)&#x2014;; and Q is hydrogen, halogen, nitrile, or hydroxyl or an optionally substituted monocyclic carbocyclic or heterocyclic radical having 3 to 6 ring atoms; or an optionally substituted bicyclic heterocyclic radical having 5 to 10 ring atoms.

Compounds of formula (I) have antibacterial activity: wherein: m is 0 or 1; Q is hydrogen or cyclopropyl; AIk is an optionally substituted, divalent C-Calkylene, alkenylene or alkynylene radical which may contain an ether (&#x2014;O&#x2014;), thioether (&#x2014;S&#x2014;) or amino (&#x2014;NR)&#x2014; link, wherein R is hydrogen, &#x2014;CN or C-Calkyl; X is &#x2014;C(&#x2550;O)NR&#x2014;, &#x2014;S(O)NR&#x2014;, &#x2014;C(&#x2550;O)O&#x2014; or &#x2014;S(&#x2550;O)O&#x2014; wherein Ris hydrogen, optionally substituted C-Calkyl, C-Calkenyl, C-Calkynyl, -Cyc, or &#x2014;(C-Calkyl)-Cyc wherein Cyc is optionally substituted monocyclic carbocyclic or heterocyclic having 3-7 ring atoms; Z is N or CH, or CF; Rand Rare as defined in the description. 

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Oxfordshire, United Kingdom

David John Haydon