Peter Maccallum Cancer Institute

Patrick David O'Connor

William Alexander Denny

Julie Ann Spicer

Christian Miller

Kristiina Huttunen

Joseph A Trapani

Geoff Hill

Kylie Alexander

Christian Karl Miller

Compounds of formula (1a) and pharmaceutically acceptable salts, solvates, and hydrates thereof and related methods of modulatin perforin activity on a cell: wherein Ring A is selected from a 6-10 membered aryl, 5-6 membered cycloalkyi, 5-6 membered heteroaryl or 5-6 membered heterocyclyl, wherein the heteroaryl and heterocyclyl rings comprise at least one heteroatom selected from N, O or S; and wherein the aryl, cycloalkyi, heteroaryl or heterocyclyl rings are optionally substituted with 1 to 3 substituents selected from halo, nitro, &#x2014;C-Cealkyl, &#x2014;C-Ceaminoalkyl, &#x2014;C-Chydroxyalkyl, -haloC-Calkyl, &#x2014;C-Calkoxyl, -haloC&#x2014;C&#x3c;aIkoxyl, heteroaryl, aryl, hydroxyl, &#x2014;C(0)Ci-C6alkyl, &#x2014;OC(0)Ci-Calkyl, &#x2014;CHOC(O)CrCalkyl, &#x2014;C(O)OC, &#x2014;CalkyI, &#x2014;NHC(O)C, &#x2014;C6alkyl, &#x2014;NHS(O)C-Calkyl, &#x2014;S(O)C-Calkyl, &#x2014;S(O)NH, and &#x2014;C(O)NJJ; Ring B is a 6-10 membered arylene or a 5-6 membered heteroarylene comprising at least one heteroatom selected from N, 0 or S; and wherein the aryl or heteroaryl is optionally, substituted with one or more substituents selected from &#x2014;NJJ, &#x2014;OJ, halo, C-Calkyl, -haloC-C6alkyl, &#x2014;C-Calkoxy, -haloC-Calkoxyl, and &#x2014;C(0)NJJ; Ring C is selected from a 5-10 membered heteroarylene or a 5-10 membered heterocyclene, each comprising at least one heteroatom selected from N, S and O; Ring D is an optionally substituted benzofused 9-11 membered heterocyclyl or optionally substituted ben2ofused 9-11 membered heteroaryl comprising at least one heteroatom selected from N or O; L is a linker selected from branched and unbranched C1-C4 alkylene, &#x2014;S(0)2-NH&#x2014;, &#x2014;C(0)-NH&#x2014;, &#x2014;NH&#x2014;C(0)-NH&#x2014;, &#x2014;S(0)2-NH&#x2014;C(0)-NH&#x2014;, &#x2014;S(0)2-NH&#x2014;C(0)- and &#x2014;CH&#x2550;CH&#x2014;; wherein Rings B and C, and Rings C and D, are connected to each other via a C&#x2014;C bond at any of the available C atoms on each respective ring; and J in each occurrence is independently selected from H, optionally substituted C-Calkyl or optionally substituted haloC-Calkyl. 

Perforin inhibiting benzenesulfonamide compounds, preparation and uses thereof

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Auckland, New Zealand

Patrick David O'Connor