A collaborative high throughput screen of 1.35 million compounds against mutant (R132H) isocitrate dehydrogenase IDH1 led to the identification of a novel series of inhibitors. Elucidation of the bound ligand crystal structure showed that the inhibitors exhibited a novel binding mode in a previously identified allosteric site of IDH1 (R132H). This information guided the optimization of the series yielding submicromolar enzyme inhibitors with promising cellular activity. Encouragingly, one compound from this series was found to induce myeloid differentiation in primary human IDH1 R132H AML cells in vitro.

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IAN SINCLAIR and IAN J. WORRALL. Can. J. Chem. 60, 695 (1982). The neutral complexes In2)d.2L (X = C1, Br, I; L = 1,4dioxan, tetrahydropyran, tetrahydrofuran, tetrahydrothiophene), Introduction Although the gallium halides Ga,X4 are ionic mixed oxidation state compounds they react with many ligands to form neutral gallium-gallium bonded complexes (1, 2). Recent crystal structure determinations have confirmed the presence of these bonds in Ga2X4.2disxan (X = C1, Br) (1, 3) and Ga2Br4. 2pyridine (4). The use of the structurally similar indium and thallium dihalides to prepare neutral metal-metal bonded complexes of these elements is a logical extension to the gallium work and we here report the preparation of a number of neutral indium compounds which appear to be similar to their gallium analogues and contain indium-indium bonds.A survey of previous work suggests that the indium dihalides are capable of forming both ionic and neutral complexes; aniline complexes of stoichiometry InX2-2aniline have been formulated In-(aniline),+In&-(5) and Russian workers have proposed that metal-metal bonds are present in the

and 2.3.4.5-Tetrahydro-3-benzazepin-I -one and its 3-benzyloxycarbonyl and 3-methyl derivatives have been synthesised from 2,3,4,5-tetrahydro-3-p-tolylsulphonyl-3benzazepin-I -one. 2.3.4.5-Tetrahydro-7.8-dimethoxy-3-p-tolylsulphonyl-3-benzazepin-I -one was made by cyclisation of the corresponding glycine in polyphosphoric acid at 20" but all attempts to cyclise N-alkylglycines failed.Applied Chemistry, University of Strathclyde, Glasgow G1 1 XL PREVIOUSLY 2,3,4,5-t e t rahydro-3-p-t olylsulphonyl-3benzazepin-l-ones (I; R1 = tosyl) have been made 2*3 by cyclisation of appropriate N-tosylglycines with Lewis acids. The corresponding amino-ketones (I; R1 = H or Me) have never been made: we now describe the synthesis of two of them and several other amines in the tetrahydro-3-benzazepine series.