Three 5H-indeno[1,2-c]pyridazin- 5-one derivatives, potent type-B monoamine oxidase inhibitors RaphaeÈlFre Âde Ârick,*³ Bernadette Norberg, FrancËois Durant, Frederic Ooms§ and Johan Wouters} Laboratory of Molecular and Structural Chemistry, University of Namur, 61 rue de Bruxelles, B-5000 Namur, Belgium Correspondence e-mail: raphael.frederick@fundp.ac.be Received 17 May 2004 Accepted 16 June 2004 Online 11 August 2004 The structures of three compounds, namely 7-methoxy-2- [3-(tri¯uoromethyl)phenyl]-9H-indeno[1,2-c]pyridazin-9-one, C 19 H 11 F 3 N 2 O 2 , (Id), 6-methoxy-2-[3-(tri¯uoromethyl)phenyl]- 9H-indeno[1,2-c]pyridazin-9-one, C 19 H 11 F 3 N 2 O 2 , (IId), and 2-methyl-6-(4,4,4-tri¯uorobutoxy)-9H-indeno[1,2-c]pyridazin- 9-one, C 16 H 13 F 3 N 2 O 2 , (IIf ), which are potent reversible type-B monoamine oxidase (MAO-B) inhibitors, are presented and discussed. Compounds (Id) and (IId) crystallize in a nearly planar conformation. The crystal structures are stabilized by weak CÐHO hydrogen bonds. The packing is dominated by ± stacking interactions between the heterocyclic central moieties of centrosymmetrically related molecules. In compound (IIf ), the tri¯uoroethyl termination is almost perpendicular to the plane of the ring. Comment The 5H-indeno[1,2-c]pyridazin-5-ones (Ia)±(Ie) have been described by Testa (Kneubu È hler et al., 1993, 1995) to be reversible and selective MAO-B inhibitors. As part of a project aiming to improve the biological activity of compounds of this family, we recently described a general MAO-B pharmacophore. This led to the rational design of compounds (If) and (IIf ), bearing a hydrophobic 4,4,4-tri- ¯uorobutoxy side chain on positions 7 and 6, respectively, of the indeno[1,2-c]pyridazin-5-one ring (Ooms et al. , 2003). [The values of IC 50 given for compounds (Ia)±(Id) are taken from Kneubu È hler et al. (1995).] We intended to synthesize (If), possessing the side chain on position 7, using the strategy successfully used by Testa (Kneubu È hler et al., 1995) to produce two related compounds, viz. (Ic) and (Id). Surprisingly, we found that the resulting product possesses the isomeric structure (IIf ), with the side chain on position 6. In order to validate the results obtained by Testa, we repeated the synthesis of (Id). We found that the major isomer (47% yield, yellow, m.p. 487 K, 1 H NMR spectrum identical to that published) was in fact (IId) and not (Id), as proved unambiguously by the X-ray crystal data. The minor product (3.5% yield, orange, m.p. 477 K), on the other hand, presented the structure (Id), again proved by X-ray crystallography. Compound (Id) (Fig. 1), the minor isomer, crystallized in the triclinic P 1 space group. This compound possesses the methoxy group on position C7 of the 5H-indeno[1,2-c]- pyridazine ring [O2ÐC7ÐC8ÐC9 torsion angle 178.7 (2)  ]. The dihedral angle between the phenyl ring D and the adjacent pyridazine ring C is approximately 19  (Fig. 1). Atom C10 acts as a donor for a weak intermolecular CÐHO hydrogen bond with carboxyl atom O1 (Table 1). The crystal packing is dominated by ± stacking interactions between the centrosymmetrically related molecules (Fig. 2 and Table 2). The stacking geometry is such that rings A, B and C of one molecule are superimposed on rings C, B and A, respectively, of a symmetry-related molecule at (1  x,1  y, z). On the organic compounds Acta Cryst. (2004). C60, o623±o626 DOI: 10.1107/S0108270104014660 # 2004 International Union of Crystallography o623 Acta Crystallographica Section C Crystal Structure Communications ISSN 0108-2701 Figure 1 The molecular structure of compound (Id). Displacement ellipsoids are drawn at the 30% probability level and H atoms are shown as small spheres of arbitrary radii. For clarity, only one of the disordered CF 3 groups is shown. ³ Present address: Department of Pharmacy, University of Namur, 61 rue de Bruxelles, B-5000 Namur, Belgium. § Present address: Euroscreen SA, 47 rue Adrienne Boland, B-6041 Gosselies, Belgium. } Present address: IRMW, 1 avenue E. Gryson, B-1070 Brussels, Belgium.