Dibenzo[a,g]quinolizin-8-ones: synthesis, estrogen receptor affinities, and cytostatic activity

A number of acetoxy-substituted dibenzo[a,g]quinolizin-8-ones were synthesized by the reaction of 1-oxoisoquinolines with substituted homophthalic acid anhydride. All of the derivatives with acetoxy groups in positions 3 and 10 bind to the estrogen receptor. Relative binding affinities (RBA) ranged from 1.8 to 5.6 (estradiol: RBA = 100) when the substituent at C-6 was a short alkyl group. Introduction of additional oxygen functions in the 2- and/or 11-position decreased binding affinities. Analyses of the enantiomers of 6-methyl (6b) and 6-ethyl (6c) derivatives revealed that the receptor binding is mainly due to one optical isomer (e.g. (-)-6b, 9.9; (+)-6b, 0.6). In hormone-sensitive human MCF-7 breast cancer cells, compounds with one acetoxy group in each aromatic ring strongly inhibited cellular growth. Despite marked differences in receptor affinity, the enantiomers displayed similar activities in this cell culture. In hormone-independent MDA-MB 231 mammary tumor cells, only a weak cytostatic effect was recorded at 10-5 M. In the immature mouse uterine weight test, minimal estrogenic activity was observed. At higher doses, a significant anti-estrogenic effect became evident. It is assumed that the estrogen antagonism is responsible for the specific cytostatic effect in MCF-7 breast cancer cells

Model Study of Wind Forces on Hyperbolic Paraboloid Shells

Agricultural Engineerin

3-(2-Amino­eth­yl)-2-[4-(trifluoro­meth­oxy)anilino]quinazolin-4(3H)-one

In the title compound, C17H15F3N4O2, the dihedral angle between the trifluoro­meth­oxy-substituted benzene ring and the pyrimidinone ring is 45.1 (5)°, while that between the fused benzene ring and the pyrimidinone ring is 0.67 (1)°. Part of one of the benzene rings and its trifluoro­meth­oxy substituent are disordered over two positions of approximately equal occupancy (0.51:0.49). Inter­molecular N—H⋯O and N—H⋯N hydrogen bonds contribute to the stability of the crystal structure. A weak intra­molecular C—H⋯F contact is also found. In addition, π–π stacking inter­actions, with centroid–centroid distances in the range 3.673 (6)–3.780 (8) Å, and weak C—H⋯π inter­actions are also observed

2-[2-(2-Anilino-4-oxo-3,4-dihydro­quinazolin-3-yl)phen­oxy]-3-phenyl­quinazolin-4(3H)-one methanol hemisolvate

In the title compound, C34H23N5O3·0.5CH3OH, each pyrimid­in­one heterocycle and its adjacent benzene ring are almost coplanar, making dihedral angles of 0.69 (13) and 1.87 (13)°. The lower pyrimidinone ring makes a dihedral angle of 40.41 (15)° with the —NH— bonded phenyl ring. O—H⋯O hydrogen bonds and weak C—H⋯π inter­actions are observed in the crystal structure. The methanol solvent molecule is disordered over two positions of equal occupancy

3-(2-Hydroxy­ethyl)-2-(p-tolyl­amino)­quinazolin-4(3H)-one

In the title compound, C17H17N3O2, the quinazolinone ring system is essentially planar. The benzene ring is twisted with respect to it by a dihedral angle of 32.7 (5)°. The mol­ecular conformation is stabilized by an N—H⋯O hydrogen bond, and the crystal structure is stabilized by inter­molecular O—H⋯N inter­actions

2-Anilino-3-(2-hy­droxy­phen­yl)quinazolin-4(3H)-one methanol monosolvate

In the title compound, C20H15N3O2·CH3OH, the quinazolin­one ring system is approximately planar, the dihedral angle between the pyrimidinone ring and the adjacent benzene ring being 1.73 (6)°. The pyrimidinone ring makes dihedral angles of 77.58 (6) and 29.62 (6)°, respectively, with the hy­droxy­phenyl and phenyl rings. In the crystal, the components are connected by O—H⋯O and C—H⋯O hydrogen bonds, forming a zigzag chain along the b axis