Mehdi M. Baradarani

7-Chloro-2-[1-(4-methoxy­phen­yl)pyrazol-4-yl]-3,3-dimethyl-3H-indole

In the title compound, C20H18ClN3O, the dihedral angle between the pyrazole and the 3H-indole components is only 13.28 (6)°, indicating that there is conjugation between the two heterocyclic subunits. The N-methoxyphenyl unit makes a dihedral angle of 25.10 (7)° with the pyrazole ring.

2-[(Z)-4,7-Dichloro-3,3-dimethyl-2,3-dihydro-1H-indol-2-yl­idene]-3-oxopropane­nitrile

In the title compound, C13H10Cl2N2O, the ring N atom and its three attached atoms are essentially coplanar with angles adding to 359.8°, indicating conjugation with the 2-formylacrylonitrile subunit. The aldehyde group is oriented to place the carbonyl O atom 2.02 (3) Å from the N—H hydrogen atom. Intramolecular N—H⋯O and C—H⋯Cl interactions occur. The geometry of the exocyclic double bond is Z. In the crystal, weak C—H⋯N hydrogen bonds link the molecules into chains along [10].

The specific epimerisation of phthalideisoquinoline alkaloids

Abstract 1 R ,9 S α-Narcotine has been converted to 1 S ,9 S β-narcotine by reaction with thiophosgene, followed by sodium acetate in acetic acid. Conversion to 1 R ,9 R β-narcotine was achieved by sequential reaction of α-narcotine with α-chloroethyl chlorothionoformate, followed by aqueous sodium hydroxide. Finally, 1 R ,9 R β-narcotine was converted to 1 S ,9 R α-narcotine by reaction with thiophosgene, followed by sodium acetate in acetic acid.

Synthesis of novel spiro dipyrazolo[3,4-b: 4΄,3΄-e]pyridine

α-Methylacyl-CoA racemase (AMACR; P504S) catalyzes a key step in the degradation of branched-chain fatty acids and is important for the pharmacological activation of Ibuprofen and related drugs. Both the concentration and activity of AMACR are increased in prostate and other cancer cells, and the enzyme is a recognized drug target. However, all of the reported inhibitors are acyl-CoA esters (which do not comply with Lipinski guidelines) or non-specific protein modifying agents. Libraries of ~20,000 drug-like compounds were screened using a novel colorimetric assay; Incubation of R,S-2-3-(2,4-dinitrophenoxy)-2-methylpropanoyl-CoA with active AMACR resulted in the elimination of the strongly yellow 2,4-dinitrophenoxide and allows continuous measurement of activity in a microtitre plate format. Inhibitors were identified by a reduction in the rate of reaction in the presence of the library compound vs. the control. A number of novel reversible inhibitors were identified and their potency determined using dose-response curves. The results demonstrate the utility of the assay for the discovery and characterization of AMACR inhibitors as anti-cancer agents. This work was funded by Prostate Cancer UK (PG14-009), a Biochemical Society Summer Vacation Studentship Award, The Nuffield Foundation and MRC technology.

2-(4-Chloro-3,3,7-trimethyl-2,3-dihydro-1H-indol-2-yl-idene)-2-cyano-acetamide.

Reaction of 2-(4-chloro-3,3,7-trimethyl-2,3-dihydro-1H-indol-2-ylidene)propanedial with hydroxylamine gives the title compound, C14H14ClN3O, in which the ring N atom is essentially planar [sum of angles around the ring N atom = 361°], indicating conjugation with the 2-cyanoacrylamide unit. The orientation of the acetamide group arises from intramolecular hydrogen bonding between the indole N—H and carbonyl groups. In the crystal, inversion-related acetamide groups form N—H⋯O hydrogen-bonded dimers in graph-set R 2 2(8) motifs, whilst dimers are also formed by pairs of amine–nitrile N—H⋯N hydrogen bonds in R 2 2(12) motifs. These interactions together generate ribbons that propagate along the b-axis direction.

1-[(E)-4-(5-Bromo-1H-indol-3-yl)-1-methyl-2,5,6,7-tetra-hydro-1H-azepin-2-yl-idene]propan-2-one.

In the title compound, C18H19BrN2O, the seven-membered azepine ring adopts a twist-boat conformation: the bond angles about the azepine N atom are indicative of sp 2 hybridization. The dihedral angle between the plane of the carbon–carbon double bond of the enone unit and the mean plane of the indole ring is 27.8 (1)°. In the crystal, an N—H⋯O hydrogen bond links the molecules into chains along the b axis.

3-(1-Methyl-pyrrolidin-2-yl-idene)-3H-indole sesquihydrate.

The asymmetric unit of the title compound, C13H14N2·1.5H2O, contains two similar molecules of 3-(1-methylpyrrolidin-2-ylidene)-3H-indole, (I), and three water molecules. (I) is the product of reacting indole with 1-methylpyrrolidin-2-one in the presence of phosphorus oxychloride. Both organic molecules are almost completely planar; the maximum distances above and below the least-squares plane through all the atoms of molecule 1 are 0.050 (8) and −0.045 (8) Å, respectively, and the deviations for molecule 2 are 0.096 (8) and −0.059 (8) Å, respectively. In the crystal, the two crystallographically different molecules alternate in π-stacked columns [centroid–centroid distances = 3.729 (5) and 3.858 (5) Å], which are linked by O—H⋯N hydrogen bonds to a network of hydrogen-bonded water molecules. O—H⋯O interactions are also present.