-Alkyl Carbamoylimidazoles as Versatile Synthons for the Synthesis of Urea-Based PSMA Inhibitors.

We describe -alkyl carbamoylimidazoles as readily available and highly versatile synthons for synthesizing urea-based prostate-specific membrane antigen (PSMA) inhibitors. Urea formation proceeded in high yields (>80%) at room temperature under aqueous conditions. All novel compounds were tested for their PSMA inhibitory potency in a cell-based radiometric binding assay.

[F]ONO-8430506: A novel radioligand for PET imaging of autotaxin (ATX).

We have prepared and tested radioligand [F]ONO-8430506 ([F]8) as a novel ATX PET imaging agent derived from highly potent ATX inhibitor ONO-8430506. Radioligand [F]8 could be prepared in good and reproducible radiochemical yields of 35 ± 5% (n = 6) using late-stage radiofluorination chemistry. ATX binding analysis showed that 9-benzyl tetrahydro-b-carboline 8 has about five times better inhibitory potency than clinical candidate GLPG1690 and somewhat less inhibitory potency than ATX inhibitor PRIMATX.

Synthesis and activities of new indolopyrrolobenzodiazepine derivatives toward acute myeloid leukemia cells.

The synthesis of new indolopyrrolobenzodiazepine derivatives is described. Six compounds were selected for evaluation of cytotoxicity towards acute myeloid leukemia (AML) cells and normal fibroblasts. One compound (29) showed selective AML cell death induction.

Crystal structure of 4-[(E)-(4-nitro-benzyl-idene)amino]-phenol.

The asymmetric unit of the title compound, C13H10N2O3, contains four independent mol-ecules (I, II, III and IV). Mol-ecule IV shows whole-mol-ecule disorder over two sets of adjacent sites in a 0.669 (10):0.

Diastereoselective synthesis of potent antimalarial cis-β-lactam agents through a [2 + 2] cycloaddition of chiral imines with a chiral ketene.

The effect of double asymmetric induction for the synthesis of new cis-β-lactams by [2 + 2] cycloaddition reactions of chiral imines with a chiral ketene was investigated. The cycloaddition reaction was found to be totally diastereoselective leading exclusively to the formation of the cis-β-lactam derivatives. The newly synthesized cycloadducts were evaluated for their antimalarial activities against Plasmodium falciparum K14 resistant strain with moderate to excellent IC50 values varying from 8 to 50 μM.

Synthesis of some new mono- and bis-polycyclic aromatic spiro and bis-nonspiro-beta-lactams.

Some new mono-and bis-polycyclic aromatic spiro-beta-lactams and bis-non spiro-polycyclic aromatic beta-lactams have been synthesized from imines derived from anthracene-9-carbaldehyde, 2-naphtaldehyde and a ketene derived from 9H-xanthene-9-carboxylic acid and phenoxyacetic acid by a [2+2] cycloaddition reaction. The cycloadducts were characterized by spectral data, including 1H-NMR, 13C-NMR, IR and elemental analyses. The configurations of some of these mono-spiro-beta-lactams were established by X-ray crystal analysis.

4-(9-Anthr-yl)-1-(2,4-dimethoxy-phen-yl)spiro-[azetidine-3,9'-xanthen]-2-one.

The title compound, C(37)H(27)NO(4), crystallizes with two mol-ecules in the asymmetric unit. The β-lactam ring of each mol-ecule is very nearly planar, with maximum deviations of 0.001 (2) and 0.

4-(9-Anthr-yl)-1-(2-methoxy-phen-yl)spiro-[azetidin-3,9'-xanthen]-2-one.

The stabilized conformation of the title compound, C(36)H(25)NO(3), 4-(9-anthryl)-1-(2-methoxyphenyl)-spiro[azetid-in-3,9'-xanthen]-2-one, may be compared with that of the isomeric compound 4-(9-anthr-yl)-1-(4-methoxy-phen-yl)spiro-[azetidin-3,9'-xanthen]-2-one. In the title isomer, the meth-oxy group is slightly twisted out of the plane of the attached benzene ring, with a C-O-C-C torsion angle of 31.5 (2)°.

4-(9-Anthr-yl)-1-phenylspiro-[azetidine-3,9'-xanthen]-2-one.

The β-lactam ring of the title compound, C(35)H(23)NO(2), is nearly planar with a maximum deviation of 0.003 (3) Å from the mean plane. It makes dihedral angles of 17.

4-(9-Anthr-yl)-1-(3-bromo-phen-yl)spiro-[azetidine-3,9'-xanthen]-2-one.

In the title mol-ecule, C(35)H(22)BrNO(2), the four-membered ring of the β-lactam unit is nearly planar [maximum deviation = 0.003 (3) Å] and makes dihedral angles of 87.07 (15), 59.

4-(9-Anthr-yl)-1-(1-naphth-yl)spiro-[azetidine-3,9'-xanthen]-2-one n-hexane hemisolvate.

In the title compound, C(39)H(25)NO(2)·0.5C(6)H(14), the β-lactam ring is nearly planar [maximum deviation of 0.012 (2) Å from the mean plane] and makes dihedral angles of 36.

4-(9-Anthr-yl)-1-(4-methoxy-phen-yl)spiro-[azetidin-3,9'-xanthen]-2-one.

In the title mol-ecule, C(36)H(25)NO(3), the β-lactam ring is essentially planar, with a dihedral angle of 3.3 (2)° between the two separate three-atom N/C/C planes. The β-lactam ring makes dihedral angles of 28.