422 research outputs found
3-(12-Bromododecyl)-1,5-dimethyl-1H-1,5-benzodiazepine-2,4(3H,5H)-dione
The seven-membered ring in the title compound, C23H35BrN2O2, adopts a boat-shaped conformation (with the C atoms of the fused-ring as the stern and the methine C atom as the prow). The bromododecyl substituent occupies an equatorial position, with the dodecyl chain exhibiting an extended conformation. Weak intermolecular C—H⋯O hydrogen bonding is present in the crystal structure
1,3-Diallyl-5-chloro-1H-benzimidazol-2(3H)-one
The benzimidazolone part of the title molecule, C13H13ClN2O, is almost planar (r.m.s. deviation = 0.006 Å) and its mean plane is aligned at dihedral angles of 62.5 (1) and 78.0 (1)° with respect to the mean planes of the allyl substituents
3-(6-Bromohexyl)-1,5-dimethyl-1H-1,5-benzodiazepine-2,4(3H,5H)-dione
The seven-membered ring in the title compound, C17H23BrN2O2, adopts a boat-shaped conformation (with the C atoms of the fused-ring as the stern and the methine C atom as the prow). The bromohexyl substituent occupies an equatorial position, with the hexyl chain exhibiting an extended conformation. Weak intermolecular C—H⋯O hydrogen bonding is present in the crystal structure
3-[(1-Benzyl-1H-1,2,3-triazol-4-yl)methyl]-1,5-dimethyl-1,5-benzodiazepine-2,4-dione
The title compound, C21H21N5O2, is a 1,4-dimethyl-1,2,3-triazole having dimethylbenzodiazepindione and phenyl substituents on each methyl group; the substituents are positioned on opposite sides of the five-membered ring. The seven-membered fused-ring of the larger substituent adopts a boat-shaped conformation (with the methine C atom as the prow)
3-Allyl-1,5-dibenzyl-1,5-benzodiazepine-2,4-dione
The title compound, C26H24N2O2, features a benzene ring fused with a seven-membered diazepine ring; the latter ring adopts a boat conformation (with the allyldimethylaminomethyl-bearing C atom as the prow and the fused-ring C atoms as the stern)
1,5-Dimethyl-3-propargyl-1H-1,5-benzodiazepine-2,4(3H,5H)-dione
The asymmetric unit of the title compound, C14H14N2O2, comprises two independent molecules, which slightly differ in the orientation of the propargyl chain. In both molecules, the diazepine ring adopts a boat conformation with the propargyl-bearing C atom as the prow and the C atoms at the ring junction as the stern. The carbonyl O atom of one independent molecule is hydrogen bonded to the acetylenic H atom of the other independent molecule. In the crystal, symmetry-related molecules are linked together by C—H⋯O hydrogen bonds, forming a ribbon-like structure along the c axis
Hypoxia-induced transcriptional stress is mediated by ROS-induced R-loops
Hypoxia is a common feature of solid tumors and is associated with poor patient prognosis, therapy resistance and metastasis. Radiobiological hypoxia (<0.1% O2) is one of the few physiologically relevant stresses that activates both the replication stress/DNA damage response and the unfolded protein response. Recently, we found that hypoxia also leads to the robust accumulation of R-loops, which led us to question here both the mechanism and consequence of hypoxia-induced R-loops. Interestingly, we found that the mechanism of R-loop accumulation in hypoxia is dependent on non-DNA damaging levels of reactive oxygen species. We show that hypoxia-induced R-loops play a critical role in the transcriptional stress response, evidenced by the repression of ribosomal RNA synthesis and the translocation of nucleolin from the nucleolus into the nucleoplasm. Upon depletion of R-loops, we observed a rescue of both rRNA transcription and nucleolin translocation in hypoxia. Mechanistically, R-loops accumulate on the rDNA in hypoxia and promote the deposition of heterochromatic H3K9me2 which leads to the inhibition of Pol I-mediated transcription of rRNA. These data highlight a novel mechanistic insight into the hypoxia-induced transcriptional stress response through the ROS–R-loop–H3K9me2 axis. Overall, this study highlights the contribution of transcriptional stress to hypoxia-mediated tumorigenesis
3-{[3-(4-Methoxyphenyl)-4,5-dihydro-1,2-oxazol-5-yl]methyl}-1,5-dimethyl-1H-1,5-benzodiazepine-2,4(3H,5H)-dione
The molecule of the title compound, C22H23N3O4, features a benzodiazepine fused-ring system whose seven-membered ring adopts a boat-shaped conformation (with the C atoms of the fused-ring as the stern and the methine C atom as the prow). The methylene C atom connected to the methine C atom occupies an equatorial position. The methylene C atom is connected to the five-membered oxazole ring, both of which are disordered over two positions in a 0.634 (4):0.366 (4) ratio. Weak intermolecular C—H⋯O hydrogen bonding is present in the crystal structure
7-Chloro-1,5-dipropargyl-1H-1,5-benzodiazepine-2,4(3H,5H)-dione
The seven-membered ring of the title compound, C15H11ClN2O2, adopts a boat-shaped conformation (with the C atoms of the fused-ring as the stern and the methylene C atom as the prow). The N atoms exists in a trigonal–planar coordination; one of the acetylenic H atoms forms a C—H⋯O hydrogen bond to the O atom of an adjacent molecule, generating a linear chain along a body diagonal
4-[(1,5-Dibenzyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-3-yl)methyl]-1-n-octyl-1H-1,2,3-triazole
The reaction of 1,5-dibenzyl-3-propargyl-1,5-benzodiazepine-2,4-dione with 1-azido-n-octane in the presence of catalysts leads to the formation of the title compound, C34H39N5O2, which features a phenylene ring fused with a seven-membered diazepinyl ring. The latter ring adopts a boat conformation with the octyltriazolylmethyl-bearing C atom as the prow and the fused-ring C atoms as the stern. The octyltriazolylmethyl substituent occupies an axial position
- …