(3RS,1SR)-3-Bromo-3-(1-phenylpropyl)chroman-2,4-dione
The title compound, C18H15BrO3, was obtained by bromination of phenprocoumone with N-bromosuccinimide. The X-ray structure confirms an earlier proposal concerning the regioselectivity of the reaction to introduce the Br atom at the 3-position.
1-[2-(Benzylamino)-4-pyridyl]-2-(4-fluorophenyl)ethane-1,2-dione
The crystal structure of the title compound, C20H15FN2O2, contains two crystallographically independent molecules, which are related by a pseudo-inversion center and linked into dimersviaintermolecular N—H...N hydrogen bonds. The 4-fluorophenyl ring of moleculeAmakes dihedral angles of 17.17 (16) and 62.25 (15)°, respectively, with the phenyl and pyridine rings. The 4-fluorophenyl ring of moleculeBmakes dihedral angles of 8.50 (16) and 64.59 (15)°, respectively, with the phenyl and pyridine rings. The dihedral angle between the pyridine ring and the phenyl ring of moleculeA[60.97 (15)°] is bigger than in moleculeB[59.49 (15)°]. The dihedral angle between the two pyridine rings is 1.37 (14)°…
Ethyl (2,3-dihydro-1H,1′H-2,3′-biindol-1-yl)glyoxylate
The crystal structure of the title compound, C20H18N2O3, was determined in the course of our studies of the synthesis of 3-acylindole derivatives. We obtained it as an unexpected racemic side product. The crystal structure contains chains of dimers along the a axis.
4-(4-Fluorophenyl)-3-(pyridin-4-yl)-1-(2,4,6-trichlorophenyl)-1H-pyrazol-5-amine
In the title compound, C20H12Cl3FN4, the pyrazole ring forms dihedral angles of 47.51 (9), 47.37 (9) and 74.37 (9)° with the directly attached 4-fluorophenyl, pyridine and 2,4,6-trichlorophenyl rings, respectively. Only one of the two amino H atoms is involved in hydrogen bonding. The crystal packing is characterized by N—H...N hydrogen bonds, which result in infinite chains parallel to the c axis.
Synthesis and Evaluation of a Novel Series of Pyrrolizine Derivatives as Dual Cyclooxygenase-1 and 5-Lipoxygenase Inhibitors
The aim of our study was to investigate structure activity relationship following the replacement of the 6-phenyl substituent at the 6,7-diaryl-2,3-dihydropyrrolizine template by various heteroaromatic residues. In this context we developed a new, efficient, and highly sensitive test method for the screening of dual cyclooxygenase-1 (COX-1) and 5-lipoxygenase (5-LOX) inhibitors. We used human platelets as a source of COX-1 and human PMNLs as a source of 5-LOX. Both cell types were isolated from the same volume of blood. PGE2 and LTB4 respectively were determined by highly selective and sensitive ELISA kits, using monoclonal antibodies. For a single determination at most 0.5 mL whole blood i…
(1aR,2aS,5aS,5bS)-Perhydro-4H-oxireno[3,4]cyclopenta[1,2-b]furan-4-one
The structure of the title compound, C7H8O3, was determined in the course of our studies of the synthesis of cyclopenta[1,2-b]furan-4-one derivatives. The molecule has four chiral C atoms. The X-ray crystal structure analysis shows the compound to possess an epoxide group with an endo orientation with respect to the lactone group.
4-[5-(4-Fluorophenyl)-3-isopropylisoxazol-4-yl]pyridin-2(1H)-one
The crystal structure of the title compound, C17H15FN2O2, was determined as part of a study of the biological activity of pyridine-substituted isoxazole derivatives as mitogen-activated protein kinase (MAPK) inhibitors. In the crystal structure of the title compound, the compound exists in the lactam and not in the tautomeric pyridin-2-ol form. As the aromatic pyridine nitrogen is considered to be important for accepting a hydrogen bond from p38MAPK, the structure of the lactam unit is correlated with the loss of biological activity of the title compound in the p38MAPK assay. In the crystal structure, the lactam is involved in hydrogen bonds, forming chains along the b axis.
N-{4-[3-(4-Fluorophenyl)pyrido[2,3-b]pyrazin-2-yl]-2-pyridyl}isopropylamine
In the crystal structure of the title compound, C21H18FN5, the pyridopyrazine ring system forms dihedral angles of 33.27 (7) and 48.69 (9)° with the 4-fluorophenyl and pyridine ring, respectively. The dihedral angle of the 4-fluorophenyl and pyridine rings is 57.45 (8)°. The crystal packing is characterized by an intermolecular N—H...N hydrogen bond.
ChemInform Abstract: Regioisomeric 3-, 4-, and 5-Aminomethylisoxazoles: Synthesis and Muscarinic Activity.
tert-Butyl N-benzyl-N-(4-methyl-2-pyridyl)carbamate
In the crystal structure of the title compound, C18H22N2O2, the pyridine ring makes dihedral angles of 83.71 (6) and 9.2 (1)° with the phenyl ring and the carbamate plane, respectively. The phenyl ring and the carbamate plane are nearly perpendicular to one another, with a dihedral angle of 87.17 (7)°.
2-[(1-Methyl-1H-pyrrol-2-yl)carbonyl-meth-yl]isoindoline-1,3-dione.
The asymmetric unit of the title compound, C15H12N2O3, contains two almost identical molecules forming an nearly C2-symmetric dimeric pattern. The dihedral angles between the pyrrole ring and the phthalimide unit are 82.95 (8) and 86.57 (8)° for the two molecules. Within such a dimer, the phthalimide units of the two molecules form a dihedral angle of 1.5 (5)°.
5-(4-Fluoro-phen-yl)-4-(4-pyrid-yl)-1,3-oxazol-2-amine.
In the crystal structure of the title compound, C14H10FN3O, the plane of the isoxazole ring makes dihedral angles of 35.72 (9) and 30.00 (9)°, respectively, with those of the 4-fluorophenyl and pyridine rings. The plane of the 4-fluorophenyl ring makes a dihedral angle of 45.85 (8)° with that of the pyridine ring. The crystal structure is stabilized by intermolecular N—H...N hydrogen bonding. The two types of hydrogen bonds result in two chains, extending along the a axis, which are related by centres of symmetry.
Structural Approaches to Explain the Selectivity of COX-2 Inhibitors: Is There a Common Pharmacophore?
The identification and characterisation of the isoenzyme cyclooxygenase 2 (COX-2) stimulated investigations to develop efficient non-steroidal anti-inflammatory drugs with reduced side effects compared to standard NSAIDs. This review will focus on the structural features needed to achieve COX-2 selectivity. Five structural classes can be identified together with a class bearing little or no resemblance to one another in their molecular structure. The most interesting point is the very distinct structure/activity relationship. On the one hand only minor modifications to a particular compound induce a drastic change in its COX selectivity and on the other hand the structural prerequisites in …
3-(2,4-Dimethoxyanilino)-8-methoxydibenz[b,e]oxepin-11(6H)-one
In the title compound, C23H21NO5, the two benzene rings of the tricyclic unit are oriented at a dihedral angle of 37.5 (8)°. The 2,4-dimethoxyanilino residue is oriented at a dihedral angle of 60.2 (8)° towards the phenoxy ring. In the crystal, the central carbonyl O atom accepts two hydrogen bonds from the N—H and C—H groups. A further intermolecular C—H...O interaction involving one of the methoxy O atoms is also observed.
3-(2,4-Difluoro-anilino)-9-nitro-dibenzo[b,e]oxepin-11(6H)-one.
In the title compound, C20H12F2N2O4, the two benzene rings of the tricyclic unit are oriented at a dihedral angle of 30.6 (1)°. The 2,4-difluoroanilino residue is oriented at a dihedral angle of 68.2 (1)° with respect to the phenoxy ring. In the crystal, N—H...O hydrogen bonds between the amino group and the carbonyl O atom of the oxepinone ring link the molecules into infinte chains along the c axis.
Structural Optimization of a Pyridinylimidazole Scaffold: Shifting the Selectivity from p38α Mitogen-Activated Protein Kinase to c-Jun N-Terminal Kinase 3
Starting from known p38α mitogen-activated protein kinase (MAPK) inhibitors, a series of inhibitors of the c-Jun N-terminal kinase (JNK) 3 was obtained. Altering the substitution pattern of the pyridinylimidazole scaffold proved to be effective in shifting the inhibitory activity from the original target p38α MAPK to the closely related JNK3. In particular, a significant improvement for JNK3 selectivity could be achieved by addressing the hydrophobic region I with a small methyl group. Furthermore, additional structural modifications permitted to explore structure–activity relationships. The most potent inhibitor 4-(4-methyl-2-(methylthio)-1H-imidazol-5-yl)-N-(4-morpholinophenyl)pyridin-2-a…
N-[3-(5-Oxo-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-2-ylamino)phenyl]furan-3-carboxamide
In the title compound, C26H20N2O3, the two aromatic rings of the tricyclic unit are oriented at a dihedral angle of 54.53 (9)°. The crystal structure displays intermolecular N—H...O hydrogen bonding.
tert-Butyl N-benzyl-N-[4-(4-fluorobenzoylmethyl)-2-pyridyl]carbamate
In the crystal structure of the title compound, C25H25FN2O3, the pyridine ring makes dihedral angles of 75.1 (3), 39.4 (3) and 74.6 (3)° with the phenyl ring, the carbamate plane and the 4-fluorophenyl ring, respectively. The phenyl ring makes dihedral angles of 77.2 (3) and 23.6 (3)° with the carbamate plane and the 4-fluorophenyl ring, respectively. The 4-fluorophenyl ring is perpendicular to the carbamate plane, the dihedral angle between them being 89.5 (3)°.
Design, synthesis, and biological evaluation of novel disubstituted dibenzosuberones as highly potent and selective inhibitors of p38 mitogen activated protein kinase.
Synthesis, biological testing, structure-activity relationships (SARs), and selectivity of novel disubstituted dibenzosuberone derivatives as p38 MAP kinase inhibitors are described. Hydrophilic moieties were introduced at the 7-, 8-, and 9-position of the 2-phenylamino-dibenzosuberones, improving physicochemical properties as well as potency. Extremely potent inhibitors were obtained, with half-maximal inhibitory concentration (IC(50)) values in the low nM range in a whole blood assay measuring the inhibition of cytokine release. The high potency of the target compounds together with the outstanding selectivity of this novel class of compounds toward p38 mitogen activated protein (MAP) kin…
3-(4-Fluorophenyl)-4-(4-pyridyl)quinolin-2(1H)-one
The title compound, C20H13FN2O, has the quinolin-2(1H)-one unit in the lactam form. The molecules form rows along the b axis via N—H⋯N hydrogen bonds
4-[3-(4-Fluorophenyl)quinoxalin-2-yl]-N-isopropylpyridin-2-amine
In the crystal structure of the title compound, C22H19FN4, the quinoxaline system makes dihedral angles of 32.07 (13) and 69.64 (13)° with the 4-fluorophenyl and pyridine rings, respectively. The 4-fluorophenyl ring makes a dihedral angle of 71.77 (16)° with the pyridine ring. The crystal structure is stabilized by intermolecular N—H...N hydrogen bonding.
3-(2-Fluorophenyl)-6-(phenoxymethyl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazole
The crystal structure of the title compound, C16H11FN4OS, was synthesized in the course of our studies on 1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles as inhibitors of p38 mitogen-activated protein kinase (MAPK). The three-dimensional data obtained were used to generate a three-dimensional pharmacophore model for in silico database screening. The dihedral angles between the central heterocylic system and the fluorophenyl and phenyl rings are 20.21 (3) and 5.43 (1)°, respectively; the dihedral angle between the two benzene rings is 15.80 (4)°.
2-(4-Fluorophenyl)-3-(4-pyridyl)pyrido[2,3-b]pyrazine
In the crystal structure of the title compound, C18H11FN4, the pyridopyrazine system makes dihedral angles of 45.51 (7) and 44.75 (7)° with the attached 4-fluorophenyl ring and the pyridine ring, respectively. The 4-fluorophenyl ring makes a dihedral angle of 54.54 (8)° with the pyridine ring. The pyridine ring part of the pyridopyrazine ring and the pyrazine ring of two c-glide-plane-related molecules form π–π interactions. The angle between the planes is 2.09 (7)° and the distance between the centroids is 3.557 (1)Å.
ChemInform Abstract: Regioisomeric 5(3)-Aminomethyl-3(5)-phenylisoxazoles: Synthesis, Spectroscopic Discrimination, and Muscarinic Activity.
The regioselective synthesis of isomeric 5(3)-aminomethyl-3(5)-phenyl isoxazoles using different methods is described. Spectroscopic data, especially mass spectrometric fragmentation, were used to identify and characterize the regioisomers. The muscarinic activity of these isoxazoles was assayed on isolated guinea-pig ileum and atria as well as on isolated rabbit vas deferens. Regioisomere 5(3)-Aminomethyl-3(5)-phenyl-isoxazole: Synthese, spektroskopische Unterscheidung und muskarinische Aktivitat Es werden verschiedene Verfahren zur regioselektiven Darstellung von 5(3)-Aminomethyl-3(5)-phenyl-isoxazolen beschrieben, die anhand ihrer spektroskopischen Daten, insbesondere der massenspektrosk…
tert-ButylN-(4-methyl-2-pyridyl)carbamate
The crystal structure of the title compound, C11H16N2O2, contains two crystallographically independent molecules forming dimers by pairs of intermolecular N—H...N hydrogen bonds. The two molecules are related by a pseudo-twofold axis. The dihedral angle between the pyridine ring and the carbamate plane differs in the two molecules [12.1 (3) and 3.5 (3)°].
6-Amino-1-benzyl-4-(4-chloro-phen-yl)-3-(4-pyrid-yl)-1,4-dihydro-pyrano[2,3-c]pyrazole-5-carbonitrile.
The crystal structure of the title compound, C25H18ClN5O, was determined in the course of our studies on the synthesis of 1,4-dihydropyrano[2,3-c]pyrazole as an inhibitor of the p38 mitogen-activated protein kinase (MAPK). The compound was prepared via a base-catalysed synthesis from 1-benzyl-3-(4-pyridyl)-1H-pyrazol-5(4H)-one with p-chloroaldehyde and malononitrile. The crystal data obtained were used to generate a three-dimensional pharmacophore model for in silico database screening. The phenyl ring is disordered over two positions, with site occupancy factors of 0.55 and 0.45. The dihedral angles between the 1,4-dihydropyrano[2,3-c]pyrazole unit and the chlorophenyl and pyridine rings a…
Methyl 4-[5-(4-fluorophenyl)-4-(pyridin-4-yl)-1H-imidazol-2-ylsulfanyl]butanoate
The title compound, C19H18FN3O2S, was synthesized in the course of studies on 2-alkylsufanylimidazoles as p38 mitogen-activated protein kinase inhibitors. The synthesis was achieved by nucleophilic substitution of 4-(4-fluorophenyl)-5-(pyridin-4-yl)-1,3-dihydroimidazole-2-thione with methyl 4-bromobutanoate. The five-membered heterocycle makes dihedral angles of 32.4 (2) and 18.3 (2)° with the fluorophenyl and pyridinyl rings, respectively, indicating a low degree of conjugation between these rings. Intramolecular C—H...N and intermolecular N—H...N hydrogen bonds as well as C—H...π interactions seem to be effective in stabilization of the crystal stru…
4-(4-Fluorophenyl)-1-(4-nitrophenyl)-3-(pyridin-4-yl)-1H-pyrazol-5-amine
In the crystal structure of the title compound, C20H14FN5O2, the pyrazole ring forms dihedral angles of 59.3 (2), 25.6 (2) and 46.0 (2)° with the directly attached 4-fluorophenyl, pyridine and nitrophenyl rings, respectively. The crystal packing is characterized by intermolecular N—H...N and N—H...O hydrogen bonds.
From Five- to Six-Membered Rings: 3,4-Diarylquinolinone as Lead for Novel p38MAP Kinase Inhibitors
In this study we describe the design, synthesis, and biological evaluation of 3-(4-fluorophenyl)-4-pyridin-4-ylquinoline-2(1H)-one (5) as a new inhibitor of MAPK with a p38alphaMAPK IC50 of 1.8 muM. By keeping the common vicinal pyridine/4-F-phenyl pharmacophore, such as in prototypical imidazole 20 or isoxazole 13 but in 5 connected to the six-membered quinoline core, we were particularly interested in comparing biological activity, details of molecular geometry, and different binding modes of these compounds. Compounds 20 and 13 were active both in the p38alpha- and JNK3-assay, whereas 5 was selective for p38alpha, with no JNK3 inhibition. By comparing the X-ray structures of the compound…
1-[4-(2-Aminoanilino)phenyl]-2,2,2-trifluoroethanone
In the title compound, C14H11F3N2O, the two aromatic rings are oriented at a dihedral angle of 70.84 (8)°. The crystal structure displays intermolecular N—H...O and N—H...F interactions.
2-(4-Fluorophenyl)-1-(4-pyridyl)cyclopentan-1-ol
The crystal structure of the title compound, C16H16FNO, was determined as part of a study of the biological activity of pyridine-substituted cyclopentene derivatives as p38 mitogen-activated protein kinase (MAPK) inhibitors. The 4-fluorophenyl and 4-pyridyl rings are trans positioned with respect to each other. The compound exists as a racemic mixture. The synthesis was achieved via direct interaction between the reactive complex Grignard reagent PyMgCl·LiCl and the enolizable ketone 4-fluorophenylcyclopentanone with the assistance of the neodymium salt catalyst NdCl3·2LiCl. The crystal packing is characterized by zigzag chains of molecules, which are connected by O—H⋯N hydrogen bon…
Profile and molecular modeling of 3-(indole-3-yl)-4-(3,4,5-trimethoxyphenyl)-1 H-pyrrole-2,5-dione (1) as a highly selective VEGF-R2/3 inhibitor.
We report on selectivity profiling of 1 in a panel of 20 protein kinases and molecular modeling indicating 1 to be highly active and selective for VEGF-R2/3. Sequence alignment analysis and detailed insights into the ATP binding pockets of targeted protein kinases from the panel result in a unique structural architecture of VEGF-R2 mainly caused by the hydrophobic pocket I, determining the molecular basis for activity and selectivity of 1.
A frozen analogue approach to aminopyridinylimidazoles leading to novel and promising p38 MAP kinase inhibitors.
In this study we report the design, synthesis, and biological evaluation of constrained aminopyridinylimidazoles as p38α MAP kinase inhibitors. The frozen analogue approach focused on the pyridinyl unit, using purine bioisosteres as constrained structure analogues. The identification of the most potent bioisostere was followed by a further derivatization to address hydrophobic region II. In combination with C-2 modifications of the imidazole core, we were able to design highly active inhibitors on the p38α MAP kinase. The inhibitor design presented herein represents a promising and highly efficient advancement of recent stages of development in this class of p38 MAP kinase inhibitors. In co…
4-[5-Amino-4-(4-fluorophenyl)-3-(pyridin-4-yl)-1H-pyrazol-1-yl]benzonitrile
In the crystal structure of the title compound, C21H14FN5, the pyrazole ring forms dihedral angles of 38.0 (1), 40.0 (1) and 28.5 (1)° with the directly attached 4-fluorophenyl, pyridine and benzonitrile rings, respectively. The crystal packing is characterized by N—H...N hydrogen bonds, which result in a two-dimensional network parallel to theac-plane.
3-(4-Fluorophenyl)-2-(4-pyridyl)pyrido[2,3-b]pyrazine
In the crystal structure of the title compound, C18H11FN4, the pyridopyrazine ring makes dihedral angles of 34.67 (7) and 52.24 (7)° with the 4-fluorophenyl and pyridine rings, respectively. The 4-fluorophenyl ring makes a dihedral angle of 59.56 (9)° with the pyridine ring.
Poly[[tetramethanolbis[4-oxo-3-(pyridin-4-yl)-1-(2,4,6-trichlorophenyl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-olato]disodium]–diethyl ether–methanol (1/1/2)]
In the title compound, [Na2(C16H7Cl3N5O2)2(CH3OH)4]·C4H10O·2CH3OH, the central pyrazolo[3,4-d]pyrimidine system makes dihedral angles of 82.98 (7)° with the trichlorophenyl ring and 13.11 (15)° with the pyridine ring. The sodium ion has an octahedral environment, being coordinated by four methanol molecules and one O and one N atom of two different heterocyclic ring systems.
(2aRS,3RS,4aSR,6aRS,6bSR)-3-Hydroxy-2a,3,4a,6,6a,6b-hexahydro-1,4-dioxacyclopenta[cd]pentalen-2(5H)-one
The molecular structure of the title compound [enantiomers (VIII) and (VIIIa)], C8H10O4, was determined in the course of our studies on the synthesis of cyclopenta[1,2-b]furan-4-one derivatives. Tricyclic (VIIIa) consists of a planar bridged lactone unit and the two other ring systems in the envelope conformation. It contains five chiral C atoms and was obtained as a racemic mixture. The X-ray analysis showed the compound to possess a half-acetal unit with an endo orientation of the half-acetal ether bridge with respect to the lactone unit.
Regioisomeric 5(3)-aminomethyl-3(5)-phenylisoxazoles: synthesis, spectroscopic discrimination, and muscarinic activity.
The regioselective synthesis of isomeric 5(3)-aminomethyl-3(5)-phenyl isoxazoles using different methods is described. Spectroscopic data, especially mass spectrometric fragmentation, were used to identify and characterize the regioisomers. The muscarinic activity of these isoxazoles was assayed on isolated guinea-pig ileum and atria as well as on isolated rabbit vas deferens. Regioisomere 5(3)-Aminomethyl-3(5)-phenyl-isoxazole: Synthese, spektroskopische Unterscheidung und muskarinische Aktivitat Es werden verschiedene Verfahren zur regioselektiven Darstellung von 5(3)-Aminomethyl-3(5)-phenyl-isoxazolen beschrieben, die anhand ihrer spektroskopischen Daten, insbesondere der massenspektrosk…
Licofelone, a novel 5-LOX/COX-inhibitor, attenuates leukocyte rolling and adhesion on endothelium under flow
The main mechanism of action of non-steroidal anti-inflammatory drugs (NSAIDs) is the inhibition of cycloxygenases COX-1 and COX-2. During recent years, combined 5-LOX/COX-inhibition, interfering with the biosynthesis of both prostaglandins and leukotrienes (LTs), has emerged as a possibility to avoid side effects related to COX-inhibition. The aim of the present study was to investigate if there is a contribution of mechanisms other than the reduction of inflammatory prostaglandins and leukotrienes to the anti-inflammatory effect of the LOX/COX inhibitor licofelone. In a flow chamber assay, licofelone (10-30 microM) dose-dependently decreased both the rolling and adhesion of leukocytes on …
4-[5-(4-Fluorophenyl)-3-isopropylisoxazol-4-yl]pyridine
In the title compound, C17H15FN2O, the exocyclic bond angles at the C atoms of the isoxazole ring bearing the pyridyl and 4-fluorophenyl substituents are 129.66 (17) and 134.58 (16)°, respectively. The structure was determined in a study of the molecular geometry of isoxazole derivatives with biological activity as MAPK inhibitors.
4-(4-Fluorophenyl)-1-phenyl-3-(pyridin-4-yl)-1H-pyrazol-5-amine
In the title compound, C20H15FN4, the pyrazole ring forms dihedral angles of 43.51 (6), 39.95 (6) and 32.23 (6)° with the directly attached 4-fluorophenyl, pyridine and phenyl rings, respectively. The crystal packing is stabilized by intermolecular N—H...N and N—H...F hydrogen bonds.
2-(6-Methoxy-7H-purin-7-yl)-1-phenylethanone monohydrate
The crystal structure of the title compound, C14H12N4O2·H2O, was determined in the course of our studies of the synthesis and optimization of 7-aryl-7H-purines as inhibitors of the vascular endothelial growth factor receptor (VEGF-R), c-Jun NH2-terminal protein kinase 3 (JNK3) and the p38α mitogen-activated protein kinase (MAPK). In the title compound, two molecules are associated with each other through O—H⋯N hydrogen bonds to different N atoms in the purine ring system. The compound was prepared via a regioselective synthesis using the methyl(aqua)cobaloxime complex, CH3Co(DH)2OH2, as a temporary auxiliary. The X-ray crystallographic results confirmed the regioselective N-7 alkylation …
4-[2-(4-Fluorophenyl)furan-3-yl]pyridine
In the crystal structure of the title compound, C(15)H(10)FNO, the furan ring makes dihedral angles of 40.04 (11) and 25.71 (11)° with the pyridine and 4-fluoro-phenyl rings, respectively. The pyridine ring makes a dihedral angle of 49.51 (10)° with the 4-fluoro-phenyl ring. Non-conventional C-H⋯F and C-H⋯N hydrogen bonds are effective in the stabilization of the crystal structure.
4-(4-Fluorophenyl)-2-methyl-3-(1-oxy-4-pyridyl)isoxazol-5(2H)-one
The crystal structure of the title compound, C15H11FN2O3, was determined as part of a study on the biological activity of isoxazolone derivatives as p38 mitogen-activated protein kinase (MAPK) inhibitors. The dihedral angles between rings are isoxazole/benzene = 55.0 (3)°, isoxazole/pyridine = 33.8 (2)° and benzene/pyridine = 58.1 (2)°.
Selective p38α MAP kinase/MAPK14 inhibition in enzymatically modified LDL-stimulated human monocytes: implications for atherosclerosis.
The first ATP-competitive p38α MAPK/MAPK14 inhibitor with excellent in vivo efficacy and selectivity, skepinone-L, is now available. We investigated the impact of selective p38α MAPK/MAPK14 inhibition on enzymatically modified LDL (eLDL) stimulated human monocytes with its implications for atherosclerosis. Among the different p38 MAPK isoforms, p38α/MAPK14 was the predominantly expressed and activated isoform in isolated human peripheral blood monocytes. Moreover, eLDL colocalized with macrophages positive for p38α MAPK/MAPK14 in human carotid endarterectomy specimens. Using the human leukemia cell line THP-1 and/or primary monocyte-derived macrophages, skepinone-L inhibited eLDL-induced ac…
3,4-Bis(4-fluorophenyl)-1,2,5-oxadiazole 2-oxide
The title compound, C14H8F2N2O2, also known as di(4-F-phenyl)furazan N-oxide, was found as a side product in the synthesis of isoxazole derivatives. The are two molecules in the asymmetric unit. The bond length of the dipolar N—O unit is 1.107 (7) A. X-ray analysis confirmed the compound to have the desired structure
Ethyl 5-amino-3-(pyridin-4-yl)-1-(2,4,6-trichlorophenyl)-1H-pyrazole-4-carboxylate dimethyl sulfoxide hemisolvate
The asymmetric unit of the title compound, C17H13Cl3N4O2·0.5C2H6OS, contains two almost identical molecules and one dimethyl sulfoxide (DMSO-d6) solvent molecule. The pyrazole ring forms dihedral angles of 54.6 (4) and 80.0 (4)° in one molecule, and dihedral angles of 54.2 (4) and 81.2 (4)° in the other molecule, with the directly attached pyridine and trichlorophenyl rings, respectively. The dihedral angles of the pyridine and trichlorophenyl rings are 51.2 (4) and 52.0 (4)°, respectively. The crystal packing is characterized by intra- and intermolecular hydrogen bonds. The crystal is a nonmeroh…
2,2-Dimethyl-N-[3-(3,4,5-trimethoxybenzoyl)pyridin-4-yl]propanamide
The title compound, C20H24N2O5, was found to have an intramolecular N—H⋯O bond with an N⋯O distance of 2.646 (2) A. In the crystal structure, molecules form dimers along the c axis by aromatic stacking interactions. The X-ray crystallographic analysis was carried out to correlate the solid-state geometry with virtual structural information obtained by modelling.
3-(4-Fluorophenyl)-6-methoxy-2-(4-pyridyl)quinoxaline
In the title compound, C20H14FN3O, the quinoxaline system makes dihedral angles of 32.38 (7) and 48.04 (7)° with the 4-fluorophenyl and pyridine rings, respectively. The 4-fluorophenyl ring makes a dihedral angle of 57.77 (9)° with the pyridine ring. In the crystal, the molecules form dimeric C—H...N hydrogen-bonded R22(20) ring motifs lying about crystallographic inversion centers. The dimeric units stack via π–π interactions between methoxyphenyl rings and pyridine–fluorophenyl rings with centroid–centroid distances of 3.720 (1) and 3.823 (1) Å, …
Design, Synthesis and Biological Evaluation of Novel Pyrazolo[1,2,4]triazolopyrimidine Derivatives as Potential Anticancer Agents
Three novel pyrazolo-[4,3-e][1,2,4]triazolopyrimidine derivatives (1, 2, and 3) were designed, synthesized, and evaluated for their in vitro biological activity. All three compounds exhibited different levels of cytotoxicity against cervical and breast cancer cell lines. However, compound 1 showed the best antiproliferative activity against all tested tumor cell lines, including HCC1937 and HeLa cells, which express high levels of wild-type epidermal growth factor receptor (EGFR). Western blot analyses demonstrated that compound 1 inhibited the activation of EGFR, protein kinase B (Akt), and extracellular signal-regulated kinase (Erk)1/2 in breast and cervical cancer cells at concentrations…
N-{4-[4-(4-Fluorophenyl)-1-(2-methoxyethyl)-2-methylsulfanyl-1H-imidazol-5-yl]-2-pyridyl}-2-methyl-3-phenylpropionamide
In the crystal structure of the title compound, C28H29FN4O2S, the imidazole ring makes dihedral angles of 11.85 (7), 73.33 (7) and 22.83 (8)° with the 4-fluorophenyl, pyridine and phenyl rings, respectively. The 4-fluorophenyl ring makes dihedral angles of 77.91 (7) and 26.93 (8)° with the pyridine and phenyl rings, respectively. The phenyl and pyridine rings are nearly perpendicular, making a dihedral angle of 86.47 (9)°. The crystal packing shows an intermolecular N—H...O hydrogen-bonding interaction between the N—H and carbonyl groups of the amide functions.
N-{(Z)-2-[1-(Triisopropylsilyl)-1H-indol-3-yl]-2-(triisopropylsilyloxy)vinyl}-2-(3,4,5-trimethoxyphenyl)acetamide
The molecular structure of the title compound, C39H62N2O5Si2, obtained as an unexpected side product, was determined in the course of our studies on the synthesis of N-triisopropyl-1H-indol-3-yl derivatives. Interestingly, although the triisopropylsilyl group was intended as a temporary protecting group, the compound comprises a remarkably stable N—Si bond. The vinyl C=C double bond possesses a Z configuration.
4-[5-(4-Fluorophenyl)-1H-imidazol-4-yl]pyridine
In the title compound, C(14)H(10)FN(3), the imidazole ring makes dihedral angles of 28.2 (1) and 36.60 (9)° with the pyridine ring and the 4-fluoro-phenyl ring, respectively. The pyridine ring forms a dihedral angle of 44.68 (9)° with the 4-fluoro-phenyl ring. Inter-molecular N-H⋯N hydrogen bonds are observed in the crystal structure.
4-[4-(4-Fluoro-phen-yl)-2-methyl-5-oxo-2,5-dihydro-isoxazol-3-yl]-1-methyl-pyridinium iodide-4-[3-(4-fluoro-phen-yl)-2-methyl-5-oxo-2,5-dihydro-isoxazol-4-yl]-1-methyl-pyridinium iodide (0.6/0.4).
The crystal structure of the title compound, C(16)H(16)FN(2)O(2) (+)·I(-), was determined as part of a study of the biological activity of isoxazolone derivatives as p38 mitogen-activated protein kinase (MAPK) inhibitors. The X-ray crystal structure of 4-[4-(4-fluoro-phenyl)-2-methyl-5-oxo-2,5-dihydro-isoxazol-3-yl]-1-methyl-pyridinium iodide showed the presence of the regioisomer 4-[3-(4-fluoro-phenyl)-2-methyl-5-oxo-2,5-dihydro-isoxazol-4-yl]-1-methyl-pyridinium iodide. The synthesis of the former compound was achieved by reacting 4-(4-fluoro-phenyl)-3-(4-pyridyl)isoxazol-5(2H)-one after treatment with Et(3)N in dimethyl-formamide, with iodo-methane. The unexpected formation of the regioi…
3-(4-Fluorophenyl)-1-methyl-4-(4-pyridyl)quinolin-2(1H)-one
The title compound, C21H15FN2O, was synthesized in the course of our studies of p38 mitogen-activated protein kinase inhibitors. It has been investigated by 1H and 13C NMR spectroscopy and was proven by X-ray crystallographic analysis to be the N-methyl rather than the O-methyl isomer. In the crystal structure, a three-dimensional network is formed consisting of quinolinone aromatic stacking interactions and weak C—H⋯O and C—H⋯N hydrogen bonds.
(4R)-4-Hydroxy-1-[(2S)-2-hydroxydodecyl]-L-proline monohydrate
The title compound, C17H33NO4·H2O, was found to be the S diastereoisomer with respect to the asymmetric C atom at the OH group on the chain. The X-ray structure was determined as part of a study of the molecular geometry and stereochemistry of l-proline derivatives for pre-coating thin-layer chromatography plates intended for enantiomeric separation.
N-{2-Methyl-5-[(5-oxo-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-2-yl)amino]phenyl}benzamide
In the title compound, C29H24N2O2, the two aromatic rings of the tricyclic unit are oriented at a dihedral angle of 32.27 (8)°. In the crystal N—H...O hydrogen bonds link the molecules into chains along the a axis. Further N—H...·O interactions link the chains.
4-[3-(4-Fluorophenyl)-5-isopropylisoxazol-4-yl]pyridine
The molecular structure of the title compound, C17H15FN2O, was determined in the course of our studies on mitogen-activated protein kinase inhibitors. The exocyclic bond angles at the carbon atoms of the isoxazole ring bearing the pyridyl and 4-fluorophenyl rings are 130.0 (2) and 129.2 (2)°, respectively. The pyridine and 4-fluorophenyl rings are twisted relative to the isoxazole ring by 80.2 (2) and 19.1 (1)°, respectively.
4-[2-(4-Fluorophenyl)-1H-pyrrol-3-yl]pyridine
In the crystal structure of the title compound, C(15)H(11)FN(2), the pyrrole ring makes dihedral angles of 33.19 (9) and 36.33 (10)° with the pyridine and 4-fluoro-phenyl rings, respectively. The pyridine ring makes a dihedral angle of 46.59 (9)° with the 4-fluoro-phenyl ring. In the crystal structure, an N-H⋯N hydrogen bond joins the mol-ecules into chains.
rac-(3E,3aR,6aR)-3-(Hydroxymethylene)-3,3a,6,6a-tetrahydro-2H-cyclopenta[b]furan-2-one
The crystal structure of the title compound, C8H8O3, was determined in the course of our studies of the synthesis of cyclopenta[1,2-b]furan-4-one derivatives. The title compound has two chiral C atoms and was obtained as a racemic mixture. It was found to possess a vinylogous acid group with an E configuration at the double bond. The compound exists in the hydroxymethylene and not in the tautomeric carbaldehyde form. The asymmetric unit consists of two molecules.
CCDC 2042388: Experimental Crystal Structure Determination
Related Article: Saeb Aliwaini, Bassam Abu Thaher, Ihab Al-Masri, Nabil Shurrab, Said El-Kurdi, Dieter Schollmeyer, Basem Qeshta, Mariam Ghunaim, Ren�� Csuk, Stefan Laufer, Lars Kaiser, Hans-Peter Deigner|2021|Molecules|26|4065|doi:10.3390/molecules26134065