Identification of 9-fluoro substituted (−)-cytisine derivatives as ligands with high affinity for nicotinic receptors

Houllier, Nicolas; Gopisetti, JaganMohan; Lestage, Pierre; Lasne, Marie‐Claire; Rouden, Jacques

doi:10.1016/j.bmcl.2010.09.017

Cited by 25 publications

(21 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4), and it turns out that these slight changes mean a lot for the crystal packing. First, the overall shape of the molecules can be defined by the dihedral angle between planar ring A and an approximately planar fragment from another site of the molecule, which is the mean plane of the C11, N12, C13, C14, O15, C(O) 16 The crystal structures of compounds 3 on one side and 1 and 2 on the other are determined by quite different weak intermolecular interactions. This might be regarded as another example of the competition between weak hydrogen bonds and so-called halogen bonds, and this competition in the present case influences the conformation of a side chain.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

The Role of Halogen Bonding in Crystal Structures of 3-Halogeno Cytisine Derivatives

Przybył

Kubicki

2012

J Chem Crystallogr

View full text Add to dashboard Cite

The crystal structures of three 3-halogeno derivatives of 13N-substituted cytisine have been determined by X-ray diffraction. The two 13-acetyl substituted compounds, 3-bromo (1) and 3-iodo (2) are isostructural, with the isostructurality index as high as 99%. They both crystallize in monoclinic P2 1 space group, with unit cell parameters of a = 8.4709(10) Å , b = 9.2266(12) Å , c = 8.6051(10) Å , b = 98.528 (11)8 (1) and a = 8.2322(6) Å , b = 9.1724(7) Å , c = 8.5494(6) Å , b = 98.181 (7)8 (2). In turn, 3-bromo-13-t-butyl-carbonate derivative (3) crystallizes in orthorhombic P2 1 2 1 2 1 space group with a = 6.8171(3) Å , b = 7.8994(4) Å , c = 31.4657(15) Å . Conformation of the cytisine skeleton is similar in all three molecules, with almost planar A ring, sofa conformation of B-ring and C ring being an almost ideal chair. However, the orientations of the double C=O bonds in 13N-substituents are completely different: in 1 and 2 it is cis with respect to C12 (C12-N13-C14-O15 torsion angle is 3.3(4)8 in 1 and 1.3(6)8 in 2) while in 3 it is trans (-175.4(3)8). In the structures of 1 and 2 the driving force of the crystal architecture are quite strong C-HÁÁÁX halogen bonds with CÁÁÁX distances far shorter than the sums of van der Waals radii (CÁÁÁBr in 1 is 2.9430(19) Å and CÁÁÁI in 2 2.974(3)). In contrast in 3-partially as the consequence of different orientation of the substituent-there are no halogen bondings but instead some weak C-HÁÁÁO contacts organize the molecules into two-dimensional patterns.

show abstract

Section: Resultsmentioning

confidence: 99%

“…In terms of analogues, manipulation of cytisine itself is readily achievable at C3 and C5, C10, and N12 [11][12][13][14][15][16][17][18][19][20] but interest in cytisine as a target for total synthesis has also been significant as well as the synthesis of cytisine derivatives [21,22].…”

Section: Introductionmentioning

confidence: 99%

The Role of Halogen Bonding in Crystal Structures of 3-Halogeno Cytisine Derivatives

Przybył

Kubicki

2012

J Chem Crystallogr

View full text Add to dashboard Cite

show abstract

“…Z-and E-isomers 3k were separated by column chromatography on silica gel (Scheme 2). The isomer Z-3k had a broad NH signal at low field (δ(NH) = 11.32), but the NH signal of Eisomer 3k was a doublet with a coupling constant 3 J NHCH = 12.1 Hz and chemical shift 7.13 ppm. A broad absorbance of the NH of compound Z-3k was at 3200-3600 cm -1 in its IR spectrum.…”

Section: N-(3-oxoalkyl)amides 2 and N-(3-oxoalkenyl)amides 3 Are Analmentioning

confidence: 99%

“…[1][2][3][4][5][6][7] Further, a significant number of compounds with a 2(1H)-pyridinone motif exhibit interesting activities against a number of biological targets, and are used as scaffolds in drug discovery. [8][9][10][11] Methods for 2(1H)-pyridinone ring formation can be based on bi-and multicomponent reactions, intramolecular cyclizations and transformation of other hyterocycles.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Intramolecular cyclization of N-(3-oxoalkenyl)phenylacetamides: synthesis of 3-phenyl-2(1H)-pyridones

Goncharov¹,

Garkushenko²,

Savelieva³

et al. 2015

Arkivoc

View full text Add to dashboard Cite

3-Phenyl-2(1Н)-pyridinones were obtained by base-catalyzed intramolecular aldol-type cyclization of N-(3-oxoalkenyl)phenylacetamides. The effect of substituents in the starting compounds and the experimental conditions on the reaction course were established. It was shown that the transformations of N-(3-oxoalkenyl)amides in basic medium depend on structural and electronic factors as well as the reaction conditions.

show abstract

Synthesis and specific nootropic activity of (–)-cytisine derivatives with carbamide and thiocarbamide moieties in their structure

et al. 2012

View full text Add to dashboard Cite

Identification of 9-fluoro substituted (−)-cytisine derivatives as ligands with high affinity for nicotinic receptors

Cited by 25 publications

References 35 publications

The Role of Halogen Bonding in Crystal Structures of 3-Halogeno Cytisine Derivatives

The Role of Halogen Bonding in Crystal Structures of 3-Halogeno Cytisine Derivatives

Intramolecular cyclization of N-(3-oxoalkenyl)phenylacetamides: synthesis of 3-phenyl-2(1H)-pyridones

Synthesis and specific nootropic activity of (–)-cytisine derivatives with carbamide and thiocarbamide moieties in their structure

Contact Info

Product

Resources

About