- Supramolecular architectures in 5,5′-substituted hydantoins: Crystal structures and Hirshfeld surface analyses
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A series of three 5,5′-substituted hydantoin derivatives (1-3) were synthesized, and their crystal structures were solved using single-crystal synchrotron/powder-crystal X-ray diffraction data with a detailed analysis of Hirshfeld surfaces and fingerprint plots facilitating a comparison of intermolecular interactions in building different supramolecular architectures. A comparison of supramolecular assembly in the compounds with that in similar 5,5′-substituted hydantoins in the Cambridge Structural Database (CSD) has been presented. The crystal packing in compounds 1-3 containing complementary hydrogen bonding groups, i.e. the amino NH donors and carbonyl O acceptors, exhibits three types of supramolecular synthons. In the dipropyl substituted hydantoin (1), intermolecular N-H...O hydrogen bonds with only one carbonyl O atom acting as a double acceptor generate a one-dimensional C 11(4)C11(4)[R2 2(8)] network propagating along the [100] direction, while in 3, a 5-spiro fused hydantoin, the cyclic R22(8) motifs self-organize through pairs of N-H...O hydrogen bonds to form a C 22(9)[R22(8)][R2 2(8)] framework running along the [1-10] direction. The molecular assembly in 2, with a dibutyl substitution at the hydantoin C-5 position, produces R44(17) synthons, which are edge-fused to form two-dimensional molecular sheets in the (100) plane. The formation of a supramolecular architecture built with an R44(17) synthon is unprecedented among the substituted hydantoin structures in the CSD.
- Chattopadhyay, Basab,Mukherjee, Alok K.,Narendra,Hemantha,Sureshbabu, Vommina V.,Helliwell, Madeliene,Mukherjee, Monika
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- Synthesis and biological activity of nociceptin/orphanin FQ analogues substituted in position 7 or 11 with Cα,α-dialkylated amino acids
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Previous structure-activity and NMR studies on nociceptin/orphanin FQ (N/OFQ) demonstrated that Aib substitution of Ala7 and/or Ala11 increases the peptide potency through an alpha helix structure induction mechanism. On these bases we synthesised and evaluated pharmacologically in the mouse vas deferens assay a series of N/OFQ-NH2 analogues substituted in position 7 and 11 with Cα,α-disubstituted cyclic, linear and branched amino acids. None of the 20 novel N/OFQ analogues produced better results than [Aib7]N/OFQ-NH2. Thus, this substitution was combined with other chemical modifications known to modulate peptide potency and/or efficacy generating compound 21 [Nphe1Aib7Arg14Lys15]N/OFQ-NH2 (coded as UFP-111), compound 22 [(pF)Phe4Aib7Arg14Lys15]N/OFQ-NH2 (UFP-112) and compound 23 [Phe1Ψ(CH2-NH)Gly2(pF)Phe4Aib7Arg14Lys15]N/OFQ-NH2 (UFP-113). These novel peptides behaved as highly potent NOP receptor ligands showing full (UFP-112) and partial (UFP-113) agonist and pure antagonist (UFP-111) activities in a series of in vitro functional assays performed on pharmacological preparations expressing native as well as recombinant NOP receptors.
- Arduin, Marika,Spagnolo, Barbara,Calo, Girolamo,Guerrini, Remo,Carra, Giacomo,Fischetti, Carmela,Trapella, Claudio,Marzola, Erika,McDonald, John,Lambert, David G.,Regoli, Domenico,Salvadori, Severo
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p. 4434 - 4443
(2008/03/13)
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