共查询到20条相似文献,搜索用时 15 毫秒
1.
Piotr Kowalski Jolanta Jaśkowska Andrzej J. Bojarski Beata Duszyńska Adam Bucki Marcin Kołaczkowski 《Journal of heterocyclic chemistry》2011,48(1):192-198
The synthesis and evaluation as 5‐HT1A and 5‐HT7 serotonin receptor ligands of the two sets of O‐substituted hydroxybenzamides, structurally related to 2‐{3‐[4‐(2‐methoxyphenyl)piperazin‐1‐yl]propoxy}benzamide ( 1 ), (Ki 5‐HT1A = 21 nM, 5‐HT7 = 234 nM) are reported. To affect the affinity for 5‐HT1A and 5‐HT7 receptors, an amide moiety ( 2 , 3 , 4 , 5 , 6 ) and a hydrocarbon chain length ( 7 , 8 , 9 , 10 ) were modified. The serotonergic activity of compounds 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 was generally higher in the case of 5‐HT1A receptors compared with 5‐HT7 ones; the most active 5‐HT1A ligands being meta‐isomer 2 (Ki = 7 nM) and both analogs of 1 with the longest spacer, i.e., penta‐ and hexa‐methylene derivatives 9 and 10 (Ki = 4 and 3 nM, respectively). The observed biological properties of compounds 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 were elucidated using molecular modeling procedures. J. Heterocyclic Chem., (2010). 相似文献
2.
Dr. Tiago Rodrigues Nadine Hauser Daniel Reker Dr. Michael Reutlinger Tiffany Wunderlin Dr. Jacques Hamon Dr. Guido Koch Prof. Dr. Gisbert Schneider 《Angewandte Chemie (International ed. in English)》2015,54(5):1551-1555
We report a multi‐objective de novo design study driven by synthetic tractability and aimed at the prioritization of computer‐generated 5‐HT2B receptor ligands with accurately predicted target‐binding affinities. Relying on quantitative bioactivity models we designed and synthesized structurally novel, selective, nanomolar, and ligand‐efficient 5‐HT2B modulators with sustained cell‐based effects. Our results suggest that seamless amalgamation of computational activity prediction and molecular design with microfluidics‐assisted synthesis enables the swift generation of small molecules with the desired polypharmacology. 相似文献
3.
Dr. Shuguang Yuan Dr. Qian Peng Prof. Krzysztof Palczewski Prof. Horst Vogel Prof. Slawomir Filipek 《Angewandte Chemie (International ed. in English)》2016,55(30):8661-8665
G‐protein‐coupled receptors (GPCRs) are involved in a wide range of physiological processes, and they have attracted considerable attention as important targets for developing new medicines. A central and largely unresolved question in drug discovery, which is especially relevant to GPCRs, concerns ligand selectivity: Why do certain molecules act as activators (agonists) whereas others, with nearly identical structures, act as blockers (antagonists) of GPCRs? To address this question, we employed all‐atom, long‐timescale molecular dynamics simulations to investigate how two diastereomers (epimers) of dihydrofuroaporphine bind to the serotonin 5‐HT1A receptor and exert opposite effects. By using molecular interaction fingerprints, we discovered that the agonist could mobilize nearby amino acid residues to act as molecular switches for the formation of a continuous water channel. In contrast, the antagonist epimer remained firmly stabilized in the binding pocket. 相似文献
4.
Piotr Kowalski Teresa Kowalska Andrzej J. Bojarski Beata Duszyńska 《Journal of heterocyclic chemistry》2007,44(4):889-893
Syntheses of the N‐substituted butyl derivatives of 1,8‐naphthalimide ( 1‐8 ), containing various arylpiperazines, tetrahydroisoquinoline and methylhomopiperazine moieties attached at 4‐position of the butyl chain have been described. Biological activities were evaluated in vitro for their ability to bind to serotonin 5‐HT1A and 5‐HT7 receptors. Due to the structural similarity of derivatives 1‐8 to psychotropic agents, the pharmacological properties of target compounds were predicted using PASS program. 相似文献
5.
Jian‐Li Lin Yue‐Qing Zheng 《Acta Crystallographica. Section C, Structural Chemistry》2005,61(12):m501-m503
In the title compound, [Cu2(C6H8O4)(C6H9O4)2(C10H8N2)2(H2O)2]n, the square‐pyramidally coordinated Cu atoms are bridged by both 4,4‐bipyridine and adipate ligands into ladder‐like chains, with exo‐orientated 5‐carboxypentanoate ligands pendant from both side rails. Half of the adipate ligand is related to the other half by inversion symmetry. Interchain O—H⋯O hydrogen bonds from the aqua ligands to the carbonyl O atoms of the 5‐carboxypentanoate ligands are responsible for the formation of two‐dimensional grid‐like (4,4)‐networks, which complete a twofold interpenetration. 相似文献
6.
Yi‐Fang Deng Jin‐Sheng Xu Man‐Sheng Chen Chun‐Hua Zhang 《Acta Crystallographica. Section C, Structural Chemistry》2012,68(8):m219-m222
In the title compound, {[Co(C14H8N2O5)(C10H8N2)]·3H2O}n, the CoII cation is five‐coordinated with a slightly distorted trigonal–bipyramidal geometry, and the 5‐isonicotinamidoisophthalate ligands link CoII atoms into a layered structure. These two‐dimensional arrays are further pillared by rod‐like 4,4′‐bipyridine ligands to give a three‐dimensional framework with pcu (primitive cubic) topology. The magnetic and adsorption properties of the title compound are also discussed. 相似文献
7.
Allison M. Mills Martin Lutz Gino P. F. Van Strijdonck Paul C. J. Kamer Piet W. N. M. Van Leeuwen Anthony L. Spek 《Acta Crystallographica. Section C, Structural Chemistry》2002,58(12):m583-m585
The palladium(II) centre in the title compound, [PdCl2(C21H18N2OS)], is coordinated to the pyridyl N atom and to the thiazolidinone S atom of the 5‐benzyl‐3‐phenyl‐2‐(2‐pyridyl)thiazolidin‐4‐one ligand, resulting in a five‐membered chelate ring. Two cis‐chloro ligands complete the square‐planar coordination environment of the metal. Although the geometry at the Pd centre is essentially planar, the N—Pd—S bite angle of 85.20 (8)° causes deviations in the cis angles from the ideal value of 90°. Opposite enantiomers form one‐dimensional chains in the cell via a short S?O intermolecular interaction. 相似文献
8.
Wilcox RE Ragan JE Pearlman RS Brusniak MY Eglen RM Bonhaus DW Tenner TE Miller JD 《Journal of computer-aided molecular design》2001,15(10):883-909
The serotonin 5HT7 receptor has been implicated in numerous physiological and pathological processes from circadian rhythms [1] to depression and schizophrenia. Clonal cell lines heterologously expressing recombinant receptors offer good models for understanding drug-receptor interactions and development of quantitative structure-activity relationships (QSAR). Comparative Molecular Field Analysis (CoMFA) is an important modern QSAR procedure that relates the steric and electrostatic fields of a set of aligned compounds to affinity. Here, we utilized CoMFA to predict affinity for a number of high-affinity ligands at the recombinant guinea pig 5HT7 receptor. Using R-lisuride as the template, a final CoMFA model was derived using procedures similar to those of our recent papers [2, 3, 4] The final cross-validated model accounted for >85% of the variance in the compound affinity data, while the final non-cross validated model accounted for >99% of the variance. Model evaluation was done using cross-validation methods with groups of 5 ligands. Twenty cross-validation runs yielded an average predictive r2(q2) of 0.779 ± 0.015 (range: 0.669–0.867). Furthermore, 3D-chemical database search queries derived from the model yielded hit lists of promising agents with high structural similarity to the template. Together, these results suggest a possible basis for high-affinity drug action at 5HT7 receptors. 相似文献
9.
Nicolas Kerisit Romain Ligny Etienne S. Gauthier Jean‐Paul Gugan Loïc Toupet Jean‐Claude Guillemin Yann Trolez 《Helvetica chimica acta》2019,102(3)
The synthesis of 5‐bromopenta‐2,4‐diynenitrile (BrC5N) in three steps from commercially available compounds is reported. Reacting 5‐bromopenta‐2,4‐diynenitrile with secondary amines led to the formation of stable butadiynamines or enynenitriles, depending on the nature of the amine reactant. The reaction of 5‐bromopenta‐2,4‐diynenitrile with simple terminal alkynes in the presence of secondary amines, copper, and palladium catalysts, provided a straightforward access to original polyfunctional carbon‐rich scaffolds. In this work, different alkynes and secondary amines were tested, which allowed for the preparation of a family of substituted dienes. Given the high synthetic potential of 5‐bromopenta‐2,4‐diynenitrile, we also prepared iodinated counterparts of this compound, that is, 5‐iodopenta‐2,4‐diynenitrile and its lower homologue 3‐iodopropiolonitrile. The UV‐visible spectrum of some relevant compounds was also recorded. 相似文献
10.
Graldine Calvet Nicolas Blanchard Cyrille Kouklovsky Rgis Guillot 《Acta Crystallographica. Section C, Structural Chemistry》2007,63(6):o365-o368
The crystal structures of 2,2‐dimethyl‐5‐nitroso‐1,3‐dioxan‐5‐yl benzoate, C13H15NO5, (I), 2,2‐dimethyl‐5‐nitroso‐1,3‐dioxan‐5‐yl 4‐chlorobenzoate, C13H14ClNO5, (II), and 5‐nitroso‐1,3‐dioxan‐5‐yl 4‐chlorobenzoate, C11H11NO5, (III), have been determined in order to gain insight into the conformational preference of α‐benzoyloxynitroso. Unfavourable 1,3‐diaxial interactions force (I) and (II) to crystallize in the 2,5 twist‐boat conformation, whereas compound (III), lacking this destabilizing interaction, crystallizes in the chair conformation. 相似文献
11.
As part of the structure‐activity relationship of the dopamine D2 and serotonin 5‐HT3 receptors antagonist 1, which is a clinical candidate with a broad antiemetic activity, the synthesis and dopamine D2 and serotonin 5‐HT3 receptors binding affinity of (R)‐5‐bromo‐N‐(1‐ethyl‐3‐methylhexahydro‐1,3‐diazin‐5‐yl)‐ and (R)‐5‐bromo‐N‐(1‐ethyl‐5‐methyloctahydro‐1,5‐diazocin‐3‐yl)‐2‐methoxy‐6‐methylaminopyridine‐3‐carboxam‐ides ( 2 and 3 ) are described. Treatment of 1‐ethyl‐2‐(p‐toluenesulfonyl)amino‐3‐methylaminopropane dihy‐drochloride ( 4a ) with paraformaldehyde and successive deprotection gave the 5‐aminohexahydro‐1,3‐diazine 6 in excellent yield. 3‐Amino‐1‐ethyl‐5‐methyloctahydro‐1,5‐diazocine ( 15 ) was prepared from 2‐(benzyloxycarbonyl)amino‐3‐[[N‐(tert‐butoxycarbonyl)‐N‐methyl]amino]‐1‐ethylaminopropane ( 9 ) through the intramolecular amidation of (R)‐3‐[N‐[(2‐benzyloxycarbonylamino‐3‐methylamino)propyl]‐N‐ethyl]aminopropionic acid trifluoroacetate ( 12 ), followed by lithium aluminum hydride reduction of the resulting 6‐oxo‐1‐ethyl‐5‐methyloctahydrodiazocine ( 13 ) in 41% yield. Reaction of the amines 6 and 15 with 5‐bromo‐2‐methoxy‐6‐methylaminopyridine‐3‐carboxylic acid furnished the desired 2 and 3 , which showed much less potent affinity for dopamine D2 receptors than 1 . 相似文献
12.
Wei‐Lu Xiong Yu‐Ling Wang Qing‐Yan Liu 《Acta Crystallographica. Section C, Structural Chemistry》2013,69(10):1132-1135
The asymmetric unit in the structure of the title compound, [K2(C9H4O9S)(H2O)2]n, consists of two eight‐coordinated KI cations, one 2,4‐dicarboxy‐5‐sulfonatobenzoate dianion (H2SBTC2−), one bridging water molecule and one terminal coordinated water molecule. One KI cation is coordinated by three carboxylate O atoms and three sulfonate O atoms from four H2SBTC2− ligands and by two bridging water molecules. The second KI cation is coordinated by four sulfonate O atoms and three carboxylate O atoms from five H2SBTC2− ligands and by one terminal coordinated water molecule. The KI cations are linked by sulfonate groups to give a one‐dimensional inorganic chain with cage‐like K4(SO3)2 repeat units. These one‐dimensional chains are bridged by one of the carboxylic acid groups of the H2SBTC2− ligand to form a two‐dimensional layer, and these layers are further linked by the remaining carboxylate groups and the benzene rings of the H2SBTC2− ligands to generate a three‐dimensional framework. The compound displays a photoluminescent emission at 460 nm upon excitation at 358 nm. In addition, the thermal stability of the title compound has been studied. 相似文献
13.
Reijo Sillanp Jordi Llop Clara Vias Francecs Teixidor Raikko Kiveks 《Acta Crystallographica. Section C, Structural Chemistry》2001,57(8):900-901
In the title compound, (η5‐2,5‐dimethylpyrrolyl)[(7,8,9,10,11‐η)‐7‐methyl‐7,8‐dicarba‐nido‐undecaborato]cobalt(III), [3‐Co{η5‐[2,5‐(CH3)2‐NC4H2]}‐1‐CH3‐1,2‐C2B9H10] or [Co(C3H13B9)(C6H8N)], the CoIII atom is sandwiched between the pentagonal faces of the pyrrolyl and dicarbollide ligands, resulting in a neutral molecule. The C—C distance in the dicarbollide cage is 1.649 (3) Å. 相似文献
14.
Mukesh Kumar Elizabeth T. Papish Matthias Zeller 《Acta Crystallographica. Section C, Structural Chemistry》2010,66(8):m197-m200
The X‐ray crystal structure of the title compound, [Zn(C2H5)(C24H40BN6)], or TptBu,MeZnEt [TptBu,Me is tris(3‐tert‐butyl‐5‐methylpyrazolyl)hydridoborate], reveals a distorted tetrahedral geometry around the Zn atom. The Zn center is coordinated by three N atoms of the borate ligand and by one C atom of the ethyl group. The present structure and other tetrahedral Tp zinc alkyl complexes are compared with similar Ttz ligands (Ttz is 1,2,4‐triazolylborate), but no major differences in the structures are noted, and it can be assumed that variation of the substitution pattern of Tp or Ttz ligands has little or no influence on the geometry of alkylzinc complexes. Refinement of the structure is complicated by a combination of metric pseudosymmetry and twinning. The metrics of the structure could also be represented in a double‐volume C‐centered orthorhombic unit cell, and the structure is twinned by one of the orthorhombic symmetry operators not present in the actual structure. The twinning lies on the borderline between pseudomerohedral and nonmerohedral. The data were refined as being nonmerohedrally twinned, pseudomerohedrally twinned and untwinned. None of the approaches yielded results that were unambiguously better than any of the others: the best fit between structural model and data was observed using the nonmerohedral approach which also yielded the best structure quality indicators, but the data set is less than 80% complete due to rejected data. The pseudomerohedral and the untwinned structures are complete, but relatively large residual electron densities that are not close to the metal center are found with values up to three times higher than in the nonmerohedral approach. 相似文献
15.
Cheng‐Bing Ma Hui Chen Ming‐Qiang Hu Chang‐Neng Chen 《Acta Crystallographica. Section C, Structural Chemistry》2011,67(2):m59-m61
In the title compound, [Mn(C5H2N2O4)(C12H9N3)2]·H2O, the MnII centre is surrounded by three bidentate chelating ligands, namely, one 6‐oxido‐2‐oxo‐1,2‐dihydropyrimidine‐5‐carboxylate (or uracil‐5‐carboxylate, Huca2−) ligand [Mn—O = 2.136 (2) and 2.156 (3) Å] and two 2‐(2‐pyridyl)‐1H‐benzimidazole (Hpybim) ligands [Mn—N = 2.213 (3)–2.331 (3) Å], and it displays a severely distorted octahedral geometry, with cis angles ranging from 73.05 (10) to 105.77 (10)°. Intermolecular N—H...O hydrogen bonds both between the Hpybim and the Huca2− ligands and between the Huca2− ligands link the molecules into infinite chains. The lattice water molecule acts as a hydrogen‐bond donor to form double O...H—O—H...O hydrogen bonds with the Huca2− O atoms, crosslinking the chains to afford an infinite two‐dimensional sheet; a third hydrogen bond (N—H...O) formed by the water molecule as a hydrogen‐bond acceptor and a Hpybim N atom further links these sheets to yield a three‐dimensional supramolecular framework. Possible partial π–π stacking interactions involving the Hpybim rings are also observed in the crystal structure. 相似文献
16.
Jing Li Ren‐Tao Wu Hong‐Bo Li 《Acta Crystallographica. Section C, Structural Chemistry》2011,67(8):m284-m286
In the title coordination compound, [Cd(C8H3NO6)(C5H8N3)0.5(H2O)]n, each CdII atom is six‐coordinated in a distorted octahedral environment surrounded by three carboxylate O atoms from two different 5‐nitroisophthalate (5‐NIP2−) ligands, two N atoms from two distinct 1,6‐bis(1,2,4‐triazol‐1‐yl)hexane (bth) ligands and one water molecule. The CdII centres are bridged by the bth ligands, which lie across centres of inversion, to give a honeycomb‐like two‐dimensional layer structure; the layers are further connected by the bridging 5‐NIP2− ligands with a κ2;κ1‐μ2 coordination mode to generate the final three‐dimensional structure. Topologically, taking the the CdII atoms and the bth ligands as different four‐connected nodes and the 5‐NIP2− ligands as linkers, the three‐dimensional structure can be simplified to a rare `mesh of trees' (mot) net with the Schäfli symbol (66)(64.82)2. 相似文献
17.
Young Ho Jhon Jaheon Kim 《Acta Crystallographica. Section C, Structural Chemistry》2006,62(8):m334-m336
The title compound, {[Zn(C8H4O5)(C3H7NO)2]·0.5C7H8}n, is a one‐dimensional coordination polymer in which the Zn atoms are linked by bridging 5‐hydroxybenzene‐1,3‐dicarboxylate ligands. These polymeric chains form two‐dimensional sheets via interchain hydrogen bonds, and these sheets, in turn, are stacked tightly with solvent toluene molecules in the interlayer space. The N,N′‐dimethylformamide ligands, coordinated axially to the Zn atoms, form van der Waals contacts with ligands in neighboring sheets, and enclose the guest molecules. 相似文献
18.
Xiao‐Qin Wang Jian Zhang Zhao‐Ji Li Yi‐Hang Wen Jian‐Kai Cheng Yuan‐Gen Yao 《Acta Crystallographica. Section C, Structural Chemistry》2004,60(12):m657-m658
The title compound, [Nd(C7H3O6S)(H2O)]n or [Nd(SSA)(H2O)]n (H3SSA is 5‐sulfosalicylic acid), was synthesized by the hydrothermal reaction of Nd2O3 with H3SSA in water. The compound forms a three‐dimensional network in which the asymmetric unit contains one NdIII atom, one SSA ligand and one coordinated water molecule. The central NdIII ion is eight‐coordinate, bonded to seven O atoms from five different SSA ligands [Nd—O = 2.405 (4)–2.612 (4) Å] and one aqua O atom [Nd—OW = 2.441 (4) Å]. 相似文献
19.
Guan‐Hua Wang Yong‐Qian Lei 《Acta Crystallographica. Section C, Structural Chemistry》2013,69(4):360-362
In the title compound, {[Zn(C8H4O5)(C12H10N2)]·0.5C12H10N2}n or {[Zn(HO‐BDC)(bpe)]·0.5bpe}n [HO‐H2BDC is 5‐hydroxyisophthalic acid and bpe is 1,2‐bis(pyridin‐4‐yl)ethene], the asymmetric unit contains a ZnII atom, one HO‐BDC ligand, one coordinated bpe ligand and half a noncoordinating bpe molecule with crystallographic inversion symmetry. Each ZnII centre is four‐coordinated by two O atoms from two distinct HO‐BDC ligands and two N atoms from two different bpe ligands in a ZnO2N2 coordination environment. The three‐dimensional topology of the title compound corresponds to a fourfold interpenetrating diamondoid coordination polymer network, with the uncoordinated bpe ligands located in the cavities, hydrogen bonded to the main network via the hydroxy group of the HO‐H2BDC ligand. 相似文献
20.
Dustin Bornemann Cody Ross Pitts Carmen J. Ziegler Ewa Pietrasiak Nils Trapp Sebastian Kueng Nico Santschi Antonio Togni 《Angewandte Chemie (International ed. in English)》2019,58(36):12604-12608
The TeF5 group is significantly underexplored as a highly fluorinated substituent on an organic framework, despite it being a larger congener of the acclaimed SF5 group. In fact, only one aryl‐TeF5 compound (phenyl‐TeF5) has been reported to date, synthesized using XeF2. Our recently developed mild TCICA/KF approach to oxidative fluorination provides an affordable and scalable alternative to XeF2. Using this method, we report a scope of extensively characterized aryl‐TeF5 compounds, along with the first SC‐XRD data on this compound class. The methodology was also extended to the synthesis and structural study of heretofore unknown aryl‐TeF4CF3 compounds. Additionally, preliminary reactivity studies unveiled some inconsistencies with previous literature regarding phenyl‐TeF5. Although our studies conclude that the arene‐based TeF5 (and TeF4CF3) group is not quite as robust as the SF5 group, we find that the TeF5 group is more stable than previously thought, thus opening a door to explore new applications of this motif. 相似文献