Preparation of two Cyclobutadiene-steroid derivatives Theoretical Analysis of its Interaction with the μ, d, and k Opiod-receptors

The objective of this investigation was to develop two cyclobutadiene-steroid derivatives (compounds 6 or 7) to evaluate its theoretical interaction on µ, d, and k opioid-receptors. The synthesis of 6 or 7 was carried out using a series of reactions which involves. 1) addition/cyclization: 2) imination, 3) etherification and 4) oxy-functionalization. Chemical structure of all compounds was confirmed using elemental analysis and NMR spectra. In addition, a theoretical analysis on the interaction of compounds 6 or 7 with µ, d, and k opioid-receptors was evaluated using a docking model. The results showed that 6 or 7 may interact with different type of amino acids residues on surface of the µ, d, and k opioid-receptors. Other data, indicated that inhibition constant (Ki) involved in the interaction of compounds 6 or 7 with k receptor was less compared with the Ki present in the interaction with µ, d, receptors. These data indicated that 1) compounds 6 or 7 show a high affinity by k-receptor; 2) the cyclobutadiene analogs are particularly interesting, because these drugs may constitute a novel therapy for pain.

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Pteridines, XCV

Pteridines ◽

10.1515/pteridines.1989.1.4.199 ◽

1989 ◽

Vol 1 (4) ◽

pp. 199-210 ◽

Cited By ~ 4

Author(s):

Ronan John Lockart ◽

Wolfgang Pfleiderer

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Elemental Analysis ◽

Nmr Spectra ◽

Acid Anhydride ◽

Activated Esters ◽

Amino Acid Conjugates ◽

Catalytic Hydrogenolysis ◽

Benzyl Esters

SummaryA series of new amino acid-tetrahydropterin-conjugates has been synthesized starting from N 2-isobutyryl-6,7- dimethyl-5,6,7,8-tetrahydropterin (7). The amino acids have been attached in form of their esters (10 - 16) via a succinyl spacer to the N-5 position (17 - 23) or directly via the carboxyl function applying CBZprotected activated esters (35, 39). Acylation of 7 with N-benzyloxycarbonylglutamic acid anhydride led to the y-glutamyl derivative 41. Selective deblocking experiments were achieved by catalytic hydrogenolysis to cleave the benzyl esters (24-28, 36, 42) and by DBU treatment to eliminate the p-nitrophenylethyl group (24, 25) respectively. Further reaction with ammonia hydrolysed the isobutyryl group to give the free tetrahydropterin-amino acid-conjugates 29 - 32, 37 and 43. Also a carbamoyl-type conjugate (45) was obtained from 7 and benzyl phenylalanine N-carbonylimidazolide (44). The newly synthesized compounds have been characterized by elemental analysis, UV and IH-NMR spectra.

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10-step Synthesis of 20-nor-Salvinorin A by Dynamic Strategic Bond Analysis

10.26434/chemrxiv.5318188.v1 ◽

2017 ◽

Author(s):

Jeremy Roach ◽

Yusuke Sasano ◽

Cullen Schmid ◽

Saheem Zaidi ◽

Vsevolod Katritch ◽

...

Keyword(s):

Total Synthesis ◽

Opioid Receptors ◽

Structural Modification ◽

High Selectivity ◽

Therapeutic Potential ◽

Salvinorin A ◽

High Affinity ◽

Plant Metabolite ◽

Complex Architecture ◽

Property Modification

Salvinorin A (SalA) is a plant metabolite that agonizes the human kappa-opioid receptor (κ-OR) with high affinity and high selectivity over mu- and delta-opioid receptors. Its therapeutic potential has stimulated extensive semi-synthetic studies and total synthesis campaigns. However, structural modification of SalA has been complicated by its instability, and efficient total synthesis has been frustrated by its dense, complex architecture. Treatment of strategic bonds in SalA as dynamic and dependent on structural perturbation enabled the identification of an efficient retrosynthetic pathway. Here we show that deletion of C20 simultaneously stabilizes the SalA skeleton, simplifies its synthesis and retains its high affinity and selectivity for the κ-OR. The resulting 10-step synthesis now opens the SalA scaffold to deep-seated property modification.

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THEORETICAL ANALYSIS OF THE STRUCTURE AND VIBRATIONAL SPECTR OF ASPARAGINE AND GLUTAMIC AMINO ACIDS IN WATER AT DIFFERENT pH

NATURAL SCIENCES ◽

10.21672/1818-507x-2017-60-3-094-107 ◽

2017 ◽

Vol 60 (3) ◽

pp. 094-107

Author(s):

Galina N. Ten ◽

◽

N.E. Shcherbakova ◽

Viktor I. Baranov ◽

◽

...

Keyword(s):

Amino Acids ◽

Theoretical Analysis

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Synthesis of a New Dioxaspiro[bicyclo[3.3.1]nonane-oxabicyclo[6.2.0]deca- 1(10),8-dien-4-one Derivative Using Some Chemical Strategies

Letters in Organic Chemistry ◽

10.2174/1570178617666191116123359 ◽

2020 ◽

Vol 17 (5) ◽

pp. 393-402

Author(s):

Figueroa-Valverde Lauro ◽

Rosas-Nexticapa Marcela ◽

Lopez-Ramos Maria ◽

Diaz Cedillo Francisco ◽

Mateu-Armand Virginia ◽

...

Keyword(s):

Elemental Analysis ◽

Chemical Structure ◽

Spectroscopic Techniques ◽

Easy Method ◽

Chemical Strategies

There are several protocols for the preparation of bicyclic derivatives; however, some methods use dangerous and require special conditions. The aim of this study was to synthesize a new Dioxaspiro[ bicyclo[3.3.1]nonane-oxabicyclo[6.2.0]-deca-1(10), 8-dien-4-one (compound 8). Compound 8 was prepared using some reactions such as; i) etherification, ii) reduction, iii) amidation, iv) imination and v) 2+2 addition. The chemical structure of 8 and its intermediaries were completely characterized by spectroscopic techniques and elemental analysis. The synthesis showed a yield of 85% for compound 8. In this study, an easy method for the preparation of compound 8 is reported.

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Synthesis and Antituberculotic Activity of Some Substituted 3-Arylamino-5-cyano-2-pyrazinecarboxamides

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19951236 ◽

1995 ◽

Vol 60 (7) ◽

pp. 1236-1241 ◽

Cited By ~ 7

Author(s):

Martin Doležal ◽

Jiří Hartl ◽

Antonín Lyčka ◽

Vladimír Buchta ◽

Želmíra Odlerová

Keyword(s):

Nucleophilic Substitution ◽

Elemental Analysis ◽

Nmr Spectra ◽

Substituted Anilines ◽

H Nmr

Nucleophilic substitution of 3-chloro-5-cyano-2-pyrazinecarboxamide by substituted anilines afforded substituted 3-arylamino-5-cyano-2-pyrazinecarboxamides I-X. The structures of compounds were confirmed by elemental analysis, UV, IR and 1H NMR spectra. The assessment of in vitro antimycotic and antimycobacterial activities of the compounds was carried out. The highest antituberculotic activity against M. tuberculosis in this series was shown by 3-anilino- 5-cyano-2-pyrazinecarboxamide (I), whose efficacy was the same as that of pyrazinecarboxamide.

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Molecular docking studies of tea (Thea sinensis Linn.) polyphenols inhibition pattern with Rat P-glycoprotein

Physical Sciences Reviews ◽

10.1515/psr-2018-0165 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Babar Ali ◽

Qazi Mohammad Sajid Jamal ◽

Showkat R. Mir ◽

Saiba Shams ◽

Mohammad Amjad Kamal

Keyword(s):

Amino Acids ◽

Molecular Docking ◽

Binding Energy ◽

Oral Administration ◽

Docking Studies ◽

Vital Role ◽

Glycoprotein P ◽

High Affinity ◽

P Glycoprotein ◽

Inhibition Pattern

AbstractSince 3000 B.C., evergreen plant Thea sinensis (Theaceae) is used both as a social and medicinal beverage. Leaves of T. sinensis contain amino acids, vitamins, caffeine, polysaccharides and polyphenols. Most of the natural medicinal actions of tea are due to the availability and abundance of polyphenols mainly catechins. It has also been stated that some catechins were absorbed more rapidly than other compounds after the oral administration of tea and could increase the bio-enhancing activities of anticancer drugs by inhibiting P-glycoprotein (P-gp). The results of the molecular docking showed that polyphenols bind easily to the active P-gp site. All compounds exhibited fluctuating binding affinity ranged from −11.67 to −8.36 kcal/mol. Observed binding energy required for theaflavin to bind to P-gp was lowest (−11.67 kcal/mol). The obtained data that supports all the selected polyphenols inhibited P-gp and therefore may enhance the bioavailability of drugs. This study may play a vital role in finding hotspots in P-gp and eventually may be proved useful in designing compounds with high affinity and specificity to the protein.

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HIGH AFFINITY AND IMPROVED SELECTIVITY FOR 6 OPIOID RECEPTORS EXHIBITED BY NEW LINEAR HEXAPEPTIDES

Porto Carras, Chalkidiki, Greece, Aug. 31–Sept. 5, 1986 ◽

10.1515/9783110864243-087 ◽

1987 ◽

pp. 377-380

Author(s):

G. Gaeel ◽

J. Belleney ◽

P. Delay-Goyet ◽

C. Seguin ◽

J.-L. Morgat ◽

...

Keyword(s):

Opioid Receptors ◽

High Affinity

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Human Rev1 relies on insert-2 to promote selective binding and accurate replication of stabilized G-quadruplex motifs

Nucleic Acids Research ◽

10.1093/nar/gkab041 ◽

2021 ◽

Author(s):

Amit Ketkar ◽

Lane Smith ◽

Callie Johnson ◽

Alyssa Richey ◽

Makayla Berry ◽

...

Keyword(s):

Amino Acids ◽

Mutation Frequency ◽

Control Sequence ◽

Wild Type ◽

Binding Properties ◽

High Affinity ◽

G4 Dna ◽

G Quadruplex ◽

Forward Mutagenesis

Abstract We previously reported that human Rev1 (hRev1) bound to a parallel-stranded G-quadruplex (G4) from the c-MYC promoter with high affinity. We have extended those results to include other G4 motifs, finding that hRev1 exhibited stronger affinity for parallel-stranded G4 than either anti-parallel or hybrid folds. Amino acids in the αE helix of insert-2 were identified as being important for G4 binding. Mutating E466 and Y470 to alanine selectively perturbed G4 binding affinity. The E466K mutant restored wild-type G4 binding properties. Using a forward mutagenesis assay, we discovered that loss of hRev1 increased G4 mutation frequency >200-fold compared to the control sequence. Base substitutions and deletions occurred around and within the G4 motif. Pyridostatin (PDS) exacerbated this effect, as the mutation frequency increased >700-fold over control and deletions upstream of the G4 site more than doubled. Mutagenic replication of G4 DNA (±PDS) was partially rescued by wild-type and E466K hRev1. The E466A or Y470A mutants failed to suppress the PDS-induced increase in G4 mutation frequency. These findings have implications for the role of insert-2, a motif conserved in vertebrates but not yeast or plants, in Rev1-mediated suppression of mutagenesis during G4 replication.

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