Studies on Enaminoketones

1974 ◽  
Vol 52 (1) ◽  
pp. 55-65 ◽  
Author(s):  
Ivo Jirkovsky
Keyword(s):  
Cyanogen Bromide ◽  
Spectroscopic Properties ◽  
Phenyl Isocyanate ◽  
Biologically Active ◽  
Side Chain ◽  
Phenyl Isothiocyanate ◽  
Methyl Isothiocyanate ◽  
Synthetic Utility ◽  
Concentrated Sulfuric Acid ◽  
Biologically Active Derivatives

A series of N-substituted 3-amino-2-cyclohexen-1-ones and 3-amino-5,5-dimethyl-2-cyclohexen-1-ones (1–9) has been prepared. Halogenation of these compounds with bromine, NBS, cyanogen bromide, and iodine is described. The tendency of enaminoketones to form salts of the corresponding enol-ketimine form was observed and structures of the salts are supported by their p.m.r. and i.r. properties. The reaction of 3-benzylamino-2-bromo-5,5-dimethyl-2-cyclohexen-1-one with concentrated sulfuric acid effected debenzylation. Treatment of 3-benzylamino-2-iodo-5,5-dimethyl-2-cyclohexen-1-one with dibenzoyl peroxide gave 8,8a-dihydro-5-iodo-8,8-dimethyl-2,3-diphenyl-4H-1,4-benzoxazine-6,7-diol. The above secondary enaminoketones 1–9 were shown to react with phenyl isocyanates, phenyl isothiocyanate. and methyl isothiocyanate under fusion conditions to yield substituted 2-amino-6-oxo-1-cyclo-hexene-1-carboxamides and corresponding thiocarboxamides. 2-Benzylamino-6-oxo-N-phenyl-1-cyclohexene-1-carboxamide and its 5,5-dimethyl analog were found to undergo facile transamination in position 2, when heated with a primary amine. This reaction is of synthetic utility for the preparation of biologically active derivatives with a basically substituted side chain. Addition of 4-methylamino-3-pentene-2-one to phenyl isocyanate afforded 2-acetyl-3-methylaminoisocrotonanilide; the spectroscopic properties of this product are discussed.

Oxazole-Based Compounds As Anticancer Agents

2020 ◽  
Vol 26 (41) ◽  
pp. 7337-7371 ◽  
Author(s):  
Maria A. Chiacchio ◽  
Giuseppe Lanza ◽  
Ugo Chiacchio ◽  
Salvatore V. Giofrè ◽  
Roberto Romeo ◽  
...  
Keyword(s):  
Cancer Research ◽  
Drug Discovery ◽  
Anticancer Agents ◽  
Heterocyclic Compounds ◽  
Chemical Diversity ◽  
Biologically Active ◽  
New Drugs ◽  
The Core ◽  
Anti Cancer ◽  
Biologically Active Derivatives

: Heterocyclic compounds represent a significant target for anti-cancer research and drug discovery, due to their structural and chemical diversity. Oxazoles, with oxygen and nitrogen atoms present in the core structure, enable various types of interactions with different enzymes and receptors, favoring the discovery of new drugs. Aim of this review is to describe the most recent reports on the use of oxazole-based compounds in anticancer research, with reference to the newly discovered iso/oxazole-based drugs, to their synthesis and to the evaluation of the most biologically active derivatives. The corresponding dehydrogenated derivatives, i.e. iso/oxazolines and iso/oxazolidines, are also reported.

New Potential Biologically Active Compounds: Synthesis and Characterization of Urea and Thiourea Derivativpes Bearing 1,2,4-oxadiazole Ring

2020 ◽  
Vol 17 (7) ◽  
pp. 525-534 ◽  
Author(s):  
Nevin Arıkan Ölmez ◽  
Faryal Waseer
Keyword(s):  
Microwave Irradiation ◽  
Room Temperature ◽  
Antimicrobial Activities ◽  
Phenyl Isocyanate ◽  
Single Step ◽  
Biologically Active Compounds ◽  
Biologically Active ◽  
Active Compounds ◽  
Thiourea Derivatives ◽  
Acyl Chlorides

Background: Urea, thiourea, and 1,2,4-oxadiazole compounds are of great interest due to their different activities such as anti-inflammatory, antiviral, analgesic, fungicidal, herbicidal, diuretic, antihelminthic and antitumor along with antimicrobial activities. Objective: In this work, we provide a new series of potential biologically active compounds containing both 1,2,4-oxadiazole and urea/thiouprea moiety. Materials and Methods: Firstly, 5-chloromethyl-3-aryl-1,2,4-oxadiazoles (3a-j) were synthesized from the reaction of different substituted amidoximes (2a-j) and chloroacetyl chloride in the presence of pyridine by conventional and microwave-assisted methods. In the conventional method, 1,2,4-oxadiazoles were obtained in two steps. O-acylamidoximes obtained in the first step at room temperature were heated in toluene for an average of one hour to obtain 1,2,4-oxadiazoles. The yields varied from 70 to 96 %. 1,2,4-oxadiazoles were obtained under microwave irradiation in a single step in a 90-98 % yield at 160 °C in five minutes. 5-aminomethyl-3-aryl-1,2,4- oxadiazoles (5a-j) were obtained by Gabriel amine synthesis in two steps from corresponding 5-chloromethyl-3- aryl-1,2,4-oxadiazoles. Finally, twenty new urea (6a-j) and thiourea (7a-j) compounds bearing oxadiazole ring were synthesized by reacting 5-aminomethyl-3-aryl-1,2,4-oxadiazoles with phenyl isocyanate and isothiocyanate in tetrahydrofuran (THF) at room temperature with average yields (40-70%). Results and Discussions: An efficient and rapid method for the synthesis of 1,2,4-oxadiazoles from the reaction of amidoximes and acyl halides without using any coupling reagent under microwave irradiation has been developed, and twenty new urea/thiourea compounds bearing 1,2,4-oxadiazole ring have been synthesized and characterized. Conclusion: We have synthesized a new series of urea/thiourea derivatives bearing 1,2,4-oxadiazole ring. Also facile synthesis of 3,5-disubstituted 1,2,4-oxadiazoles from amidoximes and acyl chlorides under microwave irradiation was reported. The compounds were characterized using FTIR, 1H NMR, 13C NMR, and elemental analysis techniques.

Analogues of the cholecystokinin octapeptide modified in the central part of the molecule

1991 ◽  
Vol 56 (9) ◽  
pp. 1963-1970 ◽  
Author(s):  
Jan Hlaváček ◽  
Václav Čeřovský ◽  
Jana Pírková ◽  
Pavel Majer ◽  
Lenka Maletínská ◽  
...  
Keyword(s):  
Amino Acid ◽  
Biological Activities ◽  
Point Of View ◽  
Biologically Active ◽  
Side Chain ◽  
Amino Acid Residues ◽  
Cholecystokinin Octapeptide ◽  
Biological Tests ◽  
Biological Potency ◽  
Biologically Active Conformation

In a series of analogues of the cholecystokinin octapeptide (CCK-8) the amino acid residues were gradually modified by substituting Gly by Pro in position 4, Trp by His in position 5, Met by Cle in position 6, or the Gly residue was inserted between Tyr and Met in positions 2 and 3 of the peptide chain, and in the case of the cholecystokinin heptapeptide (CCK-7) the Met residues were substituted by Nle or Aib. These peptides were investigated from the point of view of their biological potency in the peripheral and central region. From the results of the biological tests it follows that the modifications carried out in these analogues and in their Nα-Boc derivatives mean a suppression of the investigated biological activities by 2-3 orders of magnitude (at a maximum dose of the tested substance of 2 . 10-2 mg per animal).This means that a disturbance of the assumed biologically active conformation of CCK-8, connected with a considerable decrease of the biological potency of the molecule, takes place not only after introduction of the side chain into its centre (substitution of Gly4), but also after the modification of the side chains of the amino acids or by extension of the backbone in further positions around this central amino acid.

scholarly journals 21,28-Epoxy-18β,21β-Dihydroxbaccharan-3-one and Other Terpenoids from the Liverwort Lepidozia Chordulifera T. Taylor

2008 ◽  
Vol 3 (11) ◽  
pp. 1934578X0800301
Author(s):  
Hildegard Zapp ◽  
Kerstin Orth ◽  
Josef Zapp ◽  
Joseph D. Connolly ◽  
Hans Becker
Keyword(s):  
Ursolic Acid ◽  
Betulinic Acid ◽  
Spectroscopic Properties ◽  
Betulonic Acid ◽  
Side Chain

A new triterpenoid, 21,28-epoxy-18β,21β-dihydroxybaccharan-3-one (1), with a spiro-hemiketal side-chain, has been isolated from the liverwort Lepidozia chordulifera. The plant also yielded (6S*, 7S*)-3-norhimachal-1-en-3-one (3), an epimer of a known norhimachalane, the rare 3β-hydroxy-22,23,24,25,26,27-hexanordammaran-20-one and the triterpenoids shoreic acid, taraxerol, betulinic acid, betulonic acid and ursolic acid. Their structures have been assigned on the basis of their spectroscopic properties.

Synthesis of biologically active derivatives of cyclopenteno[d]-selenazole and their thioanalogs

1982 ◽  
Vol 16 (6) ◽  
pp. 460-463
Author(s):  
A. A. Tsurkan ◽  
Z. F. Gromova ◽  
�. A. Rudzit ◽  
G. N. Neshchadit ◽  
D. A. Kulikova
Keyword(s):  
Biologically Active ◽  
Derivatives Of ◽  
Biologically Active Derivatives

Conformation–activity relationships and the mechanism of action of penicillin

1988 ◽  
Vol 66 (11) ◽  
pp. 2733-2750 ◽  
Author(s):  
Saul Wolfe ◽  
Kiyull Yang ◽  
Maged Khalil
Keyword(s):  
Conformational Analysis ◽  
Carbonyl Group ◽  
Active Site ◽  
Global Minimum ◽  
Peptide Bond ◽  
Biologically Active ◽  
Penicillin G ◽  
Side Chain ◽  
Geometrical Parameters ◽  
Carboxyl Group

Using the MMPEN parameters of Allinger's MMP2(85) force field, a conformational analysis has been performed on four biologically active penicillins; D-ampicillin, L-α-phenoxyethylpenicillin, penicillin G, and penicillin V, and on five biologically inactive or much less active penicillins: L-ampicillin, D-α-phenoxyethylpenicillin, N-methylpenicillin G, 6α-methylpenicillin G, and bisnorpenicillin G. Antibacterial activity is found to be associated with the existence of a global minimum having a compact structure, whose convex face is accessible to a penicillin binding protein (PBP), with the C3-carboxyl group and the side-chain N-H exposed on this face. Using the MMPEP parameters of MMP2(85), a conformational analysis has been performed on phenylacetyl-D-Ala-D-Ala-O−, a peptide model of the normal substrate of a PBP. Labischinski's global minimum has been reproduced, along with structures that correspond to Tipper and Strominger's proposal that the N4—C7 bond of a penicillin corresponds to the Ala–Ala peptide bond, and to Hasan's proposal that the N4—C5 bond of penicillin corresponds to the peptide bond. For both models, conformations of the peptide related to the pseudoaxial and pseudoequatorial conformations of the thiazolidine ring of penicillin G have been examined. It is concluded that penicillin is not a structural analog of the global minimum of the peptide; however, comparisons based on unbound conformations of PBP substrates are unable to determine which model is more appropriate, or which conformation of penicillin G is the biologically significant one. Using the ECEPP/MMPEP strategy, a model of the active site of a PBP has been obtained, following a search of 200,000 structures of the peptide Ac-NH-Val-Gly-Ser-Val-Thr-Lys-NH-Me. This peptide contains the sequence at the active site of a PBP of Streptomyces R61, for which it is also known that the C3-carboxyl group of penicillin binds to the ε-amino group of lysine, and the β-lactam reacts chemically with the serine OH. The lysine and serine side chains and the C-terminal carbonyl group are found to occupy the concave face of the active site model.A strategy for the docking of penicillins or peptides to this model, with full minimization of the conformational energies of the complexes, has been devised. All active penicillins bind through strong hydrogen bonds to the C3-carboxyl group and the side-chain N-H, and with a four-centered relationship between the O-H of serine and the (O)C-N of the β-lactam ring. The geometrical parameters of this relationship are reminiscent of those found in the gas phase transition state of neutral hydration of a carbonyl group. When the energies of formation and geometries of the pseudoaxial and pseudoequatorial penicillin G complexes are examined, there is now a clear preference for the binding of the pseudoaxial conformation, which is the global minimum of the uncomplexed penicillin in this case. A similar examination of the peptide complexes reveals that only the conformation of the peptide that corresponds to Tipper and Strominger's model, and is based on the pseudoaxial conformation of penicillin G, can form a complex with a geometry and energy comparable to those of a biologically active penicillin.

scholarly journals The molecular design of biologically active derivatives of N-phenylanthranilic acid

2018 ◽  
Vol 16 (1(61)) ◽  
pp. 49-53
Author(s):  
O. M. Svechnikova ◽  
S. V. Kolisnyk ◽  
O. F. Vinnyk ◽  
T. A. Kostina ◽  
T. V. Zhukova
Keyword(s):  
Molecular Design ◽  
Biologically Active ◽  
Derivatives Of ◽  
Biologically Active Derivatives

Microbial transformation of methyl cyperenoate by Cunninghamella elegans AS 3.2028 and the antithrombotic activities of its metabolites

RSC Advances ◽  
2016 ◽  
Vol 6 (113) ◽  
pp. 112712-112720 ◽  
Author(s):  
Jin-Long Tian ◽  
Yu Chen ◽  
Yu-Xi Wang ◽  
Xiao-Xiao Huang ◽  
Xue Sun ◽  
...  
Keyword(s):  
Structural Modification ◽  
Microbial Transformation ◽  
Natural Compounds ◽  
Biologically Active ◽  
Cunninghamella Elegans ◽  
Biologically Active Derivatives

Microbial transformation is a remarkable tool for the structural modification of bioactive natural compounds converting them into more valuable biologically active derivatives.

Abstract 40: Prothrombotic Role of Platelet Tlr2 in Hyperlipidemia

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Sudipta Biswas ◽  
Liang Xin ◽  
Soumya Panigrahi ◽  
Alejandro Zimman ◽  
Valentin Yakubenko ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Platelet Reactivity ◽  
Biological Activities ◽  
Biologically Active ◽  
Dependent Manner ◽  
Prothrombotic State ◽  
Downstream Signaling ◽  
Subsequent Activation ◽  
Biologically Active Derivatives

A prothrombotic state and increased platelet reactivity are common in hyperlipidemia and oxidative stress. Lipid peroxidation, a major consequence of oxidative stress, generates highly reactive products including hydroxy-w-oxoalkenoic acids that modify autologous proteins generating biologically active derivatives. Phosphatidylethanolamine, the second most abundant eukaryotic phospholipid can also be modified by hydroxy-w-oxoalkenoic acids. However, the conditions leading to accumulation of such derivatives in circulation and their biological activities remain poorly understood. We now show that carboxyalkylpyrrole-phosphatidylethanolamine derivatives (CAP-PE) accumulate in plasma of hyperlipidemic ApoE -/- mice. CAP-PE directly bind to TLR2 and induce platelet integrin alpha 2b beta 3 activation and P-selectin expression in TLR2 dependent manner. Platelet activation by CAP-PE includes assembly of TLR2/TLR1 receptor complex, induction of downstream signaling via MyD88/TIRAP, phosphorylation of IRAK4, and subsequent activation of TRAF6. This in turn activates the Src family kinases, Syk and PLC gamma 2 and platelet integrins. By intravital thrombosis studies we have demonstrated that CAP-PE accelerate thrombosis in TLR2 dependent manner. Furthermore, we demonstrate that TLR2 deficient mice are protected from accelerated thrombosis induced by hyperlipidemia. Taken together, our studies demonstrate a cross-talk between innate immunity and integrin activation signaling pathways in platelets and reveal that TLR2 plays a key role in platelet hyperreactivity and prothrombotic state in hyperlipidemia.

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