Thioamide Derivatives Research Articles

Crystal structure and conformational analysis of 2-thioamide derivatives of thiazole

Molecular and crystal structures of two thioamide derivatives of thiazole were analysed based on X-ray diffraction data and results obtained from quantum chemistry (QC) and molecular mechanics (MM) calculations. It was found that within the thiazole rings, the S1–C2 bond appeared to be more affected by the action of two-substituents rather than the C2–N3 bonds. The ab initio calculations showed that the C2–C6 bond connecting the thioamide group with thiazole is shortened when both the systems are coplanar, but a conjugation is relatively weak and does not enforce such conformation. The QC and MM calculations indicated that the particular parts of the thioamide group may exist in two conformations. However, relatively high energy barrier excluded the possibility of change of one conformation into the other by simple rotation around the C2–C6 or C6–N8 bonds. Moreover, the MM calculations explained that steric hindrance is not the main reason of energy barrier for suggested rotations. The observed cis–trans conformation is stabilised by intramolecular hydrogen bonds.

Isoxazolylthioamides as potential immunosuppressants a combinatorial chemistry approach.

A library of thioamide derivatives of leflunomide 1a and of its bioactive metabolite 1b has been synthesised on solid phase. Thus, para-substituted phenylacetic acids were coupled to TentaGel and were subsequently reacted with aromatic isothiocyanates. Treatment of the resulting enaminothioamides with hydroxylamine led to their simultaneous cyclisation and cleavage from the resin affording 2-25. Their in vitro profiling demonstrated that the amide-thioamide isologous substitution was detrimental of the biological activity.

Specific binding of Cu 2+ and Ni 2+ ions by thioamide analogs of tetraalanine

Thioamide derivatives of short peptides are much more efficient ligands for Cu 2+ and Ni 2+ ions than their parent analogs. The most effective is the insertion of the thiocarbonyl group into the first, second, or third peptide linkage. In all of these cases, the sulfur atom is involved directly in metal ion binding, leading to the formation of very stable complexes. In all cases discussed, sulfur binding does not prevent an amide nitrogen deprotonation and its coordination to metal ion in basic solutions, although at the region close to physiological pH, sulfur is the basic donor for both Cu 2+ and Ni 2+ ions.

Cation complexation by chemically modified calixarenes. Part 10. Thioamide derivatives of p-tert-butylcalix[4]-, [5]- and [6]-arenes with selectivity for copper, silver, cadmium and lead. X-Ray molecular structures of calix[4]arene thioamide–lead(II) and calix[4]arene amide–copper(II) complexes

Download options Please wait... Article information DOI https://doi.org/10.1039/A605417J Article type Paper Download Citation J. Chem. Soc., Perkin Trans. 2, 1997, 575-580 BibTex EndNote MEDLINE ProCite ReferenceManager RefWorks RIS Permissions Request permissions Cation complexation by chemically modified calixarenes. Part 10. Thioamide derivatives of p-tert-butylcalix[4]-, [5]- and [6]-arenes with selectivity for copper, silver, cadmium and lead. X-Ray molecular structures of calix[4]arene thioamide–lead(II) and calix[4]arene amide–copper(II) complexes F. Arnaud-Neu, G. Barrett, D. Corry, S. Cremin, G. Ferguson, J. F. Gallagher, S. J. Harris, M. Anthony McKervey and M. Schwing‐Weill, J. Chem. Soc., Perkin Trans. 2, 1997, 575 DOI: 10.1039/A605417J To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page. If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given. If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page. Read more about how to correctly acknowledge RSC content. Search articles by author Françoise Arnaud-Neu Geraldine Barrett Denis Corry Suzanne Cremin George Ferguson John F. Gallagher Stephen J. Harris M. Anthony McKervey Marie‐Jose Schwing‐Weill

Novel carbamates as potent histamine H3 receptor antagonists with high in vitro and oral in vivo activity.

The known histamine H3 receptor antagonists burimamide, thioperamide, clobenpropit, and a related homohistamine thioamide derivative were taken as templates in search for new leads. Novel histamine H3 receptor antagonists structurally described as carbamate derivatives of 3-(1H-imidazol-4-yl)propanol were prepared in high yields by treatment of the alcohol with corresponding isocyanates or carbamoyl chlorides and investigated for their H3 receptor antagonist activity. Different chain lengths and various substituents possessing different electronic and steric parameters were introduced and structure-activity relationships established. In different functional tests, the new antagonists showed high H3 receptor antagonist potencies in vitro (-log Ki values of 6.4-8.4) at synaptosomes of rat cerebral cortex and low activities at histamine H1 and H2 receptor subtypes. They were also screened for their central in vivo activity in mice after peroral administration. The most promising compounds (2, 16, 19) showed ED(50) values of about 1-2 mg/kg and thus are potential drugs for the therapy of H3 receptor dependent diseases. Some of the novel carbamate derivatives are H3 receptor selective compounds with high in vitro and in vivo activity.

Anion selectivities of membranes based on HgII complexes of calix[4]arene derivatives

AbstractAnion selectivities of membranes based on cationic complexes of thioamide calix[4]arene derivatives are presented for the first time. HgII complexes of thioamide derivatives of calix[4]arene were applied to design perchlorate‐selective ISEs which show linear responses in the range 1–5 of pClO4 with a slope of 56.5mV decade −1. The highest selectivity over other anions (except iodides) and optimum performances of electrodes were obtained for a 0.01 M solution of HgII as an internal electrolyte.

Synthesis and evaluation of certain thiosangivamycin analogs as potential inhibitors of cell proliferation and human cytomegalovirus.

A series of 7-substituted 4-aminopyrrolo[2,3-d]pyrimidines related to the nucleosides toyocamycin and thiosangivamycin were prepared and tested for their activity against human cytomegalovirus (HCMV). The nucleosides 2'-deoxytoyocamycin (1), xylo-toyocamycin (2), 3'-deoxytoyocamycin (3), 2',3'-dideoxy-2',3'-didehydrotoyocamycin (4), 2',3'-dideoxytoyocamycin (5), ara-toyocamycin (6), 2'-deoxy-2'-amino-ara-toyocamycin (7), and 5'-deoxytoyocamycin (8) were treated with sodium hydrogen sulfide generated in situ to afford the corresponding thiosangivamycin analogs (9-16). The cyano derivatives 1-8 were synthesized by modifications of literature procedures. All of the thioamide derivatives (9-16) were active against HCMV with IC50's ranging from 0.5 to 6 microM. Most also were active against herpes simplex virus type 1 (HSV-1) but at higher concentrations. The antiviral activity was not completely separated from cytotoxicity in two human cell lines. The antiproliferative activity was strongly influenced by the position of the modification on the carbohydrate moiety. The xylosyl and 3'-deoxy derivatives were significantly more potent than those with modifications at the 2', 5', or 2',3' position(s). Interestingly, 5'-deoxythiosangivamycin (16) possessed both antiviral and antiproliferative activity suggesting that phosphorylation of the 5'-hydroxyl may not be required for these compounds to have biological activity.

The evidence for the competitive adsorption of inhibitors

The effects of two thioamide derivatives on the corrosion rate of mild steel in 2 M H 2SO 4 has been investigated at various concentrations of dimethylformamide (DMF) at 30°C. The thioamides under consideration inhibited the corrosion rate significantly. At a certain DMF concentration, the protection efficiency of the thioamide increases with increasing concentration. The protection efficiency of these thioamides was decreased with increasing the concentration of the DMF in the corrosive medium. It was also found that the thioamide molecules are more adsorbed than the DMF molecules. The results obtained were analysed and discussed on the basis of the competitive adsorption.

Patent Evaluation: Indole Excitatory Amino Acid Antagonists

SummaryNovelty: Novel urea, thiourea, carbamate, sulphonylurea, sulphonamide, amide and thioamide derivatives of 2-carboxyindoles are claimed. They are said to block glutamic and aspartic acid receptors and may be useful for the treatment of neurodegenerative disorders, including cerebrovascular disorders, as well as schizophrenia, epilepsy, and as analgesics and anxiolytics.Biology: No specific biological data are presented. The compounds are said to antagonize the strychnine-insensitive glycine receptor and hence are NMDA receptor antagonists. They also have activity as AMPA and kainate receptor antagonists.Chemistry: Eighteen compounds are specifically claimed. Preparation is described in five schemes and two examples. Methyl-4,6-dichloro-3-[2-[[(phenylamino)carbonyl]amino]ethyl]-1H-indole-2-carboxylate is a specifically claimed compound.Structure:

Synthesis of teleocidins A, B and their congeners. Part 1. An efficient synthesis method of N-(7-Alkyl-4-indolyl)- N-methyl-L-valine esters, essential intermediates for teleocidin synthesis

Details of the synthesis method of N-[7-(3,7-dimethyl-1,6-octadien-3-yl)-4-indolyl]-N-methyl-L-valine esters 19 and 20, essential precursors for the tumor promoters lyngbyatoxin A (= teleocidin A-1) ( 2) and teleocidin A-2 ( 3) are presented. Key reaction steps are i) introduction of the linalyl side chain into 12 to form 18 and ii) successive indole cyclization of 21 by way of thioamide derivatives 22.

Structure-activity relationship of 3-nitro-2,4,6-trihydroxybenzamide derivatives in photosynthetic electron transport inhibition.

Quantitative structure—activity relationship (QSAR) analyses of the 3-nitro-2,4,6-trihydroxybenzamide and thioamide derivatives in the inhibition of photosynthetic electron transport (PET) revealed that the activity would depend largely on the overall lipophilicity of the molecules, and their mode of inhibition would be similar to those of the 3-acyl analogues. However, some of the compounds had higher pI50 values than those estimated by the equations obtained from the QSAR analysis, indicating that those compounds may bind to the site in a more specific manner than the others would do.

ChemInform Abstract: Functional Monomers and Polymers. Part 189. Nonlinear Optical Effect of Thioamide Derivatives.

ChemInform Abstract: Functional Monomers and Polymers. Part 189. Nonlinear Optical Effect of Thioamide Derivatives.

Synthesis, cytotoxicity, and antiviral activity of certain 7-[(2-hydroxyethoxy)methyl]pyrrolo[2,3-d]pyrimidine nucleosides related to toyocamycin and sangivamycin

A number of 7-[(2-hydroxyethoxy)methyl]pyrrolo[2,3-d]pyrimidine derivatives related to the nucleoside antibiotics toyocamycin and sangivamycin were prepared and tested for their biological activity. Treatment of the sodium salt of 4-amino-6-bromo-5-cyanopyrrolo[2,3-d]pyrimidine (1) with (2-acetoxyethoxy)methyl bromide (2) afforded a mixture of 4-amino-6-bromo-5-cyano-7-[(2-acetoxyethoxy)methyl]pyrrolo[2,3-d] pyrimidine (3) and the corresponding N1 isomer. Debromination of this mixture gave the corresponding 4-amino-5-cyano-7-[(2-acetoxyethoxy)-methyl]pyrrolo[2,3-d]pyrimidi ne (4) and 4-amino-5-cyano-1-[(2-acetoxyethoxy)methyl]pyrrolo[2,3-d]pyrimidin e (5). Deacetylation of 4 and 5 furnished 4-amino-5-cyano-7-[(2-hydroxyethoxy)methyl]pyrrolo[2,3-d]pyrimidine (6) and the corresponding N1 isomer (7), respectively. The sites of attachment for the acyclic moiety for 6 and 7 were assigned on the basis of UV spectral studies as well as 13C NMR spectroscopy. Conventional functional group transformation of 6 provided a number of novel 5-substituted derivatives (8-10), including the sangivamycin derivative 8. The methyl formimidate derivative 10 was converted to the thioamide derivative 11 and the carbohydrazide derivative 12. Compounds 6 and 8-12 were tested for cytotoxicity to L1210 murine leukemic cells in vitro. None of these compounds caused significant inhibition of cell growth. Evaluation of compounds 4 and 6-12 for activity against human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1) revealed that only the thioamide (11) was active. It inhibited HCMV but not HSV-1 at concentrations producing only slight cytotoxicity in human foreskin fibroblasts (HFF cells) and KB cells.

ChemInform Abstract: Synthesis and Antisecretory and Antiulcer Activities of Derivatives and Analogues of 2‐(2‐Pyridyl)tetrahydrothiophene‐2‐carbothioamide.

AbstractThe pyridines (VI), which are substituted by six‐membered heterocyclic rings, are prepared from the chloromethylpyridine hydrochloride (I) or the pyridine aldehyde (VII) and transformed into the thioamide derivatives (XII).

Improved and large-scale synthesis of certain glycosyl cyanides. Synthesis of 2,5-anhydro-5-thio- d-allononitrile

The first synthesis of 2,5-anhydro-5-thio- d-allononitrile starting with l-lyxose, via a trifluoromethanesulfonic ester intermediate, has been accomplished. Methods have been developed to achieve a large-scale synthesis of 3,4,5,7-tetra- O-acetyl-2,6-anhydro- d- glycero- d- talo-heptononitrile ( 5). An improved procedure has been developed to synthesize 2,5-anhydro-3,4,6-tri- O-benzoyl- d-gulononitrile ( 9). The structures of 5 and the thioamide derivative from 9, 2,5-anhydro-3,4,6-tri- O-benzoyl- d-gulonothioamide, were confirmed by X-ray crystallographic analysis.

Studies on 3-aminoindazoles. I. Synthesis of 1- or 3-(substituted 3-amino)indazoles.

Various 1-or 3- (substituted 3-amino) indazoles with anti-inflammatory effects were synthesized by means of three methods, as follows. 1) Reactions of 3-aminoindazole (1) with acrylamides (2a and 2b) gave amide derivatives (3a and 3b) having a carbamoylethylamino group at the 3-position of 3a and 3b. The amide derivatives (3a and 3b) were converted to thioamide derivatives (4a and 4b) by treatment with P2S5. Electrode reduction of 4a and 4b gave 3- (substituted 3-amino) indazoles (5a and 5b). 2) The reaction of 1 with aminoalkyl. halides (6c-r) gave 3- (substituted 3-amino) indazoles (5c-r) and 1- (substituted 3-amino) indazoles (7c-r) in a ratio of 3 : 1. 3) The reaction of 1 with phthalic anhydride (8) gave 3-phthalimidoindazole (9). Compound 9 was allowed to react with aminoalkyl halides (6o-r) to give 1-substituted derivatives (10s-z) of 9, Reactions of 10a-z with hydrazine hydrate gave 1- (substituted 3-amino) indazole derivatives (5s-z).

Anomalous Witting Reaction of Aldonic Thioamide Derivatives. A New Mode of Thiazole Ring Formation

Observation d'un nouveau mode de formation du cycle thiazole et d'une elimination inattendue du groupe acetoxy dans la reaction des acetylamides des acides penta-O-acetyl D-thio-1galactonique et -D-thio-1gluconique avec le triphenylphosphoranylideneacetate d'ethyle: formation de diacetoxy-1',5' pentadiene-1',3' yl-2 methyl-4 thiazolecarboxylate-5 d'ethyle

ChemInform Abstract: Formation of Thioamide Derivatives from Reactions of Isothiocyanates with Oxazol‐2‐amines.

AbstractDie Reaktion der Oxazole (III) (Darstellung siehe Formelschema) mit den Isothiocyanaten (V) führt nicht nur zu den erwarteten Thioharnstoff‐Derivaten (VI); in Abhängigkeit von den jeweiligen Substituenten werden auch größere Mengen der Thioamide (VII) erhalten [mit einem Überschuß (V) entstehen die disubstituierten Produkte (VIII) ‐ die analoge Verbindung wird auch bei äquimolarer Umsetzung zu 26% neben (VIc) und (VIIc) isoliert].

Formation of Thioamide Derivatives from Reactions of Isothiocyanates with Oxazol-2-amines

4-Substituted oxazol-2-amines react with isothiocyanates to give products having a thioamide function at C5. The reaction is considered to be an electrophilic process in competition with the usual reaction of the amino group with the isothiocyanate . The nature of the isothiocyanate and the type of substituent at C4 affect the amount of the thioamide product formed. Some chemical properties of the thioamides are also investigated.

3‐α‐Bromacetyl‐cumarine als Synthesebausteine für Heterocyclisch substituierte Cumarine

3‐α‐Bromacetyl‐coumarines as Synthones for Heterocyclic Substituted Coumarines3‐α‐Bromacetyl‐coumarines 2 react easily and in high yields with thiourea and thioamide derivatives 3 and 5, resp., to 4‐coumar‐3′‐yl‐thiazoles 4 and 6, resp., as well as with N,N‐disubstituted thioamides 11 and N,N,N′,N′‐tetraalkylthiourea 12 to 5‐coumar‐3′‐yl‐oxathioliumsalts 13 and 14, respectively. In a two‐step reaction 2 can be transformed by reaction with aniline 17 to 4‐coumar‐3′‐yl‐imidazoles 21 and 5‐coumar‐3′‐yl‐oxazoliumsalts 22, resp., via aminoketone intermediates 18.