THIOAMIDE DERIVATIVES AS PROGESTERONE RECEPTOR MODULATORS. Abstract. Thioamide compounds, and specifically, thioamide pyrrole ... Thioamide compounds, and specifically, thioamide pyrrole compounds, and preparation thereof are provided. These. thioamide ... Methods for Preparing Thioamides. The thioamides of the present invention can be prepared by reacting a. compound containing a ... including thioamide compounds, and methods for preparing the same. The thioamide. compounds of the invention are useful for a ...
*  Thioamide synthesis by thionation
... corresponding thioamides in high yields. This method is easy, rapid, and high-yielding for the synthesis of thioamides from ... This method is easy, rapid, and high-yielding for the synthesis of thioamides from amides using an easily handled reagent.. B. ... A simple, efficient, and new method has been developed for the synthesis of thioamides from nitriles. The reaction of a variety ... In an efficient aqueous synthesis of thioamides from aldehydes and N-substituted formamides, sodium sulfide serves as the ...
*  Molecules | Free Full-Text | Synthesis and Antimicrobial Activity of Some New Thiadiazoles, Thioamides, 5-Arylazothiazoles and...
Keywords: hydrazonoyl halides; thioamides; 1,3,4-thiadiazoles; thiazoles; pyrimido[4,5-d][1,2,4]triazolo[4,3-a]pyrimidines; ... Synthesis and Antimicrobial Activity of Some New Thiadiazoles, Thioamides, 5-Arylazothiazoles and Pyrimido[4,5-d][1,2,4] ... Synthesis and Antimicrobial Activity of Some New Thiadiazoles, Thioamides, 5-Arylazothiazoles and Pyrimido[4,5-d][1,2,4] ... "Synthesis and Antimicrobial Activity of Some New Thiadiazoles, Thioamides, 5-Arylazothiazoles and Pyrimido[4,5-d][1,2,4] ...
*  Thioamide - Wikipedia
Thioamides or anti-thyroid drugs are also a class of drugs that are used to control thyrotoxicosis. Thioamides are typically ... Thioamides are also a class of drugs that are used to control thyrotoxicosis. Thioamides have been incorporated into peptides ... A thioamide (rarely, thionamide, but also known as thiourylenes) is a functional group with the general structure R-CS-NR′R″, ... One of the best-known thioamides is thioacetamide, which is used as a source of the sulfide ion and is a building block in ...
*  Congenital Hypothyroidism Differential Diagnoses
49] thioamides, [50, 30] or amiodarone, [51, 52] can cause a temporary hypothyroid state. Maternal antibodies to the TSH ...
*  PPT - Endocrine Physiology Thyroid PowerPoint Presentation - ID:3357360
Thioamides developed 1940's. *Concentrated in thyroid, inhibit biosynthesis by blocking organification of iodine ...
*  Patent search - Patent Attorneys - Patent Applications - Patent Sale
Arylalkyl(thio)amides. A compound which is selected from those of formula (I) : ##STR1## in which A, R.sub.1, R.sub.2, R.sub.3 ...
*  Molecules | Free Full-Text | Glucopyranosylidene-Spiro-Thiazolinones: Synthetic Studies and Determination of Absolute...
... formamides with thioamides furnished the corresponding glucopyranosylidene-spiro-thiazolin-4-one. While O-debenzoylations under ... Thioamides were purchased from Sigma-Aldrich (Steinheim, Germany). C-(2,3,4,6-tetra-O-benzoyl-1-bromo-β-d-glucopyranosyl) ... Reactions of O-peracylated C-(1-bromo-β-d-glucopyranosyl)formamides with thioamides furnished the corresponding ... and the corresponding thioamide (2.0 equiv.) were mixed in dry xylene (10 mL/mmol), in a sealed vial and the reaction mixture ...
*  Tuberculosis (TB) Treatment & Management: Approach Considerations, Treatment During Pregnancy, Treatment in Children
Tuberculosis (TB) (see the image below), a multisystemic disease with myriad presentations and manifestations, is the most common cause of infectious disease-related mortality worldwide. Although TB rates are decreasing in the United States, the disease is becoming more common in many parts of the world.
*  Myambutol - Doctor answers
thioamides: e.g. Ethionamide, prothionamide. also third line of medications. ...Read more ...
*  US Patent # 5,518,735. Meta-substituted phenylalanine derivatives - Patents.com
Thioamides (161, 162, Table 14) 0.8 g each of compounds 159 and 160 was converted into the thioamides 161 and 162 as described ... Thioamides (19-24,Table 3) 1.0 g of compounds 12-14 and 16-18 was dissolved in 20 ml of pyridine and 1.5 ml of TEA, H.sub.2 S ... Thioamides (61-71, Table 8) 1.0 g each of compounds 50-60 was dissolved in 20 ml of pyridine and 1.5 ml of TEA, H.sub.2 S was ... Thioamides (106, 107, Table 12) 1.0 g each of compounds 104 and 105 was converted and worked up as described in example 3 (61- ...
*  Patent US5612895 - Method of rational drug design based on ab initio computer simulation of ... - Google Patents
... thioamide)[CSNCH3] N-methyl thiopeptide[COO] Ester isostere[CH(OH)CH.sub.2 ] Hydroxyethylene Isostere[CHCH] Double Bond ... by looking at peptide mimics such as thioamides, N-methyl peptides and side chain modifications like the introduction of Aib ...
*  Biological | Department of Chemistry
Thioamide Quenching of Fluorescent Probes Through Photoinduced Electron Transfer: Mechanistic Studies and Applications ... Labeling Proteins with Fluorophore/Thioamide FRET Pairs by Combining Unnatural Amino Acid Mutagenesis and Native Chemical ...
*  Save Up To 80% | Synthroid Product Monograph Canada
... cramps thioamides evaluation places drugs quais cardiovasculares; risco aumentado de life; a administration; reasonsi doctor. ...
*  Heinrich Hühnerfuss : Current : Publications : Organic Chemistry : Universität Hamburg
Die elektrischen Momente N-alkyl- und N-aryl-substituierter Thioamide (Structure of thioamides and their derivatives. VIII. ... Dipole moments of N-alkyl- and N-aryl-substituted thioamides). Wolfgang Walter, Heinrich Hühnerfuss. Journal of Molecular ... Dipole moments of separated Z- and E-configurated thio amides. Wolfgang Walter, Heinrich Hühnerfuss. Tetrahedron Letters 22, ... Über die Struktur der Thioamide und ihrer Derivate, XXIV. Konfiguration und intramolekulare Wasserstoffbrücken in N- ...
*  Sohár Pál
Tautomeric equilibrium of isonicotinic acid thioamide derivatives. Acta Chim. Acad. Sci. Hung., 56, 25-37 (l968). ...
*  Patent US8097435 - Polynucleotides encoding long-acting growth hormone polypeptides and methods ... - Google Patents
... the polypeptide bonds are substituted by thioamide bonds (-CS-NH-). In some embodiments, the polypeptide bonds are substituted ...
*  Patent US5331573 - Method of design of compounds that mimic conformational features of selected ... - Google Patents
STR27##Peptide ##STR28##N-methyl peptide ##STR29##Thiopeptide (thioamide) ##STR30##N-methyl thiopeptide (thioamide) ##STR31## ... thioamide)[CSNCH3] N-methyl thiopeptide[COO] Ester isostere.[CH(OH)CH.sub.2 ] Hydroxyethylene Isostere[CHCH] Double Bond ... thioamide bond) bioisostere: ##STR13##(k) the N-methyl thiopeptide bioisostere: ##STR14##(l) the ester bioisostere: ##STR15##(m ... by looking at peptide mimics such as thioamides, N-methyl peptides and side chain modifications like the introduction of Aib ...
*  台式化学晶体学系统 | Rigaku
"Synthesis and characterization of tungsten carbonyl complexes containing thioamides." 2012, Ind. J. Chem., 53A, pp. 274-280. ...
*  PPT - BIOTRANSFORMATION PowerPoint Presentation - ID:1137530
Such a desulfuration reaction is commonly observed in thioamides such as thiopental. ...
*  Table of Contents - February 01, 1978, 6 (1) | Biochemical Society Transactions
Intermediate Metabolites of Thiocarbamides, Thioureylenes and Thioamides: Mechanism of Formation and Reactivity DANIEL M. ...
*  PPT - Abstract PowerPoint Presentation - ID:85468
EtaA also activates thiacetazone, thiobenzamide, and perhaps other thioamide drugs. Mutations in the drug-activating enzyme ...
*  Free Medical Flashcards about Ph Thyroid
pts with obstructions, malignancy, pregnancy in 2nd trimester, or those with contraindications to RAI or thioamides. ...

(1/36) MCC-134, a novel vascular relaxing agent, is an inverse agonist for the pancreatic-type ATP-sensitive K(+) channel.

The effects of a novel vasorelaxant agent, MCC-134 (1-[4-(1H-imidazol-1-yl)benzoyl]-N-methyl-cyclobutanecarbothioamide++ +), were examined on reconstituted ATP-sensitive K(+) (K(ATP)) channels, which are composed of an inwardly rectifying K(+) channel, Kir6.2, and three types of sulfonylurea receptors (SUR): SUR1, SUR2A, and SUR2B. Each type of K(ATP) channel was heterologously expressed in human embryonic kidney 293T cells. The expressed K(ATP) channel currents were measured with the whole-cell configuration of the patch-clamp method. MCC-134 activated the SUR2B/Kir6.2 channel, was a weak activator of the SUR2A/Kir6.2 channel, but did not activate the SUR1/Kir6.2 channel. MCC-134 suppressed SUR1/Kir6.2 channel currents that had been fully activated by either diazoxide or NaCN, whereas it did not affect the fully activated SUR2A/Kir6.2 or SUR2B/Kir6.2 channel currents. Thus, MCC-134, which is a relatively effective opener of the vascular smooth muscle type (SUR2B) of K(ATP) channel, is an antagonist of the pancreatic type (SUR1) of K(ATP) channel. Therefore, depending on the subtype of SUR, a pharmacological agent can cause either activation or inhibition of K(ATP) channel activity.  (+info)

(2/36) Ethionamide activation and sensitivity in multidrug-resistant Mycobacterium tuberculosis.

Ethionamide (ETA) is an important component of second-line therapy for the treatment of multidrug-resistant tuberculosis. Synthesis of radiolabeled ETA and an examination of drug metabolites formed by whole cells of Mycobacterium tuberculosis (MTb) have allowed us to demonstrate that ETA is activated by S-oxidation before interacting with its cellular target. ETA is metabolized by MTb to a 4-pyridylmethanol product remarkably similar in structure to that formed by the activation of isoniazid by the catalase-peroxidase KatG. We have demonstrated that overproduction of Rv3855 (EtaR), a putative regulatory protein from MTb, confers ETA resistance whereas overproduction of an adjacent, clustered monooxygenase (Rv3854c, EtaA) confers ETA hypersensitivity. Production of EtaA appears to be negatively regulated by EtaR and correlates directly with [(14)C]ETA metabolism, suggesting that EtaA is the activating enzyme responsible for thioamide oxidation and subsequent toxicity. Coding sequence mutations in EtaA were found in 11 of 11 multidrug-resistant MTb patient isolates from Cape Town, South Africa. These isolates showed broad cross-resistance to thiocarbonyl containing drugs including ETA, thiacetazone, and thiocarlide.  (+info)

(3/36) MCC-134, a single pharmacophore, opens surface ATP-sensitive potassium channels, blocks mitochondrial ATP-sensitive potassium channels, and suppresses preconditioning.

BACKGROUND: MCC-134 (1-[4-(H-imidazol-1-yl)benzoyl]-N-methylcyclobutane-carbothioamide), a newly developed analog of aprikalim, opens surface smooth muscle-type ATP-sensitive potassium (K(ATP)) channels but inhibits pancreatic K(ATP) channels. However, the effects of MCC-134 on cardiac surface K(ATP) channels and mitochondrial K(ATP) (mitoK(ATP)) channels are unknown. A mixed agonist/blocker with differential effects on the two channel types would help to clarify the role of K(ATP) channels in cardioprotection. METHODS AND RESULTS: To index mitoK(ATP) channels, we measured mitochondrial flavoprotein fluorescence in rabbit ventricular myocytes. MCC-134 alone had little effect on basal flavoprotein fluorescence. However, MCC-134 inhibited diazoxide-induced flavoprotein oxidation in a dose-dependent manner (EC(50)=27 micro mol/L). When ATP was included in the pipette solution, MCC-134 slowly activated surface K(ATP) currents with some delay (>10 minutes). These results indicate that MCC-134 is a mitoK(ATP) channel inhibitor and a surface K(ATP) channel opener in native cardiac cells. In cell-pelleting ischemia assays, coapplication of MCC-134 with diazoxide abolished the cardioprotective effect of diazoxide, whereas MCC-134 alone did not alter cell death. These results were reproducible in both rabbit and mouse myocytes. MCC-134 also attenuated the effect of ischemic preconditioning against myocardial infarction in mice, consistent with the results of cell-pelleting ischemia assays. CONCLUSIONS: A single drug, MCC-134, opens surface K(ATP) channels but blocks mitoK(ATP) channels; the fact that this drug inhibits preconditioning reaffirms the primacy of mitoK(ATP) rather than surface K(ATP), channels in the mechanism of cardioprotection.  (+info)

(4/36) Functional involvement of sulphonylurea receptor (SUR) type 1 and 2B in the activity of pig urethral ATP-sensitive K+ channels.

(1) We have investigated the possible roles of sulphonylurea receptor (SUR) type 1 and 2B in the activity of pig urethral ATP-sensitive K(+) channels (K(ATP) channels) by use of patch-clamp and reverse transcriptase-polymerase chain reaction (RT-PCR) techniques. (2) In voltage-clamp experiments, not only diazoxide, a SUR1 and weak SUR2B activator, but also pinacidil, a selective SUR2 activator, caused an inward current at a holding potential of -50 mV in symmetrical 140 mM K(+) conditions. (3) Gliclazide (+info)

(5/36) MCC-134, a blocker of mitochondrial and opener of sarcolemmal ATP-sensitive K+ channels, abrogates cardioprotective effects of chronic hypoxia.

We examined the effect of MCC-134, a novel inhibitor of mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channels and activator of sarcolemmal ATP-sensitive K(+) (sarcK(ATP)) channels, on cardioprotection conferred by adaptation to chronic hypoxia. Adult male Wistar rats were exposed to intermittent hypobaric hypoxia (7000 m, 8 h/day, 5-6 weeks) and susceptibility of their hearts to ventricular arrhythmias and myocardial infarction was evaluated in anesthetized open-chest animals subjected to 20-min coronary artery occlusion and 3-h reperfusion on the day after the last hypoxic exposure. MCC-134 was administered intravenously 10 min before ischemia and 5 min before reperfusion in a total dose of 0.3 mg/kg or 3 mg/kg divided into two equal boluses. The infarct size (tetrazolium staining) was reduced from 59.2+/-4.4 % of the area at risk in normoxic controls to 43.2+/-3.3 % in the chronically hypoxic group. Chronic hypoxia decreased the reperfusion arrhythmia score from 2.4+/-0.5 in normoxic animals to 0.7+/-0.5. Both doses of MCC-134 completely abolished the antiarrhythmic protection (score 2.4+/-0.7 and 2.5+/-0.5, respectively) but only the high dose blocked the infarct size-limiting effect of chronic hypoxia (54.2+/-3.7 %). MCC-134 had no effect in the normoxic group. These results support the view that the opening of mitoKATP channels but not sarcKATP channels plays a crucial role in the mechanism by which chronic hypoxia improves cardiac tolerance to ischemia/reperfusion injury.  (+info)

(6/36) Designing amino acid residues with single-conformations.

Drug design can benefit from the use of non-coded amino acids, such as alpha-amino isobutyric acids (Aib) or sarcosine (N-methyl-glycine). Non-coded amino acids can confer resistance to enzymatic degradation and increase the conformational stability of the peptides. We have simulated the conformational effects of combining N-methylation, bulky groups on the Calpha atom and/or thioamides using the class II CFF91 force field and our thioamide force field parameters. Although single amino acid substitutions (e.g. Aib) can restrict the available conformations, they do not necessarily lead to unique conformers, however, we predict that some of the amino acids described in this report will fold to a single phi, psi conformation (e.g. N-methylated and thioamide penicillamine). Several other amino acid/thiopeptide combinations were designed, which are predicted to prefer only two conformations. Novel amino acids of this type should prove useful for designing peptides with defined conformations.  (+info)

(7/36) Metabolism of thioamides by Ralstonia pickettii TA.

Information on bacterial thioamide metabolism has focused on transformation of the antituberculosis drug ethionamide and related compounds by Mycobacterium tuberculosis. To study this metabolism more generally, a bacterium that grew using thioacetamide as the sole nitrogen source was isolated via enrichment culture. The bacterium was identified as Ralstonia pickettii and designated strain TA. Cells grown on thioacetamide also transformed other thioamide compounds. Transformation of the thioamides tested was dependent on oxygen. During thioamide degradation, sulfur was detected in the medium at the oxidation level of sulfite, further suggesting an oxygenase mechanism. R. pickettii TA did not grow on thiobenzamide as a nitrogen source, but resting cells converted thiobenzamide to benzamide, with thiobenzamide S-oxide and benzonitrile detected as intermediates. Thioacetamide S-oxide was detected as an intermediate during thioacetamide degradation, but the only accumulating metabolite of thioacetamide was identified as 3,5-dimethyl-1,2,4-thiadiazole, a compound shown to derive from spontaneous reaction of thioacetamide and oxygenated thioacetamide species. This dead-end metabolite accounted for only ca. 12% of the metabolized thioacetamide. Neither acetonitrile nor acetamide was detected during thioacetamide degradation, but R. pickettii grew on both compounds as nitrogen and carbon sources. It is proposed that R. pickettii TA degrades thioamides via a mechanism involving consecutive oxygenations of the thioamide sulfur atom.  (+info)

(8/36) Covalent modification of microsomal lipids by thiobenzamide metabolites in vivo.

Thiobenzamide (TB) is hepatotoxic in rats causing centrolobular necrosis, steatosis, cholestasis, and hyperbilirubinemia. It serves as a model compound for a number of thiocarbonyl compounds that undergo oxidative bioactivation to chemically reactive metabolites. The hepatotoxicity of TB is strongly dependent on the electronic character of substituents in the meta- and para-positions, with Hammett rho values ranging from -4 to -2. On the other hand, ortho substituents that hinder nucleophilic addition to the benzylic carbon of S-oxidized TB metabolites abrogate the toxicity and protein covalent binding of TB. This strong linkage between the chemistry of TB and its metabolites and their toxicity suggests that this model is a good one for probing the overall mechanism of chemically induced biological responses. While investigating the protein covalent binding of TB metabolites, we noticed an unusually large amount of radioactivity associated with the lipid fraction of rat liver microsomes. Thin-layer chromatography showed that most of the radioactivity was contained in a single spot more polar than the neutral lipids but less polar than the phospholipid fractions. Mass spectral analyses aided by the use of synthetic standards identified the material as N-benzimidoyl derivatives of typical microsomal phosphatidylethanolamine (PE) lipids. Quantitative analysis indicated that up to 25% of total microsomal PE became modified within 5 h after a hepatotoxic dose of TB. Further studies will be required to determine the contribution of lipid modification to the hepatotoxicity of TB.  (+info)

  • group
  • A thioamide (rarely, thionamide, but also known as thiourylenes) is a functional group with the general structure R-CS-NR′R″, where R, R′, and R″ are organic groups. (wikipedia.org)