Structure-Activity Relationship of Insecticidal Steroids. III. Δ4,7-6-Ketosteroids

The toxicity of steroids 1-11 for colorado beetle (Leptinotarsa decemlineata Say.) larvae was studied by contact-intestinal treatment. Active insect-growth regulators were found among the studied compounds.     

Structure-Activity Relationship of Insecticidal Steroids. IV. 3β-Chlorosubstituted Derivatives of Cholesterol and β-Sitosterol

The toxicity of 3-chlorosteroids 1-8 for colorado beetle (Leptinotarsa decemlineata Say.) larvae was studied by a contact-intestinal method. The most active insect growth and development regulators of the studied compounds are 3-chlorocholest-5-ene (1a), 3-chloro-5,6-diol 6-formate (3b), 3-chloro-7-hydroxy-6-ketone (4a), and 3-chloro-5-bromo-⁴-6-ketone (8).     

Structure-Activity Relationship for Insecticidal Steroids. VI. 5,6-Disubstituted β-Sitosterols

The toxicity of steroids 1-14 for Colorado beetle (Leptinotarsa decemlineata Say.) larvae was studied by a contact-intestinal method. The most active are 3,5-dihydroxy-6-ketone 4a and 5-hydroxy-3,6-diketone 8a.     

Structure-Activity Relationship of Insecticidal Steroids. VII. C-7-Oxidized β-Sitosterols and Stigmasterols

The toxicity of 7-substituted steroids 1-8 for Colorado beetle (Leptinotarsa decemlineata Say.) larvae was studied. The most active compound is 3-acetoxy-⁵-7-ketone 2b.     

Three-dimensional Quantitative Structure-Activity Relationship Analyses of a Series of Butenolide ETA Antagonists

Two kinds of Three-dimensional Quantitative Structure-activity Relationship(3D-QSAR) methods,comparative molecular filed analysis(CoMFA) and comparative molecular similarity indices analysis (CoMSIA) ,were applied to analyze the structure-activity relationship of a series of 63 butenolide ETA selective antagonists with respect to their inhibition against human ETA receptor,The CoMFA and CoMSIA models were developed for the conceivable alignment of the molecules based on a template structure from the crystallized data.The statistical results from the initial orientation of the aligned molecules show that the 3D-QSAR model from CoMFA(q^2=0.543) is obviously superior to that from the conventional CoMSIA(q^2=0.407).In order to refine the model,all-space search (ASS) was applied to minimize the field sampling process.By rotating and translating the molecular aggregate within the grid systematically,all the possible samplings of the molecular fields were tested and subsequently the one with the highest q^2 was picked out .The comparison of the sensitivity of CoMFA and CoMSIA to different space orientation shows that the CoMFA q^2 values are more sensitive to the translations and rotations of the aligned molecules with respect to the lattice than those of CoMSIA.The best CoMFA model from ASS was further refined by the region focused technique.The high quality of the best model is indicated by the high corss-validated correlation and the prediction on the external test set.The CoMFA coefficient contour plots identify several key features that explain the wide range of activities,which may help us to design new effective ETA selective antagonists.     

Studies on Steroids. CLXXXIL. Determination of 6β-Hydroxycortisol in Urine by High-Performance Liquid Chromatography with Fluorescence Detection

Abstract

A new sensitive method for the determination of 6β-hydroxycortisol in urine by high-performance liquid chromatography with fluorescence detection has been developed. 6β-Hydroxycortisol and its C-6 epimer (internal standard) were transformed quantitatively into the 21-(9-anthroyl) derivatives when treated with 9-anthroyl nitrile in the presence of triethylamine in acetonitrile. The resulting fluorescent esters were readily separated on a Cosmosil SSL column using ethyl acetate/hexane (2:1) as a mobile phase with a detection limit of 25 pg. The efficient clean-up was achieved by the combined use of Bond Elut and Clin Elut cartridges. The present method is applicable to the quantification of 6β-hydroxycortiol in human urine with satisfactory accuracy and precision.     

β-Chlorocinnamonitriles in a New Synthesis of 3-Functionally Substituted 6-amino-1,2-Dihydropyridin-2-ones

β-Chlorocinnamonitriles react with methylene-active compounds containing N-substituted carboxamide group in DMSO solution in the presence of potassium hydroxide, forming 3-functionally substituted 1,2-dihydropyridin-2-ones.     

Solvent Effects on the Structure-Activity Relationship of Phenytoin-like Anticonvulsant Drugs

The absorption spectra of nine compounds structurally related to phenytoin (5,5-diphenylhydantoin) were recorded in twelve solvents over the range of 200 to 400 nm. The effects of solvent dipolarity/polarizability and solvent/solute hydrogen bonding interactions were analyzed by means of the linear solvation energy relationship (LSER) concept proposed by Kamlet and Taft. The lipophilic activity of the investigated hydantoins was estimated by calculation of their log ₁₀ P values. The calculated values of log ₁₀ P were correlated with the ratio of the contributions of specific and non-specific solute/solvent interactions. The correlation equations were combined with the corresponding ED₅₀ values to generate new equations that demonstrate exact relationship between solute/solvent interactions and the structure-activity parameters.     

Structure-Activity Relationship of Hetarylpropylguanidines Aiming at the Development of Selective Histamine Receptor Ligands†

New classes of alkylated hetarylpropylguanidines with different functionality and variation in spacer length were synthesized to determine their behavior at the four histamine receptor (H₁R, H₂R, H₃R, H₄R) subtypes. Alkylated guanidines with different terminal functional groups and varied basicity, like amine, guanidine and urea were developed, based on the lead structure SK&F 91486 ( 2 ). Furthermore, heteroatomic exchange at the guanidine structure of 2 led to simple analogues of the lead compound. Radioassays at all histamine receptor subtypes were accomplished, as well as organ bath studies at the guinea pig (gp) ileum (gpH₁R) and right atrium (gpH₂R). Ligands with terminal functionalization led to, partially, highly affine and potent structures (two digit nanomolar), which showed up a bad selectivity profile within the histamine receptor family. While the benzoylurea derivative 144 demonstrated a preference towards the human (h) H₃R, S-methylisothiourea analogue 143 obtained high affinity at the hH₄R (pK_i=8.14) with moderate selectivity. The molecular basis of the latter finding was supported by computational studies.     

Synthesis of 5α-Iodo-6-one Steroids

Abstract: The synthesis of 5-iodo-5α-cholestan-6-one (6), its 3β-acetoxy-(7) and 3β-chloro-(8) analogues, 3β-acetoxy-5-iodo-5α-stigmastan-6-one (9) and its 3β-chloro-(10) analogue by the reacion of silver chromate-iodine and pyridine with the corresponding steroidal olefins (1-5) is described. The structures of these products have been established on the basis of their elemental, analytical and spectral data.     

Organocatalytic asymmetric Michael addition of 1-acetylindolin-3-ones to α,β-unsaturated aldehydes: synthesis of 2-substituted indolin-3-ones

A highly efficient asymmetric Michael addition of 1-acetylindolin-3-ones to α,β-unsaturated aldehydes is developed to afford 2-substituted indolin-3-one derivatives in high yields (up to 94%) with good stereoselectivities (up to 11:1 dr and 96% ee). The Michael adducts can be transformed into substituted cyclopentyl[b]indoline compounds conveniently without racemization.     

Artificial Neural Networks Applied to the Quantitative Structure-Activity Relationship Study of Para-substituted Phenols

The artificial neural network (ANN) model with back-propagation of error is used to study the quantitative structure-activity relationship of para-substituted phenol derivatives between the biological activity and the physicochemical property parameters. Network parameters are optimized, and an empirical rule for dynamically adjusting the network's learning rate is proposed to improve the network's performance. The results showthat the three-layer ANN model gives satisfactory performance, with f(x)=1/(1+exp(-x)) as the network node's input-output transformation function and the number of hidden nodes 10. The network gives the mean square error (rose) of 0.036 when predicting the biological activity of 26 para-substituted phenol derivatives. This result compares favourably with that obtained by the conventional methods.     

Synthesis and stereochemistry of chiral azetidin-2-ones and azetidine-2-thiones. 3. Stereodirected construction of theβ-lactam fragment of the thienamycin molecule

It has been shown possible to introduce an -hydroxyethyl group trans-stereospecifically into position 3 of 4-methyl-1-(-methyl-benzl)azetidin-2-one. The stereochemistry of the asymmetric centers C₍₃₎, C₍₃₎, and C₍₄₎ of the diastereoisomers of the 3--hydroxyethyl derivative obtained in larger amount and of the corresponding three adjacent chiral centers C₍₈₎, C₍₆₎, and C₍₅₎ in thienamycin are the same.For part 2 see [1].M. V. Lomonosov Moscow State University, Moscow, 119899. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 254–257, February, 1995. Original article submitted December 14, 1994.     

Studies of 2-Substituted 1,3-Oxazolidin-5-ones and 1,3-Oxazinan-6-ones as Precursors for the Synthesis of N-Alkyl-β-Amino Acids

1,3-Oxazolidin-5-ones and 1,3-oxazinan-6-ones have been shown to be useful precursors for the synthesis of N-methyl α- and β-amino acids, respectively. The methodology has now been expanded to allow for the synthesis of N-alkyl-β-amino acids.     

Study on 3D Quantitative Structure-Activity Relationships of Taxoid

IntroductionTaxoll'](Paclitaxel)(1)andtaxotere['1(Docetaxel)(2)exhibitingexeellentantitUmoractivityhaVebeenusedCUrrentlinclinicaltrialforthetreatInntofawidevarietyofcarcinomas.Nowadays.taxolisconsideredbyInancltalcaloncologiStSasoneofthemoStprondsinganticanceragenLbuitalsohassomedrawacksuchasundesiredsideeffCCt5andmulhtrigresiStance.Therefore,todeVloPnoveltaxolanalogUeschendStShavcarriedollextenshestudiesonStZUCtUr-activityrelationship(SAR).ttispaperintendedto~out3DQSAnanalsisfort…     

Synthesis of 6-chloronicotinates of steroidal 3β,5α,6β-triols and 3β,5-dihydroxy-6-ketones

New esters of 3β,5α,6β-trihydroxysteroids and 3β,5-dihydroxy-6-ketosteroids containing 6-chloropyridine groups characteristic of the alkaloid epibatidine were synthesized by acylation with 6-chloronicotinoylchloride. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 175-179, March-April, 2009.     

A novel scalable and stereospecific synthesis of 3α- and 3β-amino-5α-androstan-17-ones and 3α- and 3β-amino-5α-pregnan-20-ones

A novel scalable stereoselective synthesis of 3α- and 3β-amino-5α-androstan-17-ones and 3α- and 3β-amino-5α-pregnan-20-ones has been developed using phthalimide based Mitsunobu chemistry. In all four cases, the products were isolated as single diastereoisomers in high chemical yield and purity without the need for chromatography at any stage in their syntheses.     

Synthesis and Insecticidal Activity of 5-C-Phosphonate Derivatives of Aryl-1-thio-β-D-ribofuranoside

Russian Journal of General Chemistry - The method of synthesis of phosphonate derivatives of β-D-ribofuranoside was developed. Biological tests showed that prepared compounds possess high...     

Studies on the Structure-Activity Relationship of p-Substituted Thiobenzanilides as Extractant for Pd( Ⅱ )

Introduction The metal extraction is a process of complex formation by organic ligands with metal ions or corresponding ionic groups, that is to say, it is a multicomponent coordination process in the heterogeneous phase system. The property of extraction is chiefly dependent on the stability of metal complexes, which is closely related to both the structure of ligands and the nature of metal ions. Therefore, the physicochemical behaviour of the substituent in the ligand will influence the extractive ability of the extractant for a certain     

Structural Dependence of Insecticidal Activity of 5α-Hydroxy-Δ7-6-ketosteroids

The toxicity of 5-hydroxy- ⁷ -6-ketosteroids for colorado beetleLeptinotarsa decemlineataSay. larvae was studied by topical and GI administration.