Showing papers on "Substituent published in 1986"

Cl(-)-channel blockers in the thick ascending limb of the loop of Henle. Structure activity relationship.

Abstract: On the basis of our findings with diphenylamine-2-carboxylate [5] we have searched for compounds which possess an even higher affinity for the Cl−-channels in the basolateral membrane of the thick ascending limb of the loop of Henle. To quantitiy the inhibitory potency, we performed measurements of the equivalent short circuit current, corresponding to the secondary active transport of Cl− [8] and measurements of the voltage across the basolateral membrane. A survey of 219 compounds reveals that relatively simple modifications in the structure of diphenylamine-2-carboxylate led to very potent blockers such as 5-nitro-2-(3-phenylpropylamino)-benzoate which inhibits the short circuit current half maximally (IC50) at 8·10−8 mol/l. A comparison of the structural formula and the respective IC50 values leads to several empirical conclusions: 1. The potent compounds are lipophilic due to the apolar residue (e.g. phenyl- or cycloalkyl group). Replacing this part of the molecule by an aliphatic chain (up to 4 C-atoms) leads to inactive compounds. 2. Most of the inhibitors are secondary amines. Linking other than with-NH- between the phenyl ring and the benzoic acid results in inactive compounds. Tertiary amines, such as in case of 2-(N,N-diphenylamine) benzoic acid or N-methylphenylaminebenzoic acid are poorly active. 3. The carboxylate group of the benzoate moiety must be in ortho position to the amino group. 4. Introduction of substituents into the benzoate moiety e.g.-NO2 (in meta position to the carboxylate group), or by-Cl (in para position to the carboxylate group) results in an increase of inhibitory potency. 5. A-CH2-,-C2H4-,-C3H6-) spacer between the amino bridge and the phenyl ring increases the affinity for the Cl−-channel by several orders of magnitude. The above described structure activity relationship renders it likely that these chloride channel blockers possess several sites of interaction: The negatively charged carboxylate group, the secondary amine group which probably carries a positive partial charge, and for the very potent agents (nos. 130, 143, 144, and 145) an additional negative partial charge at the respective-Cl or-NO2 substituent. Finally, also an apolar interaction with an cycloalkyl or cycloaryl residue seems to be required, and this site of interaction has a defined spacing from the secondary amino nitrogen.

Thermal imaging method

Abstract: A thermal imaging method is provided which comprises heating imagewise a di- or triarylmethane compound possessing within its di- or triarylmethane structure an aryl group substituted in the ortho position to the meso carbon atom with a moiety ring-closed on the meso carbon atom directly through a nitrogen atom, which nitrogen atom is also bound to a group with a masked acyl substituent that undergoes fragmentation upon heating to liberate the acyl group for effecting intramolecular acylation of said nitrogen atom to form a new group in the ortho position whereby the di- or triarylmethane compound is rendered colored in an imagewise pattern corresponding to said imagewise heating.

Polyphosphazenes with etheric side groups: prospective biomedical and solid electrolyte polymers

Abstract: : Poly(organophosphazenes) have been synthesized with alkyl-ether-alkoxy groups attached to the phosphorus atoms of the skeleton. These species are water-stable and either water-soluble or hydrophilic polymers. Specific members of this series form complexes with metal salts, which are excellent solid electrolyte materials. Mixed substituent polymers with hydrophobic trifluoroethoxy and alkyl-ether alkoxy side groups have also been prepared and these are of interest as membranes and biomedical materials. (Author)

[dialkylcarbamoylmethyl] phosphine oxides on their extraction capacity and selectivity

Abstract: Extraction of Am ( III), Pu( IV), U( VI) from nitric acid solutions by dialkyl ( aryl) [ dialkylcarbamoylmethyl] phosphine oxides of different structures has been studied. The nature of substituents at phosphorus and nitrogen atoms and in methylene bridge affects extraction capacity, solubility and selectivity of reagents. The increase in extraction capacity of reagents with respect to Am, U, Pu and decrease in solubility and selectivity at consecutive replacement of alkyl-( or alkoxy-) radicals at phosphorus atom by phenyl ones was found. The advantage of reagents usage with two different radicals one of which is phenyl at phosphorus atom has been shown. The nature of substituent at nitrogen atom affect solubility but does not practically affect extraction capacity of reagent.

UV-absorbing condensation polymeric compositions and products therefrom

Abstract: Polyester compositions useful in formed articles such as beverage bottles and having condensation reacted therein at least one UV-absorbing compound of formula (I), wherein X is hydroxyl, carboxy, carbalkoxy, substituted carbalkoxy, or acyloxy; Y is cyano, carbamyl, substituted carbamyl, aryl, acyl, alkylsulfonyl, substituted alkylsulfonyl, phenylsulfonyl, or substituted phenylsulfonyl; R is selected from -alkylene-O-alkylene-, -alkylene-S-alkylene-, -alkylene-N(-SO2alkyl)-alkylene-, straight or branched chain alkylene or such alkylene substituted with an X substituent; and R1 is hydrogen or 1-3 groups selected from alkyl, alkoxy and halogen.

Effects of substituent-induced strain on the electronic structure of polydiacetylenes

Abstract: The valence effective Hamiltonian technique (VEH), and modified neglect of differential overlap (MNDO) calculations are used to study the influence of strain induced by side chains on the geometry of polydiacetylene backbones and the resulting polymer band structure, band gap, and ionization potential. Simulations of strain effects on the polymer backbone yield variations in optical properties which are similar to those observed experimentally during thermochromic phase changes in urethane‐substituted polydiacetylenes. Our results suggest that these changes in optical properties are related to strain at points of substituent attachment and not to fundamental changes in the backbone geometry such as an acetylenic‐to‐butatrienic transformation.

Steric and electronic substituent effects on the carbon-carbon bond

Abstract: Correlations of various indices of the stability and reactivity of carbon-centered radicals with ESR hyperfine splitting constants have been examined. For a large number of monoand disubstituted radicals there is a moderately good linear correlation of R-proton hyperfine splitting constants (a(HR)) with radical stabilization enthalpies (RSE) and with BDE(C-H), the C-H bond dissociation energies for the corresponding parent compounds determined from thermodynamic and kinetic studies of C-C homolysis reactions. There is a similarly satisfactory linear correlation of a(HR) with BDE(C-H) determined by Bordwell’s electrochemical and acidity function method. In all cases the correlations fail for nonplanar radicals. As expected, â-proton hyperfine splitting constants (a(HâMe)) for radicals with a freely rotating methyl substituent are less sensitive to deviations from planarity and give better linear correlations with RSE and BDE(C-H). The correlations cover a range of more than 20 kcal/mol and are reliable predictors of RSE and BDE(C-H) for a variety of radicals including captodative species. However, the correlations fail for significantly nonplanar radicals and for radicals with cyclic delocalized systems, e.g., cyclopentadienyl. The ratio a(HâMe)/ a(HR) for suitably substituted radicals provides an index of pyramidalization and allows one to decide for which compounds values of RSE and BDE(C-H) can be confidently estimated.

Heterocyclic oxophthalazinyl acetic acids

Abstract: A heterocyclic oxophthalazinyl acetic acid having aldose reductast inhibitory activity of the formula ##STR1## wherein X is oxygen or sulfur; Z is a covalent bond, O, S, NH or CH2 or CHR5 Z is vinyl; R1 is hydroxy, or a prodrug group; R2 is a heterocyclic group, R3 and R4 are hydrogen or the same or a different substituent, and R5 is hydrogen, methyl or trifluoromethyl The pharmaceutically acceptable acid addition salts of the above compounds wherein R1 is di(C1 -C4)alkylamino or (C1 -C4)alkoxy substituted by N-morpholino or di(C1 -C4)alkylamino and the pharmaceutically active base addition salts of the above compounds wherein R1 is hydroxy are also aldose reductase inhibitors

Substituent effects on neutral and ionized carbon-carbon and carbon-oxygen double bonds and their implications for the stability order of keto/enol tautomers

Abstract: On etudie par des calculs d'orbitales moleculaires ab initio les effets des substituants sur des molecules d'ethylene ou de formaldehyde monosubstituees, neutres ou cationiques

The relationship between reductive dehalogenation and other aryl substituent removal reactions catalyzed by anaerobes

Abstract: Anaerobic bacteria are known to catalyze the removal of a variety of aromatic substituents, including -COOH, -OH, -OCH3, -CH3, and halogens. We investigated whether reductive dehalogenation was related to other types of aryl substituent removal reactions. A dehalogenating bacterial consortium was tested for its ability to use benzoic acids substituted in the 3 position with the functional groups listed above. In addition to dehalogenation, the enrichment (as well as the dehalogenating pure culture) was able to transform 3-methoxybenzoic acid to 3-hydroxybenzoic acid without a lag. This reaction exhibited Michaelis-Menten kinetics with an apparent Km of 5 μM. To test the hypothesis that the two reactions were related, we developed a mathematical model incorporating a competitive inhibition term to account for the influence of one substrate on the degradation of the other. However, experimental evidence showed no significant difference in the rates of 3-chlorobenzoic acid or 3-methoxybenzoic acid degradation in either the presence or absence of the other substrate. In addition, an anaerobe known to degrade methoxylated aromatic substrates was not able to transform chlorinated analogues. Finally, the isolated dechlorinating organism, strain DCB-1 was able to transform 3-methoxybenzoic acid in the presence of 1 mM thiosulfate, but the dehalogenation of 3-chlorobenzoic acid under these conditions was completely inhibited. Therefore, it is unlikely that a relationship exists between dehalogenation and other anaerobic aromatic substituent removal mechanisms.

13C‐NMR spectral studies on the distribution of substituents in some cellulose derivatives

Abstract: Spectres RMN du carbone 13 de trityle cellulose, tosyle cellulose, cellulose S-methyl xanthate et cellulose formiate dans DMSO-d 6 analyses a 50,4 MHz

Synthesis and estrogen receptor binding of 6,7-dihydro-8-phenyl-9-[4-[2-(dimethylamino)ethoxy]phenyl]-5H-benzocycloheptene, a nonisomerizable analogue of tamoxifen. X-ray crystallographic studies

Abstract: Syntheses of the title compound (5), a novel nonisomerizable antiestrogen containing a seven-membered ring, are described. In one method, 6,7-dihydro-9-(4-methoxyphenyl)-5H-benzocycloheptene was brominated at the 8-position and the bromine displaced by phenylzinc chloride with palladium complex catalysis to introduce the 8-phenyl substituent. Alternatively, benzosuberone was alpha phenylated with tricarbonyl(eta 6-fluorobenzene)chromium (0) and the product treated with the appropriate aryllithium reagent to introduce the 9-aryl group last. The relative binding affinities for estrogen receptors in cell cytosol and whole cells and growth inhibitory activity against the MCF-7 human breast tumor cell line in vitro were for 5 comparable to those of tamoxifen (1) and the corresponding six-membered ring analogue (7). X-ray crystallographic analyses of 10 and 15, which are methoxy derivatives of 5 and 7, show that in some respects 5 bears a closer structural relationship to tamoxifen than does nafoxidine (3) or 7. Thus, the aromatic ring, which is fused in the cyclic analogues, was twisted 64, 45, 20, and 19 degrees out of the plane of the double bond for 1, 10, 3, and 15, respectively. Low-temperature NMR studies indicate that 5 is more rigid than tamoxifen; interconversion between enantiomeric conformers is slow on the NMR time scale at -75 degrees C.

Extreme pressure additives for lubricants

Abstract: Lubricant additives are provided which provide extreme pressure properties without the need for lead compositions. The extreme pressure additive system includes a dithio carbamate substituent, an organic copper substituent; and an phosphate substituent which are provided in a three component or two component system.

Synthesis and calcium channel antagonist activity of dialkyl 1,4-dihydro-2,6-dimethyl-4-(pyridinyl)-3,5-pyridinedicarboxylates.

Abstract: The Hantzsch condensation of alkyl acetoacetates 3 with methyl 3-aminocrotonate (4) and pyridinecarboxaldehydes 5 afforded the unsymmetrical alkyl methyl 1,4-dihydro-2,6-dimethyl-4-(pyridinyl)-3,5-pyridinedicarboxylates 6, whereas condensation of 3 with 5 and ammonium hydroxide gave the symmetrical dialkyl 1,4-dihydro-2,6-dimethyl-4-(pyridinyl)-3,5-pyridinedicarboxylates 7. The calcium channel antagonist activities of disubstituted 1,4-dihydro-3,5-pyridinedicarboxylates 6,7, and 9 were determined with use of the muscarinic-receptor-mediated Ca2+-dependent contraction of guinea pig ileal longitudinal smooth muscle. The relative potency order for isomeric pyridinyl analogues 6 and 7 was 2-pyridinyl greater than 3-pyridinyl greater than 4-pyridinyl. Increasing the size of the alkyl ester substituents enhanced activity. Compounds having nonidentical ester substituents were more potent than those having identical ester substituents. Replacement of the C-3 and/or C-5 ester substituent(s) by a cyano substituent(s) decreased activity significantly. An approximate 1:1 correlation between the IC50 value for inhibition of [3H]nitrendipine binding and inhibition of the tonic component of the muscarinic-induced contractile response was observed. The test results suggest that a 4-(pyridinyl) substituent is bioisosteric with a 4-(nitrophenyl) substituent on a 1,4-dihydropyridine ring system where o-, m-, and p-nitrophenyl are bioisosteric with 2-pyridinyl, 3-pyridinyl, and 4-pyridinyl, respectively.

Soluble and biodegradable polyamino acid activated for bonding of biologically active compound

Abstract: The invention pertains to copolymers activated for bonding of biologically active compounds and to a method for preparation thereof. Soluble and biodegradable copolymers activated for bonding of biologically active compounds which have their main chain formed from units of aspartic acid or glutamic acid, or both, or also from units of other amino acids, according to the general formula I ##STR1## where n is 1 or 2, m is 1 or 2, a+b+c is 100, a is 0.5 to 100, b is 0 to 99.5, c is 0 to 80; the substituent R 1 is --NH--NH 2 , --N.tbd.N or ##STR2## where x is 2 to 6, R 2 is --NH(CH 2 ) x OH where x=2 to 6; and R 3 is methyl, 2-propyl, 2-methylpropyl, butyl, 2-butyl, benzyl or 4-hydroxybenzyl, and the molecular weight is 5,000 to 1,000,000.

Novel catalyst compositions and process for copolymerizing ethene and carbon monoxide

Abstract: A B S T R A C T NOVEL CATALYST COMPOSITIONS AND PROCESS FOR COPOLYMERIZING ETHENE AND CARBON MONOXIDE Novel catalyst compositions for copolymerizing ethene and carbon monoxide, characterized in that they comprise: a) a compound of a Group VIII metal chosen from palladium, cobalt and nickel, b) an anion of an acid with a pKa of less than 6, and c) a bidentate ligand of the general formula R1R2-M-R-M-R3R4, wherein M represents phosphorous, arsenic or antimony, R is a bivalent organic bridging group containing two or three carbon atoms in the bridge and R1, R2, R3 and R4 represent hydro-carbon groups which may or may not be substituted with polar groups, on the understanding that at least one hydrogen atom in at least one of the groups R1, R2, R3 and R4 is substituted with a polar substituent.

Molecular mechanics and molecular shape. Part 4. Size, shape, and steric parameters

Abstract: To deal with steric effects of substituents on reaction rates, two types of descriptor are proposed. Shape is characterised by the ratio (G) of the substituent's surface area to its volume. Bulk is characterised by the volume (Va) of the portion of the substituent that is within 0.3 nm of the reaction centre. For alkyl substituents, rate constants for several series of reactions (including the classical series, acid hydrolysis of the esters RCO2Et) correlate fairly well with Va and G. Taft's steric parameters (Es) correlate less well. Values of Es for hetero-substituents are found to be contaminated by non-steric factors. It is possible to construe whether the contaminant acts to hinder or to enhance reaction.

Methoden zur Darstellung von 4-Azido-2(1H)-chinolonen

Abstract: 4-Hydroxy-2-quinolones1 are generally found to be converted to the 4-azidocompounds3 via the 4-chloroquinolones2, the 4-tosyloxyquinolones6, or the 4-aminoquinolones4, respectively. Choice of the reaction conditions and yields depend on the substituent in position 3 of the quinoline nucleus. For comparison the O-analogous coumarin derivatives9 have been studied to give the 4-azidoderivatives11 via the 4-chlorocoumarins10.

Substituted di-t-butylphenols

Abstract: Novel compounds which are 2,6-di-t-butylphenols substituted on the 4 position by an anilino group, which anilino group is substituted by a carboxyl substituent, a tetrazolyl substituent or an N-methyltetrazolyl substituent, are useful antiallergic agents. Pharmaceutical compositions containing and pharmacological methods of using such compounds are also disclosed, as are synthetic intermediates for preparing such compounds. Certain of the synthetic intermediates also exhibit useful antiallergic activity.

Barriers to rotation adjacent to double bonds. 2. n-Propyl versus isopropyl groups

Abstract: The barriers to rotation about the C-C bonds adjacent to the carbonyl groups of isobutyraldehyde, methyl isopropyl ketone, and isobutyric acid were calculated. The 3-21G basis set was used for the geometry optimizations, and the 6-31G* basis set was used to obtain the energies. The differences in energy between R = n-propyl and isopropyl also were calculated and reproduced the observed energy differences. Whereas the more branched isomer had a significantly lower energy for the aldehydes and acids, the difference in energy was very small with the ketones. The components of the barrier are discussed. The traditional decomposition into 1-, 2-, and 3-fold terms does not provide a useful representation of the interactions which are involved. Besides the 3-fold barrier observed with compounds having R = CH3, the major contributions to the barrier arise from the stabilizing interaction between an alkyl group and the carbonyl (- 1 kcal/mol) and from the repulsive interaction between one of the methyls of the isopropyl group and the other substituent at the carbonyl. A hydroxy group (Le., in a carboxylic acid) leads to a significantly smaller steric interaction than found with a methyl group (i.e,, in a methyl alkyl ketone).

α-Substituted toluenes as carbon acids: structural reorganization and free energy changes upon carbanion formation

Abstract: 1 H, 13C, and 19F n.m.r. data of benzyl carbanions PhCH–X (VI) and p-FC6H4CH–X have been found to be appropriate monitors for probing the structural reorganization undergone by the precursor carbon acids PhCH2X upon deprotonation. Even in the highly dissociating Me2SO as solvent benzyl carbanions exhibit ion-pairing phenomena: these have been proved by the effect exerted by the [2.2.1] cryptand on 13C shifts, and by changing the countercation. 13C Parameters of benzyl anions (VI) provide experimental access to negative π charge density maps through equation (1). It is shown that the solvent greatly assists delocalization of the negative charge in these systems. The substituent-induced variations of the para-monitor in the anions are linearly related to pKa variations of the precursor acids. Carbanions appear to belong to two different classes depending on the mechanism with which the charge stabilizes the system. Thus, in enolate and nitronate anions the stabilization is provided by extensive charge transfer from the carbanion carbon, in contrast to carbanions activated by the third-row elements (P,S) and by the cyano group. Substituent electron demands qx(the amount of charge transferred to the activating substituent X) govern the charge distribution in the anions in related ways, the acidity of the precursor acids PhCH2X, and the sensitivities of these latter to remote aryl substitution.