Showing papers on "Substituent published in 1992"

The first regioregular head-to-tail poly(3-hexylthiophene-2,5-diyl) and a regiorandom isopolymer: nickel versus palladium catalysis of 2(5)-bromo-5(2)-(bromozincio)-3-hexylthiophene polymerization

Abstract: Recent research on poly(alkylthiophenes) (PAT) has concentrated on the regularity and structure of the polymer chain of PAT. The 3-alkyl substituent in a thiophene ring can be incorporated into a polymer chain with two different regioregularities: head-to-tail (HT) and head-to-head (HH). Head-to-head linkages can cause defects in the polymer chain. The highest regioregularity reported to date for HT-PAT is 91% (usually 50-60% HT regioregularity). The authors report herein a new and facile synthesis which leads to the first completely head-to-tail regioregular poly(3-hexylthiophene 2,5-diyl) (HT-PHT) and an alternative synthesis which yields an unusual regiorandom PHT with almost equal distribution of different linkages in the polymer chain. Both polymers have been characterized by NMR, IR, elemental analysis, GPC (gel-permeation chromatography), and UV-vis. 11 refs., 2 figs., 1 tab.

Derivatized oligonucleotides having improved uptake and other properties

Abstract: Linked nucleosides having at least one functionalized nucleoside that bears a substituent such as a steroid molecule, a reporter molecule, a non-aromatic lipophilic molecule, a reporter enzyme, a peptide, a protein, a water soluble vitamin, a lipid soluble vitamin, an RNA cleaving complex, a metal chelator, a porphyrin, an alkylator, a pyrene, a hybrid photonuclease/intercalator, or an aryl azide photo-crosslinking agent exhibit increased cellular uptake and other properties. The substituent can be attached at the 2′-position of the functionalized nucleoside via a linking group. If at least a portion of the remaining liked nucleosides are 2′-deoxy-2′-fluoro, 2′-O-methoxy, 2′-O-ethoxy, 2′-O-propoxy, 2′-O-aminoalkoxy or 2′-O-allyloxy nucleosides, the substituent can be attached via a linking group at any of the 3′ or the 5′ positions of the nucleoside or on the heterocyclic base of the nucleoside or on the inter-nucleotide linkage linking the nucleoside to an adjacent nucleoside.

Synthesis and antiviral activity of a series of HIV-1 protease inhibitors with functionality tethered to the P1 or P1' phenyl substituents: X-ray crystal structure assisted design.

Abstract: By tethering of a polar hydrophilic group to the P1 or P1' substituent of a Phe-based hydroxyethylene isostere, the antiviral potency of a series of HIV protease inhibitors was improved. The optimum enhancement of anti-HIV activity was observed with the 4-morpholinylethoxy substituent. The substituent effect is consistent with a model derived from inhibitor docked in the crystal structure of the native enzyme. An X-ray crystal structure of the inhibited enzyme determined to 2.25 A verifies the modeling predictions.

Novel non-nucleoside inhibitors of HIV-1 reverse transcriptase. 2. Tricyclic pyridobenzoxazepinones and dibenzoxazepinones.

Abstract: Dibenz[b,f][1,4]oxazepin-11(10H)-ones (III), pyrido[2,3-b][1,4]benzoxazepin-6(5H)-ones (IV), and pyrido[2,3-b]- [1,5]benzoxazepin-5(6H)-ones (V) were found to inhibit human immunodeficiency virus type 1 reverse transcriptase with IC50 values as low as 19 nM. A-ring substitution has a profound effect on activity, with appropriate substituents at the positions ortho and para to the lactam nitrogen providing dramatically enhanced potency. Substitution in the C-ring is generally neutral or detrimental to activity. Although a C-ring amino substituent at the position meta to the lactam carbonyl is generally beneficial to activity, it has essentially no effect when the A-ring is optimally substituted. Like the dipyridodiazepinone nevirapine, compounds III-V are specific for HIV-1 RT, exhibiting no inhibitory activity against HIV-2 RT or other virial reverse transcriptase enzymes.

Cavitands as versatile molecular receptors

Abstract: X-ray crystal structure of 3-2PhF and 1 H NMR complexation studies in solution reveal the strong tendency of cavitand 3 to selectively bind aromatic guests in organic solution. The association constants (K s ) for eight 1:1 caviplexes formed in acetone-d 6 were determined. The solvation effect is largely responsible for the relatively low K a values obeserved.The orientation assumed by the guests inside the cavity is determined by dipole-dipole interactions between the host and the guest;additional CH 3 -π interactions are present in the case of 3.3(CH 3 ) 2 CO.The modification of the structure of 3 by introducing a suitable and furtherly modifiable substituent allowed the synthesis of optically pure chiral cavitand 5. 1 H NMR complexation studies of 5 in acetone-d 6 reveal that the CH 2 OH group perching on the cavity rim affects the selectivity but not the orientation of the included aromatic guests for the 1:1 caviplexes formed

Surface effects in photochemistry: an in situ cylindrical internal reflection-Fourier transform infrared investigation of the effect of ring substituents on chemisorption onto titania ceramic membranes

Abstract: The role of phenyl substituent groups in the formation of surface complexes at the surface of titanium dioxide semiconducting ceramic membranes is investigated with cylindrical internal reflection-Fourier transform infrared (CIR-FTIR) spectroscopy. The CIR-FTIR study presented in this article allows for direct comparison between adsorption mechanisms derived from vibrational spectra at the semiconductor-liquid interface and surface structures influencing aqueous heterogeneous photochemical reactions. Therefore, chemisorption mechanisms we derived for benzoic acid and its substituted compounds could be used for the prediction of their photodegradation behavior. This IR investigation confirms that no adsorption is detectable on the rutile phase of TiO2, thus excluding the role of 5-fold coordinated Ti cations in the adsorption mechanisms. We observed that, for anatase surface, isolated carboxyl groups do not generate a favorable adsorption equilibrium (e.g., benzoic acid). It is proposed that amino and hydroxyl groups substituted in ortho position to a carboxyl group (e.g., salicylic, 3-chlorosalicylic, and anthranilic acids) may lead to a mononuclear bidentate coordination complex with 4-fold coordinated surface titanium cations. The higher adsorption level observed for phthalic acid is interpreted as due to its possibility of adsorbing on a greater number of anatase surface sites, by forming two different surface complexes, involving one or both carboxyl groups. A relationship between change in vibrational spectra of the carboxyl group, for substituted benzoic derivatives, and acidic dissociation constants is presented.

Polymers biodegradable or bioerodiable into amino acids

Abstract: The invention presents a biodegradable polyester polymer comprising ##STR1## wherein: n=number of repeating polymer units of the formula shown; p=0 or 1, 0 indicating the absence of the subscripted constituent; q=0 or 1, 0 indicating the absence of the subscripted constituent; when p=0, 1=1; when p=1, 1=0; R 1 =a divalent organic substituent which can include oxygen, nitrogen or sulfur atoms as part of the polymer backbone; R 2 =a divalent organic substituent which can include oxygen, nitrogen or sulfur atoms as part of the polymer backbone; R 3 and R 4 are each independently hydrogen or an organic substituent or together form a divalent ring which may be optionally substituted; and each R is independently H, alkyl, alkenyl or alkynyl, aryl, aralkyl, cycloalkyl, cycloalkenyl or cycloalkynyl, all optionally substituted with F, Cl, Br, I, CN or NO 2 .

Substituent effects. 4. Nature of substituent effects at carbonyl groups

Abstract: The effect of substituents on the properties of acyl derivatives has been examined. Geometry optimizations were carried out at the MP2/6-31G * theoretical level, followed by calculation of energies at the MP3/6-311++G ** level. The energies were studied via isodamic reactions with ethane leading to acetone and a methyl derivative. The calculated energy changes were in good agreement with the available experimental data and showed that groups more electronegative than carbon stabilize a carbonyl group more than methyl, whereas the opposite is true with the more electropositive groups

Synthesis, characterization, and 1/T1 NMRD profiles of gadolinium(III) complexes of monoamide derivatives of DOTA-like ligands. X-ray structure of the 10-[2-[[2-hydroxy-1-(hydroxymethyl)ethyl]amino]-1-[(phenylmethoxy)methyl]-2-oxoethyl]-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid-gadolinium(III) complex

Abstract: The synthesis of two novel DOTA-like ligands (5a,b) containing a polyhydroxy(benzyloxy)propionamide substituent and their Gd(III) complexes (6a,b) is reported. Debenzylation by hydrogenolysis of the latter complexes in the presence of Pd/C leads to the corresponding derivatives (7a,b) with a primary alcoholic function. Water proton relaxation rates of aqueous solutions of 6a,b and 7a,b strongly suggest that these complexes contain only one water molecule in their inner coordination sphere, as was previously found for the parent DOTA complex

Hydroformylation process and bisphosphite compound used therein

Abstract: A hydroformylation process for preparing a hydroformylated product by reacting an olefinic compound with hydrogen and carbon monoxide in the presence of a Group VIII metal catalyst, in the reaction of which there is present a phosphite compound having the formula (I), A¹⁅O-P(OR¹)(OR²)]n (I) wherein R¹ and R² are respectively an aromatic hydrocarbon group which may be the same or different and the aromatic hydrocarbon group has at least a hydrocarbon group on a carbon atom adjacent to a carbon atom bonded with an oxygen atom as a substituent; A¹ is an n-valent organic group having an aliphatic hydrocarbon group, a cycloaliphatic hydrocarbon group or an aromatic hydrocarbon group bonded with an adjacent oxygen atom, which may respectively have a substituent; n is an integer of from 2 to 4; and the respective ⁅O-P(OR¹)(OR²)] group may be the same or different.

Complete Thermodynamic Description of H‐Bonding in the Framework of Multiplicative Approach

Abstract: A complete thermodynamic description of H-bonding for drug design is proposed. The approach is based on applicability of multiplicative principle to enthalpy (ΔH) and free energy (ΔG) of complex formation by means of Ed(Ea) and Cd(Ca) factors: Where Ed(Ea) and Cd(Ca) characterize the proton donor (acceptor) ability of compounds. The estimation of E and C values for 163 proton donors and 195 proton acceptors was done, making it possible to predict ΔH and ΔG for 31785 reactions. The comparison of these data with experimental ones for 936 reactions was carried out: The substituent effect on H-bonding ability of compounds was considered. It was established that varying of substituents at active sites can alter its proton donor (acceptor) properties over a wide range of Ed(E3, cd(ca) with sufficient overlap between values of factors corresponding to different types of active sites. One could propose this approach to be applied to quantitative estimation of thermodynamic functions of H-bonding in substrate-receptor complexes; also for QSAR modelling, where E and C or its linear combination might be used as molecular descriptors characterizing quantitatively the relative H-bonding ability of biologically active compounds. The second type of applications is used by the authors when modelling QSAR by means of the program package CLARAS (Classification and Recognition of Active Structures).

Kinetics of hydride transfer reactions from hydrosilanes to carbenium ions. Substituent effects in silicenium ions

Abstract: Rates of hydride transfer from hydrosilanes HSiR 1 R 2 R 3 with widely varying substitution to para-substituted diarylcarbenium ions have been measured in dichloromethane solution. Generally the reactions follow a second-order rate law, -d[Ar 2 CH + ]/dt=k 2 [Ar 2 CH + ] [HSiR 1 R 2 R 3 ], and k 2 is independent of the degree of ion-pairing and the nature of the counterion (exceptions are reported). The reaction rates are almost independent of solvent polarity

Aromatic amidine derivatives and salts thereof

Abstract: An anticoagulant agent which comprises, as an active ingredient, an aromatic amidine derivative represented by the following general formula (1) or a salt thereof: ##STR1## wherein the group represented by ##STR2## is a group selected from indolyl, benzofuranyl, benzothienyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, naphthyl, tetrahydronaphthyl and indanyl; X is a single bond, an oxygen atom, a sulfur atom or a carbonyl group; and Y is a saturated or unsaturated 5- or 6-membered heterocyclic moiety or cyclic hydrocarbon moiety optionally having a substituent group, an amino group optionally having a substituent group or an aminoalkyl group optionally having a substituent group. The inventive compound has a high anticoagulant capacity based on its excellent FXa inhibition activity.

Dirhodium tetraacetate catalyzed carbon-hydrogen insertion reaction in N-substituted .alpha.-carbomethoxy-.alpha.-diazoacetanilides and structural analogs. Substituent and conformational effects

Abstract: A series of acyclic α-carbomethoxy-α-diazoacetanilides with different N-substituents, 5a-k, was prepared and the rhodium(II) acetate catalyzed reactions studied. It was found that the rhodium carhenoid reaction with these compounds occurred only at the N-substituent; when the N-substituent is a propargyl group, rhodium carbenoid addition to the triple bond is favored, resulting, ultimately, in the formation of a bicyclic furan derivative 8. With an N-(tert-butyloxycarbonyl)methyl substituent, interception of the rhodium carhenoid by the ester carbonyl oxygen occurred preferentially to give, eventually, 1,4-oxazine derivatives 9 and 9'

Catalyst and method of broadening polymer molecular weight distribution and increasing polymer tensile impact strength and products made thereof

Abstract: A catalyst and method of producing polyolefins having broadened molecular weight distributions and enhanced tensile impact strengths utilizing a silica supported metallocene-alumoxane catalyst system, wherein at least one of the metallocenes has at least one cyclopentadienyl ring being substituted by at least one optionally substituted hydrocarbon substituent having a 2° or 3° carbon atom with which it is covalently bonded to the cyclopentadienyl ring.

Synthesis of side-chain liquid crystal polymers by living ring-opening metathesis polymerization. 3. Influence of molecular weight, interconnecting unit, and substituent on the mesomorphic behavior of polymers with laterally attached mesogens

Abstract: : Norbornene derivatives containing laterally attached 2,5-bis(4'-n- alkoxybenzoyl OXY) mesogens were polymerized by controlled ring opening metathesis polymerization to provide polymers in high yield with 5-100 repeat units and narrow molecular weight distributions. Monomers with n>l displayed monotropic or enantiotropic nematic mesophases. All polymers displayed enantiotropic nematic mesophases regardless of the spacer, molecular weight or length or the n-alkoxy substituent. Constitutional isomers of poly(5-carbo(2', 5'-bis-4( methoxybenzoyloxy)benzyloxy)bicyclo(2.2.1)hep t-2-ene)s containing laterally attached mixed phenylester/benzylester units are amorphous. Side chain liquid crystal polymers (SCLCPs), living ring opening metathesis polymerization.

Method of preparing 4-aminodiphenylamine

Abstract: A method of producing 4-ADPA is disclosed wherein aniline or substituted aniline derivatives and nitrobenzene are reacted under suitable conditions to produce 4-nitrodiphenylamine or substituted derivatives thereof and/or 4-nitrosodiphenylamine or substituted derivatives thereof and/or their salts, either or both of which are subsequently reduced to produce 4-ADPA or substituted derivatives thereof. The 4-ADPA or substituted derivatives thereof can be reductively alkylated to produce p-phenylenediamine products or substituted derivatives thereof which are useful as antiozonants. A second embodiment of the invention is the tetrasubstituted ammonium salts or alkyl substituted diammonium salts of 4-nitrodiphenylamine, 4-nitrosodiphenylamine and the substituted derivatives thereof wherein each substituent of the tetrasubstituted ammonium ion is independently selected from the group consisting of alkyl, aryl and arylalkyl groups and each alkyl substituent of the alkyl substituted diammonium salt is independently selected.

Substituent variation in azabicyclic triazole- and tetrazole-based muscarinic receptor ligands.

Abstract: The effect of variation of the 1-azabicyclic substituent on the novel 1,2,3-triazol-4-yl-, 1,2,4-triazol-1-yl, tetrazol-5-yl-, and tetrazol-2-yl-based muscarinic receptor ligands has been studied, and the exo-azabicyclic[2.2.1]hept-3-yl substituent was found to give the most potent and efficacious compounds. In addition, variation of the second substituent on 1,2,4-triazol-1-yl- and tetrazol-2-yl-based muscarinic receptor ligands has yielded a series of novel compounds with high potencies and efficacies, ranging from full agonists to antagonists. Small lipophilic electron withdrawing substituents give potent but low efficacy compounds, while small polar electron donating substituents give potent and efficacious compounds. The activity of these compounds is described in terms of a model of the receptor involving lipophilic and hydrogen bonding interactions. These compounds provide muscarinic ligands with high potency and a range of efficacies suitable for testing as candidate drugs in the treatment of Alzheimer's disease.

Substituted phenylethenyl compounds having retinoid-like biological activity

Abstract: Compounds of the formula ##STR1## wherein R1, R2, R3 and R4 independently are hydrogen, lower alkyl of 1 to 6 carbons, halogen or lower alkoxy of 1 to 6 carbons; R5 and R5 ' independently are hydrogen or lower alkyl of 1 to 6 carbons; Y is oxygen or sulfur; Z is n-alkyl having 2 to 10 carbons, cyclo or branch-chained alkyl of 3 to 10 carbons, and straight chain alkenyl having 2 to 10 carbons, or cyclo or branched chained alkenyl of 3 to 10 carbons, and the Z-Y substituent is in a 1,2 (ortho) or 1,3 (meta) position on the phenyl ring relative to the ethene moiety; A is (CH2)n where n is 0-5, lower branched chain alkyl having 3 to 6 carbons, cycloalkyl having 3 to 6 carbons, alkenyl having 2 to 6 carbons and 1 or 2 double bonds, alkynyl having 2 to 6 carbons and 1 or 2 triple bonds; B is COOH or a pharmaceutically acceptable salt thereof, COOR8, CONR9 R10, --CH2 OH, CH2 OR11, CH2 OCOR11, CHO, CH(OR12)2, CHOR13 O, --COR7, CR7 (OR12)2, or CR7 OR13 O, where R7 is an alkyl, cycloalkyl or alkenyl group containing 1 to 5 carbons, R8 is an alkyl group of 1 to 10 carbons, or a cycloalkyl group of 5 to 10 carbons, or R8 is phenyl or lower alkylphenyl, R9 and R10 independently are hydrogen, an alkyl group of 1 to 10 carbons, or a cycloalkyl group of 5 to 10 carbons, or phenyl or lower alkylphenyl, R11 is alkyl of 1 to 10 carbons, phenyl or lower alkylphenyl, R12 is lower alkyl, and R13 is divalent alkyl radical of 2-5 carbons, have retinoid like biological activity.

High-valent transition-metal alkylidene complexes : effect of ligand and substituent modification

Abstract: Article on high-valent transition-metal alkylidene complexes and the effect of ligand and substituent modification.

Aqueous ink composition and colorants useful therein

Abstract: An aqueous ink composition is provided having up to 50 wt. % of a colorant of the formula: A--{Y--X--C(O)--R.sub.1 --C(O)O.sup.- }.sub.p where A is an organic chromophore; Y is a polyoxyalkylene substituent; X is a radical of a reactive hydroxy, amino or thio group; and R 1 is C 2-30 , substituted or unsubstituted alkylene, alkenylene, or phenylenealkylene. A counter ion selected from alkaline metal ions, alkaline earth metal ions, ammonium ions, amine salts, and zinc ammonium complexes is present in approximately stoichiometric proportion or greater relative to the colorant in the ink composition.

The use of π-organoiron sandwiches in aromatic chemistry

Abstract: The temporary complexation of aromatics by the FeCpn+ or FeC6R 6 m+ units (R=H or CH3; n=0 or 1; m=0–2) activates the formation of many C-C and C-element bonds. This principle and its current applications are reviewed here. In the 18-electron sandwich complexes FeIICp(arene)+ and FeII(arene) 2 ++ , advantage has been taken of the electron-withdrawing properties of the cationic moiety for (i) deprotonation-alkylation (ii) nucleophilic addition and substitution. Nucleophilic displacement of the halide(s) in halogeno- or dihalogenoarene complexes FeCp(arene)+ by amines, RO−, SR−, and stabilized carbanions was applied to the synthesis of heterocycles and of triaryldiethers. The multiple deprotonation-alkylation of FeCp(C6Me6)+ gives tentacled aromatic complexes which can be hexafunctional. In the Fe(arene) 2 ++ series, a few double alkylations have been performed, a strategy limited by the side electron-transfer pathway. Protection by hydride allows the reactions of a variety of carbanions. Deprotection is carried out using Ph3C+BF 4 − : electron-transfer gives the intermediate 17-electron radical cation and Ph3C· followed by spontaneous H-atom transfer. In the non-methylated series, a second carbanion attack opens the route to heterobifunctional cyclohexadienes with a precise regio- and stereocontrol. In the crowded permethylated series, a second functionalization is achieved by deprotonation-acylation. In each series, the polyene ligand is disengaged using oxidation of the functional sandwich with Al2O3+O2. Activation at the 19-electron or 20-electron stage proceeds by electron-transfer to the substrate and subsequent cage reaction. The isoelectronic 19-electron complexes FeICp(arene) and FeI(cyclohexadienyl)(arene) react in this way with O2 with leads to benzylic activation, a reaction inhibited by the salt effect. Subsequent functionalization can be achieved with many elements. In the 20-electron complex Fe0(C6Me6)2, double C-H activation by O2 gives an ortho-xylylene complex and electron-transfer to functional halides gives functional cyclohexadienyl complexes. The long known redox reactions of FeCp(arene)+ complexes at the benzylic position of the arene substituent are also briefly reviewed. The low cost of the activating iron moieties, the ease of complexation and decomplexation, the non-toxicity, and the possibility of using the temporary complexation for multiple activation steps make the iron-mediated reactions a powerful tool in synthetic strategies.

Reversible inhibitors of the gastric (H+/K+)-ATPase. 3. 3-substituted-4-(phenylamino)quinolines.

Abstract: Previously, gastric (H+/K+)-ATPase inhibitors such as 2 have been prepared as analogues of 1a on the presumption that the 3-carbethoxy substituent plays a key role in establishing the orientation of the 4-arylamino group. In this paper we explore further the contribution made to activity by the quinoline 3-substituent. We show that, for compounds bearing such a substituent, only a particular combination of properties provides high activity, both in vitro and as inhibitors of gastric acid secretion in vivo. The ability of the substituent to affect activity by restricting rotation about the Cquin-N bond through a combination of both a pi-electron withdrawal and hydrogen bonding is supported by the current study. However, high activity is only achieved if the effect of this group on the quinoline pK(a) is kept to a minimum. 3-Acyl substituents provide an optimum combination of electronic properties. From this series, compound 17c (SK&F 96067) was shown to be a potent inhibitor of histamine-stimulated gastric acid secretion after oral dosing in the Heidenhain pouch dog and was selected for further development and evaluation in man.

Hydrogen-bonded oxyhemoglobin models with substituted picket-fence porphyrins: the model compound equivalent of site-directed mutagenesis

Abstract: Iron(II) complexes of picket-fence-type porphyrins having one of the four pivalamide pickets replaced by a substituent capable of H-bonding have been synthetized as models for oxyhemoglobin. This synthesized as models for oxyhemoglobin. This synthetic approach is analogous to site-directed mutagenesis of the distal residues in oxygen-binding hemoproteins. Rate and equilibrium data for dioxygen binding have been determined to evaluate the effect of the H-bonding substituent and to make comparisons with more passive substituents

Synthesis of polyazamacrocycles with more than one type of side-chain chelating groups

Abstract: The pH controlled selectivity of the sulfomethylation reaction is used to prepare a series of di-, tri-, tetra- and hexaazacyclomacrocycles with specified patterns of pendent side-chain chelating groups. The prepared mono and diacetic acid derivatives, together with monomethylenephosphonate and monomethylenephosphinate derivatives of tetraazacyclododecane, and triazcyclododecane and [9]aneN3, make these types of ligands easily available by a synthetic pathway that avoids the use of protective groups. The invention thus comprises a variety of compounds, methods and uses characterized by relatively high synthetic yields of polyazamacrocyclic ligands exhibiting a wide and predictable choice of metal ion binding constants water and lipid solubilities by reason of their substituent pendent groups.