Butyl Derivative Research Articles

Structural isomerism in crystals of redox-active secondary ortho-diamides: the role of competing intra- and intermolecular hydrogen bonds in directing crystalline topologies.

The solid-state chemistry of a series of seven ortho-bis(alkylamido)ethylenedithiotetrathiafulvalene derivatives EDT-TTF-(CONHR)2 (R=Me, 1; Et, 2; Pr, 3; Bu, 4; Pent, 5; Hex, 6; and Bz, 7), in their neutral and one-electron-oxidized, radical cation states, was investigated with an eye on the topology of intra- and intermolecular hydrogen-bond motifs. In the case of neutral, monomolecular solids, an intramolecular N--H.O hydrogen bond seals a constrained seven-membered ring for 1, 2, 3, and 7, which is disrupted in butyl derivative 4 in favor of an antiparallel ladder at the expense of any intramolecular hydrogen bond. In the solid-state, the competition between intra- and intermolecular hydrogen bonding observed in solution depends on the packing of the molecules. Electrocrystallization of methyl derivative 1 with ReO4- or ClO4-, two anions of different volumes but otherwise identical charge and symmetry, revealed a fine sensitivity of the constrained seven-membered ring to the internal chemical pressure exerted by the anion. [1]2 *+ReO4 (sigmaRT=8.5 S cm(-1), activation energy Delta=600 K at high temperature) and beta"-[1]2 *+ClO4 (sigmaRT=0.03 S cm(-1), Delta=1600 K; under pressure at room temperature, the conductivity increases by three orders of magnitude up to 17 kbar with a linear variation of the activation energy with pressure, Delta=aP with a=0.202 10(6) K kbar(-1)) have vastly different architectures, dimensionalities, electronic structures, and collective properties, a consequence of the presence of the closed or open structural isomers in one or the other. This exemplifies the flexibility of functionalized TTF derivatives, even when the functional group is directly attached to the electro-active core. This allows an analogy to be drawn with tetrafunctionalized metallocenes, in which such flexibility has already been observed. The experimental data are supported by theoretical calculations of the energy profile of a model molecule on rotation of the amido groups.

New Soluble n-Type Conjugated Polymers for Use as Electron Transport Materials in Light-Emitting Diodes

We report the synthesis of a series of six new soluble n-type conjugated copolymers that incorporate bis(phenylquinoline) and regioregular dialkylbithiophene in the backbone, the investigation of their electrochemical, photophysical, and electroluminescent properties, and their use as electron transport materials in light-emitting devices. Variation of the alkyl chain length of the head-to-head dialkylbithiophene linkage from butyl (C4) to dodecyl (C12) had little or no effect on the photophysical or redox properties of the new polyquinolines. However, the glass transition temperature decreased from 256 °C for the butyl derivative to 76 °C for the dodecyl derivative. A single-crystal X-ray structure of a model compound allowed quantification of the intramolecular torsion angles which explain the significant difference in optical band gap and redox properties between the head-to-tail and head-to-head polymers. The high electron affinity (2.88−2.97 eV), robust thermal stability, suitable solution processability, and weak-to-moderate intrinsic electroluminescence of the polymers make them attractive for use as electron transport materials in organic LEDs. Initial use of the polymers as the electron transport materials in bilayer poly(2-methoxy-5-(2‘-ethylhexyloxy)-1,4-phenylenevinylene) (MEH−PPV) LEDs showed substantial enhancement in device performance under ambient air conditions (1.4% external quantum efficiency, 2170 cd/m2) compared to most current electron transport polymers for LEDs.

Computational approach to estimate layer structures of organic derivatives of boehmite

The observed basal spacings of the alkyl derivatives of boehmite, AlO(OH) 1− x (OR) x , obtained by the reaction of aluminum metal or aluminum alkoxides with alcohols at 250–300 °C was only slightly affected by the population ( x) of the alkyl groups ( x=0.39−0.21) (Chem. Mater. 12 (2000) 55). In order to clarify the origin of this independency, the molecular mechanics (MM) calculation was carried out, and the effect of the alkyl population upon the basal spacing of the butyl derivative of boehmite, AlO(OH) 1− x (OCH 2CH 2 CH 2CH 3) x , was examined in a range of x=0.00–0.30. The calculated results clearly suggested that in the range of x from 0.3 to 0.2, the boehmite derivative has the bilayer arrangement of the alkyl groups with essentially all-trans conformation. In this range, the basal spacing was only slightly affected by the population of the alkyl groups because it is determined by the most crowded part of the assembly of the alkyl chains. Since the alkyl chains are fixed to the host layers through the covalent bonding, decrease in the alkyl population does not affect essential feature of the alkyl derivatives of layered inorganics.

Synthesis, β‐Adrenergic Blocking Activity and β‐Receptor Binding Affinities of 1‐Substituted‐3‐(2‐isopropyl‐5‐methyl‐phenoxy)‐propan‐2‐ol Oxalates.

Abstract The compounds 1-isopropylamino-3-(2-isopropyl-5-methyl-phenoxy)-propan-2-ol oxalate ( 5 ) and 1- tert -butylamino-3-(2-isopropyl-5-methyl-phenoxy)-propan-2-ol oxalate ( 6 ) were synthesized from thymol ( 1 ), a naturally occurring agent in Thymus vulgaris L. Pharmacological evaluation of 5 and 6 were carried out using mouse ECG and isolated rat uterus models. Pretreatment of 5 (100 μg/kg, i.v.) and 6 (50 μg/kg, i.v.) antagonized isoprenaline (2 μg/kg, i.v.) induced tachycardia, similar to that of atenolol (CAS 29122-68-7, 20 μg/kg, i.v.) pretreatment in mouse ECG experiments as measured by R-R interval. Pretreatment of 5 and 6 blocked isoprenaline and adrenaline induced relaxation of isolated rat uterus (unprimed). Also the compounds 5 and 6 were subjected to in vitro β 1 - and β 2 -adrenergic receptor binding assay using turkey erythrocyte membrane (β 1 ) and lung homogenate of rats (β 2 ). Both 5 and 6 showed β-adrenergic receptor affinity comparable with that of propranolol (propranolol hydrochloride, CAS 318-98-9) with out selectivity to any one β-adrenergic receptor. These results suggest that both the compounds possess non-selective β-adrenergic blocking activity, with the tert -butyl derivative 6 being more active than the isopropyl derivative 5 .

QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS PREDICT THE DELAYED NEUROTOXICITY POTENTIAL OF A SERIES OF O-ALKYL-O-METHYLCHLOROFORMIMINO PHENYLPHOSPHONATES

Inhibition of acetylcholinesterase (AChE) versus inhibition and aging of neuropathy target esterase (NTE) by organophosphorus (OP) compounds in vivo can give rise to distinct neurological consequences: acute cholinergic toxicity versus OP compound-induced delayed neurotoxicity (OPIDN). Previous work has shown that the relative potency of an OP compound to react with NTE versus AChE in vitro may predict its capability to produce OPIDN. The present study was conducted to evaluate further the validity of such predictions and to enhance them with quantitative structure-activity relationships (QSAR) using a homologous series of alkyl phenylphos-phonates, (RO)C6H5P(O)ON=CClCH3 (PhP; R=alkyl). Neuropathic potential of PhP was assessed by measuring ki(NTE)/ki(AChE) ratios in vitro and comparing these with ED50 ratios in vivo. Selectivity for NTE increased with rising R-group hydrophobicity. The ki(NTE)/ki(AChE) ratios were 0.42 (methyl), 3.6 (ethyl), 15 (isopropyl), 36 (propyl), 69 (isobutyl), 105 (butyl), and 124 (pentyl). Ratios >1 suggest the potential to produce OPIDN at doses lower than the LD50. Inhibition of NTE and AChE in hen brain in vivo was studied 24 h after im injection of hens with increasing doses of methyl and butyl derivatives. Analysis of dose-response curves yielded ED50(AChE)/ED50(NTE) ratios of 0.86 for methyl PhP and 22.1 for butyl PhP. These results predict that the butyl derivative should be more neuropathic than the methyl analogue. Excellent correspondence between in vivo and in vitro predictions of neuropathic potential indicate that valid predictive QSAR models may be based on the in vitro approach. Adoption of this system would result in reducing experimental animal use, lowering costs, accelerating data production, and enabling standardization of a biochemically based risk assessment of the neuropathic potential of OP compounds.

Methylated analogues of methyl (R)-4-(3,4-dichlorophenylacetyl)- 3-(pyrrolidin-1-ylmethyl)piperazine-1-carboxylate (GR-89,696) as highly potent kappa-receptor agonists: stereoselective synthesis, opioid-receptor affinity, receptor selectivity, and functional studies.

Analogues of the kappa-receptor agonist methyl (R)-4-(3,4-dichlorophenylacetyl)-3-(pyrrolidin-1-ylmethyl)piperazine-1-carboxylate (GR-89,696, 6) bearing an additional methyl substituent in the side chain are synthesized and evaluated for their kappa-receptor affinity and selectivity. A key step in the synthesis is the stereoselective reductive amination of the ketones 9, 18, and 19 with pyrrolidine and NaBH(3)CN, which succeeds only in the presence of the Lewis acid Ti(OiPr)(4). Whereas the BOC-substituted ketone 9 affords the unlike and like diastereomers of 10 in a ratio of 70:30, the diastereoselectivity during the reductive amination of the butyl and phenyl substituted ketones 18 and 19 is enhanced to 85:15 (butyl derivative) and >95:<5 (phenyl derivative) in favor of the unlike diastereomers. In receptor binding studies using the radioligand [(3)H]U-69,593 the (S,S)-configured methyl carbamate (S,S)-14 reveals the highest kappa-receptor affinity (K(i) = 0.31 nM) within this series, even exceeding the lead kappa-agonist 6 (GR-89,696). A slightly reduced kappa-receptor affinity is observed with the propionamide (S,S)-13 (K(i) = 0.67 nM). The kappa-receptor affinity of piperazines with acyl or alkoxycarbonyl residues at both nitrogen atoms (11, 13, 14) decreases in the order (S,S) > (R,R) > (S,R) > (R,S). The methyl carbamate (S,S)-14 discloses a unique activity profile also binding at mu-receptors in the subnanomolar range (K(i) = 0.36 nM). In a functional assay, i.e., by measuring acetylcholine release in rabbit hippocampus slices, the agonistic effects of the methyl carbamate (S,S)-14 and the propionamide (S,S)-13 are demonstrated. Only weak kappa- and mu-receptor affinities are found with the butyl- and phenyl-substituted piperazines 22 and 23. However, considerable sigma(1)-receptor affinity is determined for the enantiomeric, unlike-configured butyl derivatives (R,S)-22 and (S,R)-22 with K(i)-values of 40.2 nM and 81.0 nM, respectively.

Synthesis and chemical behaviour of 17α-butyl-3β,17β-dihydroxy-16-oximino-5-androstene

Starting from 3 -hydroxy-16-oximino-5-androsten-17-one (1), the recently synthesized 16-oximino-17 -hydroxy-17 -butyl derivative 2 gave by the Beckmann fragmentation reactionwith titanium(III) chloride or p-toluenesulphonyl chloride the corresponding D-seco derivative 3. However, using acetic anhydride, in addition to the 3 -acetoxy D-seco derivative 4, the 17-aza D-homo derivative 5 was obtained. The structure of compound 5 was proposed on the basis of NMR-spectroscopy.

Influence of Alkyl Chain Length on the Crystal Structures and Optical SHG of N-n-Alkyl-2,4-dinitroanilines: Role of Dipolar and Dispersion Energies

The length of alkyl chains attached to NLO chromophores exerts a critical control on their crystal structures and SHG capability. Systems with short as well as long alkyl chains form centrosymmetric lattices whereas those with chains of intermediate length, typically butyl chains, form noncentrosymmetric lattices and show SHG. Investigation of a series of N-n-alkyl-2,4-dinitroanilines is reported along with crystal structure analysis of the propyl, butyl, and pentyl derivatives. Packing energy calculations are carried out for the three structures. There are no intermolecular H-bonds in these crystals. The maximum values of dipole-dipole and dispersion energies in the set are found in the centrosymmetric crystals of the propyl and pentyl derivatives, respectively. Intermediate values of the two energy components are observed in the butyl derivative, which alone has a noncentrosymmetric crystal structure and is SHG active.

Unusual Thermal Polymerization of 1,4-Bis-5-(4,4‘-dialkyl-2,2‘-bithiazolyl)-1,3-butadiynes: Soluble Polymers from Diacetylenes

The syntheses of the 1,4-bis-5-(4,4‘-dialkyl-2,2‘-bithiazole)-1,3-butadiynes, ABDs, (6a−c) are reported. The crystal and molecular structure of the butyl derivative was determined by single-crystal X-ray diffraction. The BBD (the 4,4‘-di-n-butyl ABD) molecules are properly aligned in the solid state for topotactic 1,4-polymerization to occur, but these materials do not undergo such polymerization under a variety of conditions. The lack of topotactic polymerization is attributed to the rigidity of the aromatic groups directly bonded to the butadiyne. These compounds do polymerize in the molten state to give soluble polymers that are characterized by UV−vis, FT-IR, and NMR spectroscopies and cyclic voltammetry. Molecular modeling was also used to explore some representative conformation space. These data suggest that the polymerization occurs primarily via 1,2-addition, but some 1,4-addition also occurs.

Pyrrolidinium Imides: A New Family of Molten Salts and Conductive Plastic Crystal Phases

A new family of molten salts is reported, based on the N-alkyl, N-alkyl pyrrolidinium cation and the bis(trifluoromethane sulfonyl)imide anion. Some of the members of the family are molten at room temperature, while the smaller and more symmetrical members have melting points around 100 °C. Of the room-temperature molten salt examples, the methyl butyl derivative exhibits the highest conductivity; at 2 × 10-3 S/cm this is the highest molten salt conductivity observed to date at room temperature among the ammonium salts. This highly conductive behavior is rationalized in terms of the role of cation planarity. The salts also exhibit multiple crystalline phase behavior below their melting points and exhibit significant conductivity in at least their higher temperature crystal phase. For example, the methyl propyl derivative (mp = 12 °C) shows ion conductivity of 1 × 10-6 S/cm at 0 °C in its higher temperature crystalline phase.

Sulfonation of trans‐10b,10c‐dimethyl‐10b,10c‐dihydropyrene and its 2,7‐di‐tert‐butyl derivative with sulfur trioxide

AbstractThe sulfodeprotonation of trans‐10b,10c‐dimethyl‐10b,10c‐dihydropyrene (1) with sulfur trioxide has been studied in dioxane as solvent, as well as in dichloromethane, using 4.0–5.0 equivalents of dioxane relative to the amount of SO3 as reactivity moderator. Reaction of 1 with 0.6 mol‐equiv. of SO3 in dioxane at 22°C yields initially only the 2‐ and 4‐sulfonic acid in a 84/16 ratio. Using 3.0‐6.0 mol‐equiv. of SO3 in dichloromethane with the temperature increasing from −78 up to 22°C the initially very rapid formation of the 1‐, 2‐ and 4‐sulfonic acid (formed in a ratio of 11/82/7) is followed by a much slower conversion into a mixture of 1,7‐, 2,4‐, 2,5‐ and 2,7‐disulfonic acid. These four acids are subsequently converted even more slowly into a mixture of the 1,4,7‐, 2,4,7‐ and 2,5,9‐trisulfonic acids to yield in part the 1,4,7,9‐, 2,4,7,9‐ and 2,4,7,10‐tetrasulfonic acids. trans‐2,7‐Di‐tert‐butyl‐10b, 10c‐dimethyl‐10b, 10c‐dihydropyrene (2) with 0.8–2.0 equiv. of SO3 in dioxane as solvent gives the 4‐sulfonic acid which is slowly converted into a 16/84 mixture of the 4,9‐ and 4,10‐disulfonic acids.The observed distributions of sulfonic acid isomers are discussed in terms of the directing effects of the “ideal” ‐ almost planar ‐ [14] annulene and the sulfo and/or tert‐butyl substituent(s) already present.

Poly(α‐butyl β‐L‐aspartate): A second alkoxycarbonyl nylon‐3 derivative in helical conformation

AbstractA structural study was carried out on poly(α‐butyl β‐L‐aspartate), which is a stereoregular nylon‐3 derivative with an alkoxycarbonyl group attached to the β‐carbon of the main‐chain repeating unit. Two crystal forms, namely hexagonal and tetragonal, made of 13/4 and 4/1 helices, respectively, and bearing a structural resemblance to the polypeptide α‐helix, were characterized by X‐ray diffraction. Though these forms are basically identical to those previously reported for poly(α‐isobutyl β‐L‐aspartate), the crystal transition from hexagonal to tetragonal known to take place in this polymer by effect of heating, was not observed in the present case. Modeling calculations revealed that although similar conformations are favoured for the two polymers in both crystal forms, the relative stability of the 13/4 helix to the 4/1 helix was found to be significantly reduced in the case of the butyl derivative. The presence of helical conformation in solution has been evidenced by both 1H NMR and circular dichroism and the helix‐coil transition promoted by acids was investigated by means of these techniques.

Novel (4-phenylpiperidinyl)- and (4-phenylpiperazinyl)alkyl-spaced esters of 1-phenylcyclopentanecarboxylic acids as potent sigma-selective compounds.

A series of novel 4-phenylpiperidinyl and (4-phenylpiperazinyl)alkyl 1-phenylcyclopentanecarboxylates was synthesized and evaluated for affinity at sigma 1 and sigma 2 sites by inhibition of [3H]-(+)-pentazocine (PENT) and [3H]-1,3-di(2-tolyl)guanidine (DTG) binding in guinea pig brain. The phenylpiperidines were more potent sigma ligands than the corresponding piperazines. Structural modifications varying the optimal spatial distance between the piperidine nitrogen and ester functions led to the identification of the propyl compound 24 ([3H]PENT Ki = 0.50 nM; [3H]DTG Ki = 1.17 nM) and the butyl derivative 32 ([3H]PENT Ki = 0.51 nM; [3H]DTG Ki = 0.69 nM) as novel high-affinity sigma-selective agents. An ethylene spacer was optimum with para-substituted analogs. A notable finding was the discovery of 2-(4-phenylpiperidinyl)ethyl 1-(4-nitrophenyl)-cyclopentanecarboxylate hydrochloride (15) (RLH-033), which demonstrated potent affinity for the [3H]PENT-defined sigma site with a Ki of 50 pM, selectivity for sigma 1 over muscarinic M1 (> 17,600-fold), M2 (> 34,200-fold), dopamine D1 (> 58,000-fold), and D2 (> 7000-fold) receptors, and inactivity at phencyclidine, NMDA, and opioid receptors. RLH-033 is a valuable tool which will aid further in understanding the biology of the sigma recognition site. Information from this research has further defined the topography of the sigma recognition site, which may provide an explanation for the diverse structures which bind with relatively high affinity.

Butyllithium cubane tetramers linked by Li-TMEDA-Li bridges in an infinite, zig-zag chain arrangement: first crystallographic study of a simple butyl compound of an early main group element

Herein we report the structure of the crystalline alkyllithium complex [((BU~L~)~.TMEDA(B],u] nLi,n -butyllithium; TMEDA, N,N,NW'-tetramethylethylenediamine)w hich, to the best of our knowledge, is the first crystal structure of a simple butyl derivative of a group 1 (Li, Na, etc.) or a group 2 (Be, Mg, etc.) metal (Le. of formula BunMn or *Bun2Mn).

Synthesis and chemical characterization of N-substituted phenoxazines directed toward reversing vinca alkaloid resistance in multidrug-resistant cancer cells.

A series of 21 N-substituted phenoxazines has been synthesized in an effort to find more specific and less toxic modulators of multidrug resistance (MDR) in cancer chemotherapy. Thus, N-(omega-chloroalkyl)- and N-(chloroacyl)phenoxazines were found to undergo iodide-catalyzed nucleophilic substitution on reaction with various secondary amines, including N,N-diethylamine, N,N-diethanolamine, morpholine, piperidine, pyrrolidine and (beta-hydroxyethyl)piperazine. Products were characterized by UV, IR, 1H-, and 13C-NMR, mass spectral data, and elemental analyses. All of the compounds were examined for cytotoxicity and for their ability to increase the accumulation of the vinca alkaloids, vincristine (VCR) and vinblastine (VLB) in multidrug-resistant GC3/Cl (human colon adenocarcinoma) and KBChR-8-5 (HeLa variant) cell lines. Compounds were compared to the standard modulator verapamil (VRP). Substitutions on the phenoxazine ring at position 10 were associated with an increase in antiproliferative and anti-MDR activities. Modification of the length of the alkyl bridge and the type of amino side chain also influenced the potency of these effects. From among the compounds examined, 10 derivatives were found to increase the accumulation of VCR and VLB in GC3/Cl and KBChR-8-5 cells relative to the effect of VRP, suggesting that with the exception of pyrrolidinyl, the tertiary amine attachments to the phenoxazine nucleus linked through a three- or four-carbon alkyl chain resulted in enhanced anti-MDR activity. On the basis of their 50% growth inhibitory (IC50) values, five of the ten compounds, namely, 10-(3'-chloropropyl)phenoxazine, 10-[3'-[N-bis(hydroxyethyl)- amino]propyl]phenoxazine, 10-(3'-N-morpholinopropyl)phenoxazine, 10-(4'-N-morpholinobutyl)phenoxazine and 10-(N-piperidinoacetyl)phenoxazine were selected as relatively nontoxic chemosensitizers. These modulators, at nontoxic concentrations, potentiated the cytotoxicity of VCR and VLB in GC3/Cl and KBChR-8-5 cells. Further, two compounds 10-(3'-N-morpholinopropyl)phenoxazine, and the butyl derivative, enhanced accumulation of VLB in GC3/Cl, KBChR8-5 and highly resistant KB-V1 cells to a level significantly greater than the maximal level achieved with VRP. Additional experiments to understand the mechanism of action of these agents in modulating MDR are in progress.

ChemInform Abstract: Reaction of Thiolo and Selenolo Esters of Phosphorus Acids with Halogens. Part 2. Interaction of S‐Methyl t‐Butyl(phenyl)‐ and Di‐t‐butyl‐phosphinothiolates with Elemental Bromine and Iodine.

AbstractThe reaction of the title compound (I), or its di‐tert.‐butyl derivative, with bromine or iodine under various conditions leads to a variety of intermediates and products such as (II)‐(VI).

Derivatives of 9,10-anthraquinone; emission spectra in polymer matrices at 77K and efficiency as initiators of degradation

The emission spectra (phosphorescence) of 10 derivatives of 9,10-anthraquinone (2-methyl, 2,3-dimethyl, 2-ethyl, 2-isopropyl, 2- n-butyl, 2-tert butyl, 2-acetoxy, 2-octanoyloxy, 1-chloro and 2-chloro) in five polymeric matrices (polyethylene-PE, isotactic polypropylene-iPP, polystyrene-PS, poly(methyl methacrylate)-PMMA and poly(vinyl alcohol)-PVA were measured at 77K. In nonpolar hydrocarbon matrices vibrationally well resolved spectra were obtained which were dominated by the fundamental vibration of the carbonyl group (1680 cm −1). Lower vibrations in the region 700-250 cm −1 cannot be assigned unequivocally to active IR vibrations. In PS and PMMA matrices the fine vibration in the region 700-250 cm −1 is lost and the valence vibrations of the carbonyl group are shortened. In polar PVA the vibrational structure is completely lost and the intensity is decreased by a factor of 5–10. The life-time of monosubstituted derivatives of anthraquinone in PE, IPP, PS and PMMA lies in the range 2–4 ms. The 2,3-dimethyl derivative exhibits biexponential decay in PS and PMMA matrices. Since the emission of 9,10-anthraquinone derivatives in a PVA matrix was rather low, the life-time was not determined. The photo-degradation of PE, iPP and PS are accelerated by 9,10-anthraquinone and its derivatives and they themselves decompose in the first step of the degradation process. The 2- tert butyl derivative has been found to be the most effective photoinitiator for the polymers under study.

Nitrite inhalants: patterns of abuse in Baltimore and Washington, D.C.

Nitrite inhalants, as drugs of abuse, have received a new prominence in the literature since their use has been associated with Kaposi's Sarcoma and possibly other manifestations of acquired immunodeficiency syndrome (AIDS). Changes in patterns and prevalence of use have not been investigated since the onset of the AIDS epidemic. We have examined the abuse patterns of nitrite inhalants (poppers) in several different groups. The use of poppers among drug abusers in the Baltimore-Washington, D.C. metropolitan area has remained constant over the past 5 years, with the prevalence of use being approximately 11% for recreational drug users and 22% for heavy abusers. Self-reported use by a homosexual group had decreased over the same time period. Sixty-nine percent of the homosexual sample had experience with nitrities, but only 21% had used them in the 6 months prior to being surveyed. The mean interval since last use was 25 months, and since peak use, 4.1 years. Among substance abusers, nitrites appear to be a drug whose use starts late, with the mean age of first use being 25.6 years compared to 14.6 years for glue, 17.6 years for marijuana, and 18.5 years for heroin. We found both heterosexual and homosexual groups utilize nitrites primarily to "get high," but homosexuals more often use them during overt sexual activity. Experience with amyl nitrite was much more prevalent than that with the butyl derivative in both populations. We conclude that the prevalence of nitrite abuse among drug users has not changed as a result of the AIDS epidemic, but such use appears to have decreased within the homosexual community.

Thromboxane synthetase inhibitors and antihypertensive agents. 2. N-[(1H-imidazol-1-yl)alkyl]-1H-isoindole-1,3(2H)-diones and N-[(1H-1,2,4-triazol-1-yl)alkyl]-1H-isoindole-1,3(2H)-diones as unique antihypertensive agents.

A series of N-[(1H-heteroaryl)alkyl]-1H-isoindole-1,3(2H)-diones were prepared as part of a continuing investigation into the biological properties of compounds that were both thromboxane synthetase inhibitors and potential antihypertensive agents. The most active thromboxane synthetase inhibition was found for the title imidazole derivatives wherein a hexyl or octyl chain separated the heterocyclic ends of the molecule (5,6) or with substitution on the isoindole portion of the molecule (18, 19, 21, 22, 25, 26). Compounds with shorter alkyl chain separations had good antihypertensive effects (1-5, 8-10, 19-22, 27-30). Butyl derivative 3 was chosen for further evaluation as a potential antihypertensive agent with thromboxane synthetase inhibitory properties.

ChemInform Abstract: INHIBITION OF LIVER ALCOHOL DEHYDROGENASE AND ETHANOL METABOLISM BY 3‐SUBSTITUTED THIOLANE 1‐OXIDES

AbstractDargestellt und auf Leber‐Alkohol‐Dehgdrogenase‐inhibierende Wirkung untersucht werden die S‐Oxide (VII).