- Design, synthesis and evaluation of naphthalene-2-carboxamides as reversal agents in MDR cancer
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A novel class of molecules with structure N-[3-(4-substituted-1-piperazinyl) propyl]-6-methoxy naphthalene-2-carboxamides were designed by generating a pharmacophore for potent MDR reversal activity, using Elacridar (GF 120918) as a query molecule and using MOE software. They were synthesized by condensing 6-methoxynaphthalene-2-carboxylic acid with N-[3-(4-substituted-1-piperazinyl) propyl] amines in the presence of DCC in DMF. They were evaluated in P388 murine lymphocytic leukemia cell line (P388) in vitro using SRB assay for cytotoxicity and in adriamycin-resistant P388 murine lymphocytic leukemia cell line (P388/ADR) using MTT assay for resistant reversal activity. Test compounds were non-toxic at the doses studied (upto 80 μg/ml). They effectively reversed adriamycin resistance at the doses studied (40 and 80 μg/ml). The percentage enhancement in adriamycin activity was in the range 33.58 -90.67 (at 40 μg/ml) and 8.80-46.04 (at 80 μg/ml) and the corresponding reversal potency values were in the range 1.33-1.90 and 1.08-1.46, respectively. Test compounds 2, 3, and 5 exhibited better activity as compared to the standard resistant reversal agent (Verapamil), at same concentration.
- Lokhande, Tushar N.,Viswanathan,Joshi, Advait,Juvekar, Aarti
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- Steric Factors in Amide-Directed Metalations of N,N-Dialkyl-6-methoxynaphthalene-2-carboxamides: Synthesis of a Sterically Perturbed Acylnaphthol
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The powerful ortho-metalating directive effect of the N,N-dialkylcarboxamide group can be used for the preparation of C-1 alkyl-substituted 2,6-acylnaphthols.The alternative reaction pathways of C-1 metalation vs. acylation (carbonyl addition) in the reaction of alkyllithium reagents with N,N-dialkyl-6-methoxy-naphthalenecarboxamides depends upon the cumulative steric nature of the N-alkyl and lithium alkyl groups: The N,N-dimethylamide 7 undergoes carbonyl addition with n-BuLi and t-BuLi; the N,N-diethylamide 8, carbonyl addition with n-BuLi, but metalation with t-BuLi; and the N,N-diisopropylamide 9 only C-1 metalation with n-BuLi.Subsequent reaction of the N,N-diethyl-1-ethyl-6-methoxynaphhtalene-2-carboxamide (13) with n-BuLi gives the desired 2,6-acylnaphthyl methyl ether, whereas the corresponding ethylated diisopropylamide 14 undergoes additional metalation on the ethyl group.These 1-ethyl-2-carboxamidonaphthalenes are very sterically crowded and show evidence in the proton NMR of hindered rotation about both the amide bond and the ethyl group.The UV and fluorescence spectra of the acylnaphthols 17 and 18 show the consequences of this steric crowding through reduced conjugation between the acyl group and the naphthalene group.The more hindered 1-ethylated acylnaphthol 18 shows lower molar absorptivity, and it fluoresces only in basic solution.
- Bindal, Rajeshwar D.,Katzenellenbogen, John A.
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- Carboxylation of Aryl Triflates with CO2 Merging Palladium and Visible-Light-Photoredox Catalysts
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We report herein a visible-light-promoted, highly practical carboxylation of readily accessible aryl triflates at ambient temperature and a balloon pressure of CO2 by the combined use of palladium and photoredox Ir(III) catalysts. Strikingly, the stoichiometric metallic reductant is replaced by a nonmetallic amine reductant providing an environmentally benign carboxylation process. In addition, one-pot synthesis of a carboxylic acid directly from phenol and modification of estrone and concise synthesis of pharmaceutical drugs adapalene and bexarotene have been accomplished via late-stage carboxylation reaction. Furthermore, a parallel decarboxylation-carboxylation reaction has been demonstrated in an H-type closed vessel that is an interesting concept for the strategic sector. Spectroscopic and spectroelectrochemical studies indicated electron transfer from the Ir(III)/DIPEA combination to generate aryl carboxylate and Pd(0) for catalytic turnover.
- Bhunia, Samir Kumar,Das, Pritha,Nandi, Shantanu,Jana, Ranjan
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supporting information
p. 4632 - 4637
(2019/06/27)
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- Naphthyl, (substituted) aryl, piperazine base trunk apperception composition
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The invention discloses (substituted) naphthyl, (substituted) aryl, piperazinyl amidine compound with new structures and salt of medical acid, a preparation method and a purification method of the compound and the salt of the medical acid, and a medicine composition containing the compound, wherein the compound has double inhibition activities of 5-hydroxytryptamine (5-HT) reuptake and noradrenalin (NE) reuptake, and shows strong depression resistance in animal experiments. The compound can be used for treating tristimania, and can also be used for treating other nervous system diseases related to the 5-HT and the NE.
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Paragraph 0081; 0082
(2016/10/08)
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- The influence of the thioalkyl terminal group on the mesomorphic behavior of some 6-alkoxy-2-naphthoates derived from 1,3,4-oxadiazole
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A new series of mesogenic compounds having a naphthalene moiety has been synthesized by esterification of 4-(5-(alkyllthio)-1,3,4-oxadiazol-2-yl)phenol and 6-alkoxy-2-naphthoic acid and their liquid crystalline properties have been studied. All the members of the series are enantiotropic and exhibit smectic as well as nematic mesophase. The plot of transition temperatures versus number of carbon atoms in the alkoxy chain exhibits no odd even effect and falling tendency for isotropic transition temperatures. High anisotropy, linearity confers rich mesomorphic properties on the system.
- Chothani,Akbari,Patel,Patel
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- N-heterocyclic carbene-assisted, Bis(phosphine)nickel-catalyzed cross-couplings of diarylborinic acids with aryl chlorides, tosylates, and sulfamates
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Efficient bis(phosphine)nickel-catalyzed cross-couplings of diarylborinic acids with aryl chlorides, tosylates, and sulfamates have been effected with an assistance of N-heterocyclic carbene (NHC) generated in situ from N,N′-dialkylimidazoliums, e.g., N-butyl-N′-methylimidazolium bromide ([Bmim]Br), in toluene using K3PO4·3H2O as base. In contrast to bis(NHC)nickel-catalyzed conventional Suzuki coupling of arylboronic acids, mono(NHC)bis(phosphine)nickel species generated in situ from Ni(PPh3)2Cl2/[Bmim]Br displayed high catalytic activities in the cross-couplings of diarylborinic acids. The structural influences from diarylborinic acids were found to be rather small, while electronic factors from aryl chlorides, tosylates, and sulfamates affected the couplings remarkably. The couplings of electronically activated aryl chlorides, tosylates, and sulfamates could be efficiently effected with 1.5 mol % NiCl2(PPh3)2/[Bmim]Br as catalyst precursor to give the biaryl products in excellent yields, while 3-5 mol % loadings had to be used for the couplings of non- and deactivated ones. A small ortho-substitutent on the aromatic ring of aryl chlorides, tosylates, and sulfamates was tolerable. Applicability of the nickel-catalyzed cross-couplings in practical synthesis of fine chemicals has been demonstrated in process development for a third-generation topical retinoid, Adapalene.
- Ke, Haihua,Chen, Xiaofeng,Zou, Gang
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p. 7132 - 7140
(2014/08/18)
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- An improved protocol for the oxidative cleavage of alkynes, alkenes, and diols with recyclable Ru/C
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Efficient synthesis of carboxylic acids from alkynes; aldehydes from alkenes and diols employing Ru/C-based recyclable catalytic system is reported with good to excellent yields. Georg Thieme Verlag Stuttgart.
- Vijay Kumar,Prakash Reddy,Sridhar,Srinivas,Rama Rao
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experimental part
p. 739 - 742
(2009/07/18)
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- SAR studies of capsazepinoid bronchodilators 3: The thiourea part (coupling region) and the 2-(4-chlorophenyl)ethyl moiety (C-region)
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Certain derivatives and analogues of capsazepine are potent in vitro inhibitors of bronchoconstriction in human small airways. During an investigation of the dependency of the potency on the structural features of the capsazepinoids in the thiourea moiety (coupling region) and the 2-(4-chlorophenyl)ethyl moiety (C-region), it was revealed that capsazepinoids with a thiourea or an amide link between the B-ring and the C-region in general have a good bronchorelaxing activity, while urea is a less attractive choice. Further, it was shown that 1,2,3,4-tetrahydroisoquinolines with a 2-(phenyl)ethyl derivative as the C-region are considerably more potent than those with an octyl group, while 2,3,4,5-tetrahydro-1H-2-benzazepines were found to be more insensitive to the nature of the C-region.
- Berglund, Magnus,Dalence-Guzman, Maria F.,Skogvall, Staffan,Sterner, Olov
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p. 2529 - 2540
(2008/09/21)
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- Synthesis of aromatic carboxylic acids by carbonylation of aryl halides in the presence of epoxide-modified cobalt carbonyls as catalysts
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A new procedure was developed for synthesis of aromatic and heteroaromatic acids and their derivatives (esters, salts) by carbonylation of the corresponding aryl halides. The acids are selectively formed in a high yield under very mild conditions. Highly active catalytic systems, base-containing alcoholic solutions of cobalt carbonyl modified with epoxides, were used to activate aryl halides. 2005 Pleiades Publishing, Inc.
- Boyarskii,Zhesko,Lanina
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p. 1844 - 1848
(2007/10/03)
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- Behavior of naphthoyloxyl and methoxynaphthoyloxyl radicals generated from the photocleavage of dinaphthoyl peroxides and 1-(naphthoyloxy)-2-pyridones
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1-Naphthoyloxyl and 2-naphthoyloxyl radicals were generated from photocleavage of dinaphthoyl peroxides and 1-(naphthoyloxy)-2-pyridones in acetonitrile. The difference in product distribution between the precursors is ascribed to the contribution of the two-bond cleavage in the peroxide decomposition in the singlet state. A series of methoxynaphthoyloxyl radicals were also generated from the corresponding (methoxynaphthoyloxy)pyridones and their behavior was compared with that of unsubstituted naphthoyloxyl radicals. The introduction of a methoxy group in the naphthalene ring stabilizes the naphthoyloxyl radicals to prevent their decarboxylation completely and reduces remarkably their reactivities in the addition to olefins and hydrogen-atom abstraction. The structure of the naphthoyloxyl radicals was discussed on the basis of their absorption spectra and MO calculations.
- Najiwara, Toshihiro,Hashimoto, Ji-ichiro,Segawa, Katsunori,Sakuragi, Hirochika
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p. 575 - 585
(2007/10/03)
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- Highly selective and efficient conversion of alkyl aryl and alkyl cyclopropyl ketones to aromatic and cyclopropane carboxylic acids by aerobic catalytic oxidation: A free-radical redox chain mechanism
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An efficient and convenient method has been developed for the oxidation of aryl alkyl and cyclopropyl alkyl ketones to aromatic and cyclopropane carboxylic acids by molecular oxygen at atmospheric pressure, catalysed by Mn(NQ3)2 in combination with Co(NO3)2 or Cu(NO3)2. This simple, cheap and highly selective process has a general character for the synthesis of carboxylic acids and it is particularly suitable for industrial applications.
- Minisci, Francesco,Recupero, Francesco,Fontana, Francesca,Bj?rsvik, Hans-Rene?,Liguori, Lucia
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p. 610 - 612
(2007/10/03)
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- Enantioselective hydrolysis of naproxen ethyl ester catalyzed by monoclonal antibodies
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This report described that a hapten of racemic phosphonate 3 designed as the mimic of the transition state of hydrolysis of naproxen ethyl ester was successfully synthesized from easily available 2-acetyl-6-methoxy-naphthalene 5. Then BALB/C mice were immunized and one of the monoclonal catalytic antibodies, N116-27, which enantioselectively accelerated the hydrolysis of the R-(-)-naproxen ethyl ester was given. The Michaelis-Menton parameter for the catalyzed reaction was KM=6.67 mM and kcat/kuncat=5.8×104. This enantioselective result was explained by the fact that the R-isomer of rac-hapten was more immunogenic than the S-isomer.
- Shi, Zhen-Dan,Yang, Bing-Hui,Zhao, Jing-Jing,Wu, Yu-Lin,Ji, Yong-Yong,Yeh, Ming
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p. 2171 - 2175
(2007/10/03)
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- Utilization of a peptide lead for the discovery of a novel PTP1B-binding motif
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Examination of the PTP1B inhibitory potency of an extensive series of phosphotyrosyl (pTyr) mimetics (Xxx) expressed in the EGFr-derived hexapeptide platform Ac-Asp-Ala-Asp-Xxx-Leu-amide previously led to the finding of high inhibitory potency when Xxx = 4-(phosphonodifluoromethyl)phenylalanyl (F2Pmp) (Ki = 0.2 μM) and when Xxx = 3-carboxy-4-carboxy-methyloxyphenylalanyl (Ki = 3.6 μM). In the first instance, further work led from the F2Pmp-containing peptide to monomeric inhibitor, 6-(phosphonodifluoromethyl)-2-naphthoic acid (Ki = 22 μM), and to the pseudo-dipeptide mimetic, N-[6-(phosphonodifluoromethyl)-2-naphthoyl]-glutamic acid (Ki = 12 μM). In the current study, a similar approach was applied to the 3-carboxy-4-carboxymethyloxyphenylalanyl-containing peptide, which led to the preparation of monomeric 5-carboxy-6-carboxymethyloxy-2-naphthoic acid (Ki = 900 μM). However, contrary to expectations based on the aforementioned F2Pmp work, incorporation of this putative pTyr mimetic into the pseudo-dipeptide, N-[5-carboxy-6-carboxymethyloxy-2-naphthoyl]-glutamic acid, resulted in a substantial loss of binding affinity. A reevaluation of binding orientation for 5-carboxy-6-carboxymethyloxy-2-naphthoic acid was therefore undertaken, which indicated a 180° reversal of the binding orientation within the PTP1B catalytic site. In the new orientation, the naphthyl 2-carboxyl group, and not the o-carboxy carboxymethyloxy groups, mimics a phosphoryl group. Indeed, when 5-carboxy-2-naphthoic acid itself was examined at neutral pH for inhibitory potency, it was found to have Ki = 31 ± 7 μM, which is lower than parent 5-carboxy-6-carboxymethyloxy-2-naphthoic acid. In this fashion, 5-carboxy-2-naphthoic acid (or more appropriately, 6-carboxy-1-naphthoic acid) has been identified as a novel PTP1B binding motif.
- Gao,Voigt,Zhao,Pais,Zhang,Wu,Zhang,Burke Jr.
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p. 2869 - 2878
(2007/10/03)
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- A general method for the alkaline cleavage of enolisable ketones
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An efficient method is described for the cleavage of enolisable aryl methyl and aryl ethyl ketones using an excess of KOH in DMF at an elevated temperature. It presents a general hydrolytic method yielding aromatic carboxylic acids, and is complementary to the widely used oxidative methods for ketone cleavage.
- Zabjek, Alenka,Petric, Andrej
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p. 6077 - 6078
(2007/10/03)
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- Method of inhibiting leukotriene biosynthesis by oral administration of p-aminophenols or derivatives thereof
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A method is provided for inhibiting leukotriene biosynthesis and thus treating asthma, psoriasis or inflammation by oral administration of p-aminophenols having the structure STR1 wherein m is 0 to 5; X is CH or N; R1 and R2 may be the same or different and are H, lower alkyl, aryl, hydroxy, hydroxyalkyleneoxy, alkylthio, alkoxy, alkanoyloxy, aryloxy, halo, carboxy, alkoxycarbonyl or amido; R3 is H, lower alkyl, alkanoyl or aroyl; and R4 is H, lower alkyl, benzoyl or alkanoyl, and including acid-addition salts thereof, with the proviso that when R4 is benzoyl, R2 is other than H.
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- Process for producing azo pigment
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A process for producing an azo pigment, which comprises coupling an aromatic diazonium compound with 3-hydroxy-2-naphthoic acid and at least one binaphthol and optionally, laking the resulting pigment.
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- Quinoline compounds and compositions thereof
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p-Aminophenols are provided having the structure STR1 wherein m is 0 to 5; X is CH or N; R1 and R2 may be the same or different and are H, lower alkyl, aryl, hydroxy, hydroxyalkyleneoxy, alkylthio, alkoxy, alkanoyloxy, aryloxy, halo, carboxy, alkoxycarbonyl or amido; R3 is H, lower alkyl, alkanoyl or aroyl; and R4 is H, lower alkyl or alkanoyl, and including acid-addition salts thereof, with the proviso that when X is CH, m is 0 and R1 is H, and when R4 is H, R2 is other than alkoxy, H or hydroxy, and when R4 is benzoyl, R2 is other than H. These compounds together with the compounds defined in the above proviso are useful as inhibitors of leukotriene production and as such are useful as antiallergy, anti-inflammatory and anti-psoriatic agents.
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- Reductive Methylation of Naphthoic Esters
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Reductive methylation of the naphthoic esters (3), (9), (13), and (15) was carried out in distilled liquid ammonia in the presence of sodium to give the esters (19), (20), (21), and (22), respectively.
- Basu, Basudeb,Mukherjee, Debabrata
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p. 105 - 106
(2007/10/02)
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- Synthesis and biological activities of 3-aminomethyl-1,2-dihydronaphthalene derivatives
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A series of 3-aminomethyl-1,2-dihydronaphthalene derivatives was prepared from the corresponding 3,4-dihydro-1(2H)-naphthalenone derivatives in three steps, namely the Mannich reaction, reduction of the carbonyl group with sodium borohydride, and dehydrat
- Itoh,Miyake,Tanabe,Hirata,Oka
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p. 2006 - 2015
(2007/10/02)
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- Kinetics of Base-catalysed Iodination of Substituted Acetonaphthones
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Kinetics of iodination of 6-substituted 2-acetonaphthones and of 4-substituted 1-acetonaphthones in 20percent pyridine-20percent methanol-60percent water (v/v) have been followed at three temperatures.The Hammett equation applies very well to these reactions.The rate constants for various heterocyclic base-catalysed iodination of acetophenone and of 1- and 2-acetonaphthones in 60percent (v/v) methanol-water solvent have been correlated with pKa values of the conjugate acids of the heterocyclic bases via the Broensted equation giving β values of 0.88, 1.01 and 0.92 for acetophenone, 1-acetonaphthone and 2-acetonaphthone respectively.The influence of solvent on the rates of pyridine-catalysed iodination of acetophenone and of 1- and 2-acetonaphthones has also been studied.
- Ananthakrishnanadar, P.,Gnanasekaran, C.
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p. 646 - 649
(2007/10/02)
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