- Polyhydroxybenzoic acid derivatives as potential new antimalarial agents
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With more than 200 million cases and 400,000 related deaths, malaria remains one of the deadliest infectious diseases of 2021. Unfortunately, despite the availability of efficient treatments, we have observed an increase in people infected with malaria since 2015 (from 211 million in 2015 to 229 million in 2019). This trend could partially be due to the development of resistance to all the current drugs. Therefore, there is an urgent need for new alternatives. We have, thus, selected common natural scaffolds, polyhydroxybenzoic acids, and synthesized a library of derivatives to better understand the structure–activity relationships explaining their antiplasmodial effect. Only gallic acid derivatives showed a noticeable potential for further developments. Indeed, they showed a selective inhibitory effect on Plasmodium (IC50 ~20 μM, SI > 5) often associated with interesting water solubility. Moreover, this has confirmed the critical importance of free phenolic functions (pyrogallol moiety) for the antimalarial effect. Methyl 4-benzoxy-3,5-dihydroxybenzoate (39) has, for the first time, been recognized as a potential lead for future research because of its marked inhibitory activity against Plasmodium falciparum and its significant hydrosolubility (3.72 mM).
- Degotte, Gilles,Francotte, Pierre,Pirotte, Bernard,Frédérich, Michel
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- Structure-activity relationship study and biological evaluation of SAC-Garlic acid conjugates as novel anti-inflammatory agents
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A series of S-allyl-L-cysteine (SAC) with garlic acid conjugates as anti-inflammatory agents were designed and synthesized. Among the 40 tested compounds, SMU-8c exhibited the most potent inhibitory activity to Pam3CSK4-induced nitric oxide (NO) in RAW264.7 macrophages with IC50 of 22.54 ± 2.60 μM. The structure-activity relationship (SAR) study suggested that the esterified carboxyl group, carbon chain extension and methoxylation phenol hydroxy could improve the anti-inflammatory efficacy. Preliminary anti-inflammatory mechanism studies showed that SMU-8c significantly down-regulated the levels of Pam3CSK4 triggered TNF-α cytokine in human THP-1 cells, mouse RAW 264.7 macrophages, as well as in ex-vivo human peripheral blood mononuclear cells (PBMC) with no influence on cell viability. SMU-8c specifically blocked the Pam3CSK4 ignited secreted embryonic alkaline phosphatase (SEAP) signaling with no influence to Poly I:C or LPS triggered TLR3 or TLR4 signaling. Moreover, SMU-8c suppressed TLR2 in HEK-Blue hTLR2 cells and inhibited the formation of TLR1-TLR2, and TLR2-TLR6 complex in human PBMC. In summary, SMU-8c inhibited the TLR2 signaling pathway to down-regulate the inflammation cytokines, such as NO, SEAP and TNF-α, to realize its anti-inflammatory activity.
- Bi, Jingjie,Wang, Wenqing,Du, Junxi,Chen, Kun,Cheng, Kui
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p. 233 - 245
(2019/07/02)
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- Preparation method of 3,5-dihydroxybenzyl alcohol
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The invention relates to a preparation method of a medical and chemical intermediate 3,5-dihydroxybenzyl alcohol. The method comprises the following steps of: with commercially available 3,5-dihydroxy-benzoic acid as a raw material, preparing 3,5-diacetoxybenzoic acid through an acetylation reaction; reducing carboxyl into alcohol by a sodium borohydride/iodine borohydride system; and finally, performing acetyl de-protection using a weak base solution to obtain the target product 3,5-dihydroxybenzyl alcohol. The synthesis path has the characteristics of cheap and easily available reagent, mild reaction conditions, easiness in operation, easiness in product separation, relatively high yield and the like.
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Paragraph 0007; 0011; 0012
(2017/05/27)
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- The application of template selectophores for the preparation of molecularly imprinted polymers
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Molecularly imprinted polymers are versatile materials with wide application scope for the detection, capture and separation of specific compounds present in complex feed stocks. A major challenge associated with their preparation has been the need to sacrifice one mole equivalent of the template molecule to generate the complementary polymer cavities that selectively bind the target molecule. Moreover, template molecules can often be difficult to synthesise, expensive or lack stability. In this study, we describe a new approach, directed at the use of synthetic selectophores, chosen as readily prepared and low cost structural analogues with recognition groups in similar three-dimensional arrangements as found in the target molecule. To validate the approach, a comparative study of selectophores related to the polyphenolic compound (E)-resveratrol has been undertaken using traditional and green chemical synthetic approaches. These molecular mimic compounds were employed as polymer templates and also as binding analytes to interrogate the recognition sites associated with the molecularly imprinted polymers. Importantly, the study confirms that the use of selectophores has the potential to confer practical advantages, including access to more efficient methods for selection and preparation of suitable template molecules with a broader range of molecular diversity, as well as delivering imprinted polymers capable of recognizing the target compound and structurally related products.
- Danylec, Basil,Schwarz, Lachlan J.,Harris, Simon J.,Boysen, Reinhard I.,Hearn, Milton T. W.
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supporting information
p. 17601 - 17613
(2015/10/12)
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- Bimolecular catalysis and turnover from a macromolecular host system
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The synthesis of a globular macromolecule and its application as a bimolecular catalyst are reported. The macromolecular structure supports (at least) two zinc-metalated porphyrin units, each capable of binding a single reactant. The proximity of the two
- Ellis, Adam,Gooch, David,Twyman, Lance J
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p. 5364 - 5371
(2013/07/26)
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- PREPARATION METHOD OF ACYLBENZENES
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A process for the production of acylbenzenes, comprising reacting diacetoxybenzoyl chloride with a Grignard reagent in the presence of an iron-containing catalyst. The acylbenzenes are useful intermediates in a multistep process for the preparation of resveratrol.
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Page/Page column 2
(2012/02/03)
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- PREPARATION METHOD OF ACYLBENZENES
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A process for the production of acylbenzenes, comprising reacting diacetoxybenzoyl chloride with a Grignard reagent in the presence of an iron-containing catalyst. The acylbenzenes are useful intermediates in a multistep process for the preparation of resveratrol.
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Page/Page column 4
(2012/02/04)
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- MOLECULARLY IMPRINTED POLYMERS
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The present invention provides methods of designing molecularly imprinted polymers (MIPs) which have applications in extracting bioactive compounds from a range of bioprocessing feedstocks and wastes. The present invention is further directed to MIPs designed by the methods of the present invention.
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- Studies on depigmenting activities of dihydroxyl benzamide derivatives containing adamantane moiety
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Six diphenolic compounds containing adamantane moiety were synthesized and evaluated as potent inhibitors on tyrosinase activity and melanin formation in melan-a cells. The inhibitory activity of 4-adamantyl resorcinol 1 was similar to that of 4-n-butyl resorcinol in both assays. However, dihydroxyl benzamide derivatives 6a-e showed different inhibitory patterns. All derivatives significantly suppressed the cellular melanin formation without tyrosinase inhibitory activities. These behaviors indicated that the introduction of amide bond changes the binding mode of dihydroxyl groups to tyrosinase. Among derivatives, 6d (3,4-dihydroxyl compound) and 6e (2,3-dihydroxyl compound) showed stronger inhibitory activities (IC50 = 1.25 μM and 0.73 μM, respectively) as compared to 4-n-butyl resorcinol (IC50 = 21.64 μM) and hydroquinone (IC50 = 3.97 μM). This study showed that the position of dihydroxyl substituent at aromatic ring is important for the intercellular inhibition of melanin formation, and also amide linkage and adamantane moiety enhance the inhibition.
- Rho, Ho Sik,Baek, Heung Soo,Ahn, Soo Mi,Yoo, Jae Won,Kim, Duck Hee,Kim, Han Gon
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scheme or table
p. 1532 - 1533
(2009/12/01)
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- Novel Sirtuin Activating Compounds and Methods for Making the Same
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The present invention includes methods for preparing resveratrol, resveratrol esters and substituted and unsubstituted stilbenes of the formula given below; where each Y is —O or halogen, each Z is —O or halogen, each n and each m is independently the value of 0, 1, 2, 3, 4 or 5, each A and each B is independently selected from Pn, R or absent, each V and each W is independently selected from Pn, straight or branched alkyl of from (2) to (6) carbon atoms and cycloalkyl of from (3) to (8) carbon atoms, alkoxy, phenyl, benzyl or halogen, R is independently selected from the group comprising alkyl with at least one carbon atom, aryl and aralkyl, Pn is an alcohol protecting group and diastereoisomers of the foregoing. The compounds are made from a multi-step process including a N-heterocyclic carbon-type ligand coupling in the presence of a base with benzyol halide and styrene coupling partners. These compounds show increased stability for use in the food, cosmetic and pharmaceutical industries.
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Page/Page column 25
(2008/12/04)
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- Hydroxybenzamide Derivatives, the Method For Preparing Thereof and the Cosmetic Composition Containing the Same
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Disclosed is a hydroxybenzamide derivative represented by the following Formula. A method for preparing the same and a cosmetic composition comprising the same are also disclosed. More particularly, the hydroxybenzamide derivative is obtained by reacting
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Page/Page column 2; 3
(2008/12/08)
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- HYDROXYBENZAMIDE DERIVATIVES, THE METHOD FOR PREPARING THEREOF AND THE COSMETIC COMPOSITION CONTAINING THE SAME
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Disclosed is a hydroxybenzamide derivative represented by the following Formula (1). A method for preparing the same and a cosmetic composition comprising the same are also disclosed. More particularly, the hydroxybenzamide derivative is obtained by react
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Page/Page column 4-5; 8
(2010/11/26)
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- First gallamine-tacrine hybrid: Design and characterization at cholinesterases and the M2 muscarinic receptor
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Gallamine and tacrine are allosteric antagonists at muscarinic M 2 acetylcholine receptors and inhibitors of acetylcholinesterase. At both acetylcholine-binding proteins, gallamine and tacrine are known to occupy two different binding sites: in M2 receptors within the allosteric binding area and in acetylcholinesterase at its catalytic and its peripheral site. To find new ligands of both targets, we designed a gallamine-tacrine dimer and several derived hybrid compounds to address the two binding sites. Their M2 receptor allosteric and acetylcholinesterase inhibitory potential was determined. The hybrid compounds revealed an allosteric potency in the low nanomolar range exceeding the allosteric potency of gallamine and tacrine by factors of 100 and 4800, respectively. Cholinesterase inhibition was augmented by hybrid formation, and all compounds exhibited IC50 values in the lower nanomolar range. Thus, gallamine-tacrine hybrid formation is a valuable approach toward high affinity ligands concurrently targeting these acetylcholine-binding proteins.
- Elsinghorst, Paul W.,Cieslik, Julia S.,Mohr, Klaus,Tr?nkle, Christian,Gütschow, Michael
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p. 5685 - 5695
(2008/03/17)
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- Synthesis of polyhydroxylated ester analogs of the stilbene resveratrol using decarbonylative Heck couplings
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Protected 3,5-hydroxy-benzoyl chlorides 3 were coupled with styrenes 4 to give hydroxylated stilbenes, analogs of resveratrol, an important antioxidant disease preventative agent isolated from grape skins and other dietary sources. Levulinate and chloroacetate protecting groups allowed for the selective production of mono- and di-acetate variations under palladium-N-heterocyclic carbene (NHC) catalyzed decarbonylative coupling conditions. Fluorinated analogs were also produced using Heck conditions with bromofluorobenzenes. Human HL-60 cell assays showed the 4′-acetoxy variant 11 to have improved activity (ED50 17 μM) relative to resveratrol (24 μM).
- Andrus, Merritt B.,Liu, Jing
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p. 5811 - 5814
(2007/10/03)
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- HIV-1 integrase inhibition of biscoumarin analogues
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Nineteen biscoumarins bearing free and modified hydroxyl substituents at benzoyloxyphenyl linker have been synthesized by multiple step synthesis. Among these biscoumarins, thirteen were found to be active molecules against HIV-1 integrase (HIV-1 IN). The structure-activity relationship of the nineteen compounds on HIV IN may be useful for the design of potent therapeutic agents.
- Chang-Xiao,Mouscadet, Jean-Francois,Chiang, Chih-Chia,Tsai, Hou-Jen,Hsu, Ling-Yih
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p. 682 - 686
(2007/10/03)
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- Synthesis of selenium-containing polyphenolic acid esters and evaluation of their effects on antioxidation and 5-lipoxygenase inhibition
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Six novel selenium-containing polyphenolic acid esters were synthesized and evaluated as antioxidants and 5-lipoxygenase inhibitors. Synthesis of the title compounds involved the Mitsunobu reaction of polyphenolic acids (4-8, 14) with 2-phenylselenoethanol (3). Compounds 22, 23, and 25 were found to be very effective antioxidants and 5-lipoxygenase inhibitors with activity comparable to or better than caffeic acid (3,4-dihydroxycinnamic acid) phenethyl ester (CAPE).
- Lin, Chi-Fu,Chang, Tsu-Chung,Chiang, Chih-Chia,Tsai, Hou-Jen,Hsu, Ling-Yih
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p. 1402 - 1407
(2007/10/03)
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- Synthesis of resveratrol using a direct decarbonylative Heck approach from resorcylic acid
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The phytoalexin resveratrol has been made using a decarbonylative Heck reaction. The acid chloride derived from 3,5-dihydroxybenzoic acid was coupled with 4-acetoxystyrene in the presence of palladium acetate and N,N-bis-(2,6-diisopropylphenyl)dihydroimidazolium chloride to give the substituted stilbene in 73% yield as the key step.
- Andrus, Merritt B.,Liu, Jing,Meredith, Erik L.,Nartey, Edward
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p. 4819 - 4822
(2007/10/03)
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- Synthesis and biological evaluation of CX-659S and its related compounds for their inhibitory effects on the delayed-type hypersensitivity reaction
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In order to find novel nonsteroidal compounds possessing an inhibitory activity against delayed-type hypersensitivity (DTH) reactions, we conducted random screening using a picryl chloride (PC)-induced contact hypersensitivity reaction (CHR) in mice, and found compound 1 as a lead compound. Then we synthesized and evaluated an extensive series of 5-carboxamidouracil derivatives focused on both the uracil and the antioxidative moieties. Among them, we found that the hindered phenol moiety was necessary to exhibit the activities; especially, compounds 28a-28c having the partial structure of vitamin E were found to exert potent activities against the DTH reaction by both oral and topical administration. And compound 28c showed antioxidative activity against lipid peroxidation with an IC50 of 5.9μM. Compound 28c (CX-659S) was chosen as a candidate drug for the treatment of cutaneous disorders such as atopic dermatitis and allergic contact dermatitis. Copyright (C) 2000 Elsevier Science Ltd.
- Tobe, Masanori,Isobe, Yoshiaki,Goto, Yuso,Obara, Fumihiro,Tsuchiya, Masami,Matsui, Junko,Hirota, Kosaku,Hayashi, Hideya
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p. 2037 - 2047
(2007/10/03)
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- Novel Enzymatic De-esterification Studies on Substituted Polyacetoxybenzamides
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The regioselective capabilities of porcine pancreatic lipase in tetrahydrofuran and Candida rugosa lipase in diisopropyl ether have been investigated for selective deacetylation of peracetates of primary, secondary and tertiary amides of 2-hydroxy-, 2,4-dihydroxy-, 2,5-dihydroxy-, 3,5-dihydroxy- and 3,4,5-trihydroxybenzoic acids. The lipases exhibit random selectivity for the deacetylation of ortho-, meta- and para-acetoxy functions of di/triacetoxybenzamides leading to the formation of the corresponding partially and/or completely deacetylated benzamides. The amide group of all substrates under investigation remains inert to enzymatic hydrolysis. The results of deesterification are in good agreement with our earlier proposed mechanism of action of porcine pancreatic lipase on diaryl or aryl alkyl ketones in organic solvents.
- Parmar, Virinder S.,Kumar, Ajay,Prasad, Ashok K.,Kumar, Rajesh,Bisht, Kirpal S.,Poonam,Jain, Subhash C.,Olsen, Carl E.
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p. 810 - 822
(2007/10/03)
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- Process for preparing substituted aryls
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The present invention provides a novel one-step process for preparing substituted aryls which can be used as end-capping monomers for preparing highly branched macromolecule polymers that have highly controlled molecular architectures. The process compris
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- Hyperbranched polymers
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The present invention provides novel highly branched macromolecule polymers that have highly controlled molecular architectures, and having the formula: STR1 wherein R4, R5, and R6 are defined herein.
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- 1-arylpyrimidine derivatives and pharmaceutical use thereof
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The present invention relates to 1-arylpyrimidine derivatives represented by general formula (I): STR1 wherein R1 is H, alkyl or aralkyl; Ar is 1-naphthyl, or a substituted or unsubstituted phenyl group; R4 is a substituted phenyl, a substituted styryl, 1-methylcyclohexyl, 4-methylcyclohexyl, 4-oxo-4H-pyran-2-yl or 2-oxo-2H-pyran-5-yl group; R5 and R6 are each independently H or alkyl; R3 is H, and R7 and R8 are combined together to be oxo, or else R3 and R7 are combined together to be another direct bond, and R5 and R8 are combined together to be a direct bond, or pharmaceutically acceptable salts thereof; and methods for treating allergic diseases with such compounds.
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- H-bonded oxyhemoglobin models with substituted picket-fence porphyrins: The model compound equivalent of site-directed mutagenesis
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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 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. The effect of H-bonding on the dioxygen affinity under standard conditions (25 °C, toluene solvent, 1,2-dimethylimidazole as axial ligand) is best illustrated by the ca. 10-fold increase observed when one pivalamide substituent of picket-fence porphyrin is replaced by a phenylurea substituent. Other substituents influence dioxygen adduct stability in a variety of ways to reveal that even with an apparently straightforward systematic approach, there can be considerable difficulty in partitioning the various factors that influence O2 affinity. This applies to both model compounds and mutant proteins.
- Wuenschell, Gerald E.,Tetreau, Catherine,Lavalette, Daniel,Reed, Christopher A.
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p. 3346 - 3355
(2007/10/02)
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- Disubstituted piperazines
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Piperazines of the formula STR1 and their salts, in which each of Ar1 and Ar2, independently of the other, represents phenyl that is unsubstituted or mono- or di-substituted by C1 -C7 -alkyl, C1 -C7 -alkoxy, cyano, halogen, trifluoromethyl, amino, C1 -C7 -alkylamino, di-C1 -C7 -alkylamino and/or by C1 -C7 -alkanoylamino, can be used as the active ingredients of medicaments and are manufactured in a manner known per se.
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- Natural Benzofurans. Synthesis of Moracin A and B
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2-(3,5-Dihydroxyphenyl)-4,6-dimethoxybenzofuran (Moracin A) and 2-(3-hydroxy-5-methoxyphenyl)-5-hydroxy-6-methoxybenzofuran (Moracin B), phytoalexins isolated from diseased mulberry have been synthesized by short routes in which the benzofuran heterocyclic system is formed by an intramolecular Wittig reaction.
- Burke, John M.,Stevenson, Robert
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p. 451 - 466
(2007/10/02)
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