- Synthesis and anti-inflammatory activity evaluation of novel chroman derivatives
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In an effort to develop potent anti-inflammatory agents, a series of novel chroman derivatives including acyclic amidochromans, chromanyl esters and chromanyl acrylates have been designed, synthesized and fully characterized. These chroman analogues were screened for their anti-inflammatory activities through inhibition of the TNF-α-induced ICAM-1 expression on human endothelial cells. A structure-activity relationship was also established and it has been found that in the case of carboxy chromans and amidochromans, the chain length of the amide moiety, branching of the side chain and the presence of the substituents on the phenyl ring have significant effects on their inhibitory activities, while in chromanyl acrylates, the number of methoxy groups, their relative positions on the phenyl ring, and presence of functional groups in the α,β-unsaturated ester moiety played a critical role on their activities. Compound 14 (N-hexyl-7-hydroxy-2,2-dimethylchromane-6-carboxamide) was found to be the most potent compound in inhibiting the TNF-α-induced expression of ICAM-1 on endothelial cells. This journal is
- Balwani, Sakshi,Cao, Pei,Depass, Anthony L.,Ghosh, Balaram,Kumar, Sandeep,Len, Christophe,Matta, Akanksha,Parmar, Virinder S.,Prasad, Ashok K.,Sharma, Ajendra K.,Singh, Brajendra K.,Tomar, Shilpi,Van Der Eycken, Erik V.,Wengel, Jesper
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p. 13716 - 13727
(2020/09/07)
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- Concise, stereocontrolled and modular syntheses of the anti-influenza rubrolides R and S
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The fungal metabolites rubrolide R and S were synthesized in concise, entirely stereoselective fashion through the combined use of bromine-stereodirected vinylogous aldol condensation (SVAC) and Suzuki cross-coupling. A bioinspired, high-yield conversion
- Moreira, Thaís A.,Lafleur-Lambert, Rapha?l,Barbosa, Luiz C.A.,Boukouvalas, John
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supporting information
(2019/11/13)
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- CHROMANE-SUBSTITUED TETRACYCLIC COMPOUNDS AND USES THEREOF FOR TREATMENT OF VIRAL DISEASES
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Disclosed are novel chromane-substituted tetracyclic compounds of Formula (I), and pharmaceutically acceptable salts thereof, wherein A, A', R2 R3, R4 and R5 are as defined in the description. Also disclosed are compositions comprising a chromane-substituted tetracyclic compound, and methods of using the chromane-substituted tetracyclic compounds for treating or preventing HCV infection in a patient.
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- Efficient, collective synthesis and nitric oxide inhibitory activity of rubrolides E, F, R, S and their derivatives
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An efficient first synthesis of biologically significant natural butenolides, rubrolides F (1f), R (1r), S (1s) & its 7″,8″-didehydro derivative (1sa), and 3″-bromo rubrolide (1fa) along with the synthesis of rubrolide E (1e) and its di-O-methyl derivative (1ea) is accomplished in a collective fashion from commercially available and inexpensive precursors in overall yields of 14–48.5%. Key features are Wittig-Horner reaction, SeO2-induced tandem allylic hydroxylation/intramolecular cyclization and Knoevenagel condensation. Next, in their inhibitory activity towards nitric oxide (NO) production in lipopolysaccharide-induced RAW 264.7 macrophages as an indicator of anti-inflammatory activity, all compounds displayed good inhibitory activity in a concentration-dependent manner. None of the compound exhibited notable cytotoxicity at the highest concentration (10?μM) and IC50values are found in the range from 8.53 to 17.85?μM.
- Damodar, Kongara,Kim, Jin-Kyung,Jun, Jong-Gab
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supporting information
p. 50 - 53
(2016/12/23)
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- Synthetic method for rubrolide compounds E, F, R, S and their derivatives
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Rubrolide F (compound 1f), R (compound 1r), and S (compound 1s), which are biological important natural butenolides, 7andPrime;,8andPrime;-didihydro derivatives (compound 1sa) thereof, 3andPrime; -bromorubrolide (compound 1fa), rubrolide E (compound 1e) and di-O-methyl derivatives thereof (compound 1ea) can be industrially obtained and are effectively synthesized with the overall yield of 14-48.5% from low-priced precursors. The rubrolide compounds can be synthesized through a Knoevenagel condensation reaction after a Wittig-Horner reaction and SeO_2-induced tandem allylic hydroxylation/intramolecular cyclization for preparing butenolide rings and a rubrolide cores structure.COPYRIGHT KIPO 2017
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Paragraph 0127; 0128
(2018/03/28)
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- Flavone acetic acid derivatives, pharmaceutical composition thereof as well as preparation methods and applications of flavone acetic acid derivatives and pharmaceutical composition
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The invention belongs to the field of medication chemistry, and relates to flavone acetic acid derivatives, pharmaceutical composition thereof as well as preparation methods and applications of the flavone acetic acid derivatives and the pharmaceutical co
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Paragraph 0147; 0148; 0149; 0150; 0151
(2017/01/02)
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- Discovery of Chromane Containing Hepatitis C Virus (HCV) NS5A Inhibitors with Improved Potency against Resistance-Associated Variants
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The discovery of potent and pan-genotypic HCV NS5A inhibitors faces many challenges including the significant diversity among genotypes, substantial potency shift conferred on some key resistance-associated variants, inconsistent SARs between different genotypes and mutants, and the lacking of models of inhibitor/protein complexes for rational inhibitor design. As part of ongoing efforts on HCV NS5A inhibition at Merck, we now describe the discovery of a novel series of chromane containing NS5A inhibitors. SAR studies around the "Z" group of the tetracyclic indole scaffold explored fused bicyclic rings as alternates to the phenyl group of elbasvir (1, MK-8742) and identified novel chromane and 2,3-dihydrobenzofuran derivatives as "Z" group replacements offered good potency across all genotypes. This effort, incorporating the C-1 fluoro substitution at the tetracyclic indole core, led to the discovery of a new series of NS5A inhibitors, such as compounds 14 and 25-28, with significantly improved potency against resistance-associated variants, such as GT2b, GT1a Y93H, and GT1a L31V. Compound 14 also showed reasonable PK exposures in preclinical species (rat and dog).
- Yu, Wensheng,Tong, Ling,Hu, Bin,Zhong, Bin,Hao, Jinglai,Ji, Tao,Zan, Shuai,Coburn, Craig A.,Selyutin, Oleg,Chen, Lei,Rokosz, Laura,Agrawal, Sony,Liu, Rong,Curry, Stephanie,McMonagle, Patricia,Ingravallo, Paul,Asante-Appiah, Ernest,Chen, Shiying,Kozlowski, Joseph A.
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p. 10228 - 10243
(2016/12/07)
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- SPIROXAZOLIDINONE COMPOUNDS
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Substituted spirocyclic amines of structural formula (I) are selective antagonists of the somatostatin subtype receptor 5 (SSTR5) and are useful for the treatment, control or prevention of disorders responsive to antagonism of SSTR5, such as Type 2 diabetes, insulin resistance, lipid disorders, obesity, atherosclerosis, Metabolic Syndrome, depression, and anxiety.
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- Search of antimycobacterial activities in hybrid molecules with benzopyran skeleton
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A series of hybrid molecules (7-9, 12, 13, and 14-18) consisting of chromans and pyrolidines or cyclic amines were prepared either by (3 + 2) cycloaddition of nitrostyrenes and azomethine ylide or by three component reactions of chromanyl aldehydes, acetylenes, and cyclic amines. All the synthesized compounds were evaluated against both avirulent (H37Ra) and virulent (H37Rv) strains of Mycobacterium tuberculosis. Out of all the compounds screened, compounds 16, 17, and 18 were found to be active against the virulent strain M. tubercolosis H37Rv displaying MIC in the range of 6.25-1.56 μg/ml against. Springer Science+Business Media, LLC 2010.
- Tripathi, Rama P.,Bisht, Surendra Singh,Pandey, Vivek Parashar,Pandey, Sarvesh K.,Singh, Shubhra,Sinha, Sudhir Kumar,Chaturvedi, Vinita
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experimental part
p. 1515 - 1522
(2012/06/15)
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- Synthesis of (±)Abyssinone I and related compounds: Their anti-oxidant and cytotoxic activities
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An efficient and facile synthesis of naturally occurring prenylated flavonoids and their analogs have been described. Abyssinone I (9a) was prepared by condensing 2,2-dimethyl chrom-3-en-6-carboxaldehyde (5a) with protected resacetophenone under phase transfer conditions followed by deprotection and cyclization. The influence of prenyl group on anti-oxidant and cytotoxic activities was studied. The presence of 3′-prenyl group as in 8c enhanced radical scavenging activity but decreased reducing power activity when compared to non-prenylated analog 8f. In vitro testing in MCF-7 cell line revealed that prenylated chalcones and flavanones showed better inhibitory activity than their non-prenylated counterparts. Abyssinone I and its chalcone though exhibited negligible anti-oxidant activity their cytotoxic activities were comparable with other prenylated analogs.
- Rao, Gudapati Venkateswara,Swamy, Badrappa Narayana,Chandregowda, Venkateshappa,Reddy, G. Chandrasekara
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experimental part
p. 2239 - 2245
(2009/09/08)
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- Design, synthesis, and biological evaluation of novel diarylalkyl amides as TRPV1 antagonists
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We have developed a new class of diarylalkyl amides as novel TRPV1 antagonists. They exhibited potent 45Ca2+ uptake inhibitions in rat DRG neuron. In particular, the amide 59 was identified as a potent antagonist with IC50 of 57 nM. The synthesis and structure-activity relationship of the diarylalkyl amides are also described.
- Li, Fu-Nan,Kim, Nam-Jung,Paek, Seung-Mann,Kwon, Do-Yeon,Min, Kyung Hoon,Jeong, Yeon-Su,Kim, Sun-Young,Park, Young-Ho,Kim, Hee-Doo,Park, Hyeung-Geun,Suh, Young-Ger
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experimental part
p. 3557 - 3567
(2009/09/27)
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- Montmorillonite clays in organic synthesis: A one-pot conversion of phenols to 2,2-dimethylbenzopyrans
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2,2-Dimethylbenzopyran derivatives were generated through a one-pot Montmorillonite K10 clay-catalyzed condensation of substituted phenols with prenyl bromide.
- Dintzner, Matthew R.,McClelland, Kristen M.,Morse, Kara M.,Akroush, Michael H.
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p. 2028 - 2030
(2007/10/03)
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- Structure-activity relationship of piperine and its synthetic analogues for their inhibitory potentials of rat hepatic microsomal constitutive and inducible cytochrome P450 activities
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Inhibitors of drug metabolism have important implications in pharmaco- toxicology and agriculture. We have reported earlier that piperine, a major alkaloid of black and long peppers inhibits both constitutive and inducible cytochrome P450 (CYP)-dependent drug metabolising enzymes. In the present study, an attempt has been made to prepare several novel synthetic analogues so as to relate various modifications in the parent molecule to the inhibition of CYP activities. Two types of mono-oxygenase reactions arylhydrocarbon hydroxylase (AHH) and 7-methoxycoumarin-O-demethylase (MOCD) have been studied. Inhibition studies were investigated in rat microsomal fraction prepared from untreated, 3MC- and PB- treated rat liver in vitro. Modifications were introduced into the piperine molecule: (i) in the phenyl nucleus, (ii) in the side chain and (iii) in the basic moiety. Thus, 38 compounds have been subjected to such studies, and simultaneously an attempt has also been made to arrive at the structure-activity relationship of synthetic analogues. In general, most of the inhibitory potential of the parent molecule is lost with modification in either of the three components of piperine. Saturation of the side chain resulted in significantly enhanced inhibition of CYP while modifications in the phenyl and basic moieties in few analogues offered maximal selectivity in inhibiting either constitutive or inducible CYP activities. Thus few novel analogues as CYP inactivators have been synthesized which may have important consequences in pharmacokinetics and bioavailability of drugs. (C) 2000 Elsevier Science Ltd.
- Koul, Surrinder,Koul, Jawahir L.,Taneja, Subhash C.,Dhar, Kanaya L.,Jamwal, Deshvir S.,Singh, Kuldeep,Reen, Rashmeet K.,Singh, Jaswant
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p. 251 - 268
(2007/10/03)
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- Facile synthesis of 2,2-Dimethylchromans by Mo(CO)6 Catalyzed reaction of aryl prenyl ethers
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2,2-Dimethylchromans 3a-g are synthesized in good yields by a one-pot reaction of the aryl prenyl ethers 1a-g with a catalytic amount of Mo(CO)6 in refluxing toluene.
- Bernard, Angela M.,Cocco, Maria T.,Onnis, Valentina,Piras, Pier P.
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p. 256 - 258
(2007/10/03)
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- Design, synthesis, and testing of potential antisickling agents. 10. (2,2-Dimethylchroman-6-yl)alkanoic acids
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Five (2,2-dimethylchroman-6-yl)alkanoic acids were synthesized and tested for antigelling activities. It was envisioned that these agents might bind via hydrophobic bonding to nonpolar sites of the 'donor-acceptor' regions of hemoglobin S. Several (2,2-di
- Fatope,Abraham
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p. 1973 - 1977
(2007/10/02)
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- Synthesis of 6-(1-Hydroxyethyl)-2,2-dimethyl-2H--benzopyrans: Eupatoriachromene-C and Desmethoxyencecalinol
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6-Acetyl-5,8-dimethoxy-2,2-dimethyl-2H--benzopyran (2) on reduction with potassium borohydride gives eupatoriochromene-C (1).Condensation of 4-Hydroxyacetophenone with isoprene in the presence of orthophosphoric acid gives the chroman (5) which on dehydrogenation with NBS furnishes desmethoxyencecalin (4). 4 on reduction with potassium borohydride affords desmethoxyencecalinol (3).Alternatively, 4-hydroxybenzaldehyde on condensation with isoprene gives the monochroman (6) which is also obtained by a similar condensation of 4-methylphenol with isoprene followed by reaction with DDQ.Dehydrogenation of 6 with NBS affords 6-formyl-2,2-dimethyl-2H--benzopyran (8) and 6-phenacyl bromide derivative (9). 8 on reaction with methylmagnesium iodide furnishes 3.
- Ahluwalia, V. K.,Mukherjee, Irani,Mukherjee, Keya
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p. 1124 - 1125
(2007/10/02)
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