- Modified coumarins. 32. Synthesis of amino-acid derivatives of dihydropyranocoumarins
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Linear dihydropyranocoumarins containing natural and synthetic amino acids were synthesized using activated esters.
- Veselovskaya,Garazd, Ya. L.,Garazd,Ogorodniichuk
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Read Online
- Modified coumarins. 13. Synthesis of cyclopentane-annelated pyranocoumarins
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Modified pyranocoumarins containing a condensed cyclopentane fragment were synthesized by adjoining a 2,2-dimethyltetrahydropyran ring to a 2,3-dihydrocyclopenta[c]chromen-4-one system and annelation of a pyrone ring to a 2,2-dimethylchromane.
- Garazd,Garazd,Khilya
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Read Online
- Design, synthesis and biological evaluation of novel benzoxaborole derivatives as potent PDE4 inhibitors for topical treatment of atopic dermatitis
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In this work, a series of structurally novel benzoxaborole derivatives were designed, synthesized and biologically evaluated as PDE4 inhibitors for battling atopic dermatitis (AD). Among them, the majority exhibited superior PDE4B inhibitory activities to that of the lead compound Crisaborole, an approved PDE4 inhibitor. In particular, 72, the most potent PDE4B inhibitor throughout this series, displayed 136-fold improved enzymatic activity (IC50 = 0.42 nM) as compared to Crisaborole (IC50 = 57.20 nM), along with favorable isoform specificity. In the phorbol ester (PMA)-induced mouse ear oedema model, 72 exerted remarkably greater efficacy than Crisaborole at the same dosage (P 0.05). Moreover, the ointment of 72 exerted dramatically enhanced therapeutic potency than the ointment of Crisaborole (P 0.05) in the calcipotriol-induced mouse AD model. In addition to the potent in vitro and in vivo activity, 72 displayed favorable safety in the repeated oral dose toxicity study and did not exhibit phototoxicity. With the above attractive biological performance, 72 is worthy of further functional investigation as a novel anti-AD therapeutic agent.
- Chu, Zhaoxing,Xu, Qinlong,Zhu, Qihua,Ma, Xiaodong,Mo, Jiajia,Lin, Gaofeng,Zhao, Yan,Gu, Yuanfeng,Bian, Lincui,Shao, Li,Guo, Jing,Ye, Wenfeng,Li, Jiaming,He, Guangwei,Xu, Yungen
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Read Online
- Synthesis and biological evaluation of substituted amide derivatives of C4-ageratochromene dimer analog
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Substituted amide derivatives of C4-ageratochromene dimer analog (19) were synthesized through structural modification of precocene-I (4a), isolated from the essential oil of Ageratum conyzoides L. The target compounds (18–20, 23I-VI, 24I-VI, and 25I-VI) were evaluated for their bone-forming effect using osteoblast differentiation assay. Seven compounds (23I, 23II, 23IV, 23VI, 24III, 24VI, and 25VI) presented good activity within 1 pM–1 nM concentration. At 1 pM concentration, the most active compound i.e. 23II showed effective mineralization of osteoblast cells along with expression of osteogenic marker genes viz RUNX 2, BMP-2, and type 1 collagen (Type-1 col) without any toxicity towards osteoblast cells. Single crystal X-ray analysis of 18 and 20 revealed that the core nucleus of these molecules bear phenyl rings in a Trans-stilbenoid system and had a good structural correlation with 17β-estradiol (1) and diethylstilbestrol (DES, 3). In-silico study about 23II showed its structural complementarities with the LBD of estrogen receptor (ER) which indicated possible ER-mediated activity of compounds.
- Agarwal, Karishma,Gupta, Kratika,Sharma, Kriti,Khanka, Sonu,Singh, Shilpi,Singh, Jyoti,Trivedi, Laxmikant,Vasdev, Prema G.,Luqman, Suaib,Khan, Feroz,Singh, Divya,Gupta, Atul
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- Design and structural optimization of novel 2H-benzo[h]chromene derivatives that target AcrB and reverse bacterial multidrug resistance
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Drug efflux pumps have emerged as a new drug targets for the treatment of bacterial infections in view of its critical role in promoting multidrug resistance. Herein, novel chromanone and 2H-benzo[h]chromene derivatives were designed by means of integrated molecular design and structure-based pharmacophore modeling in an attempt to identify improved efflux pump inhibitors that target Escherichia coli AcrB. The compounds were tested for their efflux inhibitory activity, ability to inhibit efflux, and the effect on bacterial outer and inner membranes. Twenty-three novel structures were identified that synergized with antibacterials tested, inhibited Nile Red efflux, and acted specifically on the AcrB. Among them, WK2, WL7 and WL10 exhibiting broad-spectrum and high-efficiency efflux inhibitory activity were identified as potential ideal AcrB inhibitors. Molecular modeling further revealed that the strong π-π stacking interactions and hydrogen bond networks were the major contributors to tight binding of AcrB.
- Wang, Yinhu,Alenazy, Rawaf,Gu, Xinjie,Polyak, Steven W.,Zhang, Panpan,Sykes, Matthew J.,Zhang, Na,Venter, Henrietta,Ma, Shutao
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- Synthesis of 3,5-Disubstituted isoxazoles containing privileged substructures with a diverse display of polar surface area
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We designed and synthesized the molecular framework of 3,5-disubstituted isoxazoles containing privileged substructures with various substituents which uniquely display polar surface area in a diverse manner. A library of 3,5-disubstituted isoxazoles were systematically prepared via 1,3-dipolar cycloaddition of alkynes with nitrile oxides prepared by two complementary synthetic routes; method A utilized a halogenating agent with a base and method B utilized a hypervalent iodine reagent. Through the biological evaluation of corresponding isoxazoles via three independent phenotypic assays, the different pattern of biological activities was shown according to the type of privileged substructure and substituent. These results demonstrated the significance of molecular design via introducing privileged substructures and various substituents to make a diverse arrangement of polar surface area within a similar 3-dimensional molecular framework.
- Kim, Mingi,Hwang, Yoon Soo,Cho, Wansang,Park, Seung Bum
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supporting information
p. 407 - 413
(2017/06/19)
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- Modified Coumarins. 36. Synthesis of Linear and Angular Dihydropyranocoumarincarboxylic Acids
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The syntheses of linear and angular dihydropyranocoumarincarboxylic acids, modified structural derivatives of dihydroxanthyletin and dihydroseselin, were described.
- Garazd, Ya. L.,Garazd
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p. 399 - 404
(2016/07/26)
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- 2,2-dimethyl-chromanone compound and its analogue medical use
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The invention belongs to the technical field of medicines and relates to a pharmaceutical use of a 2, 2-dimethyl chromanone type compound and analogs thereof. The structural general formula is as follows, wherein X can be selected from CH2 or C=O; and R and R' are as described in the description. The new compound provided by the invention can be used as an effective anti-platelet medicament, can be particularly applied to the preparation of medicaments for preventing or treating coronary syndrome, myocardial infarction, myocardial ischemia and cardiovascular and cerebrovascular diseases caused by platelet aggregation and can further treat thrombus formation, ischemia, stroke, restenosis or inflammation.
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Paragraph 0052; 0053; 0054
(2016/10/10)
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- Neuroprotective effects of benzyloxy substituted small molecule monoamine oxidase B inhibitors in Parkinson's disease
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The benzyloxy substituted small molecules are well-known highly potent monoamine oxidase B inhibitors, but their therapeutic potential against Parkinson's disease have not been investigated in detail. In this paper, a series of representative benzyloxy substituted derivatives were synthesized and evaluated for MAO-A/B inhibition. In addition, their neuroprotective effects were investigated in 6-OHDA- and rotenone-treated PC12 cells. It was observed that most of the compounds exhibited a marked increase in survival of PC12 cells which treated with the neurotoxins. Among them, 13 exhibited remarkable and balanced neuroprotective potency. The protective effects of 13 against neurotoxins-induced apoptosis were confirmed with flow cytometry and staining methods. Furthermore, 13 also showed good BBB permeability and low toxicity according to in vitro BBB prediction and in vivo acute toxicity test. The results indicated that 13 is an effective and promising candidate to be further developed as disease-modifying drug for Parkinson's disease therapy.
- Wang, Zhimin,Wu, Jiajia,Yang, Xuelian,Cai, Pei,Liu, Qiaohong,Wang, Kelvin D.G.,Kong, Lingyi,Wang, Xiaobing
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supporting information
p. 5929 - 5940
(2016/11/09)
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- The structure containing piperazine 2,2-dimethyl-chromanone compound and its analogue medical use
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The invention belongs to the technical field of medicines and relates to a medical application of 2, 2-dimethyl thiochromanone compounds containing piperazine structures and analogues thereof. The structural general formula of the 2, 2-dimethyl thiochroma
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Paragraph 0050-0052
(2017/04/06)
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- Efficient total synthesis of naturally occurring anti-TMV compound gramniphenol G
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An efficient synthesis of Gramniphenol G identified as 2-(4′-Methoxyphenyl)-7,7-dimethyl-7H-furo[3,2-g]chromene and originally isolated from the plant Arundina gramnifolia belonging to orchidaceae family was accomplished starting from resorcinol. The key
- Walunj, Raju M.,Natu, Arun D.,Paradkar, Madhusudan V.,Rojatkar, Supada R.
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p. 1425 - 1431
(2016/09/14)
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- Chromanones: selective and reversible monoamine oxidase B inhibitors with nanomolar potency
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A new series of C7-substituted chromanones has been designed, synthesized and evaluated for hMAO-B inhibitory activity in vitro. Most of the studied compounds were remarkably potent and selective MAO-B inhibitors and showed weak or no inhibition of MAO-A. Especially, compound 4f (IC50 = 8.62 nM) was the best MAO-B inhibitor and exhibited the highest selectivity for MAO-B (SI > 11 627.9-fold). In addition, the structure-activity relationships for MAO-B inhibition indicated that substitutions at the C7 of the chromanone moiety, particularly with the halogen substituted benzyloxy, were more favorable for MAO-B inhibition. Molecular docking studies have been performed to explore the interaction modes of C7-substituted chromanones with MAO-B. Furthermore, the representative compounds 4f and 5d showed low neurotoxicity in SH-SY5Y cells in vitro. So the C7-substituted chromanones could be used to develop promising drug candidates for the therapy of neurodegenerative diseases.
- Lan, Jin-Shuai,Xie, Sai-Sai,Huang, Ming,Hu, Ya-Jian,Kong, Ling-Yi,Wang, Xiao-Bing
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supporting information
p. 1293 - 1302
(2015/07/15)
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- A new class of bactericidal agents against S. aureus, MRSA and VRE derived from bisindolylmethane
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A series of bisindolylmethanes (BIMs) (1a -7j) including hybrid BIMs 6a-6c were prepared for bioevaluation. The results of initial antimicrobial screening of compounds 1a-6c showed compounds 2b, 2m, 4a and 5b to be the most potent inhibitors, exhibiting M
- Sharma, Deepak K.,Tripathi, Anil K.,Sharma, Rashmi,Chib, Reena,Ur Rasool, Reyaz,Hussain, Altaf,Singh, Baldev,Goswami, Anindya,Khan, Inshad A.,Mukherjee, Debaraj
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p. 1643 - 1653
(2014/05/06)
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- Preparation of 2,2-dimethylchroman-4-ones from 5-alkyl-substituted resorcinols: Microwave-assisted synthesis and theoretical calculations
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The influence of different 5-alkyl-substituted resorcinols on the formation of 2,2-dimethylchroman- 4-ones is examined experimentally and theoretically. Structures are fully assigned by means of experimental and theoretical 13C and 1H NMR chemical shifts.
- Morales, Paula,Azofra, Luis Miguel,Cumella, Jose,Hernandez-Folgado, Laura,Roldan, Maria,Alkorta, Ibon,Jagerovic, Nadine
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p. 319 - 332
(2014/03/21)
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- N-SUBSTITUTED BENZAMIDES AND METHODS OF USE THEREOF
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The invention provides novel compounds having the general formula: and pharmaceutically acceptable salts thereof, wherein the variables RA, subscript n, ring A, X2, L, subscript m, X1, B, R1, R2, R3, R4, R5 and RN have the meaning as described herein, and compositions containing such compounds and methods for using such compounds and compositions.
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Paragraph 0480-0482
(2013/12/04)
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- Enantioselective reduction of 4-chromanone and its derivatives by selected filamentous fungi
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Biotransformation of 4-chromanone and its derivatives in the cultures of three biocatalysts: Didymosphaeria igniaria, Coryneum betulinum and Chaetomium sp. is presented. The biocatalysts were chosen due to their capability of enantiospecific reduction of low-molecular-weight ketones (acetophenone and its derivatives and α- and β-tetralone). The substrates were reduced to the respective S-alcohols with high enantiomeric excesses, according to the Prelog's rule. In the culture of Chaetomium sp. after longer biotransformation time an inversion of configuration of the formed alcohols was also observed. The highest yield of transformation was observed for 6-methyl-4-chromanone. In all the tested cultures, the higher was the molecular weight of a chromanone, the lower conversion percent was observed.
- Janeczko, Tomasz,Dmochowska-Gladysz, Jadwiga,Szumny, Antoni,Kostrzewa-Suslow, Edyta
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p. 278 - 282
(2013/10/22)
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- Construction of polyheterocyclic benzopyran library with diverse core skeletons through diversity-oriented synthesis pathway: Part II
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As a continuation of our previous report (J. Comb. Chem.2010, 12, 548-558), we accomplished the diversity-oriented synthesis of polyheterocyclic small-molecule library with privileged benzopyran substructure. To ensure the synthetic efficiency, we utilized the solid-phase parallel platform and the fluorous-tag-based solution-phase parallel platform to construct a 284-member polyheterocyclic library with six distinct core skeletons with an average purity of 87% on a scale of 5-10 mg. This library was designed to maximize the skeletal diversity with discrete core skeletons in three-dimensional space and the combinatorial diversity with four different benzopyranyl starting materials and various building blocks. Together with our reported benzopyranyl library, we completed the construction of polyheterocyclic benzopyran library with 11 unique scaffolds and their molecular diversity was visualized in chemical space using principle component analysis (PCA).
- Zhu, Mingyan,Lim, Byung Joon,Koh, Minseob,Park, Seung Bum
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scheme or table
p. 124 - 134
(2012/04/10)
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- TRICYCLIC COMPOUNDS AS mPGES-1 INHIBITORS
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The present invention relates to tricyclic compounds of formula (I) or pharmaceutically acceptable salt thereof as mPGES-1 inhibitors. These compounds are inhibitors of the microsomal prostaglandin E synthase-1 (mPGES-1) enzyme and are therefore useful in the treatment of pain and/or inflammation from a variety of diseases or conditions, such as asthama, osteoarthritis, rheumatoid arthritis, acute or chronic pain and neurodegenerative diseases. (I)
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Page/Page column 60
(2012/09/10)
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- An excellent protocol for the synthesis of benzopyrans using basic resin under MWI
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A convenient, microwave promoted novel protocol for the synthesis of diverse kinds of substituted benzopyrans from the corresponding variety of substituted hydroxy acetophenones and keto compounds using Amberlite IRA 400 resin (basic resin) under solvent-free conditions, has been developed. This protocol is mild and more efficient than the other reported methods.
- Tripathi,Koul,Taneja, Subhash C
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experimental part
p. 1561 - 1564
(2011/02/22)
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- Discovery of novel benzopyranyl tetracycles that act as inhibitors of osteoclastogenesis induced by receptor activator of NF-κB ligand
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A novel benzopyran-fused molecular framework 7ai was discovered as a specific inhibitor of RANKL-induced osteoclastogenesis using a cell-based TRAP activity assay from drug-like small-molecule libraries constructed by diversity-oriented synthesis. Its inhibitory activity was confirmed by in vitro evaluations including specific inhibition of RANKL-induced ERK phosphorylation and NF-κB transcriptional activation. 7ai can serve as a specific small-molecule modulator for mechanistic studies of RANKL-induced osteoclast differentiation as well as a potential lead for the development of antiresorptive drugs.
- Zhu, Mingyan,Kim, Myung Hee,Lee, Sanghee,Bae, Su Jung,Kim, Seong Hwan,Park, Seung Bum
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supporting information; experimental part
p. 8760 - 8764
(2011/02/23)
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- Total synthesis of the pyranoisoflavone kraussianone 1 and related isoflavones
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The first total synthesis of the pyranoisoflavone kraussianone 1 (1) is described. The key steps involved the Suzuki-Miyaura reaction for the construction of the isoflavone core and the regioselective formation of the dimethylpyran scaffolds to the phloroglucinol (ring A) and resorcinol (ring B) moieties of kraussianone 1 (1). This route also provided access to the related isoflavones eriosemaone D (2) and genistein (3) via simple structural modifications.
- Selepe, Mamoalosi A.,Drewes, Siegfried E.,Van Heerden, Fanie R.
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experimental part
p. 1680 - 1685
(2011/02/21)
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- Microwave assisted facile and efficient synthesis of benzopyran
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A convenient, fast and high yielding method for the preparation of 3,4-dihydrobenzopyrans has been achieved by the condensation of various acetophenones with different keto compounds in the presence of a base, assisted by microwave activation under solvent free conditions with or without use of a solid support.
- Tripathi,Koul,Taneja
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experimental part
p. 301 - 304
(2009/12/03)
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- COMPOUNDS WITH EMBEDDED BENZOPYRAN MOTIF FOR CORE STRUCTURES AND PREPARATION METHOD THEREOF
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The present invention relates to a compound having benzopyran core, a preparation method of the derivatives by liquid phase synthesis and solid phase synthesis through diversity-oriented synthesis, and an anticancer agent comprising the compound that exhi
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Page/Page column 16-17
(2010/01/31)
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- COMPOUNDS WITH EMBEDDED BENZOPYRAN MOTIF FOR CORE STRUCTURES AND PREPARATION METHOD THEREOF
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The present invention relates to a compound having benzopyran core, a preparation method of the derivatives by liquid phase synthesis and solid phase synthesis through diversity-oriented synthesis, and an anticancer agent comprising the compound that exhi
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Page/Page column 25-26
(2008/12/06)
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- New synthetic route towards 2,2-dimethylchromene and synthesis of substituted 7-(dimethylpropargyl)chromene
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(Chemical Equation Presented) Trifluoromethansufonic acid (TFA) was found a proper reagent for regioselectively ring closure of resorcinol to afford 7-hydroxy-2,2-dimethyl-2,3-dihydrochromen-4-one 3. The propargylation of 3 gave rise to 2,2-dimethyl-7-(2-methylbut-3-yn-2-yloxy)-2,3-dihydrochromen-4-one 4. Condensation of 4 with substituted phenyl or benzyl Grignard reagents afforded substituted phenyl or benzylidene chromenes 6a-d and 4-(substitutedbenzylidene)- 3,4-dihydro chromenes 8a-e, respectively.
- Alizadeh, Babak H.,Foroumadi, Alireza,Shafiee, Abass
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p. 909 - 912
(2008/09/21)
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- Concise and diversity-oriented synthesis of novel scaffolds embedded with privileged benzopyran motif
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A branching DOS strategy for an unbiased natural product-like library with embedded privileged benzopyran motif was established to provide complexity and diversity of resulting heterocycles with desired drug-likeness. The importance of skeletal diversity
- Ko, Sung Kon,Jang, Hwan Jong,Kim, Eunha,Park, Seung Bum
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p. 2962 - 2964
(2008/09/19)
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- Enantioselective syntheses of decursinol angelate and decursin
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The practical enantioselective syntheses of decursinol angelate and decursin were achieved in eight steps from resorcinol. The stereochemistry was addressed using the catalytic asymmetric epoxidation of 7-acetoxy-2,2-dimethylchromene by chiral (salen)Mn complexes as the key step.
- Lim, Jongdoo,Kim, Ik-Hwan,Kim, Hyeon Ho,Ahn, Kyung-Seop,Han, Hogyu
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p. 4001 - 4003
(2007/10/03)
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- Total Synthesis of Pterocarpan: (+/-)-Neorautenane
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A new approach to the total synthesis of (+/-)-neorautenane 14 is described, using the chemoselective coupling of benzodipyran 12 and o-chloromercuriophenol 13 as the key step.Compound 12 is synthesized in four steps from chromanone 7.
- Lichtenfels, Ricardo A.,Coelho, Antonio L.,Costa, R. R.
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p. 949 - 952
(2007/10/02)
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- Modification of hydroxybenzopyranoids: Facile deoxygenation of 2,2-dimethyl-7-hydroxy-4-chromanones and a new approach to their novel mercapto analogs
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A facile deoxygenation of a systematic series of substituted 2,2-dimethyl-7-hydroxy-4-chromanones via their sulfonate, isourea, and thiocarbamate derivatives is reported. The synthesis of novel 2,2-dimethyl-7-mercapto-4-chromanones has been accomplished b
- Sebok,Timar,Eszenyi,Patonay
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p. 6318 - 6321
(2007/10/02)
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- ON THE REACTION OF SUBSTITUTED PHENOLS AND 3-METHYLBUT-2-ENOIC ACID. A COMPARATIVE STUDY
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A systematic and comparative study of the reaction of a series of substituted phenols and 3-methylbut-2-enoic acid in zinc chloride/phosphorus oxychloride and aluminum chloride/phosphorus oxychloride reveals that the formation of phenolic esters and 2,2-dimethyl-4-chromanones is strongly influenced by the substituents, their popsition on the aromatic ring of the starting phenols.Based on our study, a mixed Friedel-Crafts and Fries rearrangement mechanism is in operation in these reactions.
- Seboek, Peter,Jekoe, Jozsef,Timar, Tibor,Jaszberenyi, Joseph Cs.
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p. 2099 - 2114
(2007/10/02)
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- An efficient synthesis of 2,2-dimethyl-4-chromanones
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Chromanones are obtained in high yields by treating substituted phenols with dimethyl acrylic acid in the presence of trifluoroacetic acid.
- Chaturvedi, R.,Mulchandani, N. B.
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p. 338 - 339
(2007/10/02)
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- On the synthesis of substituted 2,2-dimethyl1-4-chromanones and related compounds
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A systematic study of the reaction of a series of monosubstituted phenols 3 and 3-methylbut-2-enoic acid 4 in phosphorus oxychloride/zinc chloride revealed that the formation of 4-chromanones was strongly infuenced by the substituents and their position on the aromatic ring of the starting phenols.
- Seboek, Peter,Jekoe, Jozsef,Timar, Tibor,Jaszberenyi, Joseph Cs.
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p. 2791 - 2794
(2007/10/02)
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- SYNTHESIS OF ANALOGUES OF NATURAL PRECOCENE I CONTAINING VARIOUS 7-O-SUBSTITUENTS
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Syntheses of analogues of the benzopyran precocene I (I) with various 7-O-substituents are described.The compounds were characterized by IR, MS, (1)H and (13)C-NMR.
- Timar, Tibor,Hosztafi, Sandor,Jaszberenyi, J. Csaba,Koever, Katalin E.,Batta, Gyula
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p. 303 - 312
(2007/10/02)
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- α, β-Unsaturated N-Acylureas as Useful Intermediates for the Synthesis of Indanones, Chromanones and Coumarins
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α,β-Unsaturated N-acylureas, viz-N-formamido-2-butenamide (I), N-formamido-3-methyl-2-butenamide (II) and N-formamido-3-phenyl-2-propenamide (III) react with aryl alkyl ethers in the presence of PPA to afford the corresponding crotonophenones and chalcones (IV) at lower temperature and 1-indanones (V) at a higher temperature.Reactions of I and II with phenols in the presence of PPA afford the 4-chromanones (VI), while III gives 3,4-dihydro-4-phenylcoumarins (VII) in excellent yields.
- Ramana, M. M. V.,Kudav, N. A.
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p. 339 - 341
(2007/10/02)
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- PHENYL AND HETEROCYCLIC TETRAHYDROPYRIDYL ALKOXY-BENZHETEROCYCLIC COMPOUNDS AS ANTIPSYCHOTIC AGENTS
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Novel phenyl and heterocyclic tetrahydropyridyl and piperazinyl alkoxy benzheterocyclic compounds are described which have valuable neuroleptic properties by virtue of their dopamine autoreceptor agonist activity. Methods of preparation, pharmaceutical co
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