8-ethoxy-8-(4-methoxyphenyl)-5-methyl-8H-[1,2,4]oxadiazolo[3,4-c][1,4]thiazin-3-one

We present a series of oxadiazolothiazinones, selective inotropic agents on isolated cardiac tissues, devoid of chronotropy and vasorelaxant activity. Functional and binding data for the precursor of the series (compound 1) let us hypothesize LTCC blocking activity and the existence of a recognition site specific for this scaffold. We synthesized and tested 22 new derivatives: introducing a para-methoxyphenyl at C-8 led to compound 12 (EC₅₀ = 0.022 μM), twice as potent as its para-bromo analogue (1). For 10 analogues, we extended the characterization of the biological properties by including the assessment of metabolic stability in human liver microsomes and cytochrome P450 inhibition potential. We observed that the methoxy group led to active compounds with low metabolic stability and high CYP inhibition, whereas the protective effect of bromine resulted in enhanced metabolic stability and reduced CYP inhibition. Thus, we identified two para-bromo benzothiazino-analogues as candidates for further studies.

8-ethoxy-8-(4-methoxyphenyl)-5-methyl-8H-[1,2,4]oxadiazolo[3,4-c][1,4]thiazin-3-one

Understanding Oxadiazolothiazinone Biological Properties: Negative Inotropic Activity versus Cytochrome P450-Mediated Metabolism

Emanuele Carosati^*†‡, Barbara Cosimelli^§, Pierfranco Ioan^∥, Elda Severi^§, Kasiram Katneni^‡, Francis C. K. Chiu^‡, Simona Saponara^⊥, Fabio Fusi^⊥, Maria Frosini^⊥, Rosanna Matucci^#, Matteo Micucci^∥, Alberto Chiarini^∥, Domenico Spinelli^○, and Roberta Budriesi^∥

^† Dipartimento di Chimica, Biologia e Biotecnologie, Università di Perugia, Via Elce di Sotto 10, 06123 Perugia, Italy

^‡ Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, 381 Royal Parade, Parkville, VIC 3052, Australia

^§ Dipartimento di Farmacia, Università di Napoli “Federico II”, Via D. Montesano 49, 80131 Napoli, Italy

^∥ Dipartimento di Farmacia e Biotecnologie, Università di Bologna, Via Belmeloro 6, 40126 Bologna, Italy

^⊥ Dipartimento di Scienze della Vita, Università degli Studi di Siena, Via A. Moro 2, 53100 Siena, Italy

^# Dipartimento di Neuroscienze, Area del Farmaco e Salute del Bambino (NEUROFARBA), Viale Pieraccini 6, 50139 Firenze, Italy

^○ Dipartimento di Chimica ‘G. Ciamician’, Alma Mater Studiorum-Università di Bologna, Via Selmi 2, 40126 Bologna, Italy

J. Med. Chem., Article ASAP

DOI: 10.1021/acs.jmedchem.6b00030

Publication Date (Web): March 10, 2016

Copyright © 2016 American Chemical Society

*Phone: +39 75 5855550. Fax: +39 75 45646. E-mail: emanuele@chemiome.chm.unipg.it.

http://pubs.acs.org/doi/full/10.1021/acs.jmedchem.6b00030

/////////Cytochrome P450-Mediated Metabolism, Negative Inotropic Activity

CCOC2(c1ccc(OC)cc1)SC=C(C)n3c2noc3=O

Wilsons Promontory National Park  

4.6111 Google reviews

National park in Victoria, Australia

The Wilsons Promontory National Park, commonly known as Wilsons Prom or The Prom, is a national park in the Gippsland region of Victoria, Australia, located approximately 157 kilometres southeast of Melbourne. Wikipedia

 Wilsons Promontory National Park, Korumburra, VIC, Australia
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p-(4-Cyclohexylphenyl)aniline

p-(4-Cyclohexylphenyl)aniline (2c)

A reported procedure was generally followed to synthesize 2c. A mixture of 4-bromocyclohexylbiphenyl (12) (1.9 g, 60 mmol, 1.0 equiv), Cu₂O (0.086 g, 0.60 mmol, 0.010 equiv), aqueous ammonia (30% solution, 8.4 mL, 120 mmol, 20 equiv), and NMP (8.4 mL, 120 mmol, 20 equiv) was stirred at 100 °C in a sealed tube under Ar atmosphere. After 39 h, the solution was cooled at room temperature, quenched with water, and extracted with CH₂Cl₂.

The combined organic layer was washed with water and brine, dried over MgSO₄, and concentrated in vacuo. The residue was purified by flash silica gel column chromatography using hexane/ethyl acetate (10/1 (v/v)) to afford 2c (0.91 g, 36 mmol, 60%) as a white powder. Mp: 101.0–101.5 °C (lit. mp 102 °C).........Basford, F. R. J. Chem. Soc. 1937, 1440– 1443, DOI: 10.1039/jr9370001440

¹H NMR (500 MHz, CDCl₃) δ: 7.47 (d, J = 8.0 Hz, 2H), 7.41 (d, J = 8.0 Hz, 2H), 7.25 (d, J = 8.0 Hz, 2H), 6.75 (d, J = 8.0 Hz, 2H), 3.67 (br s, 2H), 2.53 (t, J = 10.0 Hz, 1H), 1.96–1.72 (m, 5H), 1.51–1.22 (m, 5H).

¹³C NMR (125 MHz, CDCl₃) δ: 146.3, 145.7, 138.8, 131.8, 128.0, 127.3, 126.4, 115.6, 44.3, 34.7, 27.1, 26.4.

IR (ATR): 3397, 3386, 3324, 3311, 3212, 3026, 2920, 2846, 1604, 1495, 1445, 1265, 1178, 1138, 1000, 807, 692, 515, 474 cm^–1.

Anal. Calcd for C₁₈H₂₁N: C, 86.01; H, 8.42; N, 5.57. Found: C, 86.00; H, 8.47; N, 5.58.

11H NMR BELOW

  13C NMR

 1H NMR PREDICT

 13C NMR PREDICT

 

Synthesis and Shuttling Behavior of [2]Rotaxanes with a Pyrrole Moiety

Yusuke Matsuoka^†, Yuichiro Mutoh^†, Isao Azumaya^‡, Shoko Kikkawa^‡, Takeshi Kasama^§, and Shinichi Saito^*†

^† Department of Chemistry, Faculty of Science, Tokyo University of Science, Kagurazaka, Shinjuku, Tokyo 162-8601,Japan

^‡ Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan

^§ Research Center for Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan

J. Org. Chem., Article ASAP

DOI: 10.1021/acs.joc.5b02911

Publication Date (Web): March 07, 2016

Copyright © 2016 American Chemical Society

*Tel: +81-3-5228-8715. E-mail: ssaito@rs.kagu.tus.ac.jp.

ACS Editors' Choice - This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.

Abstract

We synthesized [2]rotaxanes with a pyrrole moiety from a [2]rotaxane with a 1,3-diynyl moiety. The conversion of the 1,3-diynyl moiety of the axle component to the pyrrole moiety was accomplished by a Cu-mediated cycloaddition of anilines. The cycloaddition reaction was accelerated when the [2]rotaxane was used as the substrate. The effect of the structure of the pyrrole moiety on the rate of the shuttling was studied.

http://pubs.acs.org/doi/full/10.1021/acs.joc.5b02911
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TAKE A TOUR

Nagaon, alibaug, chaul,  alibaug,  MAHARASHTRA , INDIA

Bhimeshwar temple in Nagaon

 

Bhimeshwar Temple  

Place of Worship

Address: Alibag-Revadanda Rd, Alibag, Maharashtra 402209

 

 

 

 

 

 

 

 @ Chaul Rameshwar Temple

 

 

 

 

 

 

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Resistance to Nucleotide Excision Repair of Bulky Guanine Adducts Opposite Abasic Sites in DNA Duplexes and Relationships between Structure and Function

• 
  

Fig 1. Chemical structures of the lesions and sequences.

(A) Chemical structures of the trans-B[a]P-dG, cis-B[a]P-dG and the THF site. The THF is a stable analog of an abasic (AB) site. (B) The sequences and numbering system of the 11-mer duplexes containing the trans-B[a]P-dG adduct. G* denotes B[a]P-dG adduct.

doi:10.1371/journal.pone.0137124.g001

Citation: Liu Z, Ding S, Kropachev K, Lei J, Amin S, Broyde S, et al. (2015) Resistance to Nucleotide Excision Repair of Bulky Guanine Adducts Opposite Abasic Sites in DNA Duplexes and Relationships between Structure and Function. PLoS ONE 10(9): e0137124. doi:10.1371/journal.pone.0137124

Fig 2. 1D and 2D NMR spectra characteristics of the trans-B[a]P-dG:AB duplex.

(A) 1D spectrum (10.5–14 ppm) showing the imino proton assignments. (B) Portion of a 2D NOESY (250 ms mixing time) contour plot recorded at 10°C, in 10% H2O solution showing NOE connectivities between amino (5–8.5 ppm) and imino protons (10.8–13.8 ppm), and (C) imino- imino protons (10.8–13.8 ppm). Assignments: a, T20(NH3)—G21(NH1); b, T14(NH3)—G13(NH1); c, T4(NH3)—G18(NH1); d, T8(NH3)—G16(NH1); e, A3(H2)—T20(NH3); f, A9(H2)—T14(NH3); g, A19(H2)—T4(NH3); h, A15(H2)—T8(NH3); i,i’, C2(NH,H’)—G21(NH1); j, C2(H5)—G21(NH1); k, k’, C10(NH,H’)—G13(NH1); l, C10(H5)—G13(NH1); m, m’, C5(NH,H’)—G18(NH1); n, C5(H5)—G18(NH1); o, o’, C7(NH,H’)—G16(NH1); p, C7(H5)—G(NH1); q, A3(H2)—G21(NH1); r, A9(H2)—G13(NH1); s, A19(H2)—G18(NH1); t, A15(H2)—G16(NH1).

doi:10.1371/journal.pone.0137124.g002......http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0137124

Eco-friendly construction of highly functionalized chromenopyridinones by an organocatalyzed solid-state melt reaction and their optical properties

Green Chem., 2016, 18,1488-1494
DOI: 10.1039/C5GC02658J, Paper

Sanjay Paul, Yong Rok Lee
Diverse chromenopyridinone derivatives were synthesized under organocatalytic solid-state melt conditions. The optical properties of these [small pi]-expanded chromenopyridine derivatives were examined.
The content of this RSS Feed (c) The Royal Society of Chemistry

Eco-friendly construction of highly functionalized chromenopyridinones by an organocatalyzed solid-state melt reaction and their optical properties

http://pubs.rsc.org/en/Content/ArticleLanding/2016/GC/C5GC02658J?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

Eco-friendly construction of highly functionalized chromenopyridinones by an organocatalyzed solid-state melt reaction and their optical properties

Sanjay Paul^a and   Yong Rok Lee*^a  

Hide Affiliations

*

Corresponding authors

^a

School of Chemical Engineering, Yeungnam University, Gyeongsan 712-749, Republic of Korea
E-mail: yrlee@yu.ac.kr
Fax: +82-53-810-4631
Tel: +82-53-810-2529

Green Chem., 2016,18, 1488-1494

DOI: 10.1039/C5GC02658J

The library construction of highly functionalized and diverse chromenopyridinones was achieved by three-component reactions of various 4-hydroxycoumarins with ammonium acetate and 3-formylchromones under L-proline catalyzed solid-state melt conditions. The advantages of this protocol include the use of an inexpensive organocatalyst, avoidance of toxic organic solvents, environmentally benign conditions, an easy work-up procedure and good to excellent product yields. The optical properties of these π-expanded varieties of the synthesized chromenopyridinone derivatives were also examined. A chromeno[4,3-b]pyridine nucleus bearing an electron donating group exhibited strong emission in the blue-green region of the visible spectrum.

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A pot-economical and diastereoselective synthesis involving catalyst-free click reaction for fused-triazolobenzodiazepines

Green Chem., 2016, Advance Article
DOI: 10.1039/C6GC00497K, Communication

Xiaofeng Zhang, Sanjun Zhi, Wei Wang, Shuai Liu, Jerry P. Jasinski, Wei Zhang
A pot-economical synthesis involving two [3 + 2] cycloadditions for diastereoselective synthesis of novel triazolobenzodiazepine-containing polycyclic compounds

A pot-economical and diastereoselective synthesis involving catalyst-free click reaction for fused-triazolobenzodiazepines

http://pubs.rsc.org/en/Content/ArticleLanding/2016/GC/C6GC00497K?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

A pot-economical and diastereoselective synthesis involving catalyst-free click reaction for fused-triazolobenzodiazepines

Xiaofeng Zhang,^a   Sanjun Zhi,^b   Wei Wang,^c   Shuai Liu,^a  Jerry P. Jasinski^d and   Wei Zhang*^a  

 *Corresponding authors

^aCentre for Green Chemistry and Department of Chemistry, University of Massachusetts Boston, 100 Morrissey Boulevard, Boston, USA
E-mail: wei2.zhang@umb.edu

^bJiangsu Key Laboratory for the Chemistry of Low-Dimensional Materials, Huaiyin Normal University, Huaian, PR China

^cSchool of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an, PR China

^dDepartment of Chemistry, Keene State College, Keene, USA

Green Chem., 2016, Advance Article

DOI: 10.1039/C6GC00497K

A pot-economical synthesis involving sequential [3 + 2] cycloadditions of an azomethine ylide and an azide–alkyne (click reaction) has been developed for diastereoselective synthesis of novel triazolobenzodiazepine-containing polycyclic compounds. A new example of catalyst-free click chemistry of non-strained alkynes is also disclosed

/////A pot-economical, diastereoselective synthesis, catalyst-free click reaction, fused-triazolobenzodiazepines

Cycloaddition of epoxides and CO2 catalyzed by bisimidazole-functionalized porphyrin cobalt(III) complexes

Cycloaddition of epoxides and CO2 catalyzed by bisimidazole-functionalized porphyrin cobalt(III) complexes

Green Chem., 2016, Advance Article
DOI: 10.1039/C6GC00370B, Paper

Xu Jiang, Faliang Gou, Fengjuan Chen, Huanwang Jing
Bisimidazole-functionalized cobaltoporphyrin acted as efficient bifunctional catalysts to facilitate the synthesis of cyclic carbonates from epoxides and CO₂.

see

http://pubs.rsc.org/en/Content/ArticleLanding/2016/GC/C6GC00370B?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

Cycloaddition of epoxides and CO₂ catalyzed by bisimidazole-functionalized porphyrin cobalt(III) complexes

Xu Jiang,^a   Faliang Gou,^a   Fengjuan Chen^a and  Huanwang Jing*^ab  

 *Corresponding authors

^aState Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering Lanzhou University, Gansu 730000, PR China

^bState Key Laboratory of Coal Conversion, Institute of Coal Chemistry, Chinese Academy of Sciences, Taiyuan 030001, P R China
E-mail: hwjing@lzu.edu.cn

Green Chem., 2016, Advance Article

DOI: 10.1039/C6GC00370B

A series of innovative bisimidazole-functionalized porphyrin cobalt(III) complexes have been devised, synthesized and characterized using NMR, MS and elemental analysis. These homogeneous catalysts were applied to the cycloaddition of epoxides and carbon dioxide without organic solvent and co-catalyst. It was found that the performance of the catalysts deeply relies on their structural features. The alkoxyl chain length of the linkage and the imidazole position relative to the phenyl rings of porphyrin evidently affects the catalyst activities. [5,15-Di(3-((8-imidazolyloctyl)oxy)phenyl)porphyrin] cobalt(III) chloride (J-m8) and [5,15-di(2-((6-imidazolylhexyl)oxy)phenyl)porphyrin] cobalt(III) chloride (J-o6) demonstrated excellent activity under optimal reaction conditions. Synchronously, a preliminary kinetic investigation of this reaction was carried out using three catalysts and illustrated the activation energies of cyclic carbonate formation. Furthermore, a tri-synergistic catalytic mechanism has been carefully proposed in light of the features of the new catalysts and experimental results.

References [1] L. Jin, H. Jing, T. Chang, X. Bu, L. Wang and Z. Liu, J. Mol. Catal. A: Chem., 2007, 261, 262. [2] X. Jiang, F. Gou and H. Jing, J. Catal., 2014, 313, 159. [3] B. Li, L. Zhang, Y. Song, D. Bai and H. Jing, J. Mol. Catal. A: Chem., 2012, 363– 364, 26.

///Cycloaddition of epoxides,   CO2 catalyzed,  bisimidazole-functionalized porphyrin cobalt(III) complexes