- Site-Specific Synthesis of Carbazole Derivatives through Aryl Homocoupling and Amination
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We synthesized various carbazoles from anilines through a three-step process with good overall yields (up to 48percent). This process comprises N -acetylation, copper(0)-mediated Ullmann homocoupling, and acid-mediated intramolecular amination. It permits various functional groups on the substrate. Scale-up of the developed three-step synthetic route to carbazoles was also demonstrated.
- Baek, Junghyun,Ban, Jaeyoung,Lim, Minkyung,Rhee, Hakjune,Shabbir, Saira
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p. 917 - 927
(2020/03/13)
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- Synthesis and antileishmanial activity of fluorinated rhodacyanine analogues: The ‘fluorine-walk’ analysis
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In a search for potent antileishmanial drug candidates, eighteen rhodacyanine analogues bearing fluorine or perfluoroalkyl substituents at various positions were synthesized. These compounds were tested for their inhibitory activities against Leishmania martiniquensis and L. orientalis. This ‘fluorine-walk’ analysis revealed that the introduction of fluorine atom at C-5, 6, 5′, or 6′ on the benzothiazole units led to significant enhancement of the activity, correlating with the less negative reduction potentials of the fluorinated analogues confirmed by the electrochemical study. On the other hand, [sbnd]CF3 and [sbnd]OCF3 groups were found to have detrimental effects, which agreed with the poor aqueous solubility predicted by the in silico ADMET analysis. In addition, some of the analogues including the difluorinated species showed exceptional potency against the promastigote and axenic amastigote stages (IC50 = 40–85 nM), with the activities surpassing both amphotericin B and miltefosine.
- Lasing, Thitiya,Phumee, Atchara,Siriyasatien, Padet,Chitchak, Kantima,Vanalabhpatana, Parichatr,Mak, Kit-Kay,Hee Ng, Chew,Vilaivan, Tirayut,Khotavivattana, Tanatorn
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supporting information
(2019/12/09)
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- Discovery of Potent, Selective, and State-Dependent NaV1.7 Inhibitors with Robust Oral Efficacy in Pain Models: Structure-Activity Relationship and Optimization of Chroman and Indane Aryl Sulfonamides
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Voltage-gated sodium channel NaV1.7 is a genetically validated target for pain. Identification of NaV1.7 inhibitors with all of the desired properties to develop as an oral therapeutic for pain has been a major challenge. Herein, we report systematic structure-activity relationship (SAR) studies carried out to identify novel sulfonamide derivatives as potent, selective, and state-dependent NaV1.7 inhibitors for pain. Scaffold hopping from benzoxazine to chroman and indane bicyclic system followed by thiazole replacement on sulfonamide led to identification of lead molecules with significant improvement in solubility, selectivity over NaV1.5, and CYP2C9 inhibition. The lead molecules 13, 29, 32, 43, and 51 showed a favorable pharmacokinetics (PK) profile across different species and robust efficacy in veratridine and formalin-induced inflammatory pain models in mice. Compound 51 also showed significant effects on the CCI-induced neuropathic pain model. The profile of 51 indicated that it has the potential for further evaluation as a therapeutic for pain.
- Ramdas, Vidya,Talwar, Rashmi,Kanoje, Vijay,Loriya, Rajesh M.,Banerjee, Moloy,Patil, Pradeep,Joshi, Advait Arun,Datrange, Laxmikant,Das, Amit Kumar,Walke, Deepak Sahebrao,Kalhapure, Vaibhav,Khan, Talha,Gote, Ganesh,Dhayagude, Usha,Deshpande, Shreyas,Shaikh, Javed,Chaure, Ganesh,Pal, Ravindra R.,Parkale, Santosh,Suravase, Sachin,Bhoskar, Smita,Gupta, Rajesh V.,Kalia, Anil,Yeshodharan, Rajesh,Azhar, Mahammad,Daler, Jagadeesh,Mali, Vinod,Sharma, Geetika,Kishore, Amitesh,Vyawahare, Rupali,Agarwal, Gautam,Pareek, Himani,Budhe, Sagar,Nayak, Arun,Warude, Dnyaneshwar,Gupta, Praveen Kumar,Joshi, Parag,Joshi, Sneha,Darekar, Sagar,Pandey, Dilip,Wagh, Akshaya,Nigade, Prashant B.,Mehta, Maneesh,Patil, Vinod,Modi, Dipak,Pawar, Shashikant,Verma, Mahip,Singh, Minakshi,Das, Sudipto,Gundu, Jayasagar,Nemmani, Kumar,Bock, Mark G.,Sharma, Sharad,Bakhle, Dhananjay,Kamboj, Rajender Kumar,Palle, Venkata P.
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supporting information
p. 6107 - 6133
(2020/07/10)
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- A Visible Light-Mediated Regioselective Halogenation of Anilides and Quinolines by Using a Heterogeneous Cu-MnO Catalyst
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A simple and practical heterogeneous Cu-MnO catalyzed regioselective halogenation of anilides and quinolines under irradiation with household 40 W incandescent lamp was developed. This method uses a recyclable Cu-MnO catalyst, acetonitrile as an industrially friendly solvent, and economic N-halo succinimides as a halogenating source. The reaction is scalable and well tolerated with a broad range of functional groups.
- Singh, Harshvardhan,Sen, Chiranjit,Sahoo, Tapan,Ghosh, Subhash Chandra
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p. 4748 - 4753
(2018/09/06)
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- SULFONAMIDE COMPOUNDS AS VOLTAGE-GATED SODIUM CHANNEL MODULATORS
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The present invention relates to sulfonamide compounds Formula (I) wherein the substituents are as described herein, and their use in a medicine for the treatment of diseases, disorders associated with the inhibition of Voltage-gated sodium channels (VGSC) particularly NaV1.7. It further relates to the compounds herein and their pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof useful in treating diseases, disorders, syndromes and/or conditions associated with the inhibition of Voltage-gated sodium channels (VGSC) particularly NaV1.7. The invention also relates to process for the preparation of the compounds of the invention. (I)
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Page/Page column 53
(2017/03/28)
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- Copper-catalyzed regiospecific synthesis of N-alkylbenzimidazoles
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(Chemical Equation Presented) A copper-catalyzed method is described for the preparation of N-alkylbenzimidazoles in regioisomerically pure form starting from o-haloanilines. The method utilizing CuI and trans-N,N′-dimethyl-1, 2-cyclohexanediamine allows the preparation of N-alkylbenzimidazoles in good to excellent yields.
- Zheng, Nan,Buchwald, Stephen L.
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p. 4749 - 4751
(2008/03/14)
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- Combined C-H functionalization/C-N bond formation route to carbazoles
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A new method in which a series of substituted carbazoles is efficiently produced by the combination of an amide and an arene is described. The key feature of this method is the palladium-catalyzed tandem directed C-H functionalization and amide arylation. The method tolerates substitution on either ring of the biaryl amide substrates, and the products can be assembled in a simple two-step protocol from readily available reagents. The Pd(0) species generated are reoxidized to Pd(II) in the presence of Cu(OAc)2 and an atmosphere of oxygen. Copyright
- Tsang, W. C. Peter,Zheng, Nan,Buchwald, Stephen L.
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p. 14560 - 14561
(2007/10/03)
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