Exploring Synthetic Strategies for 1H‐Indazoles and Their N‐Oxides: Electrochemical Synthesis of 1H‐Indazole N‐Oxides and Their Divergent C−H Functionalizations

Article

Author: Kim, Gyeongho ; Arepally, Sagar ; Park, Jin Kyoon ; Kim, Taehoon ; Yang, Haesik

AbstractThe selective electrochemical synthesis of 1H‐indazoles and their N‐oxides and the subsequent C−H functionalization of the 1H‐indazole N‐oxides are described. The electrochemical outcomes were determined by the nature of the cathode material. When a reticulated vitreous carbon cathode was used, a wide range of 1H‐indazole N‐oxides were selectively synthesized, and the electrosynthesis products were deoxygenated to N‐heteroaromatics, owing to cathodic cleavage of the N−O bond via paired electrolysis, when a Zn cathode was used. The scope of this electrochemical protocol is broad, as both electron‐rich and electron‐poor substrates were tolerated. The potency of this electrochemical strategy was demonstrated through the late‐stage functionalization of various bioactive molecules, making this reaction attractive for the synthesis of 1H‐indazole derivatives for pharmaceutical research and development. Detailed mechanistic investigations involving electron paramagnetic resonance spectroscopy and cyclic voltammetry suggested a radical pathway featuring iminoxyl radicals. Owing to the rich reactivity of 1H‐indazole N‐oxides, diverse C−H functionalization reactions were performed. We demonstrated the synthetic utility of 1H‐indazole N‐oxides by synthesizing the pharmaceutical molecules lificiguat and YD (3); key intermediates for bendazac, benzydamine, norepinephrine/serotonin reuptake inhibitors, SAM‐531, and gamendazole analogues; and a precursor for organic light‐emitting diodes.

01 Aug 2018·Pharmaceutical ResearchQ3 · MEDICINE

Investigation into the Emerging Role of the Basic Amino Acid L-Lysine in Enhancing Solubility and Permeability of BCS Class II and BCS Class IV Drugs

Q3 · MEDICINE

Article

Author: Abdelkader, Hamdy ; Fathalla, Zeinab

BACKGROUNDThe search for a simple and scalable approach that can improve the two key biopharmaceutical processes (solubility and permeability) for BCS Class II and BCS Class IV has still been unmet need.PURPOSEIn this study, L-lysine was investigated as a potential excipient to tackle problems with solubility and permeability. Bendazac (Class II); quercetin and rutin (Class IV) were employed.METHODSDrugs-lysine complexes in 1:1 M ratios were prepared by co-precipitation and co-grinding; characterized for solubility, partition coefficient, DSC, FTIR, SEM, dissolution rate and permeability. Chemical stability of quercetin-lysine and rutin-lysine was studied by assessing antioxidant capacity using Trolox and CUPRAC assays.RESULTS AND CONCLUSIONDrugs-lysine salt/complexes were confirmed. Solubility enhancement factors ranged from 68- to 433-fold increases and dissolution rates were also significantly enhanced by up to 6-times, compared with drugs alone. With the exception of rutin-lysine, P_app for bendazac-lysine and quercetin-lysine enhanced by 2.3- to 4-fold. P_app for quercetin (Class IV) benefited more than bendazac (Class II) when complexed with lysine. This study warrants the use of L-lysine as a promising excipient for enhanced solubility and permeability of Class II and Class IV, providing that the solubility of the drug is ensured at 'the door step' of absorption sites.

01 Oct 2013·Journal of Dermatological ScienceQ2 · MEDICINE

Reagents inducing epidermal proliferation also induce pigmentation: Induction of keratinocyte proliferation as a novel strategy for the treatment of vitiligo

Q2 · MEDICINE

Letter

Author: Mayumi Komine ; Mamitaro Ohtsuki ; Chieh-Shan Wu ; Yayoi Tada ; Kanako Kikuchi ; Seiki Fujimoto ; Hanako Ohmatsu ; Hsin-Su Yu ; Kunihiko Tamaki

A review.This article hypothesis the reagents inducing epidermal keratinocytes proliferation also induce pigmentation for treatment of vitiligo.The reagents used for proliferation are tacrolimus, alprostadil, alfadex, bendazac, etretinate, trafermin, phenytoin, bucladesine sodium, tretinoin tocoferil.

100 Deals associated with Bendazac

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KEGG	Wiki	ATC	Drug Bank
-	Bendazac	S01BC07	DB13501

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Acute eczema	JP	Sato Pharmaceutical Co., Ltd.	22 May 1979
Dermatitis, Atopic	JP	Sato Pharmaceutical Co., Ltd.	22 May 1979
Herpes Zoster	JP	Sato Pharmaceutical Co., Ltd.	22 May 1979
Plaque psoriasis	JP	Sato Pharmaceutical Co., Ltd.	22 May 1979
Pressure Ulcer	JP	Sato Pharmaceutical Co., Ltd.	22 May 1979
Ulcer	JP	Sato Pharmaceutical Co., Ltd.	22 May 1979

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