89151-44-0Relevant academic research and scientific papers
Sustainable Route Toward N-Boc Amines: AuCl3/CuI-Catalyzed N-tert-butyloxycarbonylation of Amines at Room Temperature
Cao, Yanwei,He, Lin,Huang, Yang
, (2021/12/22)
N-tert-butoxycarbonyl (N-Boc) amines are useful intermediates in synthetic/medicinal chemistry. Traditionally, they are prepared via an indirect phosgene route with poor atom economy. Herein, a step- and atom-economic synthesis of N-Boc amines from amines, t-butanol, and CO was reported at room temperature. Notably, this N-tert-butyloxycarbonylation procedure utilized ready-made substrates, commercially available AuCl3/CuI as catalysts, and O2 from air as the sole oxidant. This catalytic system provided unique selectivity for N-Boc amines in good yields. More significantly, gram-scale preparation of medicinally important N-Boc amine intermediates was successfully implement, which demonstrated a potential application prospect in industrial syntheses. Furthermore, this approach also showed good compatibility with tertiary and other useful alcohols. Investigations of the mechanisms revealed that gold catalyzed the reaction and copper acted as electron transfer mediator in the catalytic cycle.
Discovery of a Novel, Highly Potent, and Selective Thieno[3,2- d]pyrimidinone-Based Cdc7 Inhibitor with a Quinuclidine Moiety (TAK-931) as an Orally Active Investigational Antitumor Agent
Kurasawa, Osamu,Miyazaki, Tohru,Homma, Misaki,Oguro, Yuya,Imada, Takashi,Uchiyama, Noriko,Iwai, Kenichi,Yamamoto, Yukiko,Ohori, Momoko,Hara, Hideto,Sugimoto, Hiroshi,Iwata, Kentaro,Skene, Robert,Hoffman, Isaac,Ohashi, Akihiro,Nomura, Toshiyuki,Cho, Nobuo
, p. 1084 - 1104 (2020/02/05)
In our pursuit of developing a novel, potent, and selective cell division cycle 7 (Cdc7) inhibitor, we optimized the previously reported thieno[3,2-d]pyrimidinone analogue I showing time-dependent Cdc7 kinase inhibition and slow dissociation kinetics. These medicinal chemistry efforts led to the identification of compound 3d, which exhibited potent cellular activity, excellent kinase selectivity, and antitumor efficacy in a COLO205 xenograft mouse model. However, the issue of formaldehyde adduct formation emerged during a detailed study of 3d, which was deemed an obstacle to further development. A structure-based approach to circumvent the adduct formation culminated in the discovery of compound 11b (TAK-931) possessing a quinuclidine moiety as a preclinical candidate. In this paper, the design, synthesis, and biological evaluation of this series of compounds will be presented.
Synthesis and J-Dimer Formation of Tetrapyrazinoporphyrazines with Different Functional Groups for Potential Biomolecular Probe Applications
Demuth, Jiri,Kantor, Michal,Machan, Matej,Miletin, Miroslav,Novakova, Veronika,Zimcik, Petr
, p. 527 - 537 (2020/04/07)
Though tetrapyrazinoporphyrazines (TPyzPzs) are generally presented as universal dark quenchers for oligonucleotide probes, the availability of TPyzPzs bearing different functional groups suitable for attachment to 3′, and 5′ ends or intrastrand positions remains rather limited. Therefore, a synthetic route to hexa(bis(2-methoxyethyl)amino) or hexa(diethylamino) TPyzPzs functionalized by an azide, hydroxy, or carboxy group or their combinations was developed. Studies of self-assembly into J-dimers in nonpolar solvents and their stability upon titration with pyridine (association constants, KP values, ranging 0.32–12.7×102 M?1) revealed that smaller peripheral substituents and functionalization of TPyzPzs improves the stability of J-dimers. ΦΔ and ΦF were low for the monomers (ΦFΔF=0.027, ΦΔ=0.28).
6-bromo-3-(piperidine-4-yl)imidazo[1,2-a]pyridine preparation method
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Paragraph 0006, (2019/12/25)
The invention relates to a 6-bromo-3-(piperidine-4-yl)imidazo[1,2-a]pyridine preparation method. A purpose of the present invention is mainly to solve the technical problem that no suitable industrialsynthesis method exists in the prior art. According to the technical scheme, the method comprises five steps, and comprises: generating a compound 2 from a compound 1 and Boc2O in chloroform under the action of triethylamine; adding dichloromethane, oxalyl chloride and dimethyl sulfoxide into the compound 2, and oxidizing to obtain a compound 3; carrying out a reaction on the compound 3 and a bromination reagent phenyltrimethylammonium tribromide (PTAB) in tetrahydrofuran to obtain a compound 4; carrying out a reaction on the compound 4 and 2-amino-5-bromopyridine in ethyl alcohol to obtain acompound 5; and finally obtaining a compound 6 from the compound 5 under the action of ethyl acetate hydrochloride. According to the present invention, the obtained compound can be used as the intermediate or product for synthesis of a plurality of drugs.
Design and Synthesis of TASIN Analogues Specifically Targeting Colorectal Cancer Cell Lines with Mutant Adenomatous Polyposis Coli (APC)
Wang, Wentian,Zhang, Lu,Morlock, Lorraine,Williams, Noelle S.,Shay, Jerry W.,De Brabander, Jef K.
supporting information, p. 5217 - 5241 (2019/05/28)
Despite advances in targeted anticancer therapies, there are still no small-molecule-based therapies available that specifically target colorectal cancer (CRC) development and progression, the second leading cause of cancer deaths. We previously disclosed the discovery of truncating adenomatous polyposis coli (APC)-selective inhibitor 1 (TASIN-1), a small molecule that specifically targets colorectal cancer cells lines with truncating mutations in the adenomatous polyposis coli (APC) tumor suppressor gene through inhibition of cholesterol biosynthesis. Here, we report a medicinal chemistry evaluation of a collection of TASIN analogues and activity against colon cancer cell lines and an isogenic cell line pair reporting on the status of APC-dependent selectivity. A number of potent and selective analogues were identified, including compounds with good metabolic stability and pharmacokinetic properties. The compounds reported herein represent a first-in-class genotype-selective series that specifically target apc mutations present in the majority of CRC patients and serve as a translational platform toward a targeted therapy for colon cancer.
OXOPIPERAZINE DERIVATIVES
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Paragraph 1040-1041, (2019/06/30)
The present invention relates to novel compounds of formula (I) or formula (Ia) pharmaceutically-acceptable salts, hydrates, solvates, or stereoisomers thereof, and pharmaceutical compositions of these compounds which are useful for preventive and therapeutic use in human and veterinary medicine.
Tert-Butyl(3-cyano-4,6-dimethylpyridin-2-yl)carbonate as a green and chemoselective N-tert-butoxycarbonylation reagent
Du, Fangyu,Zhou, Qifan,Fu, Yang,Zhao, Hanqi,Chen, Yuanguang,Chen, Guoliang
supporting information, p. 6549 - 6554 (2019/05/04)
The use of tert-butyl(3-cyano-4,6-dimethylpyridin-2-yl)carbonate as a chemoselective tert-butoxycarbonylation reagent for aromatic and aliphatic amines has been demonstrated. To gain insight into this reaction, in situ React IR technology was used to confirm the effectivity and chemoselectivity of this novel Boc reagent. The reaction was carried out chemoselectively in high yield under mild, environment-friendly conditions and was completed quickly within 1 hour. Simultaneously, the Boc carrier was easily recyclable, and has great application prospects for industrial production.
Catalyst-Free Deaminative Functionalizations of Primary Amines by Photoinduced Single-Electron Transfer
Wu, Jingjing,Grant, Phillip S.,Li, Xiabing,Noble, Adam,Aggarwal, Varinder K.
supporting information, p. 5697 - 5701 (2019/03/21)
The use of pyridinium-activated primary amines as photoactive functional groups for deaminative generation of alkyl radicals under catalyst-free conditions is described. By taking advantage of the visible light absorptivity of electron donor–acceptor complexes between Katritzky pyridinium salts and either Hantzsch ester or Et3N, photoinduced single-electron transfer could be initiated in the absence of a photocatalyst. This general reactivity platform has been applied to deaminative alkylation (Giese), allylation, vinylation, alkynylation, thioetherification, and hydrodeamination reactions. The mild conditions are amenable to a diverse range of primary and secondary alkyl pyridiniums and demonstrate broad functional group tolerance.
Agent for Preventing or Ameliorating Hearing Impairment
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Paragraph 0093; 0094; 0116-0117, (2019/08/02)
It is to provide an agent for preventing or improving hearing loss, which comprises a low molecular compound which can be produced relatively easily and inexpensively as an active ingredient. One or more compounds selected from the group consisting of compounds represented by the following formulas (I0), (II), and (III) and a pharmaceutically acceptable salt of the compounds when R3 is OH are used as an agent for preventing or improving hearing loss.
TOLL-LIKE RECEPTOR-7 AGONIST
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Paragraph 0181-0182, (2018/06/09)
Disclosed are a novel pyrrolopyrimidine ring compound as a TLR7 agonist or a pharmaceutically acceptable salt thereof, used for preventing or treating allergic rhinitis and asthma. In particular, disclosed is a compound represented by formula (I) or a pharmaceutically acceptable salt thereof.
