37787-77-2Relevant academic research and scientific papers
Design, synthesis and biological evaluation of new bivalent quinazoline analogues as IAP antagonists
Bae, Inhwan,Kim, Daejin,Choi, Jaeyul,Kim, Jisook,Kim, Minjeong,Park, Bokyung,Kim, Young Hoon,Ahn, Young Gil,Hyung Kim, Ha,Kim, Dae Kyong
supporting information, (2021/01/26)
We recently reported the biological evaluations of monovalent IAP antagonist 7 with good potency (MDA-MB-231, IC50 = 19 nM). In an effort to increase cellular activity and improve favorable drug-like properties, we newly designed and synthesized bivalent analogues based on quinazoline structure of 7. Optimization of cellular potency and CYP inhibition led to the identification of 27, which showed dramatic increase of over 100-fold (IC50 = 0.14 nM) and caused substantial tumor regressions in MDA-MB-231 xenograft model. These results strongly support 27 as a promising bivalent antagonist for the development of an effective anti-tumor approaches.
Synthesis and evaluation of in Vivo anti-hypothermic effect of the N- And C-terminus modified thyrotropin-releasing hormone mimetic: [(4S,5S)-(5-methyl-2-oxooxazolidine-4-yl)-carbonyl]-[3-(thiazol-4-yl)-L-alanyl]-L-prolinamide
Kobayashi, Naotake,Sato, Norihito,Sugita, Katsuji,Kihara, Tsuyoshi,Koike, Katsumi,Sugawara, Tamio,Tada, Yukio,Yoshikawa, Takayoshi
, p. 314 - 324 (2021/04/30)
We explored orally effective thyrotropin-releasing hormone (TRH) mimetics, which show high central nervous system effects in structure–activity relationship studies based on in vivo antagonistic activity on reserpine-induced hypothermia (anti-hypothermic effect) in mice starting from TRH. This led us to the TRH mimetic: [(4S,5S)-(5-methyl-2-oxooxazolidine-4-yl)carbonyl]-[3-(thiazol-4-yl)-L-alanyl]-L-prolinamide 1, which shows a higher anti-hypothermic effect compared with that of TRH after oral administration. We next attempted further chemical modification of the N- and C-terminus of 1 to find more orally effective TRH mimetics. As a result, we obtained several N- and C-terminus modified TRH mimetics which showed high anti-hypothermic effects.
Modular Synthesis of Carbazole-Substituted Phthalimides as Potential Photocatalysts
F?ldesi, Tamás,Gonda, Zsombor,Nagy, Bálint,Novák, Zoltán
supporting information, (2021/11/22)
The modular synthesis of carbazole functionalized phthalimides (PIs) and their applicability as catalyst in selected photocatalytic transformations are reported. The developed synthetic approach provides high variability of phthalimide considering that the synthesis of the phthalimide core can be easily performed. Starting from fluorophthalic acid anhydrides, the corresponding fluorophthalimides were prepared with various amines, and the fluoro function ensured the introduction of carbazoles into the phthalimide framework through aromatic nucleophilic substitution. Besides the synthetic developments, some of the carbazolyl phthalimides were tested in four different photocatalytic transformations, which showed attractive and comparable activity to the known 4-CzIPN and noble metal complexes.
Synthesis of Amide Enol Carbamates and Carbonates through Cu(OTf)2-Catalyzed Reactions of Ynamides with t-Butyl Carbamates/Carbonates
Han, Pan,Mao, Zhuo-Ya,Li, Ming,Si, Chang-Mei,Wei, Bang-Guo,Lin, Guo-Qiang
, p. 4740 - 4752 (2020/04/30)
A highly regioselective approach to access amide enol carbamates and carbonates 5a-5c′, 7a-7h, and 9 was developed through Cu(OTf)2-catalyzed reactions of ynamides 4 with t-butyl carbamates 2 and 8 and t-butyl carbonates 6. Moreover, this strategy was successfully applied to generate amide enol carbamates 11a-11s and 14a-14f from imides 10 and 13 with ynamides through an N-Boc cleavage-addition ring-opening process. A range of substituents was amenable to this transformation, and the desired amide enol carbamates and carbonates were obtained in moderate to good yields.
A Ni–Ir Dual Photocatalytic Liebeskind Coupling of Sulfonium Salts for the Synthesis of 2-Benzylpyrrolidines
Varga, Bálint,Gonda, Zsombor,Tóth, Balázs L.,Kotschy, András,Novák, Zoltán
, p. 1466 - 1471 (2019/11/03)
A new method has been developed for the synthesis of 2-benzylpyrrolidines utilizing cross-coupling and photoredox catalysis. Using a well-established dual Ni–Ir system, we were able to successfully couple benzylsulfonium salts with proline utilizing radical forming through CO2 extrusion. This enabled the simple one-step synthesis of 2-benzylpyrrolidines from stable, inexpensive starting materials.
Enantioselective Radical Cyclization for Construction of 5-Membered Ring Structures by Metalloradical C-H Alkylation
Wang, Yong,Wen, Xin,Cui, Xin,Zhang, X. Peter
, p. 4792 - 4796 (2018/04/17)
Radical cyclization represents a powerful strategy for construction of ring structures. Traditional radical cyclization, which is based on radical addition as the key step, necessitates the use of unsaturated substrates. Guided by the concept of metalloradical catalysis, a different mode of radical cyclization that can employ saturated C-H substrates is demonstrated through the development of a Co(II)-based system for catalytic activation of aliphatic diazo compounds for enantioselective radical alkylation of various C(sp3)-H bonds. It allows for efficient construction of chiral pyrrolidines and other valuable 5-membered cyclic compounds. This alternative strategy of radical cyclization provides a new retrosynthetic paradigm to prepare five-membered cyclic molecules from readily available open-chain aldehydes through the union of C-H and C=O elements for C-C bond formation.
Zn-Catalyzed tert-Butyl Nicotinate-Directed Amide Cleavage as a Biomimic of Metallo-Exopeptidase Activity
Wybon, Clarence C. D.,Mensch, Carl,Hollanders, Charlie,Gadais, Charlène,Herrebout, Wouter A.,Ballet, Steven,Maes, Bert U. W.
, p. 203 - 218 (2018/01/17)
A two-step catalytic amide-to-ester transformation of primary amides under mild reaction conditions has been developed. A tert-butyl nicotinate (tBu nic) directing group is easily introduced onto primary amides via Pd-catalyzed amidation with tert-butyl 2-chloronicotinate. A weak base (Cs2CO3 or K2CO3) at 40-50 °C can be used provided that 1,1′-bis(dicyclohexylphosphino)ferrocene is selected as ligand. The tBu nic activated amides subsequently allow Zn(OAc)2-catalyzed nonsolvolytic alcoholysis in tBuOAc at 40-60 °C under neutral reaction conditions. The activation mechanism is biomimetic: the C3-ester substituent of the pyridine in the directing group populates the trans-conformer suitable for Zn-chelation, C=Oamide-Zn-Ndirecting group, and Zn-coordinated alcohol is additionally activated as a nucleophile by hydrogen bonding with the acetate ligand of the catalyst. Additionally, the acetate ligand assists in intramolecular O-to-N proton transfer. The chemoselectivity versus other functional groups and compatibility with challenging reaction partners, such as peptides, sugars, and sterols, illustrates the synthetic applicability of this two-step amide cleavage method. The tBu nic amides do not require purification before cleavage. Preliminary experiments also indicate that other weak nucleophiles can be used such as (hetero)arylamines (transamidation) as exemplified by 8-aminoquinoline.
Levorotatory meptazinol prodrug as well as preparation method and purpose thereof
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Paragraph 0183; 0184; 0186; 0187, (2017/07/19)
The invention provides a levorotatory meptazinol prodrug as well as a preparation method and a purpose thereof, wherein the levorotatory meptazinol prodrug is a compound as shown in a formula I or a stereoisomer, a geometrical isomer, a tautomer, oxynitride, a hydrate, a solvate, a metabolite or a pharmaceutically acceptable salt of the compound as shown in the formula I. The compound is low in hepatic first pass effect and high in bioavailability; a medicine which uses the compound as an active component can be used for treating a neurodegenerative disease or various kinds of acute and chronic pain, such as a wound, postoperative, obstetrical and cancer pain, hemicrania, neuropathic pain and the like.
Catalytic Synthesis of N-Heterocycles via Direct C(sp3)-H Amination Using an Air-Stable Iron(III) Species with a Redox-Active Ligand
Bagh, Bidraha,Broere, Dani?l L. J.,Sinha, Vivek,Kuijpers, Petrus F.,Van Leest, Nicolaas P.,De Bruin, Bas,Demeshko, Serhiy,Siegler, Maxime A.,Van Der Vlugt, Jarl Ivar
supporting information, p. 5117 - 5124 (2017/05/04)
Coordination of FeCl3 to the redox-active pyridine-aminophenol ligand NNOH2 in the presence of base and under aerobic conditions generates FeCl2(NNOISQ) (1), featuring high-spin FeIII and an NNOISQ radical ligand. The complex has an overall S = 2 spin state, as deduced from experimental and computational data. The ligand-centered radical couples antiferromagnetically with the Fe center. Readily available, well-defined, and air-stable 1 catalyzes the challenging intramolecular direct C(sp3)-H amination of unactivated organic azides to generate a range of saturated N-heterocycles with the highest turnover number (TON) (1 mol% of 1, 12 h, TON = 62; 0.1 mol% of 1, 7 days, TON = 620) reported to date. The catalyst is easily recycled without noticeable loss of catalytic activity. A detailed kinetic study for C(sp3)-H amination of 1-azido-4-phenylbutane (S1) revealed zero order in the azide substrate and first order in both the catalyst and Boc2O. A cationic iron complex, generated from the neutral precatalyst upon reaction with Boc2O, is proposed as the catalytically active species.
PROCESS FOR THE CATALYTIC DIRECTED CLEAVAGE OF AMIDE-CONTAINING COMPOUNDS
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Page/Page column 53, (2017/04/11)
The present invention relates to a catalytic method for the conversion of amide-containing compouds by means of a build-in directing group and upon the action of a heteronucleophilic compound (in se an amine (RNH2 or RNHR') or an alcohol (ROH) or a thiol (RSH)) in the presence of a metal catalyst to respectively esters, thioesters, carbonates, thiocarbonates and to what is defined as amide-containing compounds (such as carboxamides, urea, carbamates, thiocarbamates). The present invention also relates to these amide-containing compounds having a build-in directing group (DG), as well as the use of such directing groups in the catalytic directed cleavage of N-DG amides with the use of heteronucleophiles (in se an amine (RNH2 or RNHR') or an alcohol (ROH) or thiol (RSH)).
