22433-76-7Relevant articles and documents
N-Tetrahydroquinolinyl, N-quinolinyl and N-isoquinolinyl biaryl carboxamides as antagonists of TRPV1
Westaway, Susan M.,Chung, Ying-Kit,Davis, John B.,Holland, Vicky,Jerman, Jeffrey C.,Medhurst, Stephen J.,Rami, Harshad K.,Stemp, Geoffrey,Stevens, Alexander J.,Thompson, Mervyn,Winborn, Kim Y.,Wright, James
, p. 4533 - 4536 (2006)
Starting from the high throughput screening hit (3), novel N-tetrahydroquinolinyl, N-quinolinyl and N-isoquinolinyl carboxamides have been identified as potent antagonists of the ion channel TRPV1. The N-quinolinylnicotinamide (46) showed excellent potenc
WEE1 inhibitors as well as preparation and application thereof
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Paragraph 0686-0691, (2020/10/14)
The invention relates to WEE1 inhibitors as well as preparation and application thereof. The present invention relates to compounds of formula (I), or pharmaceutically acceptable salts, solvates, polymorphs or isomers thereof, and their use in the preparation of medicaments for the treatment of diseases associated with WEE1 activity.
Palladium-Catalyzed, ortho-Selective C-H Halogenation of Benzyl Nitriles, Aryl Weinreb Amides, and Anilides
Das, Riki,Kapur, Manmohan
, p. 1114 - 1126 (2018/06/18)
A palladium-catalyzed, ortho-selective C-H halogenation methodology is reported herein. The highlight of the work is the highly selective C(sp2)-H functionalization of benzyl nitriles in the presence of activated C(sp3)-H bond, which results in good yields of the halogenated products with excellent regioselectivity. Along with benzyl nitriles, aryl Weinreb amides and anilides have been evaluated for the transformation using aprotic conditions. Mechanistic studies yield interesting aspects with respect to the pathway of the reaction and the directing group abilities.
Generating Active L-Pd(0) via Neutral or Cationic π-Allylpalladium Complexes Featuring Biaryl/Bipyrazolylphosphines: Synthetic, Mechanistic, and Structure-Activity Studies in Challenging Cross-Coupling Reactions
Deangelis,Gildner, Peter G.,Chow, Ruishan,Colacot, Thomas J.
, p. 6794 - 6813 (2015/10/06)
Two new classes of highly active yet air- and moisture-stable π-R-allylpalladium complexes containing bulky biaryl- and bipyrazolylphosphines with extremely broad ligand scope have been developed. Neutral π-allylpalladium complexes incorporated a range of biaryl/bipyrazolylphosphine ligands, while extremely bulky ligands were accommodated by a cationic scaffold. These complexes are easily activated under mild conditions and are efficient for a wide array of challenging C-C and C-X (X = heteroatom) cross-coupling reactions. Their high activity is correlated to their facile activation to a 12-electron-based L-Pd(0) catalyst under commonly employed conditions for cross-coupling reactions, noninhibitory byproduct release upon activation, and suppression of the off-cycle pathway to form dinuclear (μ-allyl)(μ-Cl)Pd2(L)2 species, supported by structural (single crystal X-ray) and kinetic studies. A broad scope of C-C and C-X coupling reactions with low catalyst loadings and short reaction times highlight the versatility and practicality of these catalysts in organic synthesis.
Pd-catalyzed amidations of aryl chlorides using monodentate biaryl phosphine ligands: A kinetic, computational, and synthetic investigation
Ikawa, Takashi,Barder, Timothy E.,Biscoe, Mark R.,Buchwald, Stephen L.
, p. 13001 - 13007 (2008/09/17)
We present results on the amidation of aryl halides and sulfonates utilizing a monodentate biaryl phosphine-Pd catalyst. Our results are in accord with a previous report that suggests that the formation of κ2- amidate complexes is deleterious to the effectiveness of a catalyst for this transformation and that their formation can be prevented by the use of appropriate bidentate ligands. We now provide data that suggest that the use of certain monodentate ligands can also prevent the formation of the κ2-amidate complexes and thereby generate more stable catalysts for the amination of aryl chlorides. Furthermore, computational studies shed light on the importance of the key feature(s) of the biaryl phosphines (a methyl group ortho to the phosphorus center) that enable the coupling to occur. The use of ligands that possess a methyl group ortho to the phosphorus center allows a variety of aryl and heteroaryl chlorides with various amides to be coupled in high yield.
Indium metal as a reducing agent in organic synthesis
Pitts,Harrison,Moody
, p. 955 - 977 (2007/10/03)
The low first ionisation potential (5.8 eV) of indium coupled with its stability towards air and water, suggest that this metallic element should be a useful reducing agent for organic substrates. The use of indium metal for the reduction of C=N bonds in imines, the heterocyclic ring in benzo-fused nitrogen heterocycles, of oximes, nitro compounds and conjugated alkenes and the removal of 4-nitrobenzyl protecting groups is described. Thus the heterocyclic ring in quinolines, isoquinolines and quinoxalines is selectively reduced using indium metal in aqueous ethanolic ammonium chloride. Treatment of a range of aromatic nitro compounds under similar conditions results in selective reduction of the nitro groups; ester, nitrile, amide and halide substituents are unaffected. Likewise indium in aqueous ethanolic ammonium chloride is an effective method for the deprotection of 4-nitrobenzyl ethers and esters. Indium is also an effective reducing agent under non-aqueous conditions and α-oximino carbonyl compounds can be selectively reduced to the corresponding N-protected amine with indium powder, acetic acid in THF in the presence of acetic anhydride or di-tert-butyl dicarbonate. Conjugated alkenes are also reduced by indium in THF-acetic acid.
Design and Synthesis of Novel 6,7-Imidazotetrahydroquinoline Inhibitors of Thymidylate Synthase Using Iterative Protein Crystal Structure Analysis
Reich, Siegfried H.,Fuhry, Mary Ann M.,Nguyen, Dzuy,Pino, Mark J.,Welsh, Katherine M.,et al.
, p. 847 - 858 (2007/10/02)
Antifolate inhibitors of thymidylate synthase (TS) have primarily been based on the structure of folic acid.This paper describes the identification and development of novel 6,7-imidazotetrahydroquinoline TS inhibitors by iterative ligand design, synthesis, and crystallographic analysis of protein-inhibitor complexes.Beginning with a high-resolution crystal structure of E. coli TS (TS, EC 2.1.1.45), an imidazotetrahydroquinoline inhibitor was designed de novo to occupy the folate binding pocket.Structural modifications of the initial compound 1h (Ki ca. 5 μM human/E. coli TS) were then made on the basis of feedback from additional cocrystal structures and activity data.An amino group in the 2-position of the imidazole was found to increase the potency of the series by 1-2 orders of magnitude.Other substitutions on the imidazole ring (1-CH3, 2-CH3, 2-NHCH3, 2-SCH3) generally led to weaker inhibition.Additional improvements in activity were obtained by modification of the substituents on the tetrahydroquinoline nitrogen, bringing the Ki of three of the compounds below 15 nM against the human TS enzyme.The compounds were tested for cytotoxicity and were shown to inhibit the growth of three tumor cell lines in vitro.
