- Discovery of Novel 3-Amino-4-alkoxyphenylketones as PDE4 Inhibitors with Improved Oral Bioavailability and Safety against Spatial Memory Impairments
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To realize PDE4 inhibitors with good developmental potentiality for the treatment of dementia, structure-based optimizations of lead compound FCPR03 resulted in novel aminophenylketones 9c and 9H with low nanomolar potency, which displayed comparable acti
- Feng, Kai-Wen,He, Jia-Peng,Liu, Lu,Wang, Hai-Tao,Xia, Chuang,Xu, Jiang-Ping,Zheng, Lei,Zhou, Zhong-Zhen
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p. 390 - 405
(2022/02/07)
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- Photocatalyzed Triplet Sensitization of Oximes Using Visible Light Provides a Route to Nonclassical Beckmann Rearrangement Products
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Oximes are valuable synthetic intermediates for the preparation of a variety of functional groups. To date, the stereoselective synthesis of oximes remains a major challenge, as most current synthetic methods either provide mixtures of E and Z isomers or furnish the thermodynamically preferred E isomer. Herein we report a mild and general method to achieve Z isomers of aryl oximes by photoisomerization of oximes via visible-light-mediated energy transfer (EnT) catalysis. Facile access to (Z)-oximes provides opportunities to achieve regio- and chemoselectivity complementary to those of widely used transformations employing oxime starting materials. We show an enhanced one-pot protocol for photocatalyzed oxime isomerization and subsequent Beckmann rearrangement that enables novel reactivity with alkyl groups migrating preferentially over aryl groups, reversing the regioselectivity of the traditional Beckmann reaction. Chemodivergent N- or O- cyclizations of alkenyl oximes are also demonstrated, leading to nitrones or cyclic oxime ethers, respectively.
- Zhang, Xiao,Rovis, Tomislav
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supporting information
p. 21211 - 21217
(2021/12/27)
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- Selective catalytic synthesis of α-alkylated ketones and β-disubstituted ketones via acceptorless dehydrogenative cross-coupling of alcohols
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Herein, a phosphine-free pincer ruthenium(III) catalyzed β-alkylation of secondary alcohols with primary alcohols to α-alkylated ketones and two different secondary alcohols to β-branched ketones are reported. Notably, this transformation is environmentally benign and atom efficient with H2O and H2 gas as the only byproducts. The protocol is extended to gram-scale reaction and for functionalization of complex vitamin E and cholesterol derivatives.
- Bhattacharyya, Dipanjan,Sarmah, Bikash Kumar,Nandi, Sekhar,Srivastava, Hemant Kumar,Das, Animesh
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supporting information
p. 869 - 875
(2021/02/06)
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- DABCO-promoted photocatalytic C-H functionalization of aldehydes
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Herein we present a direct application of DABCO, an inexpensive and broadly accessible organic base, as a hydrogen atom transfer (HAT) abstractor in a photocatalytic strategy for aldehyde C-H activation. The acyl radicals generated in this step were arylated with aryl bromides through a well stablished nickel cross-coupling methodology, leading to a variety of interesting aryl ketones in good yields. We also performed computational calculations to shine light in the HAT step energetics and determined an optimized geometry for the transition state, showing that the hydrogen atom transfer between aldehydes and DABCO is a mildly endergonic, yet sufficiently fast step. The same calculations were performed with quinuclidine, for comparison of both catalysts and the differences are discussed.
- Cardozo, Thiago Messias,Da Silva Santos, Bruno Maia,Finelli, Fernanda Gadini,de Souza, Cauê Paula,dos Santos Dupim, Mariana
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supporting information
p. 2959 - 2967
(2022/01/12)
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- Aminophenone compounds as well as preparation method and application thereof
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The invention belongs to the technical field of medicinal chemistry, and particularly relates to aminophenone compounds as well as a preparation method and application thereof. The aminophenone compounds provided by the invention have a good inhibition effect on PDE4, also have good bioavailability, can be applied to preparation of drugs for treating PDE4-related diseases, and increase the optionsof drugs for treating PDE4-related diseases; and the effect of a part of the aminophenone compounds is equivalent to the effect of positive drugs, and the aminophenone compounds have good developmentpotential.
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Paragraph 0047; 0051-0053
(2021/02/06)
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- Palladium-Catalyzed Carbonylative Coupling of Aryl Iodides with Alkenylaluminum Reagents
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A highly reactive catalytic system for the carbonylative coupling of aryl iodides with alkenylaluminum reagents has been developed. Various β-substituted γ,δ-unsaturated ketones were produced under mild conditions in good to excellent yields even under ppm level of palladium catalyst. Notably, this also represents the first example on carbonylative transformation of alkenylaluminum compounds. Additionally, by the addition of zinc salt, the selectivity of the product can be modified.
- Chen, Bo,Wu, Xiao-Feng
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supporting information
p. 7624 - 7629
(2019/10/02)
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- Pd-catalyzed Oxidative Cross-coupling of Alkyl Chromium(0) Fischer Carbene Complexes with Organoboronic Acids
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Alkyl chromium(0) carbene complexes have been explored as the cross-coupling partners in the palladium-catalyzed reaction with aryl or alkenyl boronic acids. This coupling reaction displays the versatile reactivities of alkyl chromium(0) carbenes under palladium catalysis. Mechanistically, this transformation is proposed to involve deprotonation of the alkyl chromium carbene substrate to generate a vinyl chromium anion intermediate that undergoes transmetalation to organopalladium species and reductive elimination.
- Wang, Kang,Yang, Jinghui,Yao, Xingqi,Wang, Jianbo
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supporting information
p. 3165 - 3168
(2018/10/15)
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- A new approach to the synthesis of peptidomimetic renin inhibitors: Palladium-catalyzed asymmetric allylation of acyclic alkyl aryl ketones
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A new approach to the synthesis of Tekturna, a recently marketed drug for hypertension, takes advantage of a modified protocol of the Stoltz palladium-catalyzed asymmetric allylation with a t-BuPHOX ligand for the synthesis of allylated acyclic alkyl aryl
- Hanessian, Stephen,Chénard, Etienne
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supporting information; experimental part
p. 3222 - 3225
(2012/08/08)
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- Direct acylation of aryl chlorides with aldehydes by palladium-pyrrolidine Co-catalysis
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A palladium catalyst system has been developed that allows for the direct acylation of aryl chlorides with aldehydes. The choice of ligand, as well as the presence of pyrrolidine and molecular sieves is shown to be critical to the catalysis, which appears to proceed via an enamine intermediate. The reaction was successful for a wide range of aryl chlorides and tolerant of functionality on the aldehyde component, giving easy access to alkyl aryl ketones in modest to good yields.
- Colbon, Paul,Ruan, Jiwu,Purdie, Mark,Xiao, Jianliang
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supporting information; experimental part
p. 3670 - 3673
(2010/10/20)
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- 3-(2-Aminocarbonylphenyl)propanoic acid analogs as potent and selective EP3 receptor antagonists. Part 2: Optimization of the side chains to improve in vitro and in vivo potencies
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A series of 3-[2-{[(3-methyl-1-phenylbutyl)amino]carbonyl}-4-(phenoxymethyl)phenyl]propanoic acid analogs were synthesized and evaluated for their in vitro potency. In most cases, introduction of one or two substituents into the two phenyl moieties resulted in the tendency of an increase or retention of in vitro activities. Several compounds, which showed excellent subtype selectivity, were evaluated for their inhibitory effect against PGE2-induced uterine contraction in pregnant rats, which is thought to be mediated by the EP3 receptor subtype. The structure-activity relationships (SARs) are also discussed.
- Asada, Masaki,Iwahashi, Maki,Obitsu, Tetsuo,Kinoshita, Atsushi,Nakai, Yoshihiko,Onoda, Takahiro,Nagase, Toshihiko,Tanaka, Motoyuki,Yamaura, Yoshiyuki,Takizawa, Hiroya,Yoshikawa, Ken,Sato, Kazutoyo,Narita, Masami,Ohuchida, Shuichi,Nakai, Hisao,Toda, Masaaki
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experimental part
p. 1641 - 1658
(2010/04/29)
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- A heterogeneous Ru/CeO2 catalyst effective for transfer-allylation from homoallyl alcohols to aldehydes
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A simple heterogeneous Ru/CeO2 catalyst was found to be effective for transfer-allylation from homoallyl alcohols to aldehydes, followed by isomerization to give the saturated ketones in high yields.
- Miura, Hiroki,Wada, Kenji,Hosokawa, Saburo,Sai, Masahiro,Kondo, Teruyuki,Inoue, Masashi
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scheme or table
p. 4112 - 4114
(2009/12/25)
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- Direct acylation of aryl bromides with aldehydes by palladium catalysis
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A new protocol for the direct acylation of aryl bromides with aldehydes is established. It appears to involve palladium-amine cooperative catalysis, affording synthetically important alkyl aryl ketones in moderate to excellent yields in a straightforward manner, and broadening the scope of metal-catalyzed coupling reactions. Copyright
- Ruan, Jiwu,Saidi, Ourida,Iggo, Jonathan A.,Xiao, Jianliang
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supporting information; experimental part
p. 10510 - 10511
(2009/02/05)
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- Rhodium-catalyzed allyl transfer from homoallyl alcohols to aldehydes via retro-allylation followed by isomerization into ketones
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Retro-allylation of homoallyl alcohol by rhodium catalysis occurs to generate allylrhodium species. This allylrhodium reacts with aldehydes to give the corresponding secondary alcohols in situ. Isomerization of these alcohols proceeds in the same pots to furnish the corresponding saturated ketones in good yields.
- Takada, Yuko,Hayashi, Sayuri,Hirano, Koji,Yorimitsu, Hideki,Oshima, Koichiro
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p. 2515 - 2517
(2007/10/03)
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- AN IMPROVED PROCESS FOR PREPARING N-HYDROXY-4-{5- [4- (5-ISOPROPYL-2-METHYL-l, 3-THIAZOL-4-YL) -PHENOXY] -PENTOXY }-BENZAMIDINE
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This invention relates to an improved method of preparing N-hydroxy-4-{5- [4- (5-isopropyl-2-methyl-l, 3-thiazol-4-yl) phenoxy] pentoxy }benzamidine .
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Page/Page column 8; 13; 16-17
(2008/06/13)
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- Pyrazole ligands: Structure - Affinity/activity relationships and estrogen receptor-α-selective agonists
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We have found that certain tetrasubstituted pyrazoles are high-affinity ligands for the estrogen receptor (ER) (Fink et al. Chem. Biol. 1999, 6, 205-219) and that one pyrazole is considerably more potent as an agonist on the ERα than on the ERβ subtype (Sun et al. Endocrinology 1999, 140, 800-804). To investigate what substituent pattern provides optimal ER binding affinity and the greatest enhancement of potency as an ERα-selective agonist, we prepared a number of tetrasubstituted pyrazole analogues with defined variations at certain substituent positions. Analysis of their binding affinity pattern shows that a C(4)-propyl substituent is optimal and that a p-hydroxyl group on the N(1)-phenyl group also enhances affinity and selectivity for ERα. The best compound in this series, a propylpyrazole triol (PPT, compound 4g), binds to ERα with high affinity (ca. 50% that of estradiol), and it has a 410-fold binding affinity preference for ERα. It also activates gene transcription only through ERα. Thus, this compound represents the first ERα-specific agonist. We investigated the molecular basis for the exceptional ERα binding affinity and potency selectivity of pyrazole 4g by a further study of structure-affinity relationships in this series and by molecular modeling. These investigations suggest that the pyrazole triols prefer to bind to ERα with their C(3)-phenol in the estradiol A-ring binding pocket and that binding selectivity results from differences in the interaction of the pyrazole core and C(4)-propyl group with portions of the receptor where ERα has a smaller residue than ERβ. These ER subtype-specific interactions and the ER subtype-selective ligands that can be derived from them should prove useful in defining those biological activities in estrogen target cells that can be selectively activated through ERα.
- Stauffer,Coletta,Tedesco,Nishiguchi,Carlson,Sun,Katzenellenbogen,Katzenellenbogen
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p. 4934 - 4947
(2007/10/03)
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- Palladium-Catalyzed Reaction of Acyliron Complexes with Aryl Halydes. A Convenient Synthesis of Aromatic Ketones
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Acyliron complexes, easily prepared from disodium tetracarbonylferrate and alkyl halides, reacted with aryl iodides in the presence of a catalytic amount of Pd(PPh3)4 and a cocatalyst, ZnCl2, to give aromatic ketones in good yields. (R)-2-Methyl-1-phenyl-octanone was prepared starting from (S)-2-bromooctane in an excellent optical yield.
- Koga, Teruyoshi,Makinouchi, Shinako,Okukado, Nobuhisa
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p. 1141 - 1144
(2007/10/02)
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