- Rational design of cannabinoid type-1 receptor allosteric modulators: Org27569 and PSNCBAM-1 hybrids
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Allosteric modulation offers an alternate approach to target the cannabinoid type-1 receptor (CB1) for therapeutic benefits. Examination of the two widely studied prototypic CB1 negative allosteric modulators (NAMs) Org27569 and PSNCBAM-1 revealed structural resemblance and similar structure–activity relationships (SARs). In silico docking and dynamics simulation studies using the crystal structure of CB1 co-bound with CP55,940 and Org27569 suggested that Org27569 and PSNCBAM-1 occupied the same binding pocket and several common interactions were present in both series with the CB1 receptor. A new scaffold was therefore designed by merging the key structural features from the two series and the hybrids retained these binding features in the in silico docking studies. In addition, one such hybrid displayed similar functions to Org27569 in dynamic simulations by preserving a key R2143.50-D3386.30 salt bridge and maintaining an antagonist-like Helix3-Helix6 interhelical distance. Based on these results, a series of hybrids were synthesized and assessed in calcium mobilization, [35S]GTPγS binding and cAMP assays. Several compounds displayed comparable potencies to Org27569 and PSNCBAM-1 in these assays. This work offers new insight of the SAR requirement at the allosteric site of the CB1 receptor and provides a new scaffold that can be optimized for the development of future CB1 allosteric modulators.
- Nguyen, Thuy,Gamage, Thomas F.,Decker, Ann M.,Finlay, David B.,Langston, Tiffany L.,Barrus, Daniel,Glass, Michelle,Harris, Danni L.,Zhang, Yanan
-
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- Palladium-Catalyzed Formal (3 + 2) Cycloaddition Reactions of 2-Nitro-1,3-enynes with Vinylaziridines, -epoxides, and -cyclopropanes
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A two-step Pd-catalyzed (3 + 2) cycloaddition/HNO2 elimination reaction sequence has been developed to give novel cyclic 1,3-dien-5-yne systems from Pd-stabilized zwitterionic 1,3-dipoles and 2-nitro-1,3-enyne substrates. The process is highly atom-efficient and tolerates the reaction of 2-vinyloxirane, 1-tosyl-2-vinylaziridine, and diethyl 2-vinylcyclopropane-1,1-dicarboxylate derived 1,3-dipoles with a variety of 2-nitro-1,3-enyne substrates. The stereochemistry of the intermediate (3 + 2) cycloadducts was determined by single crystal X-ray analysis. Furthermore, a selective kinetic elimination of the cycloadduct with an antiperiplanar relationship between the NO2 group and the participating hydrogen was demonstrated, allowing for efficient isolation of a single diastereoisomer of the cycloadduct.
- Drew, Melanie A.,Tague, Andrew J.,Richardson, Christopher,Pyne, Stephen G.,Hyland, Christopher J. T.
-
supporting information
p. 4635 - 4639
(2021/06/28)
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- Organocatalytic Asymmetric Synthesis of Aza-Spirooxindoles via Michael/Friedel-Crafts Cascade Reaction of 1,3-Nitroenynes and 3-Pyrrolyloxindoles
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An asymmetric [3+3] cyclization of nitroenynes and 3-pyrrolyloxindoles has been realized with a chiral bifunctional squaramide catalyst. This Michael/Friedel-Crafts cascade strategy provides a facile and efficient access to enantioenriched polycyclic aza-spirooxindoles with 32-95% isolated yields and excellent stereocontrol under mild reaction conditions.
- Ni, Qijian,Wang, Xuyang,Zeng, Da,Wu, Qianling,Song, Xiaoxiao
-
supporting information
p. 2273 - 2278
(2021/04/05)
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- Skeletally Tunable Seven-Membered-Ring Fused Pyrroles
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We describe a copper-mediated method that enables the synthesis of seven-membered-ring fused pyrroles (7-mrFPs). The protocol proceeds via an in situ spiro-intermediate ring expansion and tolerates a library of 7-mrFP derivatives with a broad range of functional groups in a simple step with tangible parameters and substrate adaptations. These rare 7-mrFPs are now accessible on a millimolar scale, and selected examples exhibit high antioxidant activity.
- Andreou, Dimitrios,Essien, Nsikak B.,Pubill-Ulldemolins, Cristina,Terzidis, Michael A.,Papadopoulos, Athanasios N.,Kostakis, George E.,Lykakis, Ioannis N.
-
supporting information
p. 6685 - 6690
(2021/09/11)
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- One-pot and metal-free synthesis of 3-arylated-4-nitrophenols via polyfunctionalized cyclohexanones from β-nitrostyrenes
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β-Nitrostyrenes underwent a Diels-Alder reaction with Danishefsky's diene to afford cyclohexenes together with the corresponding hydrolyzed products, 3-arylated-5-methoxy-4-nitrocyclohexanones. When the reaction was conducted in the presence of water, the cyclohexenes were efficiently hydrolyzed into cyclohexanones. Subsequent aromatization by heating the cyclohexanone with a catalytic amount of iodine in dimethyl sulfoxide gave 3-arylated-4-nitrophenols. The reaction of nitrostyrenes with Danishefsky's diene could be conducted in one pot to directly afford the corresponding nitrophenols. Moreover, a heteroaryl group, e.g., a thienyl group could be introduced into the nitrophenol framework.
- Asahara, Haruyasu,Hiraishi, Minami,Nishiwaki, Nagatoshi
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p. 1830 - 1836
(2020/09/15)
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- Facile Synthesis of 1,3,5-Triarylbenzenes and 4-Aryl-NH-1,2,3-Triazoles Using Mesoporous Pd-MCM-41 as Reusable Catalyst
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We report mesoporous nano-Pd-MCM-41 catalyzed rapid and efficient synthesis of 1,3,5-triarylbenzenes via de-nitrative cyclotrimerization of β-nitrostyrenes. All the reactions were very fast and high yielding. The Pd-MCM-41 was also very effective in catalyzing de-nitrative [3+2] cycloaddition of β-nitrostyrenes with TMSN3 to synthesize 4-aryl-NH-1,2,3-triazoles. The catalyst was reused at least up to eight times with minimum loss of catalytic activity.
- Saha, Arijit,Wu, Chia-Ming,Peng, Rui,Koodali, Ranjit,Banerjee, Subhash
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p. 104 - 111
(2019/01/04)
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- Substrate promiscuity of ortho-naphthoquinone catalyst: Catalytic aerobic amine oxidation protocols to deaminative cross-coupling and n-nitrosation
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ortho-Naphthoquinone-based organocatalysts have been identified as versatile aerobic oxidation catalysts. Primary amines were readily cross-coupled with primary nitroalkanes via deaminative pathway to give nitroalkene derivatives in good to excellent yields. Secondary and tertiary amines were inert to ortho-naphthoquinone catalysts; however, secondary nitroalkanes were readily converted by ortho-naphthoquinone catalysts to the corresponding nitrite species that in situ oxidized the amines to the corresponding N-nitroso compounds. Without using harsh oxidants in a stoichiometric amount, the present catalytic aerobic oxidation protocol utilizes the substrate promiscuity feature to provide a facile access to amine oxidation products under mild reaction conditions.
- Kim, Hun Young,Oh, Kyungsoo,Si, Tengda
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p. 9216 - 9221
(2019/10/08)
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- Base-catalyzed reactions enhanced by solid acids: Amine-catalyzed nitroaldol (Henry) reactions enhanced by silica gel or mesoporous silica SBA-15
-
The reactions of various aldehydes with CH3NO2 catalyzed by Et3N, n-C6H13NH2, and Me2N(CH2)2NH2 were accelerated by the addition of silica gel to give aromatic (aliphatic) β-nitroalcohols, aromatic nitroalkenes, and aromatic 1,3-dinitroalkanes, respectively. Mesoporous silica SBA-15 showed higher activity than silica gel for the synthesis of aromatic nitroalkenes by the reactions of the corresponding aldehydes with CH3NO2 catalyzed by n-C6H13NH2.
- Tanemura, Kiyoshi,Suzuki, Tsuneo
-
supporting information
p. 392 - 396
(2017/12/28)
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- Squaramide-Linked Chloramphenicol Base Hybrid Catalysts for the Asymmetric Michael Addition of 2,3-Dihydrobenzofuran-2-carboxylates to Nitroolefins
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An array of hybrid catalysts incorporating a chloramphenicol base moiety linked to another chiral scaffold through a squaramide linker were developed and successfully used in the Michael addition of 2,3-dihydrobenzofuran-2-carboxylates to nitroolefins. Control experiments suggested that the hybrid catalysts were more reactive than nonhybridized bifunctional catalysts, and matching of the chirality between the two scaffolds was crucial for high reactivity and stereoselectivity. These hybrid organocatalysts could be used with a variety of substrates. At a 0.5 mol-% catalyst loading, a range of 2,3-dihydrobenzofuran-2-carboxylates derivatives bearing quaternary and tertiary stereogenic centers were obtained in high yields (up to 98 %) with excellent enantioselectivities (up to 99 % ee) and moderate diastereoselectivities (up to 8:92 dr).
- Yan, Linjie,Huang, Guanxin,Wang, Haifeng,Xiong, Fangjun,Peng, Haihui,Chen, Fener
-
supporting information
p. 99 - 103
(2018/01/17)
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- Synthesis of Benzo[4,5]imidazo[2,1-b]thiazole by Copper(II)-Catalyzed Thioamination of Nitroalkene with 1H-Benzo[d]imidazole-2-thiol
-
A Copper(II)-catalyzed thioamination of β-nitroalkene with 1H-benzo[d]imidazole-2-thiol has been developed for the synthesis of benzo[4,5]imidazo[2,1-b]thiazole derivatives. A variety of N-fused benzoimidazothiazole derivatives are obtained in high yields through successive C?N and C?S bond formations. This protocol is also applicable to β-substituted β-nitroalkenes to afford 2,3-disubstituted benzoimidazothiazoles. (Figure presented.).
- Jana, Sourav,Chakraborty, Amrita,Shirinian, Valerii Z.,Hajra, Alakananda
-
supporting information
p. 2402 - 2408
(2018/05/08)
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- Drug application for benzene [g] ceteroary [a, g] quinazine compound and preparation method thereof
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The invention relates to a new application of a benzene [g] ceteroary [a, g] quinazine compound and a preparation method thereof. Specifically, the invention relates to the application of the benzene [g] ceteroary [a, g] quinazine compound in preparing the drug for treating and/or preventing the metabolic diseases caused by AMPK route, especially, the diabetes, adiposis, fatty liver and complication thereof caused by insulin resistance.
- -
-
Paragraph 0107; 0108
(2017/11/16)
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- Catalyst-free sulfa-Michael addition of pyrimidine-2-thiol to nitroolefins
-
Catalyst-free sulfa-Michael addition of pyrimidine-2-thiol to nitroolefins is described. A series of 2-((2-nitro-1-arylethyl)thio)pyrimidines were efficiently synthesized. The protocol has advantages of wide range of substituents tolerance, no catalyst, additives and bases, mild condition, and high yield. The method can also extend to gram scale.
- Li, Zheng,Song, Geyang,He, Jiaojiao,Du, Yan,Yang, Jingya
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p. 686 - 698
(2017/09/06)
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- Continuous-flow synthesis using a column reactor packed with heterogeneous catalysts: A convenient production of nitroolefins by using amino-functionalized silicagel
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A continuous-flow synthesis of β-nitroolefins by using heterogeneous base catalysts has been developed. Although the use of an excess amount of nitro-donor such as nitromethane is required in conventional methods, nearly equimolar amounts of nitro-donors and carbonyl compounds are sufficient for high-yielding production of nitroolefins. Catalysts for this flow protocol are inexpensive and abundant, and high durability and high productivity were also realized by using an appropriate second support.
- Ishitani, Haruro,Furiya, Yuichi,Kobayashi, Shū
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supporting information
p. 6229 - 6232
(2017/09/30)
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- An Asymmetric Vinylogous Michael Cascade of Silyl Glyoximide, Vinyl Grignard, and Nitroalkenes via Long Range Stereoinduction
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A diastereoselective auxiliary-mediated vinylation/[1,2]-Brook rearrangement/vinylogous Michael cascade of silyl glyoximide, vinylmagnesium bromide, and nitroalkenes is described. The reaction occurs with complete regio- and diastereocontrol in good yield. The diastereoselectivity is induced by a rare instance of 1,7-chirality transfer that is hypothesized to arise from a trans-multihetero-decalin transition state. (Chemical Equation).
- Boyce, Gregory R.,Johnson, Jeffrey S.
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p. 1712 - 1717
(2016/03/01)
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- Synthesis method of ticlopidine hydrochloride drug intermediate 2-(2-nitrovinyl)thiophene
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A synthesis method of ticlopidine hydrochloride drug intermediate 2-(2-nitrovinyl)thiophene comprises steps as follows: 1.3 mol of a thiophene methyl glycol solution, 1.6-1.9 mol of a nitromethane solution and 900 ml of hexane are added to a reaction container provided with a stirrer, a thermometer and a dropping funnel, the temperature of the solution is decreased to 3-7 DEG C, the stirring speed of the solution is controlled to range from 110 rpm to 130 rpm, a reaction is conducted for 4-7 h, the temperature of the solution is increased to 50-55 DEG C, 500 ml of a potassium bromide solution is added for a reaction for 3-5 h, 300 ml of an oxalic acid solution is added, the temperature of the solution is decreased to 10-16 DEG C, a reaction is conducted for 80-110 min, the temperature is decreased to 2-5 DEG C, the solution is left to stand for 5-7 h, solids separate out, are filtered, are washed with a saline solution, ethyl acetate and chlorobenzene, are dehydrated by the aid of a dehydrating agent and are recrystallized in dimethylbenzene, and crystal 2-(2-nitrovinyl)thiophene is obtained.
- -
-
Paragraph 0007; 0015; 0016
(2016/11/09)
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- Synthesis of Heteroaryl-Substituted Pyrroles via the 1,3-Dipolar Cycloaddition of Unsymmetrical Münchnones and Nitrovinylheterocycles
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A series of furanyl-, thiophenyl-, and pyrrolo-substituted pyrroles were prepared via the 1,3-dipolar cycloaddition of unsymmetrical münchnones and nitrovinylheterocycles. The regiochemical outcome of the furan and thiophene cycloadditions compares favorably to previously reported cycloadditions with β-nitrostyrene, while the nitrovinylpyrrole cycloadditions mirror the results observed with nitrovinylindole.
- Lopchuk, Justin M.,Song, Mia,Butler, Blythe,Gribble, Gordon W.
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p. 2776 - 2780
(2015/09/15)
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- DIARYL[A, G]QUINOLIZIDINE COMPOUND, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION, AND USES THEREOF
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The present invention relates to a diarylo[a,g]quinolizidine compound of formula (I), enantiomer, diastereoisomer, racemate, mixture, pharmaceutically acceptable salt, crystalline hydrate or solvate thereof; the preparation method thereof, and uses thereof in preparing an experimental model drugs related to dopamine receptors and 5-HT receptors or a medicament for treating or preventing a disease related to dopamine receptors and 5-HT receptors.
- -
-
Paragraph 0053; 0054
(2015/03/28)
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- DIARYL[A, G]QUINOLIZIDINE COMPOUND, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION, AND USES THEREOF
-
The present invention relates to a diarylo[a,g]quinolizidine compound of formula (I), enantiomer, diastereoisomer, racemate, mixture, pharmaceutically acceptable salt, crystalline hydrate or solvate thereof; the preparation method thereof, and uses thereof in preparing an experimental model drugs related to dopamine receptors and 5-HT receptors or a medicament for treating or preventing a disease related to dopamine receptors and 5-HT receptors.
- -
-
Paragraph 0113; 0114
(2015/05/26)
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- 17a-HYDROXYLASE/C17,20-LYASE INHIBITORS
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The present invention provides compounds of Formula (I), or a pharmaceutically acceptable salt thereof, where R1, R2, R3, R4, R5, R6, A and n are as defined herein. A deuteriated derivative of the compound of Formula (I) is also provided.
- -
-
Paragraph 0253; 0254
(2014/03/21)
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- New approach to oximes through reduction of nitro compounds enabled by visible light photoredox catalysis
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A range of nitro compounds are smoothly reduced to their corresponding oximes under the synergistic effects of visible light irradiation, the Ru(bpy)3Cl2 photocatalyst, Hünig's base, Mg(ClO 4)2 activation, and MeCN solvent. This remarkably mild and environmentally benign protocol, when orchestrated with classical Beckmann rearrangement, enables such high-value industrial feedstock as caprolactam to be readily accessed from simple precursor nitrocyclohexane.
- Cai, Shunyou,Zhang, Shaolong,Zhao, Yaohong,Wang, David Zhigang
-
supporting information
p. 2660 - 2663
(2013/07/11)
-
- Urea postmodified in a metal-organic framework as a catalytically active hydrogen-bond-donating heterogeneous catalyst
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New functionally diverse urea-derived MOF hydrogen-bond-donating heterogeneous catalysts were achieved via postsynthetic modification, which exhibit excellent catalytic activity and very broad substrate scopes for the Friedel-Crafts alkylation reactions.
- Dong, Xiao-Wu,Liu, Tao,Hu, Yong-Zhou,Liu, Xin-Yuan,Che, Chi-Ming
-
supporting information
p. 7681 - 7683
(2013/09/02)
-
- 17α-HYDROXYLASE/C17,20-LYASE INHIBITORS
-
The present invention provides compounds of Formula (I), or a pharmaceutically acceptable salt thereof, where R1, R2, R3, R4, R5, R6, A and n are as defined herein. A deuteriated derivative of the compound of Formula (I) is also provided.
- -
-
Page/Page column 46
(2012/04/04)
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- Mesoporous nickel hydroxyapatite nanocomposite for microwave-assisted Henry reaction
-
The utility of nickel hydroxyapatite nanocomposite (Ni-HAp) as a green catalyst for solvent free, microwave-assisted Henry reaction using nitromethane and a series of aromatic aldehydes as substrates is presented. The selected catalyst performed well to afford the respective nitrostyrenes which were quantified by gas chromatography equipped with a mass spectral detector (GC-MS). A few of the products were identified from the respective nuclear magnetic resonance (NMR) spectral data.
- Neelakandeswari,Sangami,Emayavaramban,Karvembu,Dharmaraj,Kim, Hak Yong
-
experimental part
p. 2980 - 2984
(2012/07/28)
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- One-pot synthesis of nitroalkenes via the Henry reaction over amino-functionalized MIL-101 catalysts
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Ethylenediamine moieties with different amounts were incorporated into the metal-organic framework MIL-101 to prepare the amino-functionalized MIL-101 materials, which were used as heterogeneous catalysts in the one-pot synthesis of nitroalkenes via the Henry reaction. Various reaction conditions were optimized. Under the optimized conditions, the selectivity towards nitroalkenes is extremely high in combination with nearly complete conversion of the reactant nitroalkanes. The amino-functionalized MIL-101 behaves as a true heterogeneous catalyst, can be easily recovered by filtration, and can be reused at least twice without significant loss of its catalytic performance.
- Yu, Huixian,Xie, Jianwu,Zhong, Yijun,Zhang, Fumin,Zhu, Weidong
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p. 101 - 104
(2013/01/15)
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- Straightforward synthesis of nitroolefins by microwave- or ultrasound-assisted Henry reaction
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β-Nitroalcohol or nitroethylene derivatives can be obtained from aryl aldehydes and nitromethane under Henry condensation conditions. We present a new modification using microwave irradiation or ultrasound as the energy source. Microwave irradiation allowed a novel one-pot synthesis of nitroolefins from aryl aldehydes using ammonium acetate as a catalyst without solvent. Different reaction conditions, such as base, solvent, and reaction time were studied. Only small amounts of β-hydroxyl nitro compounds were isolated, using microwave irradiation for less than 25 min. In contrast, the use of ultrasound increased the yield of the nitroalcohols.
- Rodríguez, Jose M.,Dolors Pujol
-
scheme or table
p. 2629 - 2632
(2011/06/10)
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- Metal halide hydrates as lewis acid catalysts for the conjugated Friedel-Crafts reactions of indoles and activated olefins
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Metal halide hydrates such as SnCl2·2H2O, MnCl2·4H2O, SrCl2·6H 2O, CrCl2·6H2O, CoCl2· 6H2O e CeCl3·7H2O were investigated as mild Lewis acids catalysts for the conjugate Friedel-Crafts reaction between indoles and activated olefins. The reactions were carried out with aliphatic unsaturated ketones over a period of days at room temperature, while chalcones reacted only under reflux conditions. The reactions with nitrostyrenes were either performed in solvent or under solventless conditions. In all cases reasonable to good yields were obtained. ?2011 Sociedade Brasileira de Qui?mica.
- Schwalm, Cristiane S.,Ceschi, Marco Antonio,Russowsky, Dennis
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scheme or table
p. 623 - 636
(2012/01/05)
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- H-Y zeolite is a versatile heterogeneous catalyst for the synthesis of β-nitroamines
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Heterogeneous aza-Henry reactions of aldimes with nitromethane were examined with zeolites as catalysts. Among the zeolite used, H-Y zeolite showed satisfactory catalytic activity for various aldimines, resulting in corresponding β-nitroamines in good yields. H-Y zeolite also showed the excellent reusability until the 3rd usage without loss of its activity; further, the calcination of deactivated H-Y zeolite allowed it to rejuvenate its catalytic activity. Solid-state 13C MAS NMR revealed the predominant activation of an aldimine into the H-Y zeolite.
- Komura, Kenichi,Taninaka, Yuki,Ohtaki, Yoshifumi,Sugi, Yoshihiro
-
experimental part
p. 211 - 215
(2011/02/23)
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- Method of making imidazole-2-thiones
-
The present invention provides a method of making an imidazole-2-thione which comprises the steps of reacting a vicinal diamine with a compound having a thiocarbonyl moiety and oxidizing the resulting reaction product to obtain said imidazole-2-thione.
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-
Page/Page column 6; 11
(2008/06/13)
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- 3-Nitrochromenes for Second Order Nonlinear Optical Applications
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3-Nitrochromenes bearing various substituents have been prepared by the reaction of substituted salicylaldehydes with nitrostyrenes; some of these compounds have been found to display efficient optical second harmonic generation.
- Ono, Noboru,Sugi, Kiyoshi,Ogawa, Takuji,Aramaki, Shinji
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p. 1781 - 1782
(2007/10/02)
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- A Thiophene Analogue of Praziquantel, and Related Systems, by Intramolecular Cyclisation of Acyliminium Salts
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N--succinimide (7a) and -glutarimide (7b) on reduction with sodium borohydride in methanol at -10 deg C yield the respective hydroxylactams which on treatment with formic acid cyclise via the intermediate acyliminium ions to 4,5,9,9a-tetrahydropyrrolothienopyridin-7-one (9a) and 4,5,8,9,10,10a-hexahydropyridothienopyridin-7-one (9b) respectively.In a similar manner, 4-cyclohexylcarbonyl-1-piperazine-2,6-dione (11) is converted into the thiophene isostere (2) of praziquantel (1).Likewise, formic acid induced cyclisations of the hydroxylactams derived from N-- (16) and N-succinimide (19) furnish 5,6,10,10a-tetrahydropyrrolothienothiazepin-8(9H)-one (18) and 5,6,10,10a-tetrahydropyrrolothienothiazepin-8(9H)-one (21), respectively.
- Meth-Cohn, Otto,Vij, Rup Rani,Smalley, Robert K.,Bass, Robert J.
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p. 1001 - 1018
(2007/10/02)
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