- The formation of benzoxacin-3-ones: Via intramolecular Nicholas reactions and synthesis of 8-membered heliannuols
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The γ-carbonyl cations generated from propargyl ether-Co2(CO)6 complexes undergo intramolecular Nicholas reactions to give dehydrobenzoxacin-3-one-Co2(CO)6 complexes in good yields. Reductive decomplexation and subsequent manipulation allows the synthesis of (±)-heliannuol K methyl ether and the formal syntheses of (±)-heliannuol K, (±)-heliannuol A, and (-)-heliannuol L.
- Green, James R.,St. Onge, Brent
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supporting information
p. 7152 - 7155
(2021/08/30)
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- Design, synthesis and structure-activity relationship studies of novel phenoxyacetamide-based free fatty acid receptor 1 agonists for the treatment of type 2 diabetes
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The free fatty acid receptor 1 (FFA1) has attracted extensive attention as a novel antidiabetic target in the last decade. Several FFA1 agonists reported in the literature have been suffered from relatively high molecular weight and lipophilicity. We have previously reported the FFA1 agonist 1. Based on the common amide structural characteristic of SAR1 and NIH screened compound, we here describe the continued structure-activity exploration to decrease the molecular weight and lipophilicity of the compound 1 series by converting various amide linkers. All of these efforts lead to the discovery of the preferable lead compound 18, a compound with considerable agonistic activity, high LE and LLE values, lower lipophilicity than previously reported agonists, and appreciable efficacy on glucose tolerance in both normal and type 2 diabetic mice.
- Li, Zheng,Wang, Xuekun,Xu, Xue,Yang, Jianyong,Qiu, Qianqian,Qiang, Hao,Huang, Wenlong,Qian, Hai
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supporting information
p. 6666 - 6672
(2015/10/19)
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- Pd(II)-catalyzed ortho - Or meta-C-H olefination of phenol derivatives
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A combination of weakly coordinating auxiliaries and ligand acceleration allows for the development of both ortho- and meta-selective C-H olefination of phenol derivatives. These reactions demonstrate the feasibility of directing C-H functionalizations when functional groups are distal to target C-H bonds. The meta-C-H functionalization of electron-rich phenol derivatives is unprecedented and orthogonal to previous electrophilic substitution of phenols in terms of regioselectivity. These methods are also applied to functionalize α-phenoxyacetic acids, a fibrate class of drug scaffolds.
- Dai, Hui-Xiong,Li, Gang,Zhang, Xing-Guo,Stepan, Antonia F.,Yu, Jin-Quan
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supporting information
p. 7567 - 7571
(2013/06/27)
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- SGC STIMULATORS
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Compounds of Formula (I) are described. They are useful as stimulators of sGC, particularly NO-independent, heme-dependent stimulators. These compounds may be useful for treating, preventing or managing various disorders that are herein disclosed.
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Page/Page column 287-288
(2012/01/15)
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- AMINO ARYL ACETAMIDES AND THEIR USE IN THE TREATMENT OF MALARIA
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Amino phenyl acetamide compounds of Formula (I):and pharmaceutically acceptable salts thereof: wherein R1, R2, R3 and Ra are as defined in the description, use of such compounds in the chemotherapy of certain parasitic protozoal infections such as malaria, pharmaceutical compositions including such compounds and processes for the preparation of such compounds, are provided.
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Page/Page column 31
(2011/06/19)
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- NOVEL AMIDE AND AMIDINE DERIVATIVES AND USES THEREOF
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The present invention relates to inhibitors of 11-β-hydroxysteroid dehydrogenase type 1 enzyme and their use in treatment of non-insulin dependent type 2 diabetes, insulin resistance, obesity, lipid disorders, metabolic syndrome, central nervous system disorders, and diseases and conditions that are related to excessive glucocorticoids.
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Page/Page column 35
(2010/11/03)
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- Discovery of N-[(1S,2S)-3-(4-chlorophenyl)-2-(3-cyanophenyl)-1- methylpropyl]-2-methyl-2-{[5-(trifluoromethyl)pyridin-2-yl]oxy}propanamide (MK-0364), a novel, acyclic cannabinoid-1 receptor inverse agonist for the treatment of obesity
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The discovery of novel acyclic amide cannabinoid-1 receptor inverse agonists is described. They are potent, selective, orally bioavailable, and active in rodent models of food intake and body weight reduction. A major focus of the optimization process was to increase in vivo efficacy and to reduce the potential for formation of reactive metabolites. These efforts led to the identification of compound 48 for development as a clinical candidate for the treatment of obesity.
- Lin, Linus S.,Lanza Jr., Thomas J.,Jewell, James P.,Liu, Fing,Shah, Shrenik K.,Qi, Hongbo,Tong, Xinchun,Wang, Junying,Xu, Suoyu S.,Fong, Tung M.,Shen, Chun-Pyn,Lao, Julie,Xiao, Jing Chen,Shearman, Lauren P.,Stribling, D. Sloan,Rosko, Kimberly,Strack, Alison,Marsh, Donald J.,Feng, Yue,Kumar, Sanjeev,Samuel, Koppara,Yin, Wenji,Van Der Ploeg, Lex H. T.,Goulet, Mark T.,Hagmann, William K.
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p. 7584 - 7587
(2007/10/03)
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- The Conversion of Phenols to Primary and Secondary Aromatic Amines via a Smiles Rearrangement
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The conversion of phenols to 2-aryloxy-2-methylpropanamides (1) and the Smiles rearrangement of these to N-aryl-2-hydroxy-2-methyl propanamides are described; hydrolysis of the latter compounds yields anilines.The scope and limitations of reaction are discussed.Routes, some involving α-lactams, from phenols to N-substituted derivatives of (1) have been developed.Under the conditions of the Smiles rearrangement these secondary 2-methylpropanamides can form directly anilides, N-alkylanilines, or benzoxazinones.
- Coutts, Ian G. C.,Southcott, Mark R.
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p. 767 - 771
(2007/10/02)
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- TANDEM INTRAMOLECULAR WITTIG AND CLAISEN REARRANGEMENT REACTIONS IN THE THERMOLYSIS OF 2-METHYL-2-PHENOXY-PROPIONYL-CYANOMETHYLENETRIPHENYLPHOSPHORANES: SYNTHESIS OF SUBSTITUTED 2H-1-BENZOPYRANS AND BENZOFURANS
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The preparation and thermolysis in vacuum of 2-methyl-2-phenoxy-propionyl-cyanomethylenetriphenylphosphorane and derivatives containing methyl-, methoxy- and chloro- substituents in the phenoxy ring is reported.The method merges the preparation of phenyl
- Rehman, H.,Rao, Jampani Madhusudana
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p. 5335 - 5340
(2007/10/02)
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