- Macrocyclic Modulators of the Ghrelin Receptor
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The present invention provides novel conformationally-defined macrocyclic compounds that have been demonstrated to be selective modulators of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R1a and subtypes, isoforms and variants thereof). Methods of synthesizing the novel compounds are also described herein. These compounds are useful as agonists of the ghrelin receptor and as medicaments for treatment and prevention of a range of medical conditions including, but not limited to, metabolic and/or endocrine disorders, gastrointestinal disorders, cardiovascular disorders, obesity and obesity-associated disorders, central nervous system disorders, genetic disorders, hyperproliferative disorders and inflammatory disorders.
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Paragraph 0465
(2018/05/03)
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- Diphenyl ether structure-containing pyrazolecarboxamide compound and its preparation method and use
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The invention discloses a diphenyl ether structure-containing pyrazolecarboxamide compound. A general structural formula and substituent groups are defined in the specification. The diphenyl ether structure-containing pyrazolecarboxamide compound is suita
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Paragraph 0102; 0103
(2017/04/11)
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- Direct Conversion of Haloarenes to Phenols under Mild, Transition-Metal-Free Conditions
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A high-yielding and practical method for the synthesis of phenols from electron-deficient haloarenes and heteroarenes has been developed. The products are formed from acetohydroxamic acid as the hydroxide source via a novel SNAr reaction/Lossen rearrangement sequence. Notably, these reactions employ inexpensive and air-stable reagents, require no special handling, occur under mildly basic conditions, and form products in high yields in the presence of electrophilic and protic functionality. The utility of this methodology is demonstrated by the high-yielding hydroxylation of two base-sensitive complex substrates.
- Fier, Patrick S.,Maloney, Kevin M.
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supporting information
p. 2244 - 2247
(2016/06/01)
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- Synthesis of tetrasubstituted alkenes through a palladium-catalyzed domino carbopalladation/C-H-activation reaction
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Helical tetrasubstituted alkenes (7) were obtained in a highly efficient way through a palladium-catalyzed domino-carbopalladation/CH-activation reaction of propargylic alcohols 6 in good to excellent yields. Electron-withdrawing- and electron-donating substituents can be introduced onto the upper and lower aromatic rings. The substrates (6) for the domino process were synthesized by addition of the lithiated alkyne (20) to various aldehydes (19); moreover, the substrates were accessible enantioselectively (in 95 % ee) by reduction of the corresponding ketone using the Noyori procedure. Copyright
- Tietze, Lutz F.,Hungerland, Tim,Duefert, Alexander,Objartel, Ina,Stalke, Dietmar
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supporting information; experimental part
p. 3286 - 3291
(2012/04/17)
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- 2-PHENYL PHENOXYACETIC ACIDS USEFUL FOR TREATING INFLAMMATORY DISORDERS
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The present invention provides novel phenoxyacetic acids useful for the prevention and treatment of inflammatory disorders, including those affecting the respiratory system and skin. The compounds are of the general formula (I):
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Page/Page column 30-31
(2009/09/04)
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- Influence of aromatic substituents on metal(II)salen catalysed, asymmetric synthesis of α-methyl α-amino acids
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The influence of substituents on both the aromatic rings of the catalyst, and the benzylidene unit of the substrate are investigated in the (salen)copper(II) catalysed asymmetric benzylation of alanine derivatives. Catalysts with electron-donating, and el
- Achard, Thierry,Belokon', Yuri N.,Fuentes, Jose A.,North, Michael,Parsons, Teresa
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p. 5919 - 5930
(2007/10/03)
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- Ruthenium olefin metathesis catalysts with modified styrene ethers: Influence of steric and electronic effects
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A series of olefin metathesis catalysts with modified isopropoxybenzylidene ligands were synthesised, and the effects of ligands on the rate of metathesis investigated. Increased steric hinderance ortho to the isopropoxy group enhanced reaction rates. In the case of N-heterocyclic carbene complexes, decreasing electron density at both the chelating oxygen atom and the Ru=C bond accelerated reaction rates appreciably. Catalysts containing a tricyclohexylphosphane ligand, followed the same trend with regard to benzylidene electrophilicity, while higher electron density at oxygen enhanced reaction rates.
- Zaja, Mirko,Connon, Stephen J.,Dunne, Aideen M.,Rivard, Michael,Buschmann, Nicole,Jiricek, Jan,Blechert, Siegfried
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p. 6545 - 6558
(2007/10/03)
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- The influence of imine structure, catalyst structure and reaction conditions on the enantioselectivity of the alkylation of alanine methyl ester imines catalyzed by Cu(ch-salen)
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Systematic variation of the substrate structure has shown that the most effective substrates for Cu(ch-salen)-catalyzed asymmetric enolate alkylation reactions carried out under phase-transfer conditions are the para-chlorophenyl imines of amino esters. T
- Belokon', Yuri N.,Davies,Fuentes, Jose A.,North, Michael,Parsons, Teresa
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p. 8093 - 8096
(2007/10/03)
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- Synthesis and biological activity of novel 1,3-benzoxazine derivatives as K+ channel openers
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A new series of 1,3-benzoxazine derivatives with a 2-pyridine 1-oxide group at C4 was designed to explore novel K+ channel openers. Synthesis was carried out by using a palladium(0)-catalyzed carbon-carbon bond formation reaction of imino-triflates with organozinc reagents and via a new one-pot 1,3-benzoxazine skeleton formation reaction of benzoylpyridines. The compounds were tested for vasorelaxant activity in tetraethylammonium chloride (TEA) and BaCl2-induced and high KCl-induced contraction of rat aorta to identify potential K+ channel openers, and also for oral hypotensive effects in spontaneously hypertensive rats. An electron- withdrawing group with the proper shape at C6 and a methyl or halogens group at C7 of the 1,3-benzoxazine nucleus were required for the development of optimal vasorelaxant and hypotensive activity. In particular, 2-(6-bromo-7- chloro-2,2-dimethyl-2H-1,3-benzoxazin-4-yl)pyridine 1-oxide (71) showed more potent vasorelaxant activity (EC50=0.14 μM) against TEA and BaCL2- induced contraction and longer-lasting hypotensive effects than cromakalim (1).
- Yamamoto, Satoshi,Hashiguchi, Shohei,Miki, Shokyo,Igata, Yumiko,Watanabe, Toshifumi,Shiraishi, Mitsuru
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p. 734 - 745
(2007/10/03)
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- 1,3-benzoxazine derivatives, their production and use
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A new compound of the formula: STR1 wherein STR2 is an optionally substituted benzene ring; R1 is a carbocyclic or heterocyclic group which is linked to the 4-position of the 1,3-benzoxazine ring through a carbon-carbon bond, a hydrocarbon resi
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