- CHEMOSELECTIVE METHYLENE HYDROXYLATION IN AROMATIC MOLECULES
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A chemoselective and reactive Mn(CF3-PDP) catalyst system that enables for the first time the strategic advantages of late-stage aliphatic C—H hydroxylation to be leveraged in aromatic compounds. This discovery will benefit small molecule therapeutics by enabling the rapid diversification of aromatic drugs and natural products and identification of their metabolites.
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Paragraph 0129; 0414-0415
(2020/03/28)
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- Formation of Non-Natural α,α-Disubstituted Amino Esters via Catalytic Michael Addition
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The enolate monoanion of amino esters is explored, and the first catalytic Michael addition of α-amino esters is demonstrated. These studies indicate that the acidity of the αC-H is the primary factor determining reactivity. Thus, polyfluorophenylglycine amino esters yield novel α-amino esters in the presence of a catalytic amount of a guanidine-derived base and Michael acceptors. Reactivity requires an acidic N-H, which is accomplished using common protecting groups such as N-Bz, N-Boc, and N-Cbz. Calculations and labeling experiments provide insight into the governing principles in which a key C-to-N proton transfer occurs, resulting in an expansion of the scope to include a number of natural amino esters. The study culminates with a late-stage functionalization of peptidic γ-secretase inhibitor, DAPT.
- Teegardin, Kip A.,Gotcher, Lacey,Weaver, Jimmie D.
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supporting information
p. 7239 - 7244
(2018/11/25)
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- Ru-catalyzed C[sbnd]H functionalization of phenylglycine derivatives: Synthesis of isoquinoline-1-carboxylates and isoindoline-1-carboxylates
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The reaction of N-unprotected methylesters of phenylglycine derivatives (1a–1f) with electron-rich internal alkynes (2a–2e), catalyzed by [Ru(cymene)Cl2]2 (10%), gives the corresponding 3,4-disubstituted isoquinoline-1-carboxylates 3 through C[sbnd]H/N[sbnd]H oxidative coupling. The C[sbnd]H bond activation step is assisted by carboxylates, and N-fluoro-2,4,6-trimethylpyridinium triflate works as the terminal oxidant. The process shows a remarkable tolerance to the presence of diverse electron-releasing and electron-attracting functional groups at the phenyl ring of the amino acid. In addition, the reaction of phenylglycine derivatives (1a–1f) with methyl acrylate (4a) catalyzed by [Ru(cymene)Cl2]2 (10%) under the same experimental conditions, gives the corresponding 3,N-disubstituted isoindoline-1-carboxylates 5 through C[sbnd]H/N[sbnd]H coupling. Isoindolines 5 are obtained as a mixture of diastereoisomers, with moderate to high values of diastereomeric excess (up to 80%).
- Ruiz, Sara,Sayago, Francisco J.,Cativiela, Carlos,Urriolabeitia, Esteban P.
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p. 407 - 418
(2016/12/16)
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- Efficient C2 functionalisation of 2H-2-imidazolines
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Alkylation and oxidation of 2H-2-imidazolines, followed by regioselective deprotection, thionation and microwave-assisted Liebeskind-Srogl reaction, efficiently led to 2-aryl-2-imidazolines as new analogues of p53-hdm2 interaction inhibitors (Nutlins). Th
- Bon, Robin S.,Sprenkels, Nanda E.,Koningstein, Manoe M.,Schmitz, Rob F.,De Kanter, Frans J. J.,Doemling, Alexander,Groen, Marinus B.,Orru, Romano V. A.
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p. 130 - 137
(2008/09/20)
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- GLYT1 TRANSPORTER INHIBITORS AND USES THEREOF IN TREATMENT OF NEUROLOGICAL AND NEUROPSYCHIATRIC DISORDERS
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Compounds of Formula (I) or a salt thereof are provided: wherein R6, R7, R8, R9, X, Ar, n, and m are as defined in the description. Uses of the compounds as medicaments, and in the manufacture of medicament for
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Page/Page column 31
(2008/12/07)
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- GLYT1 TRANSPORTER INHIBITORS AND USES THEREOF IN TREATMENT OF NEUROLOGICAL AND NEUROPSYCHIATRIC DISORDERS
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Compounds of formula (I) or a salt thereof are provided: wherein R6, R7, R9, R10, R11, X, n, p, Ar and m are as defined in the description. Uses of the compounds as medicaments, and in the manufacture
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Page/Page column 29
(2008/12/07)
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- GLYT1 TRANSPORTER INHIBITORS AND USES THEREOF IN TREATMENT OF NEUROLOGICAL AND NEUROPSYCHIATRIC DISORDERS
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Compounds of formula (I) or a salt thereof are provided wherein R1, R2, R3, R4, R5, R6, R7, R9, R10, X, n, p and m are as defined in the description. Uses o
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Page/Page column 30
(2008/12/07)
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- GLYT1 TRANSPORTER INHIBITORS AND USES THEREOF IN TREATMENT OF NEUROLOGICAL AND NEUROPSYCHIATRIC DISORDERS
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Compounds of formula (I) or a salt thereof are provided wherein R1, R2, R6, R7, R8, R9 and m are as defined in the description. Uses of the compounds as medicaments, and in the manufacture
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Page/Page column 33
(2008/12/07)
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- Glyt1 Transporter Inhibitors and Uses Thereof in Treatment of Neurological and Neuropsychiatric Disorders
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The invention provides a compound of formula (I) or a solvate thereof: wherein R1, R2, R3, R4, R5, R6, and n are as defined in the specification, and uses of such compounds. The compounds i
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Page/Page column 25
(2008/12/08)
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- N-PHENYL-2-0X0-1,4-DIAZASPIR0 [4.5] DEC-3-EN-1-YL ACETAMIDE DERIVATIVES AND THEIR USE AS GLYCINE TRANSPORTER INHIBITORS
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Compounds of formula (I) and salts and solvates are provided: Formula (I) Uses of the compounds as medicaments, and in the manufacture of medicament for treating neurological and neuropsychiatric disorders, in particular psychoses, dementia or attention d
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Page/Page column 33
(2008/06/13)
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- 1-(2-ARYL-2-OXOETHYL)-3-PHENYL-1, 4-DIAZASPIRO [4.5]DEC-3-EN-2-ONE DERIVATIVES AND THEIR USE AS GLYCINE TRANSPORTER INHIBITORS
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Novel acetophenone compounds of formula (I), compositions containing (I), processes for the preparation of (I), and use of (I) as inhibitors of the glycine transporter, are provided. Definitions of Ar, R5, R6, R7, R8
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Page/Page column 31-32
(2008/06/13)
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- Asymmetric synthesis of protected arylglycines by rhodium-catalyzed addition of arylboronic acids to N-tert-butanesulfinyl imino esters
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A new method for the Rh(I)-catalyzed addition of arylboronic acids to N-tert-butanesulfinyl imino esters has been developed for the asymmetric synthesis of arylglycine derivatives. This method provides high yields (61-90%) and diastereoselectivities (>98:2) for a variety of functionalized arylboronic acids. The N-sulfinyl arylglycine ester products are versatile intermediates for further transformations, including selective protecting group removal, conversion to β-amino alcohols, and direct incorporation into peptides. Copyright
- Beenen, Melissa A.,Weix, Daniel J.,Ellman, Jonathan A.
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p. 6304 - 6305
(2007/10/03)
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- MELANIN-CONCENTRATING HORMONE RECEPTOR ANTAGONISTS CONTAINING PIPERIDINE DERIVATIVES AS THE ACTIVE INGREDIENT
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The invention provides melanin-concentrating hormone receptor antagonists containing as the active ingredient piperidine derivatives represented by the general formula [I]: ???[wherein R1 is hydrogen, hydroxyl, lower alkyl, or the like; R2, R3a, R3b, R4a, R4b, R5a, R5b and R6 each stands for hydrogen, halogen, or the like; W1 and W2 each independently stands for -O-, -CH2-, or the like; Y1, Y2, Y3 and Y4 stand for -CH-, -CF-, -N-, or the like; Z stands for lower alkyl, an aliphatic heterocyclic group, or the like; Ar is a mono- or bi-cyclic aliphatic heterocycle or an aromatic heterocycle; and n is an integer of 1 to 8]. The compounds act as antagonist against melanin-concentrating hormone receptor and are useful as drugs for central diseases, circulatory diseases, or metabolic diseases.
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Page/Page column 28
(2010/02/14)
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