- Regio- and stereoselective multi-enzymatic aminohydroxylation of β-methylstyrene using dioxygen, ammonia and formate
-
We report an enzymatic route for the formal regio- and stereoselective aminohydroxylation of β-methylstyrene that consumes only dioxygen, ammonia and formate; carbonate is the by-product. The biocascade entails highly selective epoxidation, hydrolysis and hydrogen-borrowing alcohol amination. Thus, β-methylstyrene was converted into 1R,2R and 1S,2R-phenylpropanolamine in 59-63% isolated yields, and up to >99.5 : 0.5 dr and er.
- Corrado, Maria L.,Knaus, Tanja,Mutti, Francesco G.
-
p. 6246 - 6251
(2019/12/03)
-
- BENZOLACTAM COMPOUNDS AS PROTEIN KINASE INHIBITORS
-
The invention provides a compound of formula (0): or a pharmaceutically acceptable salt, N-oxide or tautomer thereof. The compounds are inhibitors of ERK 1/2 kinases and will be useful in the treatment of ERKl/2-mediated conditions. The compounds are therefore useful in therapy, in particular in the treatment of cancer.
- -
-
Page/Page column 281
(2017/08/01)
-
- 2-AMINOOXAZOLINES AS TAAR1 LIGANDS
-
The invention relates to compounds of formula (I) wherein R1 is halogen; R2 is lower alkyl or lower alkyl substituted by halogen; R2' is hydrogen, lower alkyl or lower alkyl substituted by halogen; X is a bond, -CH2-, -CH2CH2- or -CH2CH2CH2-; Y is phenyl or cyclohexyl; and n is 0, 1 or 2; or to a pharmaceutically suitable acid addition salt thereof. The compounds of formula I are active on the TAAR1 receptor and are therefore suitable for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder, stress-related disorders, psychotic disorders, schizophrenia, neurological diseases, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease, epilepsy, migraine, substance abuse and metabolic disorders, eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders.
- -
-
Page/Page column 19; 20
(2010/12/29)
-
- Enantioselective synthesis of cyclic sulfamidates by using chiral rhodium-catalyzed asymmetric transfer hydrogenation
-
Asymmetric transfer hydrogenation (ATH) of cyclic sulfamidate imines 4 and 9, using a HCO2H/Et3N mixture as the hydrogen source and well-defined chiral Rh catalysts (S,S)- or (R,R)-2, CpRhCl(TsDPEN), effectively produces the corresponding cyclic sulfamidates with excellent yields and enantioselectivities at room temperature within 0.5 h. ATH of 4,5-disubstituted imines 9, having preexisting stereogenic centers, is shown to take place with dynamic kinetic resolution.
- Kang, Soyeong,Han, Juae,Lee, Eun Sil,Choi, Eun Bok,Lee, Hyeon-Kyu
-
supporting information; experimental part
p. 4184 - 4187
(2010/11/19)
-
- PYRAZOLE DERIVATIVES AS INHIBITORS OF RECEPTOR TYROSYNE KINASES
-
Compounds of formula (I): and their use in the inhibition of Trk activity are described.
- -
-
Page/Page column 97
(2008/06/13)
-
- Discovery of a novel class of selective non-peptide antagonists for the human neurokinin-3 receptor. 2. Identification of (S)-N-(1-phenylpropyl)-3- hydroxy-2-phenylquinoline-4-carboxamide (SB 223412)
-
Optimization of the previously reported 2-phenyl-4-quinolinecarboxamide NK-3 receptor antagonist 14, with regard to potential metabolic instability of the ester moiety and affinity and selectivity for the human neurokinin-3 (hNK-3) receptor, is described. The ester functionality could be successfully replaced by the ketone (31) or by lower alkyl groups (Et, 21, or n-Pr, 24). Investigation of the substitution pattern of the quinoline ring resulted in the identification of position 3 as a key position to enhance hNK-3 binding affinity and selectivity for the hNK-3 versus the hNK-2 receptor. All of the chemical groups introduced at this position, with the exception of halogens, increased the hNK-3 binding affinity, and compounds 53 (3-OH, SB 223412, hNK- 3-CHO binding K(i) = 1.4 nM) and 55 (3-NH2, hNK-3-CHO binding K(i) = 1.2 nM) were the most potent compounds of this series. Selectivity studies versus the other neurokinin receptors (hNK-2-CHO and hNK-1-CHO) revealed that 53 is about 100-fold selective for the hNK-3 versus hNK-2 receptor, with no affinity for the hNK-1 at concentrations up to 100 μM. In vitro studies demonstrated that 53 is a potent functional antagonist of the hNK-3 receptor (reversal of senktide-induced contractions in rabbit isolated iris sphincter muscles and reversal of NKB-induced Ca2+ mobilization in CHO cells stably expressing the hNK-3 receptor), while in vive this compound showed oral and intravenous activity in NK-3 receptor-driven models (senktide-induced behavioral responses in mice and senktide-induced miosis in rabbits). Overall, the biological data indicate that (S)-N-(1-phenylpropyl)-3-hydroxy- 2-phenylquinoline-4-carboxamide (53, SB 223412) may serve as a pharmacological tool in animal models of disease to assess the functional and pathophysiological role of the NK-3 receptor and to establish therapeutic indications for non-peptide NK-3 receptor antagonists.
- Giardina, Giuseppe A. M.,Raveglia, Luca F.,Grugni, Mario,Sarau, Henry M.,Farina, Carlo,Medhurst, Andrew D.,Graziani, Davide,Schmidt, Dulcie B.,Rigolio, Roberto,Luttmann, Mark,Cavagnera, Stefano,Foley, James J.,Vecchietti, Vittorio,Hay, Douglas W. P.
-
p. 1053 - 1065
(2007/10/03)
-
- Platinum-Catalyzed Intramolecular Hydrosilation of Allylamines: Formation of 1-Aza-2-silacyclobutanes and Application to Stereoselective Synthesis of 2-Amino Alcohols
-
N,N-Bis(dimethylsilyl)allylamines undergo intramolecular hydrosilation in the presence of Pt2O>2 (0.2 mol percent) to form four-membered cyclic compounds, 1-aza-2-silacyclobutane derivatives, which can be transformed into 2-amino alcohols by oxidation with 30percent H2O2 in the presence of KF and KHCO3.
- Tamao, Kohei,Nakagawa, Yoshiki,Ito, Yoshihiko
-
p. 3438 - 3439
(2007/10/02)
-
- DIASTEREOSELECTIVE PREPARATION OF ANTI-β-AMINO ALCOHOLS VIA MICHAEL ADDITION OF ALKOXIDE ANIONS TO NITROOLEFINS AND SUBSEQUENT HYDROGENATION REACTION
-
Diastereoselective conjugate addition of benzylalkoxide anion to nitroolefins and subsequent hydrogenation reaction provide a new convenient method for the preparation of anti-β-amino alcohols.
- Kamimura, Akio,Ono, Noboru
-
p. 731 - 734
(2007/10/02)
-
- Erythro-Directive Reduction of α-Substituted Alkanones by Means of Hydrosilanes in Acidic Media
-
Hydrosilane reduced α-oxy and α-amino ketones and β-keto acid derivatives in trifluoroacetic acid to afford the corresponding erythro alcohols with high diastereoselectivity.The reaction proceeded without racemization at the carbon α to the carbonyl group.The erythro-directive reduction was explained in terms of the proton-bridged Cram cyclic model and successfully applied to the synthesis of physiologically important amino alcohols such as l-ephedrine, l-methoxamine, and erythro-2-methyl-3-piperidino-1-phenylpropanol.
- Fujita, Makoto,Hiyama, Tamejiro
-
p. 5415 - 5421
(2007/10/02)
-
- STEREOSELECTIVE CATALYTIC HYDROGENERATION OF alpha -HYDROXY KETOXIMES.
-
Two isomers (E and Z) of benzoin oxime and 2-hydroxy-1-phenyl-1-propanone oxime were catalytically hydrogenated by using palladium on charcoal and erythro amino alcohols were obtained in about 80% diastereomeric excess. The syn-anti isomerization of these oximes in the presence of palladium on charcoal was also studied in connection with the stereoselectivity of the catalytic hydrogenation of the oximes.
- Harada,Shiono
-
p. 1040 - 1045
(2007/10/02)
-
- Anodic Oxidation of Amines. VII. Oxidation of β-Alkanolamines in Aqueous Buffer of pH 10
-
The anodic oxidation of several different types of β-alkanolamines, R1R2C(OH)CR3R4NR5R6, was studied by cyclic voltammetry and controlled potential electrolysis in an aqueous carbonat buffer of pH 10 at a glassy carbon electrode.Upon oxidation, both the (α)C-(β)C and the C-N bonds are cleaved.Substituents R1-R4 affect the first oxidation potential and product distribution.The relative rates of the bond cleavages were estimated from the oxidation products.It was found that most of the amine cleaves through the (α)C-(β)C bond when at least one of the R groups is phenyl, nearly half cleaves through this bond when R is alkyl, and only about a tenth does so when R1-R4 are all hydrogen.The stability of the transient intermediates at the e-c step of the e-c-e process seems to affect the oxidation potentials and to govern the relative rates of the (α)C-(β)C bond cleavage.A scheme for the reaction processes is proposed.Keywords---β-alkanolamines; anodic oxidation; (α)C-(βC) bond fission; C-N bond fission; carbonate buffer; aldehyde; acetone; glycolaldehyde
- Masui, Masaichiro,Kamada, Yoshiyuki,Sasaki, Etuko,Ozaki, Shigeko
-
p. 1234 - 1243
(2007/10/02)
-