- Transition Metal-Free N-Arylation of Amino Acid Esters with Diaryliodonium Salts
-
A transition metal-free approach for the N-arylation of amino acid derivatives has been developed. Key to this method is the use of unsymmetric diaryliodonium salts with anisyl ligands, which proved important to obtain high chemoselectivity and yields. The scope includes the transfer of both electron deficient, electron rich and sterically hindered aryl groups with a variety of different functional groups. Furthermore, a cyclic diaryliodonium salt was successfully employed in the arylation. The N-arylated products were obtained with retained enantiomeric excess.
- Kervefors, Gabriella,Kersting, Leonard,Olofsson, Berit
-
supporting information
p. 5790 - 5795
(2021/03/08)
-
- COMPOUNDS, COMPOSITIONS AND METHODS FOR STABILIZING TRANSTHYRETIN AND INHIBITING TRANSTHYRETIN MISFOLDING
-
Provided herein are compounds having activity against TTR related conditions, and pharmaceutically accepted salts and solvates thereof. Also provided are methods of using the compounds for inhibiting and preventing TTR aggregation and/or amyloid formation in the peripheral nerves, kidney, cardiac tissue, eye and CNS, and of treating a subject with peripheral TTR amyloidosis.
- -
-
Paragraph 0854-0857
(2021/08/06)
-
- Heterocyclic pyrrolizinone and indolizinones derived from natural lactam as potential antifungal agents
-
With the aim to develop highly potential active heterocyclic compounds, two series of multi-substituted pyrrolizinone and indolizinones derived from lactam were designed, synthesized and evaluated for their potential antifungal activities against six species of the plant pathogen fungi (Fusarium graminearum, Sclerotinia sclerotiorum, Phomopsis adianticola, Gloeosporium theae-sinensis, Alternaria tenuis Nees, Magnaporthe oryzae). The structure of all the newly molecules were confirmed by analytical spectroscopic data, including 1H NMR, 13C NMR and ESI-MS. According to the preliminary studies on bio-evaluation assay, some of the obtained compounds exhibited moderate and broad-spectrum activities against six fungi compared to the intermediates 6a, 6f and the hymexazol. Particularly, the inhibition rate of compounds 7l, 7m and 7t reached 69.25%, 74.76%, 65.38% against Phomopsis adianticola and Magnaporthe oryzae in vitro activity. Furthermore, compounds 7l and 7t displayed obviously inhibition activities against Phomopsis adianticola compared to the hymexazol. Consequently, compounds 7l and 7t with six-membered alkane ring could be used as new motifs for further investigation.
- Wang, Shuangshuang,Bao, Longzhu,Wang, Wenda,Song, Di,Wang, Jingjing,Cao, Xiufang
-
p. 257 - 266
(2018/08/04)
-
- Ferrocene-modified amino acids: synthesis and in vivo bioeffects on hippocampus
-
A method for the ferrocene modification of amino acids of natural and synthetic origin has been developed. In the in vivo studies, the hippocampal electrical activity under the action of ferrocenyl(phenylpyrazolyl)glycine (1) was assessed. A meaningful rise (up to 25% compared to the control) in the response amplitudes of the focal potentials of the hippocampal region СА1 after intraperitoneal administration of compound 1 at the dose of 2.0 mg kg–1 was established.
- Rodionov,Snegur,Simenel,Dobryakova, Yu. V.,Markevich
-
p. 136 - 142
(2017/07/05)
-
- SUBSTITUTED PYRAZOLE COMPOUNDS AS SERINE PROTEASE INHIBITORS
-
There are provided inter alia multisubstituted aromatic compounds useful for the inhibition of thrombin and/or kallikrein, which compounds include substituted pyrazolyl. There are additionally provided pharmaceutical compositions. There are additionally provided methods of treating and preventing certain diseases or disorders, which diseases or disorders are amenable to treatment or prevention by the inhibition of thrombin and/or kallikrein.
- -
-
-
- SPIRO-LACTAM NMDA RECEPTOR MODULATORS AND USES THEREOF
-
Disclosed are compounds having enhanced potency in the modulation of NMD A receptor activity. Such compounds are contemplated for use in the treatment of conditions such as depression and related disorders. Orally available formulations and other pharmaceutically acceptable delivery forms of the compounds, including intravenous formulations, are also disclosed.
- -
-
Paragraph 00110
(2014/08/19)
-
- SPIRO-LACTAM NMDA RECEPTOR MODULATORS AND USES THEREOF
-
Disclosed are compounds having enhanced potency in the modulation of NMD A receptor activity. Such compounds are contemplated for use in the treatment of conditions such as depression and related disorders. Orally available formulations and other pharmaceutically acceptable delivery forms of the compounds, including intravenous formulations, are also disclosed.
- -
-
Paragraph 00109
(2014/08/19)
-
- SPIRO-LACTAM NMDA RECEPTOR MODULATORS AND USES THEREOF
-
Disclosed are compounds having enhanced potency in the modulation of NMDA receptor activity. Such compounds are contemplated for use in the treatment of conditions such as depression and related disorders. Orally available formulations and other pharmaceutically acceptable delivery forms of the compounds, including intravenous formulations, are also disclosed.
- -
-
Paragraph 0133
(2014/08/19)
-
- Discovery of molecular switches within the ADX-47273 mGlu5 PAM scaffold that modulate modes of pharmacology to afford potent mGlu5 NAMs, PAMs and partial antagonists
-
This Letter describes a chemical lead optimization campaign directed at a weak mGlu5 NAM discovered while developing SAR for the mGlu 5 PAM, ADX-47273. An iterative parallel synthesis effort discovered multiple, subtle molecular switches that afford potent mGlu5 NAMs, mGlu5 PAMs as well as mGlu5 partial antagonists.
- Lamb, Jeffrey P.,Engers, Darren W.,Niswender, Colleen M.,Rodriguez, Alice L.,Venable, Daryl F.,Conn, Jeffrey P.,Lindsley, Craig W.
-
scheme or table
p. 2711 - 2714
(2011/06/20)
-
- Structural diversity-guided convenient construction of functionalized polysubstituted butenolides and lactam derivatives
-
A molecular diversity-oriented convenient access to multi-substituted butenolides and lactam scaffolds via four different methods from various phenylacetic acid derivatives is described. The target molecules have been identified on the basis of analytical spectra data, and are useful synthons in the fields of medicine and agrochemicals.
- Ke, Shaoyong,Zhang, Ya-Ni,Shu, Wenming,Zhang, Zhigang,Shi, Liqiao,Liang, Ying,Wang, Kaimei,Yang, Ziwen
-
experimental part
p. 1071 - 1079
(2012/03/12)
-
- SUBSTITUTED BENZAMIDE MODULATORS OF DOPAMINE RECEPTOR
-
The present invention relates to new substituted benzamide modulators of dopamine receptor, pharmaceutical compositions thereof, and methods of use thereof.
- -
-
Page/Page column 11-12
(2010/05/13)
-
- A convenient synthesis of amino acid methyl esters
-
A series of amino acid methyl ester hydrochlorides were prepared in good to excellent yields by the room temperature reaction of amino acids with methanol in the presence of trimethylchlorosilane. This method is not only compatible with natural amino acids, but also with other aromatic and aliphatic amino acids.
- Li, Jiabo,Sha, Yaowu
-
p. 1111 - 1119
(2008/09/21)
-
- Pharmaceutical compounds
-
Compounds of Formulae Ia and Ib, and stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting lipid kinases including PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula Ia and Ib for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.
- -
-
Page/Page column 91; 93
(2008/06/13)
-
- Synthesis and spin-trapping properties of a new spirolactonyl nitrone
-
(Chemical Equation Presented) Spin trapping using electron paramagnetic resonance (EPR) spectroscopy is commonly employed for the identification of transient radicals in chemical and biological systems. A spirolactonyl-nitrone with rigid H-bond acceptor, 7-oxa-1-azaspiro[4.4]non-1-en-6-one 1-oxide, CPCOMPO, has been synthesized and characterized, and its spin-trapping properties were investigated. The rate of formation of CPCOMPO-O2H was determined using competition kinetics between the superoxide/hydroperoxyl radical (O2?-/HO2?) trapping by CPCOMPO and the spontaneous dismutation of this radical in aqueous media. The rate constant of 60 M-1·s-1 is the highest rate constant thus far observed at neutral pH for any nitrones using the kinetic method employed. Decay kinetics were also experimentally investigated for CPCOMPO-O2H. The effect of rigid H-bond acceptor on the stability of the CPCOMPO-O2H were computationally rationalized and compared to that of EMPO-O2H, which has flexible H-bond acceptor, and results show the need of a "loose" H-bond acceptor for improved adduct stability.
- Han, Yongbin,Tuccio, Beatrice,Lauricella, Robert,Rockenbauer, Antal,Zweier, Jay L.,Villamena, Frederick A.
-
p. 2533 - 2541
(2008/09/20)
-
- Water-compatible iminium activation: Organocatalytic Michael reactions of carbon-centered nucleophiles with enals
-
(Chemical Equation Presented) A pool of water-compatible catalysts, namely the chiral prolinol-based catalysts 1, has been developed for highly enantioselective C-C bond-forming Michael reactions in water (see scheme). The synthesis of (S)-Rolipram, a type IV phosphodiesterase inhibitor, was also demonstrated.
- Palomo, Claudio,Landa, Aitor,Mielgo, Antonia,Oiarbide, Mikel,Puente, Angel,Vera, Silvia
-
p. 8431 - 8435
(2008/09/19)
-
- PYRIMIDINE DERIVATIVES AS PI3K INHIBITORS
-
Thienopyrimidines of formula (Ia) or (Ib): wherein R1, R2, R3, are as defined in the claims.
- -
-
Page/Page column 102-103
(2008/06/13)
-
- ENZYME INHIBITORS
-
Compounds of formula (I) are inhibitors of histone deacetylase activity, and are useful in the treatment of, for example, cancers, wherein R1 is a carboxylic acid group (-COOH), or an ester group which is hydrolysable by one or more intracellular carboxyesterase enzymes to a carboxylic acid group; R2is the side chain of a natural or non-natural alpha amino acid; Y is a bond, -C(=O)-, -S(=O)2-, -C(=O)O-, -C(O)NR3-, -C(=S)-NR3 , -C(=NH)NR3 or -S(=O)2NR3- wherein R3 is hydrogen or optionally substituted C1-C6 alkyl; L1 is a divalent radical of formula -(Alk1)m(Q)n(Alk2)p- wherein m, n and p are independently 0 or 1 , Q is (i) an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5 - 13 ring members, or (ii), in the case where both m and p are 0, a divalent radical of formula -X2-Q1- or -Q1-X2- wherein X2 is -O-, S- or NRA- wherein RA is hydrogen or optionally substituted C1-C3 alkyl, and Q1 is an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5 - 13 ring members, AIk1 and AIk2 independently represent optionally substituted divalent C3-C7 cycloalkyl radicals, or optionally substituted straight or branched, C1-C6 alkylene, C2-C6 alkenylene ,or C2-C6 alkynylene radicals which may optionally contain or terminate in an ether (-O-), thioether (-S-) or amino (-NRA-) link wherein RA is hydrogen or optionally substituted C1-C3 alkyl; X1 represents a bond; -C(=O); or -S(=O)2-; -NR4C(=O)-, -C(=O)NR4-, -NR4C(=O)NR5- , -NR4S(=O)2-, or -S(=O)2NR4-wherein R4 and R5 are independently hydrogen or optionally substituted C1-C6 alkyl; z is 0 or 1 ; A represents an optionally substituted mono-, bi- or tri-cyclic carbocyclic or heterocyclic ring system wherein the radicals R1R2NH-Y-L1-X1-[CH2]Z- and HONHCO-[LINKER]- are attached different ring atoms; and -[Linker]- represents a divalent linker radical linking a ring atom in A with the hydroxamic acid group CONHOH, the length of the linker radical, from the terminal atom linked to the ring atom of A to the terminal atom linked to the hydroxamic acid group, is equivalent to that of an unbranched saturated hydrocarbon chain of from 3-10 carbon atoms.
- -
-
Page/Page column 87
(2008/06/13)
-
- Thiadiazinecarboxamide derivatives, processes for their preparation and pharmaceuticals
-
The invention relates to thiadiazinecarboxamide derivatives of the general formula I STR1 to processes for their preparation, and to pharmaceuticals comprising them.
- -
-
-
- Formation of azomethine ylids by thermolysis of oxazolidines. Study of the reaction in solution and in the gaseous phase
-
Thermolysis of oxazolidines leads to azomethine ylids via cycloreversion.In the liquid phase, these intermediates then give 1-3 dipolar cycloaddition; in the gaseous phase, they lead to aziridines.With an alkyl group in position 2, we observed also the formation of enamines.The effect of substituents on both the cycloreversion reaction and the evolution of azomethine ylids was studied.The mechanism of the process tautomerism aziridine -> azomethine ylid -> enamine is discussed.Keywords - azomethine ylids / oxazolidines / cycloreversion / aziridines / enamines / tautomerism
- Bureau, R.,Mortier, J.,Joucla, M.
-
p. 584 - 596
(2007/10/02)
-
- Thermally Induced Intramolecular Oxime Olefin Cycloadditions (IOOC) Leading to N-Bridgehead Systems. Stereochemistry and Molecular Mechanics Calculations
-
The intramolecular oxime olefin cycloaddition (IOOC) of proline and pipecolinic acid derivatives proceeds thermally with a high degree of stereoselectivity to provide a new route to functionalized pyrrolizidines, indolizidines, or quinolizidines.The ring closure proceeds with simultaneous stereoselective introduction of three or four stereocenters.Molecular mechanics calculations have been refined to accurately predict not only which stereoisomer is preferred but also the syn and anti coupling constants in these tricyclic molecules.
- Hassner, Alfred,Maurya, Rakesh,Padwa, Albert,Bullock, William H.
-
p. 2775 - 2781
(2007/10/02)
-