50496-34-9Relevant academic research and scientific papers
Synthesis, antiplatelet activity and comparative molecular field analysis of substituted 2-amino-4H-pyrido[1,2-a]pyrimidin-4-ones, their congeners and isosteric analogues
Roma, Giorgio,Cinone, Nunzia,Di Braccio, Mario,Grossi, Giancarlo,Leoncini, Giuliana,Signorello, Maria Grazia,Carotti, Angelo
, p. 751 - 768 (2000)
2-(1-Piperazinyl)-4H-pyrido[1,2-a]pyrimidin-4-one (5a) is a recently described in vitro inhibitor of human platelet aggregation which specifically inhibits the activity of high affinity cAMP phosphodiesterase. A number of substitution derivatives, isosteres, and analogues of 5a were now synthesized and tested in vitro for their inhibitory activity on human platelet aggregation induced in platelet-rich plasma by ADP, collagen, or the Ca2+ ionophore A23187. Among the most effective compounds, the 6-methyl, 8-methyl and 6,8-dimethyl derivatives of 5a resulted nearly as active as the lead when platelet aggregation was induced by ADP or A23187, but less active when collagen was the inducer. On the basis of present results and those previously obtained by us in this and 2-aminochromone structural fields, we have developed a statistically significant 3-D QSAR model, using comparative molecular field analysis (CoMFA), describing the variation of the antiplatelet activity in terms of molecular steric and electrostatic potential changes. (C) 2000 Elsevier Science Ltd.
Hydrogen-Bonding Assisted Catalytic Kinetic Resolution of Acyclic β-Hydroxy Amides
Porey, Arka,Mondal, Bhaskar Deb,Guin, Joyram
supporting information, p. 8786 - 8791 (2021/03/17)
Enantioenriched acyclic α-substituted β-hydroxy amides are valuable compounds in chemical, material and medicinal sciences, but their enantioselective synthesis remains challenging. A catalytic kinetic resolution (KR) of such amides with selectivity factor(s) up to >200 is developed via enantioselective acylation of primary alcohol with N-heterocyclic carbene. An enhanced selectivity for the catalytic KR process is realized using cyclic tertiary amine as base additive. Diastereomeric transition state models for the process are proposed to rationalize the origin of enantioselectivity.
Enantioselective α-Amination of Acyclic 1,3-Dicarbonyls Catalyzed by N-Heterocyclic Carbene
Santra, Surojit,Maji, Ujjwal,Guin, Joyram
supporting information, p. 468 - 473 (2020/02/04)
Herein, we describe a method for the catalytic enantioselective α-amination of α-substituted acyclic 1,3-ketoamides and 1,3-amidoesters that affords the products possessing N-substituted quaternary stereocenters with a chiral N-heterocyclic carbene (NHC). The reaction is based on the utilization of an intrinsic Br?nsted base characteristic of NHC that enables the catalytic formation of a chiral ion pair comprising the enolate and the azolium ion. A series of challenging open-chain α-substituted 1,3-dicarbonyls are aminated via this method with ee's of ≤99%.
4-Hydroxy-3-methyl-2(1h)-quinolone, originally discovered from a brassicaceae plant, produced by a soil bacterium of the genus burkholderia sp.: Determination of a preferred tautomer and antioxidant activity
Igarashi, Yasuhiro,Kurokawa, Yoichi,Li, Dandan,Oku, Naoya,Shinozaki, Yukiko
supporting information, p. 1489 - 1494 (2020/07/08)
4-Hydroxy-3-methyl-2(1H)-quinolone (1), a molecule known for a long time and recently discovered from a Brassicaceae plant Isatis tinctoria without providing sufficient evidence to support the structure, was isolated from a fermentation extract of Burkholderia sp. 3Y-MMP isolated from a soil by a Zn2+ enrichment culture. Detailed spectroscopic analyses by MS and NMR, combined with 13C chemical shift comparison with literature values of the related compounds and a synthetic preparation of 1, allowed its first full NMR characterization and identification of 2-quinolone but not 2-quinolinol (2) as the preferred tautomer for this heterocyclic system. While the metal-chelating activity was negligible, compound 1 at 10 μM, a concentration lower than that in liquid production cultures, quenched hydroxy radical-induced chemiluminescence emitted by luminol by 86percent. Because some Burkholderia species are pathogenic to plants and animals, the above result suggests that 1 is a potential antioxidant to counteract reactive oxygen species-based immune response in the host organisms.
Synthetic access to 3,4-disubstituted pyroglutamates from tetramate derivatives from serine, allo-threonine and cysteine
Bagum, Halima,Christensen, Kirsten E.,Genov, Miroslav,Pretsch, Alexander,Pretsch, Dagmar,Moloney, Mark G.
, (2019/09/07)
A route allowing the conversion of substituted tetramates to 3,4-disubstituted pyroglutamates, making use of Suzuki coupling on an enol mesylate, followed by reduction, is both general and fully stereoselective.
Total Syntheses of (+)- and (-)-Tetrapetalones A and C
Dhanjee, Heemal H.,Kobayashi, Yutaka,Buergler, Jonas F.,McMahon, Travis C.,Haley, Matthew W.,Howell, Jennifer M.,Fujiwara, Koichi,Wood, John L.
supporting information, p. 14901 - 14904 (2017/10/31)
Described herein are syntheses of the naturally occurring polyketides (-)-tetrapetalones A and C and their respective enantiomers. The employed strategy involves initial assembly of a masked N-aryl tetramic acid which is advanced via a highly selective conjugate addition/intramolecular Friedel-Crafts acylation sequence to deliver a key azepine intermediate. Application of recently developed C-H activation chemistry and subsequent Heck cyclization delivers the aglycone framework in an overall 12 steps. Resolution of the aglycone via stereospecific glycosylation with an enantiopure glycosyl donor followed by separation of the derived diastereomers enables further advancement to either (+)- or (-)-tetrapetalones A and C.
Neutral nazarov-type cyclization catalyzed by palladium(0)
Shimada, Naoyuki,Stewart, Craig,Bow, William F.,Jolit, Anais,Wong, Kahoano,Zhou, Zhe,Tius, Marcus A.
supporting information; experimental part, p. 5727 - 5729 (2012/08/07)
Joining the circle: The first Pd0 catalyzed Nazarov-type cyclization of diketoesters (see scheme) proceeds in 70 % to 95 % yield under strictly neutral pH conditions. Aryl substitution of the diketoesters is not required, so the reaction shows great versatility and can also proceed with aliphatic substrates. Copyright
An organocatalytic asymmetric nazarov cyclization
Basak, Ashok K.,Shimada, Naoyuki,Bow, William F.,Vicic, David A.,Tius, Marcus A.
supporting information; experimental part, p. 8266 - 8267 (2010/08/04)
An organocatalytic asymmetric Nazarov cyclization of diketoesters that proceeds by means of a dual activation mechanism has been developed. Screening of a number of catalysts led to a new thiourea that incorporates a primary amino group. The method gives rise to cyclic products with two adjacent quaternary asymmetric carbon atoms, one of which is an all-carbon stereocenter, with complete or nearly complete diastereoselectivity and in high or very high enantiomeric excess. A brief and very convenient synthesis of the acyclic diketoester starting materials through nucleophilic addition to a ketene is also described.
1,5-Benzodiazepines XIV. Synthesis of new substituted 9H-bis-[1,2,4] triazolo[4,3-a:3′,4′-d] [1,5]benzodiazepines and relate compounds endowed with in vitro cytotoxic properties
Di Braccio, Mario,Grossi, Giancarlo,Ceruti, Maurizio,Rocco, Flavio,Loddo, Roberta,Sanna, Giuseppina,Busonera, Bernardetta,Murreddu, Marta,Marongiu, Maria Elena
, p. 113 - 125 (2007/10/03)
A series of 11 new 9H-bis-[1,2,4]triazolo[4,3-a:3′,4′-d] [1,5]benzodiazepine derivatives 8e-o was synthesized. Ten of these compounds (8e-m,o), along with four analogues (8a-d) (previously synthesized by us) were tested in vitro in order to evaluate their cytotoxic and anti-HIV-1 properties. In this connection other six original compounds, i.e., five 9-substituted compounds prepared starting from the 6,12-diphenylderivative 8c (compounds 10, 11, 12, 13a,b) and the bis-triazolone derivative 14, were synthesized and tested for the same purpose. While none of the 20 compounds tested exhibited any appreciable anti-HIV-1 activity, some of them exhibited interesting cytotoxic properties, the best results being shown by compounds 8c,d,k and 11 (CC 50 range = 3-12 μM). Therefore, these four compounds were further evaluated for their antiproliferative activity against a panel of human tumor cell lines; actually, compounds 8d, 8k and 11 showed antiproliferative properties against either or both leukemia- and lymphoma-derived cell lines in the low micromolar range.
Novel malonamide derivatives as αvβ3 antagonists. Syntheses and evaluation of 3-(3-indolin-1-yl-3-oxopropanoyl)aminopropanoic acids on vitronectin interaction with αvβ3
Nagashima,Akamatsu,Kawaminami,Kawazoe,Ogami,Matsumoto,Okada,Suzuki,Tsukamoto
, p. 1420 - 1432 (2007/10/03)
In attempt to find novel integrin of αvβ3 antagonists, we selected SC65811 and its guanidine analogue (1) as lead compounds. Modification of the glycine part of SC65811 led to a new series of malonamide derivatives that exhibited αvβ3 inhibitory activity. Among them, (R,S)-3-{3-[6-(3-benzylureido)indolin-1-yl]-3-oxopropanoylamino}-3- (pyridin-3-yl)propanoic acid (43a) showed not only potent activity with an IC50 value of 3.0 nM but also good selectivity for αvβ3 relative to αIIbβ3, α5β1, and αvβ5 with IC50 values of 19000, 11000, and 14 nM, respectively. Furthermore, optimization of 43a led to the most potent αvβ3 antagonist, (R,S)-3-(3-{6-[(4,5-dihydro-1H-imidazol-2-yl)aminoindolin-1-yl}- 3-oxopropanoylamino)-3-(quinolin-3-yl)propanoic acid (431) with an IC50 value of 0.42 nM. The synthesis and the structure-activity relationships of these malonamide derivatives are presented.
