- Dynamics in Catalytic Asymmetric Diastereoconvergent (3 + 2) Cycloadditions with Isomerizable Nitrones and α-Keto Ester Enolates
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Reaction design in asymmetric catalysis has traditionally been predicated on a structurally robust scaffold in both substrates and catalysts, to reduce the number of possible diastereomeric transition states. Herein, we present the stereochemical dynamics in the Ni(II)-catalyzed diastereoconvergent (3 + 2) cycloadditions of isomerizable nitrile-conjugated nitrones with α-keto ester enolates. Even in the presence of multiple equilibrating species, the catalytic protocol displays a wide substrate scope to access a range of CN-containing building blocks bearing adjacent stereocenters with high enantio- and diastereoselectivities. Our computational investigations suggest that the enantioselectivity is governed in the deprotonation process to form (Z)-Ni-enolates, while the unique syn addition is mainly controlled by weak noncovalent bonding interactions between the nitrone and ligand.
- Adachi, Masaya,Akakabe, Mai,Ezawa, Tetsuya,Hashizume, Daisuke,Koshino, Hiroyuki,Sodeoka, Mikiko,Sohtome, Yoshihiro
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supporting information
p. 9094 - 9104
(2021/07/01)
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- Novel carboxylated pyrroline-2-one derivatives bearing a phenylhydrazine moiety: Design, synthesis, antifungal evaluation and 3D-QSAR analysis
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Aiming to discover novel high-efficient antifungal leads that possess an innovative action mechanism, twenty-three carboxylated pyrroline-2-one derivatives, bearing a phenylhydrazine moiety, were rationally designed and firstly prepared in this letter. The in vitro bioassays showed that most of the compounds possessed excellent antifungal effects with the EC50 values of less than 1 μg/mL against the phytopathogenic fungi Fusarium graminearum (Fg), Botrytis cinerea (Bc), Rhizoctonia solani (Rs) and Colletotrichum capsici (Cc). The further bioassays showed that the compound 6u showed the comparable in vivo control effect with carbendazim against fusarium head blight and rice sheath blight. The 3D-QSAR model revealed the pivotal effects of a bulky electron-donating group at the 1-position of pyrrole ring, a bulky electron-withdrawing group at the 4-position of phenyl ring and a small alkyl at the carbonate group on the anti-Rs activities of target compounds. The abnormal mycelial morphology and delayed spore germination were observed in the treatments of compound 6u. Given the excellent and broad-spectrum antifungal effects the target compounds have, we unfeignedly anticipated that the above finding could motivate the discovery of high-efficient antifungal leads, which might possess an innovative action mechanism against phytopathogenic fungi.
- Chen, Min,Zhang, Lizhi,Lu, Aimin,Wang, Xiaobin,Si, Weijie,Yan, Jinghua,Yang, Chunlong
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- Synthesis and biological activity evaluation of azacycloheptane sulfonamide derivatives as potential orexin receptor antagonists
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As the orexin signaling system is crucial for the regulation of the sleep/wake cycle, inhibitors of orexin-1 and orexin-2 receptors are of significant interest in the treatment of insomnia. Herein, a series of novel azacycloheptane sulfonamide derivatives were designed and synthesized, and all the compounds were evaluated as potential orexin receptor inhibitors by FLIPR Tetra calcium assay. A majority of the tested azacycloheptane sulfonamide derivatives showed OX1R and OX2R inhibitory activity. Chloro-substituted derivatives functionalized at the C5 or C6 position of the benzoxazole group exhibited better inhibitory activity for OX1R and OX2R than unsubstituted derivatives functionalized at C5 or C6. In addition, phenyl group modification had positive effects on the inhibitory activities, and an electron-withdrawing fluorine group at the ortho or meta position of the phenyl ring improved the OX2R inhibitory activity of the derivatives. This suggests that azacycloheptane sulfonamide derivatives are promising scaffolds for the development of OX1R and OX2R antagonists.
- Guo, Bin,Li, Qingeng,Shen, Yi,Xiu, Jingya
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p. 30683 - 30691
(2020/09/11)
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- Reduction of selenoamides to amines using SmI2-H2O
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Selenoamides are selectively reduced to amines by SmI2 with H2O. The process is general for primary, secondary, and tertiary aryl and alkyl selenoamide substrates and selectively delivers amine products. The reduction proceeds under mild conditions using SmI2 activated by straightforward addition of H2O, and does not require an additional Lewis base additive.
- Thurow, Samuel,Lenardo, Eder J.,Just-Baringo, Xavier,Procter, David J.
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- Synthesis of 1,4-Oxazepane-2,5-diones via Cyclization of Rotationally Restricted Amino Acid Precursors and Structural Reassignment of Serratin
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Several natural products containing a 1,4-oxazepane-2,5-dione-core are known. One example is serratin, isolated from Serratia marcescens. Because of the presence of a carboxylic amide, which has a preference for a trans-conformation, and the presence of a labile lactone in this core, many synthetic methodologies commonly used for the cyclization toward medium-sized heterocycles cannot be applied. As N-acyl amino acids lacking a third substituent at nitrogen failed to undergo ring-closure, several N-protecting groups were evaluated. With the use of the removable PMB-group, an N-unsubstituted 1,4-oxazepane-2,5-dione was synthesized. Via the application of pseudoprolines (i.e. serine-derived oxazolidines as another type of protecting group), a compound with the presumed structure of the natural product serratin was obtained. As a result of the differences in spectral data, the incorrect structural assignment of the natural product serratin was identified. Instead of the predicted seven-membered heterocycle, a symmetrical serratamolide analogue is proposed to be the correct structure of serratin.
- Ruysbergh, Ewout,Van Hecke, Kristof,Stevens, Christian V.,De Kimpe, Norbert,Mangelinckx, Sven
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p. 6210 - 6222
(2017/06/23)
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- HETEROARYL DERIVATIVES AS SEPIAPTERIN REDUCTASE INHIBITORS
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Inhibitors of sepiapterin reductase of formula (I) or (I'), wherein the substituents are defined as in the claims, and uses of sepiapterin reductase inhibitors in analgesia, treatment of acute and chronic pain, anti-inflammation, and immune cell regulation are disclosed.
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-
Paragraph 001095
(2017/05/31)
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- Aza-[1,2]-Wittig rearrangements of N-benzyl glycine methyl esters. A new approach to the synthesis of N-aryl phenylalanine derivatives
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Treatment of N-(arylmethyl)-N-aryl glycine methyl ester derivatives with Bu2BOTf and iPr2NEt effects an aza-[1,2]-Wittig rearrangement that provides N-aryl phenylalanine methyl esters in good yields. Analogous substrates bearing N-carbonyl groups are converted to 1,4,2-oxazaborole derivatives under similar conditions.
- Everett, Renata K.,Wolfe, John P.
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supporting information
p. 3393 - 3395
(2015/06/02)
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- Aza-Wittig Rearrangements of N-Benzyl and N-Allyl Glycine Methyl Esters. Discovery of a Surprising Cascade Aza-Wittig Rearrangement/Hydroboration Reaction
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Treatment of N-(arylmethyl)-N-aryl or N-allyl-N-aryl glycine methyl ester derivatives with nBu2BOTf and iPr2NEt effects an aza-Wittig rearrangement that provides N-aryl phenylalanine methyl ester derivatives and N-aryl allylglycine methyl ester derivatives, respectively, in good yield with moderate to good diastereoselectivity. Under similar conditions, analogous substrates bearing N-carbonyl groups are converted to 1,4,2-oxazaborole derivatives. Additionally, N-allyl-N-aryl glycine methyl ester derivatives subjected to similar conditions at elevated temperatures undergo an aza-[2,3]-Wittig rearrangement, followed by a subsequent hydroboration oxidation reaction, to afford substituted amino alcohol products.
- Everett, Renata K.,Wolfe, John P.
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p. 9041 - 9056
(2015/09/28)
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- Structure-activity relationships of imidazole-derived 2-[ N-carbamoylmethyl-alkylamino]acetic acids, dual binders of human insulin-degrading enzyme
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Insulin degrading enzyme (IDE) is a zinc metalloprotease that degrades small amyloid peptides such as amyloid-a and insulin. So far the dearth of IDE-specific pharmacological inhibitors impacts the understanding of its role in the physiopathology of Alzheimer's disease, amyloid-a clearance, and its validation as a potential therapeutic target. Hit 1 was previously discovered by high-throughput screening. Here we describe the structure-activity study, that required the synthesis of 48 analogues. We found that while the carboxylic acid, the imidazole and the tertiary amine were critical for activity, the methyl ester was successfully optimized to an amide or a 1,2,4-oxadiazole. Along with improving their activity, compounds were optimized for solubility, lipophilicity and stability in plasma and microsomes. The docking or co-crystallization of some compounds at the exosite or the catalytic site of IDE provided the structural basis for IDE inhibition. The pharmacokinetic properties of best compounds 44 and 46 were measured in vivo. As a result, 44 (BDM43079) and its methyl ester precursor 48 (BDM43124) are useful chemical probes for the exploration of IDE's role.
- Charton, Julie,Gauriot, Marion,Totobenazara, Jane,Hennuyer, Nathalie,Dumont, Julie,Bosc, Damien,Marechal, Xavier,Elbakali, Jamal,Herledan, Adrien,Wen, Xiaoan,Ronco, Cyril,Gras-Masse, Helene,Heninot, Antoine,Pottiez, Virginie,Landry, Valerie,Staels, Bart,Liang, Wenguang G.,Leroux, Florence,Tang, Wei-Jen,Deprez, Benoit,Deprez-Poulain, Rebecca
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p. 547 - 567
(2015/03/18)
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- Efficient synthesis of some new antiproliferative N-fused indoles and isoquinolines via 1,3-dipolar cycloaddition reaction in an ionic liquid
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Syntheses of some new pyrrolo-fused pyrrolo[1,2-a] indole derivatives have been achieved by combining N-allyl-indole-2-carbaldehyde with a variety of N-alkyl-glycine esters as well as tetrahydroisoquinolines in an ionic liquid, triethylammonium acetate (TEAA), a recyclable reaction medium, via intramolecular [3+2] cycloaddition reaction. This new method is highly efficient, and the ionic liquid employed is recyclable. The stereochemistry of all the compounds was confirmed by 2D NMR NOESY and in some cases single crystal X-ray diffraction data. The in vitro screening of all new candidates against various bacterial strains and representative human solid tumor cell lines, A549 (lung), HeLa (cervix), SW1573 (lung), T-47D (breast) and WiDr (colon), revealed that many of them have good antibacterial, antifungal and antitubercular and antiproliferative activities.
- Sutariya, Tushar R.,Labana, Balvantsingh M.,Parmar, Narsidas J.,Kant, Rajni,Gupta, Vivek K.,Plata, Gabriela B.,Padrón, José M.
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supporting information
p. 2657 - 2668
(2015/04/14)
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- AMINOQUINAZOLINE DERIVATIVES AND THEIR SALTS AND METHODS OF USE
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The present invention relates to the field of medicine. Provided herein are aminoquinazoline derivatives, their salts and pharmaceutical formulations useful in modulating the protein tyrosine kinase activity, and in modulating inter- and/or intra-cellular signaling. Also provided herein are pharmaceutically acceptable compositions comprising the aminoquinazoline compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.
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- Base-promoted c→n acyl rearrangement: An unconventional approach to α-amino acid derivatives
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We have discovered that N-alkyl aminomalonates undergo a fast and selective intramolecular C→N acyl rearrangement reaction in the presence of a strong base, leading to N-protected glycinates in excellent yield. Moreover, the fact that the reaction proceeds through a nucleophilic enolate intermediate has been used for implementing a tandem rearrangement/alkylation sequence that has been applied to the preparation of synthetically relevant nonproteinogenic tertiary and quaternary N-alkyl α-amino acids in a very simple and reliable way.
- Ugarriza, Iratxe,Uria, Uxue,Carrillo, Luisa,Vicario, Jose L.,Reyes, Efraim
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p. 11650 - 11654
(2014/10/15)
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- AMINOQUINAZOLINE DERIVATIVES AND THEIR SALTS AND METHODS OF USE
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The present invention relates to the field of medicine. Provided herein are aminoquinazoline derivatives, their salts and pharmaceutical formulations useful in modulating the protein tyrosine kinase activity, and in modulating inter-and/or intra-cellular signaling. Also provided herein are pharmaceutically acceptable compositions comprising the aminoquinazoline compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.
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- Novel PCU cage diol peptides as potential targets against wild-type CSA HIV-1 protease: Synthesis, biological screening and molecular modelling studies
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We have synthesized a series of novel pentacycloundecane cage diol diacid (PCU diol diacid) incorporated C 2-symmetric peptides. Their activity against the resistance-prone wild-type C-South African (C-SA) HIV protease (HIV PR) is reported. These compounds were obtained in moderate yields of 42-72 %. Amongst the nine compounds reported herein only compound 6, 7, 10 and 11 showed moderate IC50 values of 5-10 μM. Peptides 7 and 10 contain two phenylglycine and two tryptophan amino acids, respectively as side arms to the cage diol. Phenylglycine is a non-natural amino acid. Docking and molecular dynamics (MD) studies were carried out to understand the binding mode of the PCU moiety at the active site of the HIV PR enzyme. The computational results show that the cage diol peptide fits quite comfortably inside the active site of the enzyme. Not much movement is observed during the MD simulation and the hydrogen bonds that develop between the inhibitor and the enzyme pocket suggest that the inhibitor/HIV PR complex is stable at room temperature.
- Karpoormath, Rajshekhar,Sayed, Yasien,Govender, Thavendran,Kruger, Hendrik G.,Soliman, Mahmoud E. S.,Maguire, Glenn E. M.
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p. 3918 - 3933
(2013/07/26)
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- A convenient 1,3-dipolar cycloaddition-reduction synthetic sequence from 2-allyloxy-5-nitro-salicylaldehyde to aminobenzopyran-annulated heterocycles
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A microwave-assisted, one-pot synthesis of some nitro benzopyran-annulated pyrroles as well as pyrrolo-fused isoquinolines via a 1,3-dipolar cycloaddition, which involves the in situ generation of azomethine ylide formed by reacting secondary amines with 2-allyloxy-5-nitro-salicylaldehyde, has been achieved in a solvent-free environment. Compared to methods of conventional and thermal heating, the present microwave-assisted method is rapid and highly efficient. In addition, amino analogous heterocycles were successfully accessed after treating the reaction mass further with iron in acidic medium, which also highlights a one-pot procedure for a new 1,3-dipolar cycloaddition-reduction synthetic sequence. All amino-products are new bioprofiles and anticipated to be effective drug-like candidates. All compounds were characterised based on their elemental analysis, mass, IR, and 1H and 13C NMR spectroscopic data. The stereochemistry of the product was confirmed by 2D NMR COSY and NOESY experiments, which, on the basis of single crystal X-ray diffraction data analysis, was further confirmed and supported.
- Parmar, Narsidas J.,Pansuriya, Bhavesh R.,Labana, Balvantsingh M.,Kant, Rajni,Gupta, Vivek K.
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p. 17527 - 17539
(2013/09/24)
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- An improved microwave assisted one-pot synthesis, and biological investigations of some novel aryldiazenyl chromeno fused pyrrolidines
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An improved microwave assisted one-pot method for the synthesis of twelve new aryldiazenylchromeno [4,3-b] pyrrolidines via intramolecular azomethine ylide cycloaddition route is described. The method is efficient and advantageous over conventional and solvent-free thermal methods. The stereochemistry of the compounds was confirmed on the basis of various NMR experiments, and finally by single crystal X-ray diffraction data. N-Methyl or ethyl pyrrolidine based heterocycles gave good biological activities.
- Parmar, Narsidas J.,Pansuriya, Bhavesh R.,Barad, Hitesh A.,Kant, Rajni,Gupta, Vivek K.
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supporting information; experimental part
p. 4075 - 4079
(2012/07/03)
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- 1,3-dipolar cycloaddition of nitrones with 5-methylenehydantoins: Synthesis and transformation of new spirohydantoin derivatives
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1,3-Dipolar cycloaddition of various acyclic nitrones with 5-methylenehydantoin derivatives afforded new chiral spiroadducts in good yields. All the spirohydantoins were obtained through a regio-and stereospecific pathway, and the spirocarbon atom was linked to the isoxazolidine oxygen atom. A representative example of the reduction of the spirohydantoin 8 with Zn/AcOH led to the substituted 1,3-aminoalcohol hydantoin 20.
- Bahy, Amira,Kacem, Yakdhane,Hassine, Bechir Ben
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experimental part
p. 1377 - 1390
(2010/06/21)
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- Efficient solid-phase synthesis of highly functionalized 1,4-benzodiazepin-5-one derivatives and related compounds by intramolecular aza-wittig reactions
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Due to their widespread biological activities and favorable pharmacokinetic properties, benzodiazepines were among the first classes of small molecules to be synthesized on solid supports. Since then, there have been numerous reports on the synthesis of similar skeletons. We have employed the T1 triazene linker to yield 1,4-benzodiazepin-5-one. Starting from various substituted triazene resins, cleavage in the presence of an azide donor, such as trimethylsilylazide, gave rise to aryl azides. Intramolecular aza-Wittig reactions produced the appropriately functionalized N-heterocycles. By using this route, the natural product deoxyvasicinone and related compounds were prepared.
- Gil, Carmen,Braese, Stefan
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p. 2680 - 2688
(2007/10/03)
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- Soluble Polymer-Supported Synthesis of α-Amino Acid Derivatives
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A practical and efficient synthesis of N-substituted α-amino acid derivatives on soluble polymer support is described.
- Hu, Chunling,Chen, Zuxing,Yang, Guichun
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p. 219 - 224
(2007/10/03)
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- JNK INHIBITOR
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A JNK inhibitor containing a compound having an isoquinolinone skeleton or a salt thereof, such as a compound represented by the formula wherein ring A and ring B are each an optionally substituted benzene ring, X is -O-, -N=, -NR3- or -CHR3-, R2 is an acyl group, an optionally esterified or thioesterified carboxyl group, an optionally substituted carbamoyl group or an optionally substituted amino group and the like, a broken line shows a single bond or a double bond, and R1 is a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group and the like, and the like.
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- LiOH-mediated N-monoalkylation of α-amino acid esters and a dipeptide ester using activated alkyl bromides
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Selective N-monoalkylation of α-amino esters with activated alkyl bromides was studied using various alkali or alkali earth metal bases. In the production of N-monoalkylated amino ester derivatives and suppression of N,N-dialkylation, lithium hydroxide wa
- Cho, Jong Hyun,Kim, B.Moon
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p. 1273 - 1276
(2007/10/03)
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- HIV protease inhibitors based on amino acid derivatives
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A compound selected from the group consisting of a compound of formula I 1a compound of formula II 2and when the compound of formula I and II comprises an amino group pharmaceutically acceptable ammonium salts thereof, wherein R1, R2, Cx, n, R3, R4, R5, Y are as defined in the specification.
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- Improved specific synthesis of [1′-15N]- and [3′-15N]L-histidine
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Specifically, 15N-enriched L-histidines have been prepared. The labelling methodology involves introduction of labels in its precursor 1-benzyl-5-hydroxy methyl imidazole, which is converted into L-histidine via the Schoellkopf method. The procedure allows the preparation of the intermediates and finally histidine with high 15N enrichment (99%) at each position, in 29% overall yield starting with 15NH4Cl and 56% with KSC15N, respectively. Copyright
- Soede-Huijbregts,Van Laren,Hulsbergen,Raap,Lugtenburg
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p. 831 - 841
(2007/10/03)
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- 5-alkoxy-2(3H)-oxazolone compounds and process for preparing the same
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PCT No. PCT/JP97/04157 Sec. 371 Date May 12, 1999 Sec. 102(e) Date May 12, 1999 PCT Filed Nov. 14, 1997 PCT Pub. No. WO98/22449 PCT Pub. Date May 28, 19985-Alkoxy-2(3H)-oxazolone compounds represented by general formula (1); and a R1 process for the preparation thereof, wherein R1 is hydrogen, optionally substituted C1-C10 alkyl, optionally substituted C3-C10 cycloalkyl, optionally substituted C2-C10 alkenyl or optionally substituted phenyl; R2 is hydrogen, optionally substituted C1-C10 alkyl, optionally substituted phenyl or unsubstituted C2-C10 alkenyl; R3 is optionally substituted C1-C10 alkyl, optionally substituted C3-C10 cycloalkyl, optionally substituted C2-C10 alkenyl excluding 2-alkenyl, or optionally substituted phenyl.
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- Triazenes: A useful protecting strategy for sensitive secondary amines
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The application of aryl triazene as a protecting group for sensitive secondary amines such as 4-piperidone (2) is described. The triazene protected amine is compatible with oxidative and reductive conditions as well as with lithiating and alkylating reagents. The free amine is regenerated by treatment with trifluoroacetic acid.
- Lazny, Ryszard,Poplawski, Janusz,K?bberling, Johannes,Enders, Dieter,Br?se, Stefan
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p. 1304 - 1306
(2007/10/03)
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- Diastereoselective and Enantioselective Intramolecular Amino-Zinc-Enolate Carbometalation Reactions. A New Polysubstituted Pyrrolidines Synthesis
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The amino-zinc-enolate cyclization allowed a new and straightforward route to polysubstituted pyrrolidines from simple starting materials. From this study, we have been able to determine, for the first time, the stereochemical influence of the substituents on the ring in the carbocyclization reaction. The diastereoselectivity thus obtained was explained by a chairlike amino-zinc-enolate transition state.
- Lorthiois, Edwige,Marek, Ilane,Normant, Jean F.
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p. 2442 - 2450
(2007/10/03)
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- New approach for the general synthesis of oxotetrahydroindoles via intramolecular cycloadditions of azomethine ylides with tethered alkynes
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A new method for the synthesis of oxotetrahydroindoles has been achieved employing an intramolecular dipolar cycloaddition approach involving mesoionic species (munchnones) with electron-deficient alkynes. The methodology is quite general and convergent as shown by the synthesis of a variety of tri- and tetrasubstituted oxotetrahydroindoles 18, 21, 24, 27, 30, and 34. LiI-based ester cleavage in the presence of an electrophilic acetylenic ketone was critical for formation of the requisite cycloaddition substrates. The cycloaddition is virtually unaffected by the presence of gem-dimethyl groups in the side chain (cf. 38). The presence of a substituted benzyl or a phenethyl moiety on nitrogen, a polarized acetylene, and an appropriate tether between dipole and dipolarophile are essential for obtaining optimal efficiency.
- Nayyar, Naresh K.,Hutchison, Darrell R.,Martinelli, Michael J.
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p. 982 - 991
(2007/10/03)
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- Facile synthesis of pyrazino[2,3-e][1,4]diazepine derivatives via the intramolecular aza-Wittig reaction
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Pyrazino[2,3-d][1,4]diazepine derivatives were synthesized from 3-aminopyrazine-2-carboxylic acid 1 and α-amino acid esters via the intramolecular aza-Wittig reaction.
- Okawa, Tomohiro,Eguchi, Shoji
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- A One-pot Synthesis of Nitrohydroxylated Pyrrolidine and Piperidine Ring Sytems by Tandem Michael-Henry Reaction
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Nitrohydroxylated pyrrolidine and piperidine ring systems are coveniently obtained through a one-pot procedure involving sequential Michael-Henry reaction between nitroethylene and a nitrogen nucleophile incorporating a suitably placed precursor for the generation either reductively or oxidatively of an aldehyde group which is directly trapped in the subsequent nitroaldolization step.
- Barco, Achille,Benetti, Simonetta,Risi, Carmela De,Pollini, Gian P.,Romagnoli, Romeo,Zanirato, Vinicio
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p. 9293 - 9296
(2007/10/02)
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- Formation of azomethine ylids by thermolysis of oxazolidines. Study of the reaction in solution and in the gaseous phase
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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.
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p. 584 - 596
(2007/10/02)
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- The Regioselectivity of the Ring Opening of 1-Activated or Nonactivated 2-Alkoxycarbonyl or 2-Cyanoaziridines by Carbanions of the Dicarbonyl Compounds
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Ring opening of title compounds with alkyl malonates, acetylacetone, methyl acetylacetate, and malononitrile was studied.The regioselectivity of the opening depends on several facts.A phenyl group on C-3 favours C-3-N bond cleavage, whereas C-2-N bond cleavage is predominant with C-3-substituted or C-2-H aziridines.Cyanoaziridines are predominantly cleaved at C-3-N.The aziridine configuration at C-2 and C-3 is maintained during the cyclisation in pyrrolidones.
- Bouayad, Zoheir,Chanet-Ray, Josette,Ducher, S.,Vessiere, Roger
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p. 1757 - 1768
(2007/10/02)
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- Angiotensin converting enzyme inhibitors: N-substituted monocyclic and bicyclic amino acid derivatives
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The synthesis of N-(3-mercaptopropionyl)-N-arylglycines (14a-x), -N-arylalanines (15a,b), -N-cycloalkylglycines (16a-k), and -1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids (17a-d), -1,2,3,4-tetrahydroquinoline-2-carboxylic acids (18a-f), and -indoline-2-carboxylic acids (19a-k) is described. In vitro inhibition of angiotensin converting enzyme (ACE) is reported for each compound, and the structure-activity relationship for each series is discussed. The in vivo inhibition of ACE and antihypertensive effects of representative compounds from each series are discussed. The most potent compound, 19d, had an in vitro ACE IC50 of 2.6 x 10-9 M and lowered blood pressure in spontaneous hypertensive rats 85 mm at a dose of 10 mg/kg po.
- Stanton,Gruenfeld,Babiarz,Ackerman,Friedmann,Yuan,Macchia
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p. 1267 - 1277
(2007/10/02)
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