- Linear Oligopeptides. Part 147. Chemical and Crystallographic Study of the Reaction between Benzyloxycarbonyl Chloride and α-Aminoisobutyric Acid
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From the reaction mixture of benzyloxycarbonyl chloride and α-aminoisobutyric acid three crystalline compounds were isolated and characterized by chromatographic and spectroscopic techniques and X-ray diffraction.Two of them are polymorphic forms of the N
- Valle, Giovanni,Formaggio, Fernando,Crisma, Marco,Bonora, Gian Maria,Toniolo, Claudio,et al.
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Read Online
- CHEMICAL COMPOUNDS
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A compound of formula (I), wherein Ar1, R21, R23, R24, R25, R26, R27, A, X, Y and W are as defined herein. The compounds of the present invention are inhibitors of hematopoietic prostaglandin D synthase (H-PGDS) and can be useful in the treatment of Duchenne muscular dystrophy. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting H-PGDS activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
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Page/Page column 68-69
(2020/06/01)
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- NOVEL COMPOUNDS FOR THE TREATMENT OF HEPATITIS C
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The disclosure provides compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and may be useful in treating those infected with HCV.
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Page/Page column 70
(2016/09/26)
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- PYRAZOLE DERIVATIVES AS SGC STIMULATORS
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There are described imidazole and pyrazole derivatives which are useful as stimulators of sGC, particularly NO-independent, heme-dependent stimulators. These compounds are also useful for treating, preventing or managing various disorders that are herein disclosed.
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Paragraph 00326
(2016/04/09)
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- PEPTIDOMIMETIC COMPOUNDS AND ANTIBODY-DRUG CONJUGATES THEREOF
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This invention relates to peptidomimetic linkers and anti-body drug conjugates thereof, to pharmaceutical compositions containing them, and to their use in therapy for the prevention or treatment of cancer.
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Page/Page column 215
(2015/07/07)
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- Deracemization and the first CD spectrum of a 310-helical peptide made of achiral α-amino-isobutyric acid residues in a chiral membrane mimetic environment
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Interaction of the racemic helical homo-octapeptide made by the achiral Cα-methyl alanine (Aib) amino acid with a chiral enantiopure micellar aggregate made of N-dodecylproline led to the deracemization of the helical Aib sequence thus allowing
- Ceccacci, Francesca,Mancini, Giovanna,Rossi, Paola,Scrimin, Paolo,Sorrenti, Alessandro,Tecilla, Paolo
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supporting information
p. 10133 - 10135
(2013/10/22)
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- BENZIIMIDAZOLE AND IMIDAZOPYRIDINE DERIVATIVES AS SODIUM CHANNEL MODULATORS
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The invention relates to benzimidazole and imidazopyridine derivatives, to their use in medicine, to compositions containing them, to processes for their preparation and to intermediates used in such processes. More particularly the invention relates to new Nav1.8 modulators of formula (I) or pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R6, R7. X and Y are as defined in the description. Nav1.8 modulators are potentially useful in the treatment of a wide range of disorders, particularly pain.
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Page/Page column 163
(2013/08/15)
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- Hydroxyl may not be indispensable for raltegravir: Design, synthesis and SAR Studies of raltegravir derivatives as HIV-1 inhibitors
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A series of raltegravir derivatives 20-42 were prepared and systematically evaluated for their anti-HIV activity. The bioassay results showed that most of the compounds possess good to excellent anti-HIV activity. Especially, compounds 25 and 35 with subpicomole IC50 values seemed to be the most potent anti-HIV agents among all of the reported synthesized compounds. These compounds may therefore be considered as new potent anti-HIV agents. The 5-hydroxyl modification of raltegravir derivatives significantly increased the anti-HIV activity, which indicates that the hydroxyl may not be indispensable for raltegravir. The introducing of acyl at 5-position of raltegravir derivatives is favorable for antiviral activity. In addition, a high-throughput cell-based assay method with pseudotyped virus stocks was developed and used to identify HIV inhibitors.
- Wang, Ziwen,Wang, Mingxiao,Yao, Xue,Li, Yue,Qiao, Wentao,Geng, Yunqi,Liu, Yuxiu,Wang, Qingmin
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experimental part
p. 361 - 369
(2012/06/30)
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- NOVEL PYRIDINE DERIVATIVES
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The invention relates to a compound of formula (I) wherein R1 to R4 are defined as in the description and in the claims. The compound of formula (I) can be used as a medicament.
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Page/Page column 30
(2013/02/27)
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- PYRIDIN- 2 -AMIDES USEFUL AS CB2 AGONISTS
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The invention relates to a compound of formula (I) wherein R1 to R4 are defined as in the description and in the claims. The compound of formula (I) can be used as a medicament.
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Page/Page column 73; 74
(2013/02/27)
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- Synthesis of poly-aib oligopeptides and aib-containing peptides via the 'azirine/oxazolone method', and their crystal structures
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The protected poly-Aib oligopeptides Z-(Aib)n-N(Me)Ph with n=2-6 were prepared according to the 'azirine/oxazolone method', i.e., by coupling amino or peptide acids with 2,2,N-trimethyl-N-phenyl-2H-azirin-3-amine (1a) as an Aib synthon (Schemea 2). Following the same concept, the segments Z-(Aib)3-OH (9) and H-L-Pro-(Aib)3-N(Me)Ph (20) were synthesized, and their subsequent coupling with N,N′- dicyclohexylcarbodiimide (DCC)/ZnCl2 led to the protected heptapeptide Z-(Aib)3-L-Pro-(Aib)3-N(Me)Ph (21; Schemea 3). The crystal structures of the poly-Aib oligopeptide amides were established by X-ray crystallography confirming the 310-helical conformation of Aib peptides.
- Dannecker-Doerig, Ingeborg,Linden, Anthony,Heimgartner, Heinz
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experimental part
p. 993 - 1011
(2011/08/05)
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- 4 -ISOPROPYLPHENYL GLUCITOL COMPOUNDS AS SGLTL INHIBITORS
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The present invention provides 4-isopropylphenyl glucitol compounds which have no tendency to accumulate in the body and which inhibit SGLT1 activity to suppress postprandial hyperglycemia (or impaired glucose tolerance) through suppression of glucose absorption in the small intestine, whereby the compounds, for example, can suppress the onset of diabetes and metabolic syndrome or can treat these diseases. A 4-isopropylphenyl glucitol compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof: [Chem. 1] wherein R1 represents a hydrogen atom, etc., R2 represents a methyl group, etc., R3 represents a C1-4 alkyl group substituted with an amino group(s), etc., and R4 represents a hydrogen atom, etc.
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Page/Page column 40-42
(2010/09/17)
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- Heterocyclic Compounds Useful as RAF Kinase Inhibitors
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The present invention provides compounds useful as inhibitors of Raf protein kinase. The present invention also provides compositions thereof, and methods of treating Raf-mediated diseases.
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Page/Page column 48-49
(2009/01/24)
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- COMPOUNDS USEFUL AS RAF KINASE INHIBITORS
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The present invention provides compounds useful as inhibitors of Raf protein kinase. The present invention also provides compositions thereof, and methods of treating Raf-mediated diseases.
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Page/Page column 93
(2009/03/07)
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- Characterization of the binding properties of SIRT2 inhibitors with a N-(3-phenylpropenoyl)-glycine tryptamide backbone
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SIRT2 inhibitors with a N-(3-phenylpropenoyl)-glycine tryptamide backbone were studied. This backbone has been developed in our group, and it is derived from a compound originally found by virtual screening. In addition, compounds with a smaller 3-phenylpropenoic acid tryptamide backbone were also included in the study. Binding modes for the new compounds and the previously reported compounds were analyzed with molecular modelling methods. The approach, which included a combination of molecular dynamics, molecular docking and cluster analysis, showed that certain docking poses were favourable despite the conformational variation in the target protein. The N-(3-phenylpropenoyl)-glycine tryptamide backbone is also a good backbone for SIRT2 inhibitors, and the series of compounds includes several potent SIRT2 inhibitors.
- Kiviranta, Paeivi H.,Salo, Heikki S.,Leppaenen, Jukka,Rinne, Valtteri M.,Kyrylenko, Sergiy,Kuusisto, Erkki,Suuronen, Tiina,Salminen, Antero,Poso, Antti,Lahtela-Kakkonen, Maija,Wallen, Erik A.A.
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p. 8054 - 8062
(2008/12/23)
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- N-(3-(4-Hydroxyphenyl)-propenoyl)-amino acid tryptamides as SIRT2 inhibitors
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A series of N-(3-(4-hydroxyphenyl)-propenoyl)-amino acid tryptamides was based on a previously reported new SIRT2 inhibitor from our group, and it was designed to study if the molecular size of the compound could be reduced. The most potent compounds, N-(3-(4-hydroxyphenyl)-propenoyl)-2-aminoisobutyric acid tryptamide and N-(3-(4-hydroxyphenyl)-propenoyl)-l-alanine tryptamide, were equipotent, 30% smaller in molecular weight, and slightly more selective (SIRT2/SIRT1) than the parent compound.
- Kiviranta, Paeivi H.,Leppaenen, Jukka,Rinne, Valtteri M.,Suuronen, Tiina,Kyrylenko, Olga,Kyrylenko, Sergiy,Kuusisto, Erkki,Tervo, Anu J.,Jaervinen, Tomi,Salminen, Antero,Poso, Antti,Wallen, Erik A.A.
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p. 2448 - 2451
(2008/02/03)
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- ANALOGS OF GLYCYL-PROLYL-GLUTAMATE
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Embodiments of this invention include novel analogs of Glycyl-Prolyl-Glutamate (GPE) and compositions containing such analogs of GPE. Of these, certain analogs have modified proline residues. Other embodiments of this invention include uses of analogs of GPE to protect neural cells from degeneration and/or death in response to injury or disease. Disorders treatable with compounds and compositions of this invention include hypoxia/ischemia, toxic injury, and chronic neurodegenerative disorders including Parkinson''s disease.
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Page/Page column 70-71
(2008/06/13)
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- Synthesis and pharmacological evaluation of glycine-modified analogues of the neuroprotective agent glycyl-L-prolyl-L-glutamic acid (GPE)
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The synthesis of 10 G*PE analogues, wherein the glycine residue has been modified, is described by coupling readily accessible dibenzyl-l-prolyl-l- glutamate 2 with various analogues of glycine. Pharmacological evaluation of the novel compounds was undertaken to further understand the role of the glycine residue on the observed neuroprotective properties of the endogenous tripeptide GPE.
- Lai, Michelle Y.H.,Brimble, Margaret A.,Callis, David J.,Harris, Paul W.R.,Levi, Mark S.,Sieg, Frank
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p. 533 - 548
(2007/10/03)
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- Role of secondary structure in the asymmetric acylation reaction catalyzed by peptides based on chiral Cα-tetrasubstituted α-amino acids
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In a recent series of papers, Miller and co-workers were able to show that His(π-Me)-based, terminally protected peptides are potent catalysts of the asymmetric acyl transfer reaction, useful for the kinetic resolution of alcohols. In a structure-supporting solvent, one of the most active compounds, an Aib-containing tetrapeptide, is folded in a doubly intramolecularly H-bonded β-hairpin motif incorporating a type-II′ β-turn conformation. In this work, we have expanded the study of the Miller tetrapeptide by examining a set of analogues and shorter sequences (dipeptide amides), characterized by chiral Cα-tetrasubstituted α-amino acids of diverging bulkiness and optical configuration. Peptide synthesis in solution, conformational analysis by FT-IR absorption and 1H NMR techniques, and screening of catalytic activity as well have been performed. Our results confirm the close relationship between the β-hairpin 3D-structure and the catalytic activity of the peptides. A tetrapeptide analogue slightly more selective than the Miller compound has been found. However, the terminally protected, industrially more appealing, dipeptide amides are poorly effective.
- Formaggio, Fernando,Barazza, Alessandra,Bertocco, Andrea,Toniolo, Claudio,Broxterman, Quirinus B.,Kaptein, Bernard,Brasola, Elena,Pengo, Paolo,Pasquato, Lucia,Scrimin, Paolo
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p. 3849 - 3856
(2007/10/03)
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- A simple, mild and efficient procedure for selective cleavage of prenyl esters using silica-supported sodium hydrogen sulphate as a heterogenous catalyst
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Prenyl esters were selectively and efficiently cleaved under slightly acidic reaction conditions using silica-supported sodium hydrogen sulfate as a heterogenous catalyst at room temperature to regenerate the parent carboxylic acids in very high yields.
- Ramesh,Mahender,Ravindranath,Das, Biswanath
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p. 1465 - 1467
(2007/10/03)
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- A facile and selective cleavage of prenyl esters catalyzed by CeCl3·7 H2O-NaI
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A highly selective cleavage of prenyl esters has been achieved in high yields using CeCl3·7 H2O-NaI in refluxing acetonitrile under neutral conditions. This method is mild and compatible with a wide variety of functional groups such
- Yadav,Subba Reddy,Venkateshwara Rao,Chand,Prasad
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p. 137 - 139
(2007/10/03)
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- Zinc promoted rapid and efficient synthesis of Fmoc- and Z-α,α-dialkylamino acids under neutral conditions
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The introduction of Nα-9-fluorenylmethyloxycarbonyl (Fmoc) and benzyloxycarbonyl (Z) groups into α,α-dialkylamino acids is described at neutral pH using Fmoc-Cl or Z-Cl as an acylating agent respectively in the presence of activated zing powder. The reaction is simple, fast and clean. It also permits the scale up with high yields. It is completely free from protected oligomer formation, which is a known side-reaction when Schotten-Baumann procedure is followed. All the Fmoc- and Z-amino acids prepared have been fully characterized.
- Babu, Vommina V. Suresh,Ananda, Kuppanna
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- The Azirine/Oxazolone Method in Peptide Chemistry: Synthesis of Tripeptide Models
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Tripeptides 5, containing an α,α-disubstituted α-amino acid and ethyl p-aminobenzoate, were synthesized in high yield by application of the azirine/oxazolone method (Table 2).In this versatile approach for the incorporation of disubstituted residues into the peptide chain, N-protected peptides or amino acids are coupled with 2,2-dialkyl-3-amino-2H-azirines and, after the selective hydrolysis of the newly formed C-terminal amid bond, further condensed with amino components via in situ generated oxazole-5(4H)-ones in the presence of additives (Scheme 1).A comparison with conventional procedures clearly demonstrates the advantages of this new method that works equally well with β-branched, cyclic, or acyclic disubstituted amino acids.
- Wipf, Peter,Heimgartner, Heinz
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p. 140 - 154
(2007/10/02)
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- 3-(Dimethylamino)-2,2-dimethyl-2H-azirine as an Aib Equivalent; Synthesis of Aib Oligopeptides
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3-(Dimethylamino)-2,2-dimethyl-2H-azirine (1) reacts with carboxylic acids at 0-25 degC to give 2-acylamino-N,N,2-trimethylpropionamides (=2-acylamino-N,N-dimethylisobutyramide, acyl-Aib-NMe2) in excellent yields (Scheme 2 and 3).Examples of α-amino-, α-h
- Obrecht, Daniel,Heimgartner, Heinz
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p. 102 - 115
(2007/10/02)
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- SYNTHESE VON 2-METHYLALANIN-PEPTIDEN, DIE pH-ABHAENGIGKEIT IHRER 13C-NMR-SPECTREN UND EINE NEUE METHODE ZUR AUSWERTUNG UEBER CS-DIAGRAMME
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The uncommon amino-acid 2-methylalanine (α-aminoisobutiryc acid, Aib) was investigated by 13C-NMR.The chemical shifts of amino- or carboxy-protected derivates of Aib and of protected oligopeptides are discussed with respect to neighbouring groups and amino acids.The pH-dependence of the 13C-NMR spectra of Aib, Aib-Ala, Ala-Aib, Aib-Ala-Aib and Aib-Ala-Aib-Ala-Aib was studied.Using these examples, a new and advantageous method is demonstrated for the first time for the evaluation of NMR titration curves, which uses so-called chemical shift diagrams (CS diagrams).
- Leibfritz, Dieter,Haupt, Erhard,Dubischar, Norbert,Lachmann, Heinrich,Oekonomopulos, Raymond,Jung, Guenther
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p. 2165 - 2182
(2007/10/02)
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