- Modular synthesis of functionalized bis-bispidine tetraazamacrocycles
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An effective synthesis is reported for the construction of highly rigid and preorganized bis-bispidine tetraazamacrocycles bearing either identical or different functionalities. Using essential building blocks derived from N-Boc-N'-allylbispidinone, the modular approach facilitates independent incorporation of the functional groups to the macrocyclic framework as well as selective derivatization of one functionality in the presence of another.
- Wang, Zhuo,Miller, Erin J.,Scalia, Samantha J.
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- Synthesis of a bis-cationic α,α-disubstituted amino acid (9-amino-bispidine-9-carboxylic acid) and its effects on the conformational properties of peptides
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A new bis-cationic cyclic amino acid, 9-amino-3,7-diazabicyclo[3.3.1]nonane-9-carboxylic acid (9-amino-bispidine-9-carboxylic acid; Abp), which is available for both solution phase and solid phase peptide synthesis, was designed and synthesized. Furthermore, a heterotripeptide Cbz-Leu-Abp-Ala-OMe (9) containing Abp was prepared, and its dominant conformation was analyzed by examining its nuclear magnetic resonance and infrared spectra and performing molecular modeling. The tripeptide 9 formed a β-turn structure as its preferred conformation in solution.
- Yamashita, Hiroko,Demizu, Yosuke,Misawa, Takashi,Shoda, Takuji,Kurihara, Masaaki
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- A tryptophan-containing fluorescent intramolecular complex as a designer peptidic proton sensor
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Pyrene and tryptophan groups judiciously placed on a novel molecular scaffold, namely, bispidine exhibited fluorescence due to the formation of an unprecedented emissive intramolecular complex in polar solvents. Upon protonation, the emission signal from the pyrene unit enhances at the expense of the emission signal from the complex. The probe demonstrates good sensitivity, excellent selectivity, and adequate reversibility towards proton sensing. The present design based on the bispidine scaffold opens up newer opportunities for the design of novel bispidine-peptide sensors.
- Haridas,Yadav, Anita,Sharma, Sakshi,Pandey, Siddharth
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- Methods for Treating Cognitive Disorders Using Inhibitors of Histone Deacetylase
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This disclosure relates to compounds for the inhibition of histone deacetylase and treatment of a cognitive disorder or deficit. More particularly, the disclosure provides for compounds of formula (I) wherein Q, J, L and Z are as defined in the specification.
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Paragraph 0558
(2017/01/23)
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- Unsymmetrical pincer CNN palladium complex of 7-ferrocenylmethyl-3-methyl-3,7-diazabicyclo[3.3.1]nonane
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The new unsymmetrical ferrocenyl containing bispidine derivative 7 was synthesized as a ligand precursor in five steps starting from N-Boc-4-oxopiperidine. The corresponding palladium CNN pincer complex 8 was prepared by direct cyclopalladation of the ligand 7 with Li2PdCl4 in MeOH. The molecular structure of the obtained palladacycle was determined by multinuclear NMR (1H, 13C, 15N) and confirmed by X-ray diffraction analysis. The pincer complex 8 demonstrated high catalytic activity in some cross-coupling reactions of aryl halides with phenylboronic acid, norbornene and ethyl acrylate.
- Bulygina, Ludmila A.,Kagramanov, Nikolay D.,Khrushcheva, Natalya S.,Lyssenko, Konstantin A.,Peregudov, Aleksander S.,Sokolov, Viacheslav I.
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p. 169 - 175
(2017/06/20)
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- Modulation of prion polymerization and toxicity by rationally designed peptidomimetics
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Misfolding and aggregation of cellular prion protein is associated with a large array of neurological disorders commonly called the transmissible spongiform encephalopathies. Designing inhibitors against prions has remained a daunting task owing to limited information about mechanism(s) of their pathogenic self-assembly. Here, we explore the antiprion properties of a combinatorial library of bispidine-based peptidomimetics (BPMs) that conjugate amino acids with hydrophobic and aromatic side chains. Keeping the bispidine unit unaltered, a series of structurally diverse BPMs were synthesized and tested for their prion-modulating properties. Administration of Leu- and Trp-BPMs delayed and completely inhibited the amyloidogenic conversion of human prion protein (HuPrP), respectively. We found that each BPM induced the HuPrP to form unique oligomeric nanostructures differing in their biophysical properties, cellular toxicities and response to conformation-specific antibodies. While Leu-BPMs were found to stabilize the oligomers, Trp-BPMs effected transient oligomerization, resulting in the formation of non-toxic, nonfibrillar aggregates. Yet another aromatic residue, Phe, however, accelerated the aggregation process in HuPrP. Molecular insights obtained through MD (molecular dynamics) simulations suggested that each BPM differently engages a conserved Tyr 169 residue at the α2-β2 loop of HuPrP and affects the stability of α2 and α3 helices. Our results demonstrate that this new class of molecules having chemical scaffolds conjugating hydrophobic/aromatic residues could effectively modulate prion aggregation and toxicity.
- Srivastava, Ankit,Sharma, Sakshi,Sadanandan, Sandhya,Gupta, Sakshi,Singh, Jasdeep,Gupta, Sarika,Haridas,Kundu, Bishwajit
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p. 123 - 147
(2017/03/17)
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- Cyclopalladate complex of 3-benzyl-7-methyl-3,7-diazabicyclo[3.3.1]nonane
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A new (C,N,N)-pincer cyclopalladate unsymmetrical complex of 3-benzyl-7-methyl-3,7-diazabicyclo[3.3.1]nonane (3-benzyl-7-methylbispidine) was synthesized and characterized. Catalytic performance of this complex was examined in the Heck and Suzuki reactions and in the norbornene hydroarylation.
- Bulygina,Khrushcheva,Peregudov,Sokolov
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p. 2479 - 2484
(2017/05/09)
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- 3,7-DIAZABICYCLO[3.3.1 ]NONANE CARBOXAMIDES AS ANTITHROMBOTIC AGENTS
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The present invention relates to the 3,7-diazabicyclo[3.3.1]nonane carboxamides and process for preparation thereof. The present invention further relates to the compounds of general formula (1) possessing anti-thrombotic (anti-platelet) activities. The invention also relates to use of these moieties as inhibitors of collagen induced platelet adhesion and aggregation mediated through collagen receptors both in vitro and in vivo. Further, invention also relates these class of compounds exhibiting anti-platelet efficacy through dual mechanism inhibited both collagen as well as U46619 (thromboxane receptor agonist) induced platelet aggregation. General formula (1) Wherein, R' is; wherein R is selected from alkyl, acyl, tosyl, tert-butyloxycarbonyl, araalkyl or substituted araalkyl groups; R'' is selected preferably from halogen, cyano, lower alkyl, aryl, substituted aryl, and tosyl groups; R1 is selected from hydrogen and lower alkyl groups; R2 is selected from lower alkyl and aryl groups; R3 is selected from tert-butyloxycarbonyl and bezyloxycarbonyl groups; n = 0,1.
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Page/Page column 15; 16
(2015/04/15)
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- 3,7-DIAZABICYCLO[3.3.1]NONANE AND 9-OXA-3,7-DIAZABICYCLO[3.3.1]NONANE DERIVATIVES
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The present invention relates to 3,7-diazabicyclo[3.3.1]nonane and 9-oxa-3,7- diazabicyclo[3.3.1 ]nonane derivatives of formula (I) wherein Ar1 and Ar2 are as described in the description, to their preparation, to pharmaceutically acceptable salts thereof, and to their use as pharmaceuticals, to pharmaceutical compositions containing one or more compounds of formula (I), and especially to their use as orexin receptor antagonists.
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Page/Page column 54; 55
(2013/04/24)
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- Bispidine as a secondary structure nucleator in peptides
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Here we describe bispidine as a scaffold for inducing open turn-like and beta sheet conformations on the attached peptides depending on the mode of attachment of peptides to the scaffold. Various bispidine-peptide conjugates were designed and synthesized to demonstrate the versatility of the scaffold.
- Haridas,Sadanandan, Sandhya,Sharma, Yogesh K.,Chinthalapalli, Srinivas,Shandilya, Ashutosh
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supporting information; experimental part
p. 623 - 626
(2012/03/07)
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- HDAC INHIBITORS AND USES THEREOF
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Inhibitors of histone deacetylase, including compounds having a diazabicyclo[2.2.1]heptan-2-yl moiety are described together with methods for treating various disorders with such compounds.
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Page/Page column 57-58
(2010/01/29)
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- INHIBITORS OF HISTONE DEACETYLASE
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This invention relates to compounds for the inhibition of histone deacetylase. More particularly, the inven- tion provides for compounds of formula (I) wherein (B), Q, J, L and Z are as defined in the specification
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Page/Page column 176-177
(2008/12/07)
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- Asymmetric direct aldol reaction of functionalized ketones catalyzed by amine organocatalysts based on bispidine
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Organocatalysts containing primary-secondary amine based on bispidine and amino acid have been designed to catalyze the asymmetric direct aldol reaction of functionalized ketones including α-keto phosphonates, α-keto esters, as well as α,α-dialkoxy ketones as aldol reaction acceptors. The corresponding products with chiral tertiary alcohols were obtained in moderate to high yields (up to 97%) and high enantioselectivities (up to 98% ee). A theoretical study of transition structures demonstrated that protonated piperidine was important for the reactivity and enantioselectivity of this reaction. Copyright
- Liu, Jie,Yang, Zhigang,Wang, Zhen,Wang, Fei,Chen, Xiaohong,Liu, Xiaohua,Feng, Xiaoming,Su, Zhishan,Hu, Changwei
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p. 5654 - 5655
(2008/12/23)
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- Highly efficient amine organocatalysts based on bispidine for the asymmetric Michael addition of ketones to nitroolefins
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A highly diastereoselective and enantioselective Michael addition of cyclohexanone, acetone and other ketones to nitroolefins was developed by the use of an amine organocatalyst based on bispidine. Additionally, a theoretical study of transition structures revealed that this bispidinebased primary-secondary amine catalyst could serve through an enamine intermediate and H-bond interaction, which was important for the reactivity and selectivity of this reaction.
- Yang, Zhigang,Liu, Jie,Liu, Xiaohua,Wang, Zhen,Feng, Xiaoming,Su, Zhishan,Hua, Changwei
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supporting information; experimental part
p. 2001 - 2006
(2009/08/14)
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- Diazabicyclononane scaffold for combinatorial synthesis
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Diazabicyclononanes of formula I and their synthesis are disclosed. The compounds are useful as scaffolds for constructing combinatorial libraries.
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Page/Page column 7-9
(2010/11/08)
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- Bispidine compounds useful in the treatment of cardiac arrythmias
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There is provided compounds of formula I, 1 wherein R1, R2, R3, R4, R5, R6, R7, R41, R42, R43 R44, R45, R46, A and B have meanings given in the description, which are useful in the prophylaxis and in the treatment of arrhythmias, in particular atrial and ventricular arrhythmias.
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- BISPIDINE COMPOUNDS USEFUL IN THE TREATMENT OF CARDIAC ARRHYTHMIAS
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There is provided compounds of formula I, wherein R1, R2, R3, R4, R5a, R5b, R6, X, A, B and D have meanings given in the description, which are useful in the prophylaxis and in the treatment of arrhythmias, in particular atrial and ventricular arrhythmias.
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- Dried or frozen pharmaceutical preparation containing a class III antiarrhythmic compound
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The present invention relates to dried preparations containing a class III antiarrhythmic compound in the form of a crystalline or amorphous salt or any combination thereof, where the counterion is selected from pharmaceutically acceptable water-soluble organic or inorganic acids. The present invention also relates to frozen preparations containing a class III antiarrhythmic compound in the form of a salt solution, where the counterion is selected from pharmaceutically acceptable water-soluble organic or inorganic acids. Preferred preparations contain a salt of the compound 3,7-diazabicyclo[3.3.1]-nonane-3-carboxylic acid, 7-[(2S)-3-(4-cyanophenoxy)-2-hydroxypropyl]-1,1-dimethylethyl ester (Compound A). Further aspects of the present invention include salts of Compound A per se, processes for preparing the preparations, as well as use of the preparations for prophylaxis and/or treatment of cardiac arrhytmia.
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- Combinatorial development of chiral phosphoramidite-ligands for enantioselective conjugate addition reactions.
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Chiral phosphoramidite ligands embodying bispidine frame work and a binaphthyl phosphoramidite for Cu-catalysed enantioselective conjugate addition reactions were developed employing principles of combinatorial and solid phase chemistry.
- Huttenloch, Oliver,Laxman, Eltepu,Waldmann, Herbert
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p. 673 - 675
(2007/10/03)
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- Solid-phase development of chiral phosphoramidite ligands for enantioselective conjugate addition reactions
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The development of a method for the optimization of chiral ligands for the steric steering of enantioselective Cu-catalyzed conjugate additions of Zn-alkyls to enones is described. The method is based on combinatorial principles and solid-phase techniques. It includes the combinatorial synthesis of chiral bispidine-derived ligands embodying a phosphoramidite group on the solid phase and their investigation in immobilized form in the conjugate addition of ZnEt2 to cyclohexenone as test reaction. The best identified ligands were also synthesized separately and investigated in its soluble form. The results obtained for the polymer-bound ligands correctly mirrored the performance of the soluble ligands. The library embodied members giving ee values varying between 3 and 67%. The "positional scanning" approach proved to be invalid for the study of the ligand system, indicating that this approach in general should be applied with care. Taken together, the method allowed for rapid and efficient optimization of the ligands and led to the development of the first enantioselective, Cu-catalyzed conjugate addition reaction with a polymer-bound ligand.
- Huttenloch, Oliver,Laxman, Eltepu,Waldmann, Herbert
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p. 4767 - 4780
(2007/10/03)
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- Bispidine antiarrhythmic compounds
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There is provided a compound of formula I, wherein R1, R2, R9, R10, R11, R12, X, A and B have meanings given in the description, which are useful in the prophylaxis and in the treatment of arrhythmias, in particular atrial and ventricular arrhythmias.
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