- Design, synthesis, and biological evaluation of stable β6.3-Helices: Discovery of non-hemolytic antibacterial peptides
-
Gramicidin A, a topical antibiotic made from alternating L and D amino acids, is characterized by its wide central pore; upon insertion into membranes, it forms channels that disrupts ion gradients. We present helical peptidomimetics with this characteris
- Reddy, Damodara N.,Singh, Sukrit,Ho, Chris M.W.,Patel, Janki,Schlesinger, Paul,Rodgers, Stephen,Doctor, Allan,Marshall, Garland R.
-
-
Read Online
- INHIBITORS OF RAF KINASES
-
Provided herein are inhibitors of receptor tyrosine kinase effector, RAF, pharmaceutical compositions comprising said compounds, and methods for using said compounds for the treatment of diseases.
- -
-
Paragraph 00294
(2020/10/18)
-
- Synthesis and application of a novel asymmetric azo reagent: 1-(tert-butyl)-2-(4-chlorobenzyl) azodicarboxylate (tBCAD)
-
A series of novel asymmetric azo reagents, 1-(tert-butyl)-2-(4-substituted benzyl) azodicarboxylate, were prepared. The synthetic process has the advantage of simpleness, easy operation, mild reaction condition and high yield. The 1-(tert-butyl)-2-(4-chlorobenzyl) azodicarboxylate (tBCAD) was selected for its stability and convenience to handle, and its precursor can be recycled by recrystallization with toluene. The tBCAD and DIAD were applied to a wide variety of Mitsunobu reactions. The experimental results showed that the performance of tBCAD in Mitsunobu reaction was comparable to that of DIAD, while the stability of tBCAD was much better than DIAD. Thus, tBCAD can be a novel, stable, effective azo-reagent for the Mitsunobu reaction.
- Xie, Jian,Xu, Cai,Dai, Qianjin,Wang, Xiaozhong,Xu, Gang,Chen, Yingqi,Dai, Liyan
-
p. 5321 - 5326
(2017/08/04)
-
- METHOD OF DRUG DESIGN AND OPTIMISATION UTILIZING STEREOCHEMICAL MIMICRY
-
The invention relates to a method of designing or optimizing a drug candidate by making stereodynamic derivatives as well as novel derivatives of Glyx-13 with improved biological and pharmacological properties.
- -
-
-
- Mimicking a proline tripeptide with pyrazolidines and a cyclopentane linker
-
In this work the five-step assembly of a peptidomimetic structurally resembling Prolyl-Prolyl-Proline tripeptide is reported. Proline units are mimicked by two pyrazolidine rings connected to trans-1,2-cyclopentanedicarboxylic acid. The Pro-Pro-Pro mimetic resembles a tri-l-proline unit but with increased lipophilicity and structural constraints imposed by the linker.
- Vertesaljai, Peter,Lebedyeva, Iryna O.,Oliferenko, Alexander A.,Qi, Xin,Fu, Junjie,Ostrov, David A.,Asiri, Abdullah M.,Dennis Hall,Katritzky, Alan
-
p. 6653 - 6655
(2016/01/28)
-
- INHIBITORS OF CYCLIN-DEPENDENT KINASE 7 (CDK7)
-
The present invention provides novel compounds of Formula (I) and Formula (II), and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g.,leukemia, melanoma, multiple myeloma), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase, such as a cyclin-dependent kinase (CDK) (e.g., cyclin-dependent kinase 7 (CDK7)), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject. (I)
- -
-
Paragraph 410
(2015/05/05)
-
- Histamine H3 Inverse Agonists and Antagonists and Methods of Use Thereof
-
Provided herein are fused imidazolyl compounds, methods of synthesis, and methods of use thereof. The compounds provided herein are useful for the treatment, prevention, and/or management of various disorders, including, e.g., neurological disorders and metabolic disorders. Compounds provided herein inhibit the activity of histamine H3 receptors and modulate the release of various neurotransmitters, such as, e.g., histamine, acetylcholine, norepinephrine, and dopamine (e.g. at the synapse). Pharmaceutical compositions containing the compounds and their methods of use are also provided herein.
- -
-
Page/Page column 73
(2011/04/18)
-
- Enolate amination and derivatization of a pyrroloisoquinoline template: Towards novel peptidomimetics
-
Pyrroloisoquinoline-based peptidomimetics are of significant interest in bioorganic chemistry as these targets are known to exhibit type II′ β-turn activity. In this paper we present a novel approach to such pyrroloisoquinoline templates based on a stereo
- Allin, Steven M.,Towler, Joannah,Gaskell, Sean N.,Saha, Basu,Martin, William P.,Page, Philip C. Bulman,Edgar, Mark
-
experimental part
p. 9538 - 9544
(2011/01/12)
-
- HISTAMINE H3 INVERSE AGONISTS AND ANTAGONISTS AND METHODS OF USE THEREOF
-
Provided herein are fused imidazolyl compounds, methods of synthesis, and methods of use thereof. The compounds provided herein are useful for the treatment, prevention, and/or management of various disorders, such as neurological disorders and metabolic disorders. Compounds provided herein inhibit the activity of histamine H3 receptors and modulate the release of various neurotransmitters, such as histamine, acetylcholine, norepinephrine, and dopamine (e.g. at the synapse). Pharmaceutical formulations containing the compounds and their methods of use are also provided herein.
- -
-
Page/Page column 115
(2010/08/18)
-
- Development of cyclic hydrazine and hydrazide type organocatalyst-mechanistic aspects of cyclic hydrazine/hydrazide-catalyzed diels-alder reactions
-
Some hydrazines and hydrazides were prepared and screened for their catalytic efficiencies in Diels-Alder reactions. 1H-NMR studies and ab initio calculations revealed that catalytic efficiencies of these catalysts are greatly dependent on the release of the catalysts from the Diels-Alder adducts.
- Suzuki, Ichiro,Hirata, Ai,Takeda, Kei
-
scheme or table
p. 851 - 863
(2009/12/01)
-
- The synthesis, structure and reactivity of 1-thioxotetrahydropyridazino[1,2-α][1,2,4]triazin-4(1H)-one
-
The synthesis of 1-thioxotetrahydropyridazino[1,2-a][1,2,4]triazin-4-(1H)-one 3 in five steps from tert-butyl carbazate and its transformation into 3-benzylidene and 1-amino derivatives are described. Its crystal structure is presented showing it to be an
- Jarrett, Sandra,Brown, Ainka,Singh-Wilmot, Marvadeen
-
scheme or table
p. 2755 - 2768
(2010/04/25)
-
- HETEROARYL AMIDES AS TYPE I GLYCINE TRANSPORT INHIBITORS
-
The present invention relates to a series of substituted heteroaryl amides of the Formula I, wherein HET, A, X1 -X4, and R1-R12 groups are defined as in the specification, that exhibit activity as glycine transport inhibitors, their pharmaceutically acceptable salts, pharmaceutical compositions containing them, and their use for the enhancement of cognition and the treatment of the positive and negative symptoms of schizophrenia and other psychoses in mammals, including humans.
- -
-
Page/Page column 67
(2008/12/06)
-
- Preparation of new monomers aza-β3-aminoacids for solid-phase syntheses of aza-β3-peptides
-
The preparation of new Nβ-Fmoc-protected aza-β3-amino acids (aza-β3-aa) with proteinogenic side chains as well as their Nβ-Fmoc, Nβ-Cbz or Nβ-Boc aza-β3-amino esters (from Pro, Asn, Asp, Glu, Gln) by successive nucleophilic substitutions will be described.
- Busnel, Olivier,Baudy-Floc'h, Miche?le
-
p. 5767 - 5770
(2008/02/09)
-
- A selective method for cleavage of N-Troc-protected hydrazines and amines under mild conditions using mischmetal and TMSCI
-
The Troc (2,2,2-trichloroethoxycarbonyl) protecting group was efficiently removed under neutral conditions from corresponding protected hydrazines and amines using mischmetal in good to excellent yields. Two new substituted hydrazines were synthesised.
- Vellemaee, Eerold,Lebedev, Oleg,Sillard, Rannar,Maeeorg, Uno
-
p. 685 - 687
(2007/10/03)
-
- The development of novel inhibitors of tumor necrosis factor-α (TNF-α) production based on substituted [5,5]-bicyclic pyrazolones
-
Novel substituted [5,5]-bicyclic pyrzazolones are presented as inhibitors of tumor necrosis factor-α (TNF-α) production. Many of these compounds show low nanomolar activity against lipopolysaccaride (LPS)-induced TNF-α production in THP-1 cells. This clas
- Laufersweiler, Matthew J.,Brugel, Todd A.,Clark, Michael P.,Golebiowski, Adam,Bookland, Roger G.,Laughlin, Steven K.,Sabat, Mark P.,Townes, Jennifer A.,VanRens, John C.,De, Biswanath,Hsieh, Lily C.,Heitmeyer, Sandra A.,Juergens, Karen,Brown, Kimberly K.,Mekel, Marlene J.,Walter, Richard L.,Janusz, Michael J.
-
p. 4267 - 4272
(2007/10/03)
-
- Aza-amino acid scan for rapid identification of secondary structure based on the application of N-Boc-aza1-dipeptides in peptide synthesis
-
Azapeptides, peptide analogues in which the α-carbon of one or more of the amino acid residues is replaced with a nitrogen atom, exhibit propensity for adopting β-turn conformations. A general protocol for the synthesis of azapeptides without racemization on solid phase has now been developed by introducing the aza-amino acid residue as an N-Boc-aza1-dipeptide. This approach has been validated by the synthesis of six N-Boc-aza 1-dipeptides and their subsequent introduction into analogues of the C-terminal peptide fragment of the human calcitonin gene-related peptide (hCGRP). By performing an aza-amino acid scan of such antagonist peptides, a set of aza-hCGRP analogues was synthesized to examine the relationship between turn secondary structure and biological activity.
- Melendez, Rosa E.,Lubell, William D.
-
p. 6759 - 6764
(2007/10/03)
-
- Synthesis, molecular modeling and biological evaluation of aza-proline and aza-pipecolic derivatives as FKBP12 ligands and their in vivo neuroprotective effects
-
Nonimmunosuppressant ligands, exemplified by GPI 1046 (1), for the peptidyl-prolyl isomerase FKBP12 have been found to unexpectedly possess powerful neuroprotective and neuroregenerative effects in vitro and in vivo. We have extensively explored the thera
- Wilkinson, Douglas E.,Thomas IV, Bert E.,Limburg, David C.,Holmes, Agnes,Sauer, Hansjorg,Ross, Douglas T.,Soni, Raj,Chen, Yi,Guo, Hong,Howorth, Pamela,Valentine, Heather,Spicer, Dawn,Fuller, Mike,Steiner, Joseph P.,Hamilton, Gregory S.,Wu, Yong-Qian
-
p. 4815 - 4825
(2007/10/03)
-
- Impact of azaproline on amide cis-trans isomerism: Conformational analyses and NMR studies of model peptides including TRH analogues
-
The β-turn is a well-studied motif in both proteins and peptides. Four residues, making almost a complete 180°-turn in the direction of the peptide chain, define the β-turn. Several types of the β-turn are defined according to Φ and Ψ torsional angles of
- Zhang, Wei-Jun,Berglund, Anders,Kao, Jeff L.-F.,Couty, Jean-Pierre,Gershengorn, Marvin C.,Marshall, Garland R.
-
p. 1221 - 1235
(2007/10/03)
-
- Synthesis and conformational preferences in solution and crystalline states of an aza-tripeptide
-
The aza-tripeptide Boc-Ala-AzPip-Ala-NHiPr (AzPip: 2-aza pipecolyl residue) was synthesized in seven steps using preferentially the diisopropylcarbodiimide/1-hydroxy-7-aza-benzotriazole (DIPCDI/AtOH) coupling method and via the Boc-AzPip-OBzl pivotal inte
- Hemmerlin, Christine,Cung, Manh Thong,Boussard, Guy
-
p. 5009 - 5012
(2007/10/03)
-
- Azapeptide acids as cell adhesion inhibitors
-
Azapeptide acids of Formula I are antagonists of VLA-4 and/or alpha 4 beta 7, and as such are useful in the inhibition or prevention of cell adhesion and cell-adhesion mediated pathologies. These compounds may be formulated into pharmaceutical composition
- -
-
-
- Ein prototypisches Reagens fuer die Synthese substituierter Hydrazine
-
Keywords: Alkylierungen; Hydrazine; Phasentransferkatalyse; Schutzgruppen
- Maeeorg, Uno,Grehn, Leif,Ragnarsson, Ulf
-
p. 2802 - 2803
(2007/10/03)
-
- The Couple Pro/AzaPro: a Means of β-Turn Formation Control Synthesis and Conformation of Two AzaPro-containing Dipeptides
-
On the basis of two synthesized AzaPro-containing dipeptides, the conformational influence of the azaproline residue (a nitrogen atom is substituted for the Pro-CHα) on the β-turn occurrence was tested according to its relative position in the
- Lecocq, Alain,Boussard, Guy,Marraud, Michel,Aubry, Andre
-
p. 5209 - 5212
(2007/10/02)
-