1755-15-3Relevant academic research and scientific papers
On-Resin Preparation of Allenamidyl Peptides: A Versatile Chemoselective Conjugation and Intramolecular Cyclisation Tool
Brimble, Margaret A.,Cameron, Alan J.,Harris, Paul W. R.
supporting information, p. 18054 - 18061 (2020/09/07)
The ability to modify peptides and proteins chemoselectively is of continued interest in medicinal chemistry, with peptide conjugation, lipidation, stapling, and disulfide engineering at the forefront of modern peptide chemistry. Herein we report a robust method for the on-resin preparation of allenamide-modified peptides, an unexplored functionality for peptides that provides a versatile chemical tool for chemoselective inter- or intramolecular bridging reactions with thiols. The bridging reaction is biocompatible, occurring spontaneously at pH 7.4 in catalyst-free aqueous media. By this “click” approach, a model peptide was successfully modified with a diverse range of alkyl and aryl thiols. Furthermore, this technique was demonstrated as a valuable tool to induce spontaneous intramolecular cyclisation by preparation of an oxytocin analogue, in which the native disulfide bridge was replaced with a vinyl sulfide moiety formed by thia-Michael addition of a cysteine thiol to the allenamide handle.
Method for synthesizing tetrahydroindazole compound
-
Paragraph 0035; 0036; 0047; 0048; 0059; 0060; 0075, (2019/06/27)
The invention belongs to the technical field of drug synthesis, and particularly relates to a method for synthesizing a tetrahydroindazole compound. The synthesis method comprises the steps of synthesis of 5,5-dimethyl-2-acetyl-1,3-cyclohexanedione, synthesis of 2 fluoro-4-hydrazinylbenzonitrile, synthesis of 2-fluoro-4-(3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indazol-1-)benzonitrile, synthesis of 2-(4-hydroxycyclohexylamino)-4-(3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indazol-1-)benzonitrile, and synthesis of 2-(4-hydroxycyclohexylamino)-4-(3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indazol-1-)benzamide. The yield of the intermediate 2-fluoro-4-(3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indazol-1-)benzonitrile is up to 93%, the purity is high, and the prepared tetrahydroindazolecompound is high in purity and suitable for mass production.
ONE-BEAD-TWO-COMPOUND MACROCYCLIC LIBRARY AND METHODS OF PREPARATION AND USE
-
Paragraph 0158; 0159, (2018/11/02)
A one-bead-two-compound combinatorial synthesis technique provides libraries of macrocyclic peptidomimetic compounds and compositions with use as ligands for the Ephrin type-A receptor 2 (EphA2). The one-bead-two-compound technique and libraries of macrocyclic compounds are useful as research tools in drug discovery and/or to treat or prevent a range of diseases or disorders.
Acid Chlorides as Formal Carbon Dianion Linchpin Reagents in the Aluminum Chloride-Mediated Dieckmann Cyclization of Dicarboxylic Acids
Armaly, Ahlam M.,Bar, Sukanta,Schindler, Corinna S.
supporting information, p. 3962 - 3965 (2017/08/15)
The development of acid chlorides as formal dianion linchpin reagents that enable access to cyclic 2-alkyl- and 2-acyl-1,3-alkanediones from dicarboxylic acids is described herein. Mechanistic experiments relying on 13C-labeling studies confirm the role of acid chlorides as carbon dianion linchpin reagents and have led to a revised reaction mechanism for the aluminum(III)-mediated Dieckmann cyclization of dicarboxylic acids with acid chlorides.
A 2 - (grantane - 3 - amino) - 4 - tetrahydroindazole substituted benzamide compound and use thereof
-
Paragraph 0061; 0062; 0063, (2017/08/25)
The invention belongs to the field of medicines, and particularly relates to a 2-(granatane3-amino)-4-tetrahydronaphthalene indazole-substituted benzamide compound and an application thereof. The 2-(granatane3-amino)-4-tetrahydronaphthalene indazole-substituted benzamide compound has a structure shown in a formula I in the specification, wherein R1 is a hydrogen group or an alkyl group and the like; R2 is a hydrogen group, an alkyl group or a hetero-atom-substituted alkyl group and the like. The compound is obtained by substituting the second site of 4-tetrahydronaphthalene indazole-substituted benzamide with granatane-3-amino. Growth of a plurality of tumor cells can be inhibited; the tumor cells can be induced to move towards an apoptosis channel; and the 2-(granatane3-amino)-4-tetrahydronaphthalene indazole-substituted benzamide compound has potential application value in the fields such as tumor treatment and auxiliary treatment.
One-Bead-Two-Compound Thioether Bridged Macrocyclic γ-AApeptide Screening Library against EphA2
Shi, Yan,Challa, Sridevi,Sang, Peng,She, Fengyu,Li, Chunpu,Gray, Geoffrey M.,Nimmagadda, Alekhya,Teng, Peng,Odom, Timothy,Wang, Yan,Van Der Vaart, Arjan,Li, Qi,Cai, Jianfeng
, p. 9290 - 9298 (2017/11/30)
Identification of molecular ligands that recognize peptides or proteins is significant but poses a fundamental challenge in chemical biology and biomedical sciences. Development of cyclic peptidomimetic library is scarce, and thus discovery of cyclic peptidomimetic ligands for protein targets is rare. Herein we report the unprecedented one-bead-two-compound (OBTC) combinatorial library based on a novel class of the macrocyclic peptidomimetics γ-AApeptides. In the library, we utilized the coding peptide tags synthesized with Dde-protected α-amino acids, which were orthogonal to solid phase synthesis of γ-AApeptides. Employing the thioether linkage, the desired macrocyclic γ-AApeptides were found to be effective for ligand identification. Screening the library against the receptor tyrosine kinase EphA2 led to the discovery of one lead compound that tightly bound to EphA2 (Kd = 81 nM) and potently antagonized EphA2-mediated signaling. This new approach of macrocyclic peptidomimetic library may lead to a novel platform for biomacromolecular surface recognition and function modulation.
INDAZOLYL- AND INDOLYL-BENZAMIDE DERIVATIVES
-
Paragraph 0272, (2016/04/09)
The invention relates to indazolylbenzamide, indolylbenzamide, benzo[d]imidazolyl-benzamide, and benzo[d]triazolylbenzamide derivatives of formula useful in the treatment and/or prevention of diseases and/or conditions related to cell proliferation, such as cancer, infection, inflammation and inflammation-associated disorders, and conditions associated with angiogenesis.
New Protocol for the Synthesis of 2-Alkanoyl- and 2-Aryloyl-5,5-dimethylcyclohexane-1,3-diones by the Reaction of Dimedone with Various Aldehydes and Cyanogen Bromide in the Presence of Triethylamine
Kashani, Elmira,Pesyan, Nader Noroozi,Rashidnejad, Hamid
, p. 2079 - 2084 (2016/07/06)
A new route for the synthesis of 2-alkanoyl(aryloyl)-5,5-dimethylcyclohexane-1,3-diones as cyclic β-triketones is described. This synthesis was conducted by the reaction of dimedone with cyanogen bromide and triethylamine to form first the intermediate salt, followed by the addition of various aliphatic and aromatic aldehydes. The structures of the products were characterized by IR, 1H, and 13C NMR spectroscopic techniques. A reaction mechanism is proposed.
Active immunisation of mice with GnRH lipopeptide vaccine candidates: Importance of T helper or multi-dimer GnRH epitope
Goodwin, Daryn,Simerska, Pavla,Chang, Cheng-Hung,Mansfeld, Friederike M.,Varamini, Pegah,D'Occhio, Michael J.,Toth, Istvan
, p. 4848 - 4854 (2014/11/07)
Active immunisation against gonadotropin releasing hormone (GnRH) is a potential alternative to surgical castration. This study focused on the development of a GnRH subunit lipopeptide vaccine. A library of vaccine candidates that contained one or more (up to eight) copies of monomeric or dimeric GnRH peptide antigen, an adjuvanting lipidic moiety based on lipoamino acids, and an additional T helper epitope, was synthesised by solid phase peptide synthesis. The candidates were evaluated in vivo in order to determine the minimal components of this vaccine necessary to induce a systemic immune response. BALB/c mice were immunised with GnRH lipopeptide conjugates, co-administered with or without Complete Freund's Adjuvant, followed by two additional immunisations. Significant GnRH-specific IgG titres were detected in sera obtained from mice immunised with four of the seven lipopeptides tested, with an increase in titres observed after successive immunisations. This study highlights the importance of for epitope optimisation and delivery system design when producing anti-hapten antibodies in vivo. The results of this study also contribute to the development of future clinical and veterinary immunocontraceptives.
COMPOUNDS AND METHODS FOR TARGETING HSP90
-
Paragraph 00220-00221, (2014/03/21)
Described herein are compounds that may selectively bind to Hsp90, methods of using the compounds, and kits including the compounds. The compounds may include detection moieties such as fluorophores that may allow for selective detection of Hsp90 in a sample.
