61040-22-0Relevant articles and documents
LINKING AMINO ACID SEQUENCES, MANUFACTURING METHOD THEREOF, AND USE THEREOF
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, (2021/08/20)
This invention provides compositions comprising linked amino acid sequences, pharmaceutical compositions comprising linked amino acid sequences, and methods of making thereof. This invention also provides methods of delivering said compositions to subjects and methods of treating various disorders and diseases using the said compositions.
METALLO-BETA-LACTAMASE INHIBITORS AND METHODS OF USE THEREOF
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Page/Page column 78, (2019/02/06)
The present invention relates to metallo-β-lactamase inhibitor compounds of Formula (I) and pharmaceutically acceptable salts thereof, wherein Z, RA, X1, X2 and R1 are as defined herein. The present invention also relates to compositions which comprise a metallo-β-lactamase inhibitor compound of the invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, optionally in combination with a beta lactam antibiotic and/or a beta-lactamase inhibitor. The invention further relates to methods for treating a bacterial infection comprising administering to a patient a therapeutically effective amount of a compound of the invention, in combination with a therapeutically effective amount of one or more β-lactam antibiotics and optionally in combination with one or more beta-lactamase inhibitor compounds. The compounds of the invention are useful in the methods described herein for overcoming antibiotic resistance.
A diversity-oriented synthesis strategy enabling the combinatorial-type variation of macrocyclic peptidomimetic scaffolds
Isidro-Llobet, Albert,Hadje Georgiou, Kathy,Galloway, Warren R. J. D.,Giacomini, Elisa,Hansen, Mette R.,Méndez-Abt, Gabriela,Tan, Yaw Sing,Carro, Laura,Sore, Hannah F.,Spring, David R.
supporting information, p. 4570 - 4580 (2015/04/14)
Macrocyclic peptidomimetics are associated with a broad range of biological activities. However, despite such potentially valuable properties, the macrocyclic peptidomimetic structural class is generally considered as being poorly explored within drug discovery. This has been attributed to the lack of general methods for producing collections of macrocyclic peptidomimetics with high levels of structural, and thus shape, diversity. In particular, there is a lack of scaffold diversity in current macrocyclic peptidomimetic libraries; indeed, the efficient construction of diverse molecular scaffolds presents a formidable general challenge to the synthetic chemist. Herein we describe a new, advanced strategy for the diversity-oriented synthesis (DOS) of macrocyclic peptidomimetics that enables the combinatorial variation of molecular scaffolds (core macrocyclic ring architectures). The generality and robustness of this DOS strategy is demonstrated by the step-efficient synthesis of a structurally diverse library of over 200 macrocyclic peptidomimetic compounds, each based around a distinct molecular scaffold and isolated in milligram quantities, from readily available building-blocks. To the best of our knowledge this represents an unprecedented level of scaffold diversity in a synthetically derived library of macrocyclic peptidomimetics. Cheminformatic analysis indicated that the library compounds access regions of chemical space that are distinct from those addressed by top-selling brand-name drugs and macrocyclic natural products, illustrating the value of our DOS approach to sample regions of chemical space underexploited in current drug discovery efforts. An analysis of three-dimensional molecular shapes illustrated that the DOS library has a relatively high level of shape diversity.
A short, rigid linker between pyrene and guanidiniocarbonyl-pyrrole induced a new set of spectroscopic responses to the ds-DNA secondary structure
Radi Stojkovi, Marijana,Piotrowski, Patryciusz,Schmuck, Carsten,Piantanida, Ivo
supporting information, p. 1629 - 1633 (2015/02/19)
A novel pyrene-guanidiniocarbonyl-pyrrole dye, characterised by a short, rigid linker between the two chromophores, interacts strongly with ds-DNA but only negligibly with ds-RNA. Under neutral conditions the dye shows strong selectivity toward AT-DNA (with respect to GC-DNA). Binding is accompanied by a specific ICD band at 350 nm and fluorescence quenching for all DNAs/RNAs studied. At pH 5 the affinity of the dye is reversed, now favouring GC-DNA over AT-DNA. A strong emission increase for AT-DNA is observed but with quenching for GC-DNA.
2-PYRIDYL CARBOXAMIDE-CONTAINING SPLEEN TYROSINE KINASE (SYK) INHIBITORS
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, (2013/04/24)
The invention provides certain 2-pyridyl carboxamide-containing compounds of the Formula (I) or pharmaceutically acceptable salts thereof, wherein A and B are as defined herein. The invention also provides pharmaceutical compositions comprising such compounds, and methods of using the compounds for treating diseases or conditions mediated by Spleen Tyrosine Kinase (Syk) kinase.
Aminomethylene peptide nucleic acid (am -PNA): Synthesis, regio-/stereospecific DNA binding, and differential cell uptake of (α/γ, R / S) am- PNA analogues
Mitra, Roopa,Ganesh, Krishna N.
experimental part, p. 5696 - 5704 (2012/08/07)
Inherently chiral, cationic am-PNAs having pendant aminomethylene groups at α(R/S) or γ(S) sites on PNA backbone have been synthesized. The modified PNAs are shown to stabilize duplexes with complementary cDNA in a regio- and stereo-preferred manner with γ(S)-am PNA superior to α(R/S)-am PNAs and α(R)-am PNA better than the α(S) isomer. The enhanced stabilization of am-PNA:DNA duplexes is accompanied by a greater discrimination of mismatched bases. This seems to be a combined result of both electrostatic interactions and conformational preorganization of backbone favoring the cDNA binding. The am-PNAs are demonstrated to effectively traverse the cell membrane, localize in the nucleus of HeLa cells, and exhibit low toxicity to cells.
Highly enantioselective synthesis of orthogonally protected (2S)-2,3-diaminopropanoates through catalytic phase-transfer aza-Henry reaction
Kumaraswamy, Gullapalli,Pitchaiah, Arigala
scheme or table, p. 1543 - 1550 (2011/10/08)
The syntheses of enantiomer-enriched orthogonally protected different (2S)-2,3-diaminopropanoates and unnatural furyl-substituted (tert-butoxy) carbonyl (Boc) as well as (benzyloxy)carbonyl (Cbz) protected amino acid esters are accomplished by means of an
PNAs grafted with (α/γ, R/S)-aminomethylene pendants: Regio and stereo specific effects on DNA binding and improved cell uptake
Mitra, Roopa,Ganesh
supporting information; experimental part, p. 1198 - 1200 (2011/03/20)
PNAs grafted with cationic aminomethylene (am) pendants on the backbone at the glycyl (α) or ethylenediamine (γ) segments show regio (α/γ) and stereochemistry (R/S) dependent binding with complementary DNA. These are efficiently taken up by cells, with γ(S-am) aeg-PNA being the best in all properties.
Capped diaminopropionamide-glycine dipeptides are inhibitors of CC chemokine receptor 2 (CCR2)
Carter, Percy H.,Brown, Gregory D.,Friedrich, Sarah R.,Cherney, Robert J.,Tebben, Andrew J.,Lo, Yvonne C.,Yang, Gengjie,Jezak, Heather,Solomon, Kimberly A.,Scherle, Peggy A.,Decicco, Carl P.
, p. 5455 - 5461 (2008/12/23)
A new series of CCR2 antagonists has been discovered that incorporates intramolecular hydrogen bonding as a strategy for rigidifying the scaffold. The structure-activity relationship was established through initial systematic modification of substitution pattern and chain length, followed by independent optimization of three different substituents (benzylamine, carboxamide, and benzamide). Several of the acyclic compounds display 10-30 nM binding affinity for CCR2. Moreover, these antagonists are able to block both MCP-1-induced Ca2+ flux and monocyte chemotaxis, and are selective for binding to CCR2 over CCR1 and CCR3.
Facile way to synthesize Nα-Boc-Nβ-Cbz-2, 3-diaminopropionic acid derivatives via 5-oxazolidinone
Teng, Hanbing,Jiang, Zhengguo,Wu, Lamei,Su, Jiangtao,Feng, Xichun,Qiu, Guofu,Liang, Shucai,Hu, Xianming
, p. 3803 - 3807 (2007/10/03)
An economical and facile synthesis of Nα-Boc-N β-Cbz-2,3-diaminopropionic acid derivatives is reported. The key aspect of this method is employment of N-Boc-5-oxazolidinone moiety to simultaneously provide proper protection of α-amid
