335280-19-8Relevant articles and documents
Modular Chemoenzymatic Synthesis of GE81112 B1 and Related Analogues Enables Elucidation of Its Key Pharmacophores
Zwick, Christian R.,Sosa, Max B.,Renata, Hans
, p. 1673 - 1679 (2021/01/25)
The GE81112 complex has garnered much interest due to its broad antimicrobial properties and unique ability to inhibit bacterial translation initiation. Herein we report the use of a chemoenzymatic strategy to complete the first total synthesis of GE81112 B1. By pairing iron and α-ketoglutarate dependent hydroxylases found in GE81112 biosynthesis with traditional synthetic methodology, we were able to access the natural product in 11 steps (longest linear sequence). Following this strategy, 10 GE81112 B1 analogues were synthesized, allowing for identification of its key pharmacophores. A key feature of our medicinal chemistry effort is the incorporation of additional biocatalytic hydroxylations in modular analogue synthesis to rapidly enable exploration of relevant chemical space.
PCSK9 ANTAGONIST COMPOUNDS
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Page/Page column 42; 43, (2021/06/26)
Disclosed are compounds of Formula (I), or a pharmaceutically acceptable salt thereof: (I) wherein A, A1, A2, R1, R2 and R3 are as defined herein, which compounds have properties for antagonizing PCSK9. Also described are pharmaceutical formulations comprising the compounds of Formula I or their salts, and methods of treating cardiovascular disease and conditions related to PCSK9 activity, e.g. atherosclerosis, hypercholesterolemia, coronary heart disease, metabolic syndrome, acute coronary syndrome, or related cardiovascular disease and cardiometabolic conditions.
PYRROLIDINE OREXIN RECEPTOR AGONISTS
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Page/Page column 40-41, (2020/08/28)
The present invention is directed to pyrrolidine compounds which are agonists of orexin receptors. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which orexin receptors are involved.
PCSK9 ANTAGONIST BICYCLO-COMPOUNDS
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Page/Page column 72; 74-75, (2020/01/11)
Disclosed are compounds of Formula I, or a salt thereof cyclic polypeptide of Formula I: Formula I where A, B, E, R4, and R8 are as defined herein, which compounds have properties for antagonizing PCSK9. Also described are pharmaceut
SULFONAMIDE COMPOUNDS HAVING TNAP INHIBITORY ACTIVITY
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Page/Page column 112; 205; 206, (2018/07/29)
The present invention relates to a compound or a pharmacologically acceptable salt thereof having excellent tissue non-specific alkaline phosphatase inhibitory activity. The present invention provides a compound represented by the formula (I) or a pharmacologically acceptable salt thereof.
CONFORMATIONALLY CONSTRAINED MACROCYCLIC COMPOUNDS
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Page/Page column 45, (2017/05/02)
Conformationally constrained macrocyclic compounds of formula (I), including substituents E with at least one ester moiety, G and Q, as defined in the description and the claims, and salts thereof, can be metabolized to compounds that have the property to
THERAPEUTIC COMPOUNDS AND METHODS OF USE THEREOF
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Page/Page column 171; 172, (2016/01/25)
The invention provides compounds having the general Formula (I); and pharmaceutically acceptable salts thereof; wherein the variables RA, RAA, subscript n, subscript q, ring A, X2, L, subscript m, X1, R1, R2, R3, R4, R5, D and E have the meaning as described herein, and compositions containing such compounds and methods for using such compounds and compositions.
DIFLUOROPYRROLIDINES AS OREXIN RECEPTOR MODULATORS
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Page/Page column 72, (2016/02/29)
The present application relates to certain difluoropyrrolidine compounds, pharmaceutical compositions containing them, and methods of using them, including methods for treating substance addiction, panic disorder, anxiety, post-traumatic stress disorder, pain, depression, seasonal affective disorder, an eating disorder, or hypertension.
ANTI-VIRAL COMPOUNDS
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Paragraph 0504, (2015/11/24)
Compounds effective in inhibiting replication of Hepatitis C virus (“HCV”) are described. This invention also relates to processes of making such compounds, compositions comprising such compounds, and methods of using such compounds to treat HCV infection.
Propargyloxyproline Regio- and Stereoisomers for Click-Conjugation of Peptides: Synthesis and Application in Linear and Cyclic Peptides
Northfield, Susan E.,Mountford, Simon J.,Wielens, Jerome,Liu, Mengjie,Zhang, Lei,Herzog, Herbert,Holliday, Nicholas D.,Scanlon, Martin J.,Parker, Michael W.,Chalmers, David K.,Thompson, Philip E.
, p. 1365 - 1372 (2015/09/15)
The use of the click reaction for the introduction of conjugate groups, such as affinity or fluorescent labels, to a peptide for the study of peptide biochemistry and pharmacology is widespread. However, the nature and location of substituted 1,2,3-triazoles in peptide sequences may markedly affect conformation or binding as compared with native sequences. We have examined the preparation and application of propargyloxyproline (Pop) residues as a precursor to such peptide conjugates. Pop residues are available in a range of regio- and stereoisomers from hydroxyproline precursors and are readily prepared in Fmoc-protected form. They can be incorporated routinely in peptide synthesis and broadly retain the conformational properties of the parent proline containing peptides. This is exemplified by the preparation of biotin- and fluorophore-labelled peptides derived from linear and cyclic peptides.
