124072-61-3Relevant articles and documents
In Vitro and Cellular Probes to Study PARP Enzyme Target Engagement
Blackwell, Danielle J.,Church, W. David,Desai, Hetvi J.,Keilhack, Heike,Kuntz, Kevin W.,Lu, Alvin Z.,Majer, Christina R.,Niepel, Mario,Perl, Nicholas R.,Ren, Yue,Santospago, Andrew G.,Schenkel, Laurie B.,Swinger, Kerren K.,Vasbinder, Melissa M.,Wigle, Tim J.
, p. 877 - 887 (2020)
Poly(ADP-ribose) polymerase (PARP) enzymes use nicotinamide adenine dinucleotide (NAD+) to modify up to seven different amino acids with a single mono(ADP-ribose) unit (MARylation deposited by PARP monoenzymes) or branched poly(ADP-ribose) polymers (PARylation deposited by PARP polyenzymes). To enable the development of tool compounds for PARP monoenzymes and polyenzymes, we have developed active site probes for use in in vitro and cellular biophysical assays to characterize active site-directed inhibitors that compete for NAD+ binding. These assays are agnostic of the protein substrate for each PARP, overcoming a general lack of knowledge around the substrates for these enzymes. The in vitro assays use less enzyme than previously described activity assays, enabling discrimination of inhibitor potencies in the single-digit nanomolar range, and the cell-based assays can differentiate compounds with sub-nanomolar potencies and measure inhibitor residence time in live cells. Wigle et al. describe a versatile set of NAD+-competitive probes for PARP enzymes that are used to build high-throughput in vitro and cellular biophysical assays that enable inhibitor screening and determination of residence time.
HETEROARYL COMPOUNDS
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Paragraph 00236, (2021/05/29)
Provided herein are compounds and pharmaceutical compositions comprising said compounds that are useful for treating cancers. Specific cancers include those that are mediated by YAP/TAZ or those that are modulated by the interaction between YAP/TAZ and TEAD.
Preparation method 3 - (tert-butyloxycarbonylamino) propionic acid
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Paragraph 0047; 0054; 0057-0061; 0064-0067, (2021/11/19)
The preparation method of 3 - (t-butoxycarbonylamino) propionic acid comprises the following steps: Step S1, reacting methylaminopropanol with Boc anhydride to generate 3 - (t-butoxycarbonylamino) propanol. Step S2: The 3 - (t-butoxycarbonyl) propanol is subjected to an oxidation reaction under the action of a catalyst to generate the 3 - (t-butoxycarbonylamino) propionic acid. To the preparation method disclosed by the embodiment of the invention, the steps are simple, and the reaction is easy to process. Can be suitable for a pot method, can effectively reduce the waste water that is difficult to handle. The method is more suitable for industrial production.
FLUOROMETHYL-SUBSTITUTED PYRROLE CARBOXAMIDES
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Paragraph 0779, (2014/03/25)
The invention relates to pyrrole carboxamides bearing a fluoromethyl-moiety as voltage gated calcium channel blockers, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.
FLUOROMETHYL-SUBSTITUTED PYRROLE CARBOXAMIDES
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Page/Page column 157, (2014/03/25)
The invention relates to pyrrole carboxamides bearing a fluoromethyl- moiety as voltage gated calcium channel blockers, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.
Constructions of tetrahydro-γ-carboline skeletons via intramolecular oxidative carbon-carbon bond formation of enamines
Lv, Jinglei,Li, Ji,Zhang-Negrerie, Daisy,Shang, Siyun,Gao, Qingzhi,Du, Yunfei,Zhao, Kang
supporting information, p. 1929 - 1932 (2013/06/04)
The synthetically and biologically important 4-methyl and 4-methoxy tetrahydro-γ-carboline compounds were readily synthesized in high yields from an aryl amine and a 5-amino-3-oxopentanoate derivative through a series of reactions of enamination, oxidative annulation, deprotection/lactamization and the final reduction reaction of the carbonyl group. The underpinning strategy involves the oxidative C(sp2)-C(sp2) bond formation realized by either Pd(OAc)2/Cu(OAc)2 or a hypervalent iodine reagent.
Adenine receptor ligands
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Page/Page column 15-16, (2010/01/29)
The invention relates to adenine receptor ligands useful for treating, alleviating and/or preventing diseases and disorders related to adenine receptor function as well as pharmaceutical compositions comprising such compounds and methods for preparing such compounds. The invention is further directed to the use of these compounds, alone or in combination with other therapeutic agents, for the alleviating, preventing and/or treating diseases and disorders, especially the use as antinociceptive or neuroprotective drugs.
RENIN INHIBITORS
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Page/Page column 73, (2009/01/23)
The present invention is directed to aspartic protease inhibitors. The present invention is also directed to pharmaceutical compositions comprising the disclosed aspartic protease inhibitors. The present invention is further directed to methods of antagonizing one or more aspartic proteases in a subject in need thereof, and methods for treating an aspartic protease mediated disorder in a subject using the disclosed aspartic protease inhibitors.
RENIN INHIBITORS
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Page/Page column 95-96, (2009/01/23)
The present invention is directed to aspartic protease inhibitors. The present invention is also directed to pharmaceutical compositions comprising the disclosed aspartic protease inhibitors. The present invention is further directed to methods of antagon
QUINAZOLINE DERIVATIVES
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Page/Page column 151, (2008/06/13)
A quinazoline derivative of the formula (I) wherein: R1, R2, R3, R3a, R4, R5, R5a R6, R7, a, m and p are as defined in the description. Also claimed are pharmaceutical compositions containing the quinazoline derivative, the use of the quinazoline derivatives as medicaments and processes for the preparation of the quinazoline derivative. The quinazoline derivatives of formula (I), are useful in the treatment of hyperproliferative disorders such as a cancer.