38070-80-3Relevant academic research and scientific papers
USP30 INHIBITORS AND USES THEREOF
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Paragraph 00613-00614, (2021/03/19)
The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of USP30, and the treatment of USP30-mediated disorders.
Design, Synthesis, and Evaluation of the Highly Selective and Potent G-Protein-Coupled Receptor Kinase 2 (GRK2) Inhibitor for the Potential Treatment of Heart Failure
Okawa, Tomohiro,Aramaki, Yoshio,Yamamoto, Mitsuo,Kobayashi, Toshitake,Fukumoto, Shoji,Toyoda, Yukio,Henta, Tsutomu,Hata, Akito,Ikeda, Shota,Kaneko, Manami,Hoffman, Isaac D.,Sang, Bi-Ching,Zou, Hua,Kawamoto, Tetsuji
, p. 6942 - 6990 (2017/09/07)
A novel class of therapeutic drug candidates for heart failure, highly potent and selective GRK2 inhibitors, exhibit potentiation of β-adrenergic signaling in vitro studies. Hydrazone derivative 5 and 1,2,4-triazole derivative 24a were identified as hit compounds by HTS. New scaffold generation and SAR studies of all parts resulted in a 4-methyl-1,2,4-triazole derivative with an N-benzylcarboxamide moiety with highly potent activity toward GRK2 and selectivity over other kinases. In terms of subtype selectivity, these compounds showed enough selectivity against GRK1, 5, 6, and 7 with almost equipotent inhibition to GRK3. Our medicinal chemistry efforts led to the discovery of 115h (GRK2 IC50 = 18 nM), which was obtained the cocrystal structure with human GRK2 and an inhibitor of GRK2 that potentiates β-adrenergic receptor (βAR)-mediated cAMP accumulation and prevents internalization of βARs in β2AR-expressing HEK293 cells treated with isoproterenol. Therefore, 115h appears to be a novel class of therapeutic for heart failure treatment.
MnO2/TiO2 catalyzed synthesis of coenzyme pyridoxamine-5′-phosphate analogues: 3-deoxypyridoxamine-5′-phosphate
Abbas, Sk Jahir,Ramacharyulu,Ke, Shyue-Chu
, p. 10242 - 10248 (2016/02/05)
The highly efficient-selective synthetic route of the pyridoxal-5′-phosphate (vitamin B6, PLP) analogues: C3 substituted deoxy derivatives of pyridoxal (PL), pyridoxal-N-oxide (PLNO), pyridoxamine (PM), pyridoxamine-5′-phosphate (PMP) and pyridoxal-5′-phosphate (PLP), were developed via reduction and followed by selective oxidation in one pot using solid supported nanoparticles. The salient features of this strategy are: economic two-fold conversion, more Lewis acid sites, vacancies on the nanoparticle surfaces, and good yields of 3-deoxypyridoxal and 3-deoxypyridoxamine-5′-phosphate.
Efficient and Selective Cu/Nitroxyl-Catalyzed Methods for Aerobic Oxidative Lactonization of Diols
Xie, Xiaomin,Stahl, Shannon S.
, p. 3767 - 3770 (2015/04/14)
Cu/nitroxyl catalysts have been identified that promote highly efficient and selective aerobic oxidative lactonization of diols under mild reaction conditions using ambient air as the oxidant. The chemo- and regioselectivity of the reaction may be tuned by changing the identity of the nitroxyl cocatalyst. A Cu/ABNO catalyst system (ABNO = 9-azabicyclo[3.3.1]nonan-N-oxyl) shows excellent reactivity with symmetrical diols and hindered unsymmetrical diols, whereas a Cu/TEMPO catalyst system (TEMPO = 2,2,6,6-tetramethyl-1-piperidinyl-N-oxyl) displays excellent chemo- and regioselectivity for the oxidation of less hindered unsymmetrical diols. These catalyst systems are compatible with all classes of alcohols (benzylic, allylic, aliphatic), mediate efficient lactonization of 1,4-, 1,5-, and some 1,6-diols, and tolerate diverse functional groups, including alkenes, heterocycles, and other heteroatom-containing groups.
A facile synthesis of 5,6-dihydro-4H-pyrrolo[3,4-d]thiazole and other pyrrolidine-fused aromatic ring systems via one-step cyclization from diols
Yoshikawa, Kenji,Nagata, Tsutomu,Yoshino, Toshiharu,Nakamoto, Yumi,Haginoya, Noriyasu,Muto, Ryo,Mochizuki, Akiyoshi,Kanno, Hideyuki,Ohta, Toshiharu
experimental part, p. 1711 - 1720 (2012/09/07)
A facile synthetic method of 5,6-dihydro-4H-pyrrolo[3,4-d]thiazole, which is a subunit of a potent factor Xa (fXa) inhibitor was developed. This new approach employs one-step cyclization from a diol and can be applied to the syntheses of other pyrrolidine-fused aromatic ring sytems.
Synthesis and structure-activity relationships of 5,6,7,8-tetrahydropyrido[3,4-b]pyrazine-based hydroxamic acids as HB-EGF shedding inhibitors
Yoshiizumi, Kazuya,Yamamoto, Minoru,Miyasaka, Tomohiro,Ito, Yasuko,Kumihara, Hiroshi,Sawa, Masaaki,Kiyoi, Takao,Yamamoto, Takeshi,Nakajima, Fumio,Hirayama, Ryoichi,Kondo, Hirosato,Ishibushi, Etsuko,Ohmoto, Hiroshi,Inoue, Yoshimasa,Yoshino, Kohichiro
, p. 433 - 450 (2007/10/03)
HB-EGF Shedding inhibitors have been expected to become effective medicines for skin diseases caused by the proliferation of keratinocytes. In order to discover novel HB-EGF shedding inhibitors and clarify their structure-activity relationships, 5,6,7,8-tetrahydronaphthylidine-based hydroxamic acid and 5,6,7,8-tetrahydropyrido[3,4-b]pyrazine-based hydroxamic acids have been synthesized. Among the synthesized compounds, the ethoxyethoxy derivative 3o and the methoxypropoxy derivative 3p exhibited much more potent HB-EGF shedding inhibitory activity than CGS 27023A. The structural modification of 5,6,7,8-tetrahydropyrido[3,4-b]pyrazine-based hydroxamic acids enabled us to establish the following structure-activity relationships; the existences of the hydroxamic acid, the sulfonamide, and the phenyl moieties are crucial for a potent HB-EGF shedding inhibitory activity, and the stereochemistry of the alpha carbon of hydroxamic acid is also important. In addition, from the comparison of their HB-EGF shedding inhibitory activities with their MMPs inhibitory activities, we found that the S1′ pocket of the responsible enzyme for HB-EGF shedding is deep unlike that of MMP-1.
