1330286-50-4Relevant academic research and scientific papers
Discovery of Pamiparib (BGB-290), a Potent and Selective Poly (ADP-ribose) Polymerase (PARP) Inhibitor in Clinical Development
Wang, Hexiang,Ren, Bo,Liu, Ye,Jiang, Beibei,Guo, Yin,Wei, Min,Luo, Lusong,Kuang, Xianzhao,Qiu, Ming,Lv, Lei,Xu, Hong,Qi, Ruipeng,Yan, Huibin,Xu, Dexu,Wang, Zhiwei,Huo, Chang-Xin,Zhu, Yutong,Zhao, Yuan,Wu, Yiyuan,Qin, Zhen,Su, Dan,Tang, Tristin,Wang, Fan,Sun, Xuebing,Feng, Yingcai,Peng, Hao,Wang, Xing,Gao, Yajuan,Liu, Yong,Gong, Wenfeng,Yu, Fenglong,Liu, Xuesong,Wang, Lai,Zhou, Changyou
, p. 15541 - 15563 (2020/12/22)
Poly (ADP-ribose) polymerase (PARP) plays a significant role in DNA repair responses; therefore, this enzyme is targeted by PARP inhibitors in cancer therapy. Here we have developed a number of fused tetra- or pentacyclic dihydrodiazepinoindolone derivatives with excellent PARP enzymatic and cellular PARylation inhibition activities. These efforts led to the identification of pamiparib (BGB-290, 139), which displays excellent PARP-1 and PARP-2 inhibition with IC50 of 1.3 and 0.9 nM, respectively. In a cellular PARylation assay, this compound inhibits PARP activity with IC50 = 0.2 nM. Cocrystal of pamiparib shows similar binding sites with PARP with other PARP inhibitors, but pamiparib is not a P-gp substrate and shows excellent drug metabolism and pharmacokinetics (DMPK) properties with significant brain penetration (17-19%, mice). The compound is currently being investigated in phase III clinical trials as a maintenance therapy in platinum-sensitive ovarian cancer and gastric cancer.
SOLID FORMS OF TERT-BUTYL (S)-2-((2S,3R) -1-AMINO-3-HYDROXY-1-OXOBU TAN-2-YL)-1-OXO-2, 5-DIAZASPIRO [3.4] OCTAN E-5-CARBOXYLATE AND METHODS OF PREPARING THEM
-
Paragraph 00154-00155, (2021/01/23)
Solid state forms of tert- buty1 (S)-2-((2S,3R)-1 -amino-3-hydroxy- 1-oxobutan-2-y1)- 1 -oxo-2,5- diazaspiro[3.4] octane- 5-carboxylate, pharmaceutical compositions, preparation, and uses thereof.
PROCESSES AND INTERMEDIATES FOR PRODUCING DIAZASPIRO LACTAM COMPOUNDS
-
Paragraph 00293-00294, (2021/01/23)
Processes for producing diazaspiro lactam compounds and intermediates useful in the processes.
ARGINASE INHIBITORS AND METHODS OF USE THEREOF
-
Page/Page column 35, (2019/09/04)
Disclosed are compounds of formula (Ia) or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising compounds of formula (Ia) and methods of using the same for treating cancer or a respiratory inflammatory disease and inhibiting arginase, wherein R1 is -NHR1a; R1a is -H or -C(O)CH(R1b)NHR1c; and R1b is selected from -H, -(C1-C4 ) alkyl and CH2OR1d and R1cis -H; or R1b and R1c, together with the atom to which they are attached, form a 5-membered heterocyclic ring; and R1d is H or -CH3.
1,3-Oxazolidin-5-ones derived from proline as chiral components in the synthesis of predictive enantioselective coupling reagents
KAsperowicz-Frankowska, Katarzyna,Kolesińska, Beata,Gzik, Anna,Jastrzabek, Konrad,Kamiński, Zbigniew J.
, p. 921 - 927 (2018/09/22)
1,3-Oxazolidin-5-ones derived from both enantiomers of proline and trichloroacetaldehyde were prepared and applied as an amine component in the synthesis of chiral predictive triazine-based coupling reagents. The reagents were found to be useful in condensations yielding enantiomerically enriched products from racemic substrates.
SPIRO-LACTAM NMDA RECEPTOR MODULATORS AND USES THEREOF
-
Page/Page column 34, (2017/12/15)
Disclosed are compounds having enhanced potency in the modulation of NMDA receptor activity. Such compounds can be used in the treatment of conditions such as depression and related disorders. Orally available formulations and other pharmaceutically acceptable delivery forms of the compounds, including intravenous formulations, are also disclosed.
SPIRO-LACTAM NMDA RECEPTOR MODULATORS AND USES THEREOF
-
Page/Page column 33, (2017/12/16)
Disclosed are compounds having enhanced potency in the modulation of NMDA receptor activity. Such compounds are contemplated for use in the treatment of conditions such as depression and related disorders. Orally available formulations and other pharmaceutically acceptable delivery forms of the compounds, including intravenous formulations, are also disclosed. Formula (I).
DIPEPTIDE AND TRIPEPTIDE EPOXY KETONE PROTEASE INHIBITORS
-
Paragraph 00304; 00305, (2014/10/04)
Provided herein are dipeptide and tripeptide epoxy ketone protease inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula (X): and pharmaceutically acceptable salts and compositions including the same. The compounds and compositions provided herein may be used, for example, in the treatment of proliferative diseases including cancer and autoimmune diseases.
Enantioselective approach to 13a-methylphenanthroindolizidine alkaloids
Su, Bo,Cai, Chunlong,Wang, Qingmin
, p. 7981 - 7987 (2013/01/15)
The first enantioselective approach to 13a-methylphenanthroindolizidine alkaloids is reported, featuring an efficient stereoselective Seebach's alkylation and Pictet-Spengler cyclization. The proposed and other three most probable structures were ruled out, indicating hypoestestatin 1 needs further assignment.
