51392-54-2Relevant academic research and scientific papers
Changing for the Better: Discovery of the Highly Potent and Selective CDK9 Inhibitor VIP152 Suitable for Once Weekly Intravenous Dosing for the Treatment of Cancer
Lücking, Ulrich,Kosemund, Dirk,B?hnke, Niels,Lienau, Philip,Siemeister, Gerhard,Denner, Karsten,Bohlmann, Rolf,Briem, Hans,Terebesi, Ildiko,B?mer, Ulf,Sch?fer, Martina,Ince, Stuart,Mumberg, Dominik,Scholz, Arne,Izumi, Raquel,Hwang, Stuart,Von Nussbaum, Franz
, p. 11651 - 11674 (2021/07/31)
Selective inhibition of exclusively transcription-regulating positive transcription elongation factor b/CDK9 is a promising new approach in cancer therapy. Starting from atuveciclib, the first selective CDK9 inhibitor to enter clinical development, lead optimization efforts aimed at identifying intravenously (iv) applicable CDK9 inhibitors with an improved therapeutic index led to the discovery of the highly potent and selective clinical candidate VIP152. The evaluation of various scaffold hops was instrumental in the identification of VIP152, which is characterized by the underexplored benzyl sulfoximine group. VIP152 exhibited the best preclinical overall profile in vitro and in vivo, including high efficacy and good tolerability in xenograft models in mice and rats upon once weekly iv administration. VIP152 has entered clinical trials for the treatment of cancer with promising longterm, durable monotherapy activity in double-hit diffuse large B-cell lymphoma patients.
Late-Stage Sulfoximination: Improved Synthesis of the Anticancer Drug Candidate Atuveciclib
Glachet, Thomas,Franck, Xavier,Reboul, Vincent
, p. 971 - 975 (2019/02/10)
An efficient synthesis of racemic atuveciclib was accomplished in five steps with an excellent 51% overall yield, using cheap reagents and mild reaction conditions. The key sulfoximination reaction was realized during the last step of the synthesis from t
Identification of Atuveciclib (BAY 1143572), the First Highly Selective, Clinical PTEFb/CDK9 Inhibitor for the Treatment of Cancer
Lücking, Ulrich,Scholz, Arne,Lienau, Philip,Siemeister, Gerhard,Kosemund, Dirk,Bohlmann, Rolf,Briem, Hans,Terebesi, Ildiko,Meyer, Kirstin,Prelle, Katja,Denner, Karsten,B?mer, Ulf,Sch?fer, Martina,Eis, Knut,Valencia, Ray,Ince, Stuart,von Nussbaum, Franz,Mumberg, Dominik,Ziegelbauer, Karl,Klebl, Bert,Choidas, Axel,Nussbaumer, Peter,Baumann, Matthias,Schultz-Fademrecht, Carsten,Rühter, Gerd,Eickhoff, Jan,Brands, Michael
, p. 1776 - 1793 (2017/10/23)
Selective inhibition of exclusively transcription-regulating PTEFb/CDK9 is a promising new approach in cancer therapy. Starting from lead compound BAY-958, lead optimization efforts strictly focusing on kinase selectivity, physicochemical and DMPK properties finally led to the identification of the orally available clinical candidate atuveciclib (BAY 1143572). Structurally characterized by an unusual benzyl sulfoximine group, BAY 1143572 exhibited the best overall profile in vitro and in vivo, including high efficacy and good tolerability in xenograft models in mice and rats. BAY 1143572 is the first potent and highly selective PTEFb/CDK9 inhibitor to enter clinical trials for the treatment of cancer.
FLUORINATED BENZOFURANYL-PYRIMIDINE DERIVATIVES CONTAINING A SULFONE GROUP
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Page/Page column 52, (2016/05/24)
The present invention relates to fluorinated benzofuranyl-pyrimidine derivatives containing a sulfone group of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disord
FLUORINATED BENZOFURANYL-PYRIMIDINE DERIVATIVES CONTAINING A SULFOXIMINE GROUP
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Page/Page column 63, (2016/12/26)
The present invention relates to fluorinated benzofuranyl-pyrimidine derivatives containing a sulfoximine group of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of di
METHODS FOR INHIBITING NECROPTOSIS
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Page/Page column 115, (2015/12/30)
The present invention relates to methods for inhibiting necroptosis; screening methods for identifying compounds which inhibit necroptosis; and compounds for the inhibition of necroptosis, which may be useful in the treatment of conditions associated with deregulated necroptosis.
4-(ORTHO)-FLUOROPHENYL-5-FLUOROPYRIMIDIN-2-YL AMINES CONTAINING A SULFOXIMINE GROUP
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Page/Page column 88, (2014/06/11)
The present invention relates to 4-(ortho)-fluorophenyl-5-fluoropyrimidin-2-yl amine derivatives containing a sulfoximine group of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or p
PYRIDINE CDK9 KINASE INHIBITORS
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Paragraph 1976, (2014/09/29)
Disclosed are compound of Formula (Ia), wherein R2, R12, R16, J, Q, X, Y and Z are as defined in the specification, and pharmaceutically acceptable salts thereof.The compounds may be used as agents in the treatment of diseases, including cancer. Also provided are pharmaceutical compositions comprising one or more compounds of Formula (Ia).
DISUBSTITUTED 5-FLUORO-PYRIMIDINES
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Page/Page column 67, (2013/03/28)
The present invention relates to disubstituted 5-fluoro-pyrimidines of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferativ
DISUBSTITUTED 5-FLUORO PYRIMIDINE DERIVATIVES CONTAINING A SULFOXIMINE GROUP
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Page/Page column 84, (2013/03/28)
The present invention relates to disubstituted 5-fluoro pyrimidine derivatives containing a sulfoximine group of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of diso
