A Tiny Pocket Packs a Punch: Leveraging Pyridones for the Discovery of CNS-Penetrant Aza-indazole IRAK4 Inhibitors.

Autor: Bolduc PN; Department of Medicinal Chemistry;Department of Multiple Sclerosis and Immunology;Drug Metabolism and Pharmacokinetics;Physical Biochemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Pfaffenbach M; Department of Medicinal Chemistry;Department of Multiple Sclerosis and Immunology;Drug Metabolism and Pharmacokinetics;Physical Biochemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Evans R; Department of Medicinal Chemistry;Department of Multiple Sclerosis and Immunology;Drug Metabolism and Pharmacokinetics;Physical Biochemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Xin Z; Department of Medicinal Chemistry;Department of Multiple Sclerosis and Immunology;Drug Metabolism and Pharmacokinetics;Physical Biochemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Henry KL; Department of Medicinal Chemistry;Department of Multiple Sclerosis and Immunology;Drug Metabolism and Pharmacokinetics;Physical Biochemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Gao F; Department of Medicinal Chemistry;Department of Multiple Sclerosis and Immunology;Drug Metabolism and Pharmacokinetics;Physical Biochemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Fang T; Department of Medicinal Chemistry;Department of Multiple Sclerosis and Immunology;Drug Metabolism and Pharmacokinetics;Physical Biochemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Silbereis J; Department of Medicinal Chemistry;Department of Multiple Sclerosis and Immunology;Drug Metabolism and Pharmacokinetics;Physical Biochemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Vera Rebollar J; Department of Medicinal Chemistry;Department of Multiple Sclerosis and Immunology;Drug Metabolism and Pharmacokinetics;Physical Biochemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Li P; Department of Medicinal Chemistry;Department of Multiple Sclerosis and Immunology;Drug Metabolism and Pharmacokinetics;Physical Biochemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Chodaparambil JV; Department of Medicinal Chemistry;Department of Multiple Sclerosis and Immunology;Drug Metabolism and Pharmacokinetics;Physical Biochemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Metrick C; Department of Medicinal Chemistry;Department of Multiple Sclerosis and Immunology;Drug Metabolism and Pharmacokinetics;Physical Biochemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Peterson EA; Department of Medicinal Chemistry;Department of Multiple Sclerosis and Immunology;Drug Metabolism and Pharmacokinetics;Physical Biochemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States.

Publikováno v: ACS medicinal chemistry letters [ACS Med Chem Lett] 2024 Apr 26; Vol. 15 (5), pp. 714-721. Date of Electronic Publication: 2024 Apr 26 (Print Publication: 2024).

The Discovery of 7-Isopropoxy-2-(1-methyl-2-oxabicyclo[2.1.1]hexan-4-yl)- N -(6-methylpyrazolo[1,5- a ]pyrimidin-3-yl)imidazo[1,2- a ]pyrimidine-6-carboxamide (BIO-7488), a Potent, Selective, and CNS-Penetrant IRAK4 Inhibitor for the Treatment of Ischemic Stroke.

Autor: Evans R; Department of Medicinal Chemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Bolduc PN; Department of Medicinal Chemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Pfaffenbach M; Department of Medicinal Chemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Gao F; Department of Medicinal Chemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., May-Dracka T; Department of Medicinal Chemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Fang T; Department of Acute Neurology, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Hopkins BT; Department of Medicinal Chemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Chodaparambil JV; Physical Biochemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Henry KL; Department of Acute Neurology, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Li P; Drug Metabolism and Pharmacokinetics, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Metrick C; Physical Biochemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Nelson A; Department of Acute Neurology, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Trapa P; Drug Metabolism and Pharmacokinetics, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Thomas A; Department of Acute Neurology, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Burkly L; Department of Acute Neurology, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States., Peterson EA; Department of Medicinal Chemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States.

Publikováno v: Journal of medicinal chemistry [J Med Chem] 2024 Mar 28; Vol. 67 (6), pp. 4676-4690. Date of Electronic Publication: 2024 Mar 11.

Nickel-Electrocatalytic Decarboxylative Arylation to Access Quaternary Centers.

Autor: Laudadio G; Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA., Neigenfind P; Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA., Péter Á; Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA., Rubel CZ; Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA., Emmanuel MA; Chemical Process Development, Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, NJ 08901, USA., Oderinde MS; Small Molecule Drug Discovery, Bristol Myers Squibb Research & Early Development, Route 206 & Province Line Road, Princeton, NJ 08543, USA., Ewing TE; Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA., Palkowitz MD; Small Molecule Drug Discovery, Bristol Myers Squibb, Research & Early Development, 250 Water Street, Cambridge, MA 02141, USA., Sloane JL; Small Molecule Drug Discovery, Bristol Myers Squibb, Research & Early Development, 250 Water Street, Cambridge, MA 02141, USA., Gillman KW; Small Molecule Drug Discovery, Bristol Myers Squibb, Research & Early Development, 250 Water Street, Cambridge, MA 02141, USA., Ridge D; Small Molecule Drug Discovery, Bristol Myers Squibb, Research & Early Development, 250 Water Street, Cambridge, MA 02141, USA., Mandler MD; Small Molecule Drug Discovery, Bristol Myers Squibb Research & Early Development, Route 206 & Province Line Road, Princeton, NJ 08543, USA., Bolduc PN; Biogen Inc., 225 Binney Street, Cambridge, MA 02142, USA., Nicastri MC; Biogen Inc., 225 Binney Street, Cambridge, MA 02142, USA., Zhang B; Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA., Clementson S; Research and Early Development, LEO Pharma A/S, 2750, Ballerup, Denmark., Petersen NN; Research and Early Development, LEO Pharma A/S, 2750, Ballerup, Denmark., Martín-Gago P; Research and Early Development, LEO Pharma A/S, 2750, Ballerup, Denmark., Mykhailiuk P; Enamine Ltd., Winston Churchill Street 78, 02094, Kyiv, Ukraine.; Chemistry Department, Taras Shevchenko National University of Kyiv, Volodymyrska 64, 01601, Kyiv, Ukraine., Engle KM; Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA., Baran PS; Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

Publikováno v: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2024 Feb 19; Vol. 63 (8), pp. e202314617. Date of Electronic Publication: 2024 Jan 18.

Overcoming Limitations in Decarboxylative Arylation via Ag-Ni Electrocatalysis.

Autor: Palkowitz MD; Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, California 92037, United States., Laudadio G; Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, California 92037, United States., Kolb S; Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, California 92037, United States., Choi J; Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, California 92037, United States., Oderinde MS; Bristol Myers Squibb Research and Development, P.O. Box 4000, Princeton, New Jersey 08534, United States., Ewing TE; Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, California 92037, United States., Bolduc PN; Biogen Inc., 225 Binney Street, Cambridge, Massachusetts 02142, United States., Chen T; Biogen Inc., 225 Binney Street, Cambridge, Massachusetts 02142, United States., Zhang H; Bristol Myers Squibb Research and Development, P.O. Box 4000, Princeton, New Jersey 08534, United States., Cheng PTW; Bristol Myers Squibb Research and Development, P.O. Box 4000, Princeton, New Jersey 08534, United States., Zhang B; Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, California 92037, United States., Mandler MD; Bristol Myers Squibb Research and Development, P.O. Box 4000, Princeton, New Jersey 08534, United States., Blasczak VD; Biogen Inc., 225 Binney Street, Cambridge, Massachusetts 02142, United States., Richter JM; Bristol Myers Squibb Research and Development, P.O. Box 4000, Princeton, New Jersey 08534, United States., Collins MR; Oncology Medicinal Chemistry Department, Pfizer Pharmaceuticals, 10770 Science Center Drive, San Diego, California 92121, United States., Schioldager RL; Oncology Medicinal Chemistry Department, Pfizer Pharmaceuticals, 10770 Science Center Drive, San Diego, California 92121, United States., Bravo M; Oncology Medicinal Chemistry Department, Pfizer Pharmaceuticals, 10770 Science Center Drive, San Diego, California 92121, United States., Dhar TGM; Bristol Myers Squibb Research and Development, P.O. Box 4000, Princeton, New Jersey 08534, United States., Vokits B; Bristol Myers Squibb Research and Development, P.O. Box 4000, Princeton, New Jersey 08534, United States., Zhu Y; Bristol Myers Squibb Research and Development, P.O. Box 4000, Princeton, New Jersey 08534, United States., Echeverria PG; Minakem Recherche, 145 Chemin des Lilas, Beuvry-La-Forêt 59310, France., Poss MA; Bristol Myers Squibb Research and Development, P.O. Box 4000, Princeton, New Jersey 08534, United States., Shaw SA; Bristol Myers Squibb Research and Development, P.O. Box 4000, Princeton, New Jersey 08534, United States., Clementson S; Research and Early Development, LEO Pharma A/S, 2750 Ballerup, Denmark., Petersen NN; Research and Early Development, LEO Pharma A/S, 2750 Ballerup, Denmark., Mykhailiuk PK; Enamine Ltd., Chervonotkatska 60, 02094 Kyiv, Ukraine., Baran PS; Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.

Publikováno v: Journal of the American Chemical Society [J Am Chem Soc] 2022 Sep 28; Vol. 144 (38), pp. 17709-17720. Date of Electronic Publication: 2022 Sep 15.

Switching from 2-pyridination to difluoromethylation: ligand-enabled nickel-catalyzed reductive difluoromethylation of aryl iodides with difluoromethyl 2-pyridyl sulfone.

Autor: Du, Wei, Luo, Qinyu, Wei, Zhiqiang, Wang, Xiu, Ni, Chuanfa, Hu, Jinbo

Publikováno v: SCIENCE CHINA Chemistry; Oct2023, Vol. 66 Issue 10, p2785-2790, 6p