- Identification of azabenzimidazoles as potent JAK1 selective inhibitors
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We have identified a class of azabenzimidazoles as potent and selective JAK1 inhibitors. Investigations into the SAR are presented along with the structural features required to achieve selectivity for JAK1 versus other JAK family members. An example from
- Vasbinder, Melissa M.,Alimzhanov, Marat,Augustin, Martin,Bebernitz, Geraldine,Bell, Kirsten,Chuaqui, Claudio,Deegan, Tracy,Ferguson, Andrew D.,Goodwin, Kelly,Huszar, Dennis,Kawatkar, Aarti,Kawatkar, Sameer,Read, Jon,Shi, Jie,Steinbacher, Stefan,Steuber, Holger,Su, Qibin,Toader, Dorin,Wang, Haixia,Woessner, Richard,Wu, Allan,Ye, Minwei,Zinda, Michael
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Read Online
- An improved large scale synthesis of 2-amino-4-chloropyridine and its use for the convenient preparation of various polychlorinated 2-aminopyridines
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An efficient large scale synthesis of 2-amino-4-chloropyridine (3) has been achieved through a modification of existing literature procedures. Compound 3 was used to prepare the previously unreported 2-amino-4,5-dichloropyridine (4). The known 2-amino-3,4-dichloropyridine (5) and 2-amino-3,4,5-trichloropyridine (6) were pepared from 3 by new routes and in higher yields than previously reported.
- Gudmundsson, Kristjan S.,Hinkley, Jack M.,Brieger, Michael S.,Drach, John C.,Townsend, Leroy B.
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Read Online
- IMPROVED METHODS, KITS, COMPOSITIONS AND DOSING REGIMENS FOR THE USE OF HETEROCYCLIC INHIBITORS OF ERK1 AND ERK2
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The present application provides improved compositions, methods, kits and dosing regimens for the use of heterocyclic compounds and pharmaceutically acceptable salts, prodrugs, solvates, hydrates, or stereoisomers thereof. These compositions, methods, kit
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Page/Page column 132-134
(2021/05/07)
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- 2-PHENYLIMIDAZO[4,5-B]PYRIDIN-7-AMINE DERIVATES USEFUL AS INHIBITORS OF MAMMALIAN TYROSINE KINASE ROR1 ACTIVITY
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Compound of formula (I′) or (I′′) or a pharmaceutically acceptable salt thereof. The compound is an inhibitor of mammalian kinase enzyme activity, including ROR1 tyrosine kinase activity and may be used in the treatment of disorders associated with such activity.
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Page/Page column 69-70
(2018/03/26)
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- HETEROCYCLIC INHIBITORS OF ERK1 AND ERK2 AND THEIR USE IN THE TREATMENT OF CANCER
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The present application provides novel heterocyclic compounds and pharmaceutically acceptable salts thereof. Also provided are methods for preparing these compounds. These compounds are useful for inhibiting ERK1/2. By administering to a patient in need a
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Paragraph 0558-0559
(2017/01/02)
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- Discovery and analgesic evaluation of 8-chloro-1,4-dihydropyrido[2,3- b ]pyrazine-2,3-dione as a novel potent d -amino acid oxidase inhibitor
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A series of 5-azaquinoxaline-2,3-dione derivatives were synthesized and evaluated on d-amino acid oxidase (DAAO) inhibition as potential α-hydroxylactam-based inhibitors. The potent inhibitory activities in vitro suggested that 5-nitrogen could significantly enhance the binding affinity by strengthening relevant hydrogen bond interactions. The analgesic effects of intrathecal and systemic injection of 8-chloro-1,4-dihydropyrido[2,3-b]pyrazine-2,3-dione, a representative molecule of 5-azaquinoxaline-2,3-dione, were investigated in rodents. This research not only confirmed the analgesic effect of the DAAO inhibitors but provided a new class of chemical entities with oral application potential for the treatment of chronic pain and morphine analgesic tolerance.
- Xie, Dongsheng,Lu, Jun,Xie, Jin,Cui, Junjun,Li, Teng-Fei,Wang, Yan-Chao,Chen, Yuan,Gong, Nian,Li, Xin-Yan,Fu, Lei,Wang, Yong-Xiang
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- 2-PHENYL-3H-IMIDAZO[4,5-B]PYRIDINE DERIVATES USEFUL AS INHIBITORS OF MAMMALIAN TYROSINE KINASE ROR1 ACTIVITY
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A compound of formula (I′) or (I′′) or a pharmaceutically acceptable salt thereof. The compound is an inhibitor of mammalian kinase enzyme activity, including ROR1 tyrosine kinase activity and may be used in the treatment of disorders associated with such activity.
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Page/Page column 71-72
(2016/09/22)
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- COMBINATION THERAPY WITH MDM2 AND EFGR INHIBITORS
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Provided is a method of treating a proliferative disease, condition, or disorder in a subject by administering a combination of an inhibitor of p53 and MDM2 binding and an EGFR inhibitor. Various embodiments of the disclosed methods provide a synergistic
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Page/Page column 162-163
(2016/01/29)
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- 3 -AZABICYCLO [4.1.0] HEPTANES USED AS OREXIN ANTAGONISTS
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This invention relates to 3-azabicyclo[4.1.0] heptane derivatives (I) and their use as orexin receptor antagonists.
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Page/Page column 66
(2010/11/05)
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- Enzyme Inhibitors
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Compounds of formula (I), are aurora kinase inhibitors: wherein X is —N—, —CH2—N—, —CH2—CH—, or —CH—; R1 is a radical of formula (IA) wherein Z is —CH2—, —NH—, -0-, —S(O)— —S—, —S(O)2 or a divalent monocyclic carbocyclic or heterocyclic radical having 3-7 ring atoms; Alk is an optionally substituted divalent C1-C6 alkylene radical; A is hydrogen or an optionally substituted monocyclic carbocyclic or heterocyclic ring having 5-7 ring atoms; r, s and t are independently 0 or 1, provided that when A is hydrogen then at least one of r and s is 1; R2 is halogen, —CN, —CF3, —OCH3, or cyclopropyl; and R3 is a radical of formula (IB) wherein Q is hydrogen or an optionally substituted phenyl or monocyclic heterocyclic ring with 5 or 6 ring atoms; Z[!It!]1> is —S—, —S(O)—, —S(O)2—, —O—, —SO2NH—, —NHSO2—, NHC(═O)NH, —NH(C═S)NH—, Or —N(R4)—wherein R4 is hydrogen, C1-C3 alkyl, cycloalkyl, or benzyl; and Alk[!It!]1> and Alk[!It!]2> are, independently, optionally substituted divalent C1-C3 alkylene radicals; and m, n and p are independently 0 or 1. Data supplied from the esp@cenet datatbase—Worldwide d77
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Page/Page column 7
(2009/10/06)
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