- WEE1 inhibitors as well as preparation and application thereof
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The invention relates to WEE1 inhibitors as well as preparation and application thereof. The present invention relates to compounds of formula (I), or pharmaceutically acceptable salts, solvates, polymorphs or isomers thereof, and their use in the preparation of medicaments for the treatment of diseases associated with WEE1 activity.
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- Pyrazolone-fused pyrimidine compound as well as preparation method and application thereof
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The invention discloses a pyrazolone-fused pyrimidine compound as well as a preparation method and application thereof. The invention provides a pyrazolone-fused pyrimidine compound as shown in a formula I which is described in the specification. The pyrazolone-fused pyrimidine compound has better inhibitory activity on WEE1 kinase.
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Paragraph 0523-0526
(2021/01/11)
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- HETEROCYCLIC COMPOUNDS AND USES THEREOF
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Heterocyclic compounds as Wee1 inhibitors are provided. The compounds may find use as therapeutic agents for the treatment of diseases and may find particular use in oncology.
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- Synthesis and evaluation of 2,9-disubstituted 8-phenylthio/phenylsulfinyl-9H-purine as new EGFR inhibitors
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In present study, we described the synthesis and biological evaluation of a new class of EGFR inhibitors containing 2,9-disubstituted 8-phenylthio/phenylsulfinyl-9H-purine scaffold. Thirty-one compounds were synthesized. Among them, compound C9 displayed the IC50 of 29.4 nM against HCC827 cell line and 1.9 nM against EGFRL858R. Compound C12 showed moderate inhibitory activity against EGFRL858R/T790M/C797S (IC50 = 114 nM). Western bolt assay suggested that compound C9 significantly inhibited EGFR phosphorylation. In vivo test, compound C9 remarkably exhibited inhibitory effect on tumor growth at 5.0 mg/kg by oral administration in established nude mouse HCC827 xenograft model. These results indicate that the 2,9-disubstituted 8-phenylsulfinyl/phenylsulfinyl-9H-purine derivatives can act as potent EGFR(L858R) inhibitors and effective anticancer agents. Additionally, optimization of compound C12 may result in discovering the fourth-generation EGFR-TKIs.
- Hei, Yuan-Yuan,Shen, Ying,Wang, Jin,Zhang, Hao,Zhao, Hong-Yi,Xin, Minhang,Cao, Yong-Xiao,Li, Yan,Zhang, San-Qi
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p. 2173 - 2185
(2018/03/28)
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- 2,4-dibasic miazines compound
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The invention belongs to the field of medical chemistry, relates to a 2,4-dibasic miazines compound and specifically relates to a compound shown as formula (I) or a pharmaceutically acceptable salt thereof, a drug compound thereof and an application thereof in treating EGFR or/and ALK mediated diseases.
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- PYRIMIDINE DERIVATIVES AS KINASE INHIBITORS AND THEIR THERAPEUTICAL APPLICATIONS
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The present invention provides kinase inhibitors with anti-proliferative activity comprising substituted pyrimidine derivatives and pharmaceutically-acceptable formulations thereof. In addition, the invention provides methods for making novel compounds and methods for using the compounds.
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- Design and synthesis of new [1,2,3]triazolo[4,5-d]pyrimidine derivatives as potential antiproliferative agents
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A new series possessing [1,2,3]triazolo[4,5-d]pyrimidine scaffold was synthesized and biologically evaluated for potential antiproliferative activity. Fourteen compounds were selected for in vitro anticancer assay over a panel of 60 cell lines at National Cancer Institute (NCI), USA. The most sensitive cell lines to the synthesized compounds were leukemia (K-562 and SR), nonsmall cell lung cancer HOP-92, and melanoma MDA-MB- 435. Compounds 12 and 24 exerted broad spectrum activity against most cell panel, while compounds 14, 21, and 23 exhibited effectiveness toward specific cell lines belong to different tumor subpanels. Accordingly, SAR, COMPARE analyses, and in silico ADME profiling were discussed for the target compounds. In addition, compounds 11 and 22 exerted good FGFR3 inhibitory activity with 58.8 and 46.7% at 100 μM, respectively. Taken as a whole, the present study revealed that the new series can be considered as promising lead for further development of more potent anticancer agents as well as FGFR3 kinase potential inhibitors.
- Elkamhawy, Ahmed,Al-Sanea, Mohammad M.,Song, Chiman,Sim, Taebo,Roh, Eun Joo
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p. 1863 - 1873
(2015/07/15)
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- TRICYCLIC INHIBITORS OF KINASES
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The present invention relates to compounds of formula (I) or pharmaceutical acceptable salts, wherein X, Y, Z, R3 and R4 are defined in the description. The present invention relates also to compositions containing said compounds which are useful for inhibiting kinases such as wee-1 and methods of treating diseases such as cancer.
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Page/Page column 78
(2012/09/10)
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- IMIDAZOPYRIDINES AS A NOVEL SCAFFOLD FOR MULTI-TARGETED KINASE INHIBITION
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Compounds that inhibit protein kinases, compositions containing the compounds and methods of treating diseases using the compounds are disclosed. Formula (I).
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Page/Page column 232
(2011/05/11)
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- PYRIMIDINE INHIBITORS OF KINASE ACTIVITY
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Described herein are compounds of formula (I) or pharmaceutical acceptable salts or solvates thereof, wherein L1, R1, R2, R3, R4, R5, and m are defined in the description. Methods of making said compounds, and compositions containing said compounds which are useful for inhibiting kinases such as IGF-IR are also disclosed.
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Page/Page column 79
(2010/12/26)
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- PYRIMIDINE INHIBITORS OF KINASE ACTIVITY
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The present invention relates to compounds of formula (I) or pharmaceutical acceptable salts or solvates thereof, wherein G1, R2, R3, R4, R5, n, p, q, Ar1, and Ar2 are defined in the description. The present invention relates also to methods of making said compounds, and compositions comprising said compounds which are useful for inhibiting kinases such as IGF-IR.
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Page/Page column 79
(2010/12/26)
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- INDOLINONE DERIVATIVES AND THEIR USE IN TREATING DISEASE-STATES SUCH AS CANCER
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The present invention encompasses compounds of general formula (1) wherein R1 to R4 are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and their use for preparing a pharmaceutical composition having the above-mentioned properties.
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Page/Page column 20
(2009/01/24)
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- PHARMACEUTICAL COMPOUNDS
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The invention provides a cyclin dependent kinase (e.g. cdk-4 kinase) inhibitor of the formula (I) or a salt, tautomer, solvate or N-oxide thereof; wherein R1 is an optionally substituted monocyclic or bicyclic aryl or heteroaryl group containing 0-2 heteroatoms selected from O, N and S wherein the optional substituents are selected from halogen, C1-4 alkyl, C1-4 alkoxy, C3-4 cycloalkyl and cyano, and wherein the C1-4 alkyl and C1-4 alkoxy groups are each optionally further substituted by C1-2 alkoxy or one or more halogen atoms; and E is a group E1, E2, E3 or E4: formulae E1, E2, E3, E4 wherein n, q, A5 B, T, U, V, W, Z, R2, R5, R6 and R7 are as defined in the claims.
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Page/Page column 117
(2008/06/13)
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- Diaminothiazoles
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Novel diaminothiazoles of formula (I): [image] are discussed. These compounds selectively inhibit the activity of Cdk4 and are thus useful in the treatment or control of cancer, in particular, the treatment or control of solid tumors. This invention also provides pharmaceutical compositions containing such compounds and methods of treating or controlling cancer, most particularly, the treatment or control of breast, lung, colon, and prostate tumors.
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Page/Page column 14
(2008/06/13)
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- Pyridopyrimidinone derivatives for treatment of neurodegenerative disease
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This invention provides pyridopyrimidines and 4-aminopyrimidines that are useful for treating cell proliferatives disorders, such as cancer and restenosis. We have now discovered a group of 7,8-dihydro-2 (amino and thio)pyrido[2,3-d]pyrimidines and 2,4-di
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- Benzodiazepines as potent and selective bradykinin B1 antagonists
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Antagonism of the bradykinin B1 receptor was demonstrated to be a potential treatment for chronic pain and inflammation. Novel benzodiazepines were designed that display subnanomolar affinity for the bradykinin B1 receptor (Ki = 0.59 nM) and high selectivity against the bradykinin B2 receptor (Ki > 10 nM). In vivo efficacy, comparable to morphine, was demonstrated for lead compounds in a rodent hyperalgesia model.
- Wood, Michael R.,Kim, June J.,Han, Wei,Dorsey, Bruce D.,Homnick, Carl F.,DiPardo, Robert M.,Kuduk, Scott D.,MacNeil, Tanya,Murphy, Kathy L.,Lis, Edward V.,Ransom, Richard W.,Stump, Gary L.,Lynch, Joseph J.,O'Malley, Stacey S.,Miller, Patricia J.,Chen, Tsing-Bau,Harrell, Charles M.,Chang, Raymond S. L.,Sandhu, Punam,Ellis, Joan D.,Bondiskey, Peter J.,Pettibone, Douglas J.,Freidinger, Roger M.,Bock, Mark G.
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p. 1803 - 1806
(2007/10/03)
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- Pyrido[2,3-D]pyrimidines and 4-aminopyrimidines as inhibitors of cellular proliferation
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This invention provides pyridopyrimidines and 4-aminopyrimidines that are useful for treating cell proliferative disorders, such as cancer and restenosis. We have now discovered a group of 7,8-dihydro-2-(amino and thio)pyrido[2,3-d]pyrimidines and 2,4-dia
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