- MACROCYCLIC COMPOUND SERVING AS WEE1 INHIBITOR AND APPLICATIONS THEREOF
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Disclosed in the present invention are a macrocyclic compound serving as a Weel inhibitor, and applications thereof in the preparation of drugs for treating Weel-related diseases. The present invention specifically relates to a compound represented by for
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- Pyrrolopyrimidine compound, pharmaceutical composition containing thereof, and preparation method and applications
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The invention relates to a pyrrolopyrimidine compound represented by formula I, a pharmaceutical composition containing thereof, and a preparation method and applications in preventing or treating Weel protein kinase related diseases.
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- Macrocyclic derivative of pyrazole[3,4-d]pyrimidin-3-one and pharmaceutical composition and application thereof
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The present invention relates to a macrocyclic derivative of pyrazole[3,4-d]pyrimidin-3-one as shown in the formula (I) and/or a pharmaceutically acceptable salt thereof, and a composition of a compound of the formula (I) and/or a pharmaceutically acceptable salt thereof, a preparation method thereof, application thereof as a Wee1 inhibitor and application thereof as a sensitizer for cancer chemotherapy or radiotherapy. The macrocyclic derivative of pyrazole[3,4-d]pyrimidin-3-one can effectively inhibit Wee1 and related signaling pathways, and has good cancer treatment and/or relieving effect.The formula is shown in the description.
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Paragraph 0332; 0408; 0409; 0410
(2018/10/19)
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- Discovery of the macrocycle 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7, 26-triaza-tetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27) ,16,21,23-decaene (SB1518), a potent Janus Kinase 2/Fms-like tyrosine kinase-3 (JAK2/FLT3) inhibitor for the treatment of myelofibrosis and lymphoma
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Discovery of the activating mutation V617F in Janus Kinase 2 (JAK2 V617F), a tyrosine kinase critically involved in receptor signaling, recently ignited interest in JAK2 inhibitor therapy as a treatment for myelofibrosis (MF). Herein, we describe the design and synthesis of a series of small molecule 4-aryl-2-aminopyrimidine macrocycles and their biological evaluation against the JAK family of kinase enzymes and FLT3. The most promising leads were assessed for their in vitro ADME properties culminating in the discovery of 21c, a potent JAK2 (IC50 = 23 and 19 nM for JAK2 WT and JAK2V617F, respectively) and FLT3 (IC50 = 22 nM) inhibitor with selectivity against JAK1 and JAK3 (IC50 = 1280 and 520 nM, respectively). Further profiling of 21c in preclinical species and mouse xenograft and allograft models is described. Compound 21c (SB1518) was selected as a development candidate and progressed into clinical trials where it is currently in phase 2 for MF and lymphoma.
- William, Anthony D.,Lee, Angeline C.-H.,Blanchard, Stéphanie,Poulsen, Anders,Teo, Ee Ling,Nagaraj, Harish,Tan, Evelyn,Chen, Dizhong,Williams, Meredith,Sun, Eric T.,Goh, Kee Chuan,Ong, Wai Chung,Goh, Siok Kun,Hart, Stefan,Jayaraman, Ramesh,Pasha, Mohammed Khalid,Ethirajulu, Kantharaj,Wood, Jeanette M.,Dymock, Brian W.
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p. 4638 - 4658
(2011/09/14)
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- 7-CHLORO-QUINOLIN-4-AMINE COMPOUNDS AND USES THEREOF FOR THE PREVENTION OR TREATMENT OF DISEASES INVOLVING FORMATION OF AMYLOID PLAQUES AND/OR WHERE A DYSFUNCTION OF THE APP METABOLISM OCCURS
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The present invention relates to compounds having the following Formula (I) for use in the prevention and/or the treatment of diseases involving formation of amyloid plaques and/or where a dysfunction of the APP metabolism occurs.
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- Optimized and convergent synthesis of potent anti-malarial aminoquinoline compounds: Easy access to analogs
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Amodiaquine is one of the most active antimalarial 4-aminoquinoline. Previously we have described new analogs of amodiaquine and amopyroquine, in which the hydroxyl group was replaced by various amino groups and identified highly potent compounds. Here we
- Le Fur, Nicolas,Larchanche, Paul-Emmanuel,Melnyk, Patricia
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p. 235 - 239
(2011/06/21)
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- PYRIDYL SUBSTITUTED PYRIMIDINE DERIVATIVES
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The present invention relates to pyridyl substituted pyrimidine compounds that are useful as agents for the treatment of kinase related disorders such as proliferative disorders. More particularly, the present invention relates to oxygen linked and pyridy
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- PYRAZOLO-QUINAZOLINE DERIVATIVES,PROCESS FOR THEIR PREPARATION AND THEIR USE AS KINASE INHIBITORS
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Pyrazolo-quinazoline derivatives of formula (Ia) or (Ib) as defined in the specification, and pharmaceutically acceptable salts thereof, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful, in therapy, in the treatment of diseases associated with a disregulated protein kinase activity, like cancer.
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