- A convergent strategy towards febrifugine and related compounds
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We report a modular five step synthetic route to the febrifugines that employs 2-(chloromethyl)allyl-trimethylsilane as a conjunctive reagent for the coupling of the piperidine and quinazolinone groups. We also demonstrate the application of a recent Rh-catalyzed quinazolinone synthesis for the facile generation of febrifugine analogs.
- Maiden,Mbelesi,Procopiou,Swanson,Harrity
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- HETEROCYCLIC INHIBITORS OF TYROSINE KINASE
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The present disclosure relates to heterocyclic compounds and methods which may be useful as inhibitors of HER2 or EGFR for the treatment or prevention of disease, including cancer.
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Paragraph 0511
(2020/11/03)
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- A pyrido [3,4-d] pyrimidine -4 (3H)-one derivatives method for the preparation of
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Belonging to the field of chemical synthesis, the invention discloses a preparation method for a pyridine[3, 4-d]pyrimidine-4(3H)-one derivative. The method includes: taking a 3-aminopyridine-4-carboxylic acid compound and an amidine compound as raw materials, adopting sodium acetate as a nucleophilic catalyst, subjecting the reaction system to reflux reaction for 4-10h in an organic solvent, and carrying out TLC detection, washing, extraction, concentration, beating and filtering so as to obtain the product pyridine[3, 4-d]pyrimidine-4(3H)-one derivative. The 3-aminopyridine-4-carboxylic acid compound, the amidine compound and sodium acetate are in a mole ratio of 1:3-5:2-4. The method provided by the invention has the advantages of easily available raw materials, mild reaction condition, well operable after-treatment, higher yield, and easy realization of large scale production.
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Paragraph 0027; 0028; 0030
(2016/10/10)
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- HETEROCYCLIC COMPOUNDS USEFUL AS PDK1 INHIBITORS
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The present invention provides compounds useful as inhibitors of PDK1. The present invention also provides compositions thereof, and methods of treating PDK1-mediated diseases.
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Page/Page column 93
(2016/10/08)
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- Synthesis of Functionalized Pyridines via a Regioselective Oxazoline Promoted C-H Amidation Reaction
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The first Rh-catalyzed C-H amidation of pyridines is reported. The incorporation of a substituent at the C2 position both is crucial to the success of this transformation and provides considerable scope for further elaboration of the resulting products. Among these compounds, 2-chloropyridines allow access to a selection of intermediates including a versatile azaquinazoline scaffold.
- Maiden, Tracy M. M.,Swanson, Stephen,Procopiou, Panayiotis A.,Harrity, Joseph P. A.
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supporting information
p. 3434 - 3437
(2016/07/26)
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- Discovery of selective 4-amino-pyridopyrimidine inhibitors of MAP4K4 using fragment-based lead identification and optimization
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Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) is a serine/threonine kinase implicated in the regulation of many biological processes. A fragment-based lead discovery approach was used to generate potent and selective MAP4K4 inhibitors. The fragment hit pursued in this article had excellent ligand efficiency (LE), an important attribute for subsequent successful optimization into drug-like lead compounds. The optimization efforts eventually led us to focus on the pyridopyrimidine series, from which 6-(2-fluoropyridin-4-yl)pyrido[3,2-d]pyrimidin-4-amine (29) was identified. This compound had low nanomolar potency, excellent kinase selectivity, and good in vivo exposure, and demonstrated in vivo pharmacodynamic effects in a human tumor xenograft model.
- Crawford, Terry D.,Ndubaku, Chudi O.,Chen, Huifen,Boggs, Jason W.,Bravo, Brandon J.,Delatorre, Kelly,Giannetti, Anthony M.,Gould, Stephen E.,Harris, Seth F.,Magnuson, Steven R.,McNamara, Erin,Murray, Lesley J.,Nonomiya, Jim,Sambrone, Amy,Schmidt, Stephen,Smyczek, Tanya,Stanley, Mark,Vitorino, Philip,Wang, Lan,West, Kristina,Wu, Ping,Ye, Weilan
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supporting information
p. 3484 - 3493
(2014/05/20)
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- PYRIMIDO [5,4-D] PYRIMIDINE DERIVATIVES FOR THE INHIBITION OF TYROSINE KINASES
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The present invention encompasses compounds of general formula (1), wherein the groups R1 to R4, X1, X2, X3, X4, X5, Q, L1 and L2 are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, as well as pharmaceutical preparations and formulations of these compounds.
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Page/Page column 35
(2010/09/17)
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- PYRIDO [3,4-D] PYRIMIDINE DERIVATIVES AS MATRIX METALLOPROTEINASE-13 INHIBITORS
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This invention relates to a pyrido[3,4-d]pyrimidine derivative of Formula (I), or a pharmaceutically acceptable salt thereof, wherein R, L', L2, V, L3, and R2 are as defined in the specification, that inhibits a matrix metalloproteinase-13 enzyme and thus is useful for treating diseases resulting from MMP-13 mediated tissue breakdown such as osteoarthritis, rheumatoid arthritis, cartilage damage, psoriatic arthritis, ankylosing spondylitis, heart failure, atherosclerosis, inflammatory bowel disease, multiple sclerosis, age-related macular degeneration, chronic obstructive pulmonary disease, asthma, periodontal diseases, psoriasis, cancer, and osteoporosis.
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Page/Page column 123-124
(2010/02/11)
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- Anilinoquinazaolines as protein tyrosine kianse inhibitors
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Heteroaromatic compounds are described, methods for their preparation, pharmaceutical compositions containing them, methods of use, and their use in medicines. In particular, the invention relates to quinazoline and pyridopyrimidine derivatives which exhibit protein tyrosine kinase inhibition.
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Page/Page column 45
(2008/06/13)
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- Indazolylamino quinazolines and pyridopyrimidines as inhibitors of the EGFr and c-erbB-2
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Described herein is the design and synthesis of indazolylaminopyridopyrimidines and quinazolines as inhibitors of the class 1 tyrosine kinase receptor family. Data is presented for N4-(1-benzyl-1H-indazol-5-yl)-N6,N6- dime
- Cockerill, Stuart,Stubberfield, Colin,Stables, Jeremy,Carter, Malcolm,Guntrip, Stephen,Smith, Kathryn,McKeown, Steve,Shaw, Robert,Topley, Peter,Thomsen, Lindy,Affleck, Karen,Jowett, Amanda,Hayes, David,Willson, Malcolm,Woollard, Patrick,Spalding, David
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p. 1401 - 1405
(2007/10/03)
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- Synthesis of 6-substituted pyrido[3,4-d]pyrimidin-4(3H)-ones via directed lithiation of 2-substituted 5-aminopyridine derivatives
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Directed lithiation of Boc or pivaloyl derivatives of 2-substituted 5-aminopyridines with BuLi-TMEDA in diethyl ether at -10°C gave 4-lithio derivatives which were quenched with CO2 to give the analogous C-4 carboxylic acids. Hydrolysis of the protecting groups with either TFA or aqueous KOH gave 2-substituted 5-aminopyridine-4-carboxylic acids which were converted to 6-substituted pyrido[3,4-d]pyrimidin-4(3H)-ones by reaction with formamide or, more optimally, formamidine acetate. Boc protected aminopyridines provided the best overall results, with synthesis of these derivatives best achieved by direct reaction of the aminopyridine with di-tert-butyl dicarbonate in the absence of added base.
- Rewcastle, Gordon W.,Denny, William A.,Winters, R. Thomas,Colbry, Norman L.,Showalter, H. D. Hollis
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p. 2221 - 2226
(2007/10/03)
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