- Selective palladium-catalysed amination of 4-chloropyridines with benzylamines using the Josiphos ligand
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A synthetic strategy for the synthesis of a library of 4-N-benzylamino-2-N-phenyl-pyridines is herein described. The approach involves a Pd-assisted cross-coupling of a 4-chloro-N-phenylpyridin-2-amine intermediate with a range of benzylamines. A variety of ligands were screened, the most successful being the Josiphos ligand, which gave the desired products in good to moderate yields. The reactions occur quickly, within 30 min, with full conversion of the intermediate into the desired product.
- Hawkins, Janet L.,Gregson, Clare L.,Hassall, Lorraine A.,Holmes, Jane L.
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Read Online
- HETEROCYCLIC COMPOUNDS AS CBP/EP300 BROMODOMAIN INHIBITORS
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The present invention provides heterocyclic compounds of formula (I), which are therapeutically useful as CBP/EP300 inhibitors. These compounds are useful in the treatment and/or prevention of diseases or disorders mediated by CBP and/or EP300 in an individual. The present invention also provides preparation of the compounds and pharmaceutical compositions comprising at least one of the compounds of formula (I) or a pharmaceutically acceptable salt, or a stereoisomer or a tautomer, an N-oxide or an ester thereof.
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Page/Page column 61-62
(2022/04/03)
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- Structural and chemical insights into the covalent-allosteric inhibition of the protein kinase Akt
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The Ser/Thr kinase Akt (Protein Kinase B/PKB) is a master switch in cellular signal transduction pathways. Its downstream signaling influences cell proliferation, cell growth, and apoptosis, rendering Akt a prominent drug target. The unique activation mechanism of Akt involves a change of the relative orientation of its N-terminal pleckstrin homology (PH) and the kinase domain and makes this kinase suitable for highly specific allosteric modulation. Here we present a unique set of crystal structures of covalent-allosteric interdomain inhibitors in complex with full-length Akt and report the structure-based design, synthesis, biological and pharmacological evaluation of a focused library of these innovative inhibitors.
- Uhlenbrock, Niklas,Smith, Steven,Weisner, J?rn,Landel, Ina,Lindemann, Marius,Le, Thien Anh,Hardick, Julia,Gontla, Rajesh,Scheinpflug, Rebekka,Czodrowski, Paul,Janning, Petra,Depta, Laura,Quambusch, Lena,Müller, Matthias P.,Engels, Bernd,Rauh, Daniel
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p. 3573 - 3585
(2019/03/28)
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- Pd-catalyzed amidation of aryl(Het) halides with tert-butyl carbamate
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Pd-catalyzed cross-coupling reaction of tert-butyl carbamate with various aryl(Het) halides with Cs2CO3 as base in 1,4-dioxane as solvent was investigated, which resulted in the formation of the desired compounds in moderate to excellent yields.
- Qin, Lijin,Cui, Hongmeng,Zou, Dapeng,Li, Jingya,Wu, Yangjie,Zhu, Zhiwu,Wu, Yusheng
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experimental part
p. 4445 - 4448
(2010/09/12)
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- Rearrangement of N,N-di-tert-butoxycarbonylpyridin-4-amines and formation of polyfunctional pyridines
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(Chemical Equation Presented) N,N-Di-tert-butoxycarbonylpyridin-4-amines were found to be rearranged to tert-butyl 4-(tert-butoxycarbonylamino) nicotinates by treatment with LDA in THF.
- Liu, Yahua,Ding, Qiang,Wu, Xu
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p. 6025 - 6028
(2008/12/21)
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- Discovery of potent and cell-active allosteric dual Akt 1 and 2 inhibitors
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This paper describes the improvement of cell potency in a class of allosteric Akt 1 and 2 inhibitors. Key discoveries include identifying the solvent exposed region of the molecule and appending basic amines to enhance the physiochemical properties of the
- Siu, Tony,Liang, Jun,Arruda, Jeannie,Li, Yiwei,Jones, Raymond E.,Defeo-Jones, Deborah,Barnett, Stanley F.,Robinson, Ronald G.
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scheme or table
p. 4186 - 4190
(2009/04/07)
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- NOVEL COMPOUNDS THAT MODULATE PPARγ TYPE RECEPTORS, AND USE THEREOF IN COSMETIC OR PHARMACEUTICAL COMPOSITIONS
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The invention relates to novel compounds corresponding to the general formula (I) below: and also to the method for preparing them, and to their use in pharmaceutical compositions intended for use in human or veterinary medicine (in dermatology, and also
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Page/Page column 49-50
(2010/11/08)
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- INHIBITORS OF AKT ACTIVITY
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The instant invention provides for compounds that inhibit Akt activity. In particular, the compounds disclosed selectively inhibit one or two of the Akt isoforms. The invention also provides for compositions comprising such inhibitory compounds and method
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Page/Page column 40
(2008/06/13)
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- INHIBITORS OF AKT ACTIVITY
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The present invention is directed to compounds which contain substituted naphthyridines which inhibit the activity of Akt, a serine/threonine protein kinase. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for treating cancer comprising administration of the compounds of the invention. These substituted naphthyridines have unexpected advantageous properties when compared to other naphthyridines reported in PCT publication WO2003/086394, such unexpected advantageous properties may include increased cellular potency/solubility, greater selectivity, enhanced pharmacokinetic properties, lack of off target activity and so on.
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Page/Page column 42-43
(2010/11/08)
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- INHIBITORS OF AKT ACTIVITY
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The instant invention provides for compounds that inhibit Akt activity. In particular, the compounds disclosed selectively inhibit one or two of the Akt isoforms. The invention also provides for compositions comprising such inhibitory compounds and method
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Page/Page column 37-38
(2008/06/13)
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- INHIBITORS OF AKT ACTIVITY
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The instant invention provides for substituted naphthyridine compounds that inhibit Akt activity. In particular, the compounds disclosed selectively inhibit one or two of the Akt isoforms. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting Akt activity by administering the compound to a patient in need of treatment of cancer.
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Page/Page column 79-80
(2010/11/25)
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- HETEROCYCLIC AMIDES AND SULFONAMIDES
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The invention is directed to compounds and methods to inhibit p38 kinase wherein the compounds are a pyrimidine or pyridine coupled to two mandatory substituents.
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Page/Page column 26
(2010/02/11)
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- PHENYL OR HETEROARYL AMINO ALKANE DERIVATIVES AS IP RECEPTOR ANTAGONIST
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The present invention relates to a phenyl or heteroaryl amino alkane derivatives which are useful as an active ingredient of pharmaceutical preparations. The phenyl or heteroaryl amino alkanes of the present invention have IP receptor antagonistic activity, and can be used for the prophylaxis and treatment of diseases associated with IP receptor antagonistic activity. Such diseases include urological diseases or disorder as follows: bladder outlet obstruction, overactive bladder, urinary incontinence, detrusor hyper-reflexia, detrusor instability, reduced bladder capacity, frequency of micturition, urge incontinence, stress incontinence, bladder hyperreactivity, benighn prostatic hypertrophy (BPH), prostatitis, urinary frequency, nocturia, urinary urgency, pelvic hypersensitivity, urethritis, pelvic pain syndrome, prostatodynia, cystitis, or idiophatic bladder hypersensitivity. The compounds of the present invention are also useful for treatment of pain including, but not limited to inflammatory pain, neuropathic pain, acute pain, chronic pain, dental pain, premenstrual pain, visceral pain, headaches, and the like; hypotension; hemophilia and hemorrhage; and inflammation, since the diseases also is alleviated by treatment with an IP receptor antagonist.
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- Substituted oxoazaheterocyclyl compounds
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This invention is directed to oxoazaheterocycyl compounds which inhibit Factor Xa, to oxoazaheterocycyl compounds which inhibit both Factor Xa and Factor IIa, to pharmaceutical compositions comprising these compounds, to intermediates useful for preparing these compounds, to a method of directly inhibiting Factor Xa and to a method of simultaneously directly inhibiting Factor Xa and Factor IIa..
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Page/Page column 100
(2008/06/13)
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- Discovery of an orally efficacious inhibitor of coagulation factor Xa which incorporates a neutral P1 ligand
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The discovery and SAR of ketopiperazino methylazaindole factor Xa inhibitors are described. Structure-activity data suggesting that this class of inhibitors does not bind in the canonical mode were confirmed by an X-ray crystal structure showing the neutral haloaromatic bound in the S1 subsite. The most potent azaindole, 33 (RPR209685), is selective against related serine proteases and attains higher levels of exposure upon oral dosing than comparable benzamidines and benzamidine isosteres. Compound 33 was efficacious in the canine AV model of thrombosis.
- Choi-Sledeski, Yong Mi,Kearney, Robert,Poli, Gregory,Pauls, Henry,Gardner, Charles,Gong, Yong,Becker, Michael,Davis, Roderick,Spada, Alfred,Liang, Guyan,Chu, Valeria,Brown, Karen,Collussi, Dennis,Leadley Jr., Robert,Rebello, Sam,Moxey, Phillip,Morgan, Suzanne,Bentley, Ross,Kasiewski, Charles,Maignan, Sebastien,Guilloteau, Jean-Pierre,Mikol, Vincent
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p. 681 - 684
(2007/10/03)
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- 1-aroyl-piperidinyl benzamidines
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This invention relates to compounds of formula which inhibit Factor Xa or tryptase, to pharmaceutical compositions containing the compounds, and to the use of the compounds for the treatment of patients suffering from conditions which can be ameliorated by the administration of an inhibitor of Factor Xa or tryptase.
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