- Palladium-Catalyzed Regioselective C?H Arylation of 4-Azaindazole at C3, C5 and C7 Positions
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Direct and site-selective C5 and C7 palladium-catalyzed C?H arylations of 4-azaindazole N-oxide have been achieved. A bidentate ligand and Pd(OAc)2 catalyst in toluene promoted the activation of C5 position, while a phosphine ligand and PdCl2 catalyst in DMA directed the arylation at C7 position. Using this new method, the synthesis of C5, C7-diarylated 4-azaindazole N-oxides as well as the C3, C5, C7-triarylated 4-azaindazoles was achieved towards future medicinal compounds development. (Figure presented.).
- Faarasse, Soukaina,El Kazzouli, Sa?d,Bourzikat, Otmane,Bourg, Stéphane,Aci-Sèche, Samia,Bonnet, Pascal,Suzenet, Franck,Guillaumet, Gérald
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supporting information
p. 3937 - 3945
(2021/03/29)
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- Palladium-Catalyzed C3-Arylations of 1H- and 2H-Pyrazolo[4,3- b]pyridines on Water
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Direct C3-arylation of 1H-pyrazolo[4,3-b]pyridines and direct C3-arylation of 2H-pyrazolo[4,3-b]pyridines in water has been developed. A new protocol for a sequential C3-arylation procedure on a mixture of 1H- and 2H-pyrazolo[4,3-b]pyridines followed by in situ PMB cleavage has also been achieved. This procedure led to unprotected (NH) C3-arylated 1H-pyrazolo[4,3-b]pyridines in good yields.
- Faarasse, Soukaina,El Kazzouli, Sa?d,Suzenet, Franck,Guillaumet, Gérald
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p. 12847 - 12854
(2018/10/20)
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- PYRIDINE AND PYRIMIDINE DERIVATIVES AND THEIR USE IN TREATMENT, AMELIORATION OR PREVENTION OF INFLUENZA
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Provided herein is a compound of formula (I), optionally in the form of a pharmaceutically acceptable salt, solvate, polymorph, prodrug, codrug, cocrystal, tautomer, racemate, enantiomer,or diastereomer or mixture thereof, which is useful in treating, ameliorating or preventing influenza.
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Page/Page column 60; 61
(2017/09/02)
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- PYRIMIDINE AND PYRIDINE DERIVATIVES AND USE IN TREATMENT, AMELIORATION OR PREVENTION OF INFLUENZA THEREOF
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Provided herein is a compound of formula (I), optionally in the form of a pharmaceutically acceptable salt, solvate, polymorph, prodrug, codrug, cocrystal, tautomer, racemate, enantiomer, or diastereomer or mixture thereof, which is useful in treating, ameliorating or preventing influenza.
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Page/Page column 172
(2017/12/28)
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- Discovery, Synthesis, and Preclinical Characterization of N-(3-Chloro-4-fluorophenyl)-1H-pyrazolo[4,3-b]pyridin-3-amine (VU0418506), a Novel Positive Allosteric Modulator of the Metabotropic Glutamate Receptor 4 (mGlu4)
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The efficacy of positive allosteric modulators (PAMs) of the metabotropic glutamate receptor 4 (mGlu4) in preclinical rodent models of Parkinson's disease has been established by a number of groups. Here, we report an advanced preclinically characterized mGlu4 PAM, N-(3-chloro-4-fluorophenyl)-1H-pyrazolo[4,3-b]pyridin-3-amine (VU0418506). We detail the discovery of VU0418506 starting from a common picolinamide core scaffold and evaluation of a number of amide bioisosteres leading to the novel pyrazolo[4,3-b]pyridine head group. VU0418506 has been characterized as a potent and selective mGlu4 PAM with suitable in vivo pharmacokinetic properties in three preclinical safety species.
- Engers, Darren W.,Blobaum, Anna L.,Gogliotti, Rocco D.,Cheung, Yiu-Yin,Salovich, James M.,Garcia-Barrantes, Pedro M.,Daniels, J. Scott,Morrison, Ryan,Jones, Carrie K.,Soars, Matthew G.,Zhuo, Xiaoliang,Hurley, Jeremy,Macor, John E.,Bronson, Joanne J.,Conn, P. Jeffrey,Lindsley, Craig W.,Niswender, Colleen M.,Hopkins, Corey R.
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p. 1192 - 1200
(2016/10/03)
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- PYRROLOPYRAZINE KINASE INHIBITORS
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The present invention relates to the use of novel pyrrolopyrazine derivatives of Formula I, wherein the variables are defined as described herein, which inhibit JAK and SYK and are useful for the treatment of auto-immune and inflammatory diseases.
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Page/Page column 253
(2013/03/28)
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- Optimisation of ITK inhibitors through successive iterative design cycles
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Based on a hit cluster of compounds inhibiting interleukin-2 inducible T-cell kinase (ITK) in the submicromolar range a series of ITK inhibitor libraries were synthesized. Through iterative design cycles including kinase crystal structure information, indolylindazole libraries were identified which showed low nanomolar activity in enzymatic and cellular assays. The potential of these novel lead series was confirmed through in vivo tests in an anti-CD3-IL2 mouse model. The intravenous administration of highly potent ITK inhibitor 11o resulted in dose-dependent, efficient suppression of IL-2.
- Herdemann, Matthias,Weber, Alexander,Jonveaux, Jér?me,Schwoebel, Frank,Stoeck, Michael,Heit, Isabelle
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p. 1852 - 1856
(2011/05/05)
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- PYRAZOLOPYRIDINE, PYRAZOLOPYRAZINE, PYRAZOLOPYRIMIDINE, PYRAZOLOTHIOPHENE AND PYRAZOLOTHIAZOLE COMPOUNDS AS MGLUR4 ALLOSTERIC POTENTIATORS, COMPOUNDS, AND METHODS OF TREATING NEUROLOGICAL DYSFUNCTION
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Pyrazolopyridine, pyrazolopyrazine, pyrazolopyrimidine, pyrazolothiophene and pyrazolothiazole compounds which are useful as allosteric potentiators/positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4); synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of using the compounds, for example, in treating neurological and psychiatric disorders or other disease state associated with glutamate dysfunction.
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Page/Page column 78
(2011/09/15)
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- Identification of potent ITK inhibitors through focused compound library design including structural information
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A series of novel compound libraries inhibiting interleukin-2 inducible T cell kinase (ITK) were designed, synthesized and evaluated. In the first design cycle two library scaffolds were identified showing low micromolar inhibition of ITK. Further iterative design cycles including crystal structure information of ITK and structurally related kinases led to the identification of indolylindazole and indolylpyrazolopyridine compounds with low nanomolar ITK inhibition.
- Herdemann, Matthias,Heit, Isabelle,Bosch, Frank-Uwe,Quintini, Gianluca,Scheipers, Claudia,Weber, Alexander
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scheme or table
p. 6998 - 7003
(2010/12/25)
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- PYRAZOLE COMPOUND AND MEDICINAL COMPOSITION CONTAINING THE SAME
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The present invention provides a novel compound having an excellent JNK inhibitory effect. That is, it provides a compound represented by the following formula, a salt thereof or a hydrate of them. Wherein R1 designates -(CO)h-(NRa)j-(CRb=CRc)k-Ar (wherein Ra, Rb and Rc each independently designate a hydrogen atom, a halogen atom, hydroxyl group, an optionally substituted C1-6 alkyl group or the like; Cy designates a 5- or 6-membered heteroaryl; and V each independently designate the formula -L-X-Y (wherein L designates a single bond, an optionally substituted C1-6 alkylene group or the like; X designates a single bond or the formula -A- (wherein A designates NR2, O, CO, S, SO or SO2) and so on; and Y designates a hydrogen atom, a halogen atom, nitro group or the like).
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Page/Page column 135
(2008/06/13)
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- New broad-spectrum parenteral cephalosporins exhibiting potent activity against both methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. Part 2: Synthesis and structure-activity relationships in the S-3578 series
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Among the prepared novel cephalosporin derivatives related to S-3578, a series of 7β-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(Z)-ethoxyiminoacetamido] -3-[1-(aminoalkyl)-1H-pyrazolo[4,3-b]pyridinium-4-yl]methyl-3-cephem-4- carboxylate showed potent activity against both MRSA and Pseudomonas aeruginosa, and displayed good water solubility.
- Yoshizawa, Hidenori,Kubota, Tadatoshi,Itani, Hikaru,Ishitobi, Hiroyuki,Miwa, Hideaki,Nishitani, Yasuhiro
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p. 4211 - 4219
(2007/10/03)
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- Acyclic analogues of deoxyadenosine 3',5'-bisphosphates as P2Y1 receptor antagonists
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P2Y1 receptors are activated by ADP and occur on endothelial cells, smooth muscle, epithelial cells, lungs, pancreas, platelets, and in the central nervous system. With the aid of molecular modeling, we have designed nucleotide analogues that act as selective antagonists at this subtype. The present study has tested the hypothesis that acyclic modifications of the ribose ring, proven highly successful for nucleoside antiviral agents such as gancyclovir, are generalizable to P2Y receptor ligands. Specifically, the binding site of the P2Y1 receptor was found to be sufficiently accommodating to allow the substitution of the ribose group with acyclic aliphatic and aromatic chains attached to the 9-position of adenine. Three groups of adenine derivatives having diverse side-chain structures, each containing two symmetrical phosphate or phosphonate groups, were prepared. Biological activity was demonstrated by the ability of the acyclic derivatives to act as agonists or antagonists in the stimulation of phospholipase C in turkey erythrocyte membranes. An acyclic N6-methyladenine derivative, 2-[2-(6- methylaminopurin-9-yl)-ethyl]-propane-1,3-bisoxy(diammoniumphosphate) (10), containing an isopentyl bisphosphate moiety, was a full antagonist at the P2Y1 receptor with an IC50 value of 1.60 μM. The corresponding 2-Cl derivative (11) was even more potent with an IC50 value of 0.84 μM. Homologation of the ethylene group at the 9-position to 3-5 methylene units or inclusion of cis- or trans-olefinic groups greatly reduced antagonist potency at the P2Y1 receptor. Analogues containing a diethanolamine amide group and an aryl di(methylphosphonate) were both less potent than 10 as antagonists, with IC50 values of 14 and 16 μM, respectively, and no agonist activity was observed for these analogues. Thus, the ribose moiety is clearly not essential for recognition by the turkey P2Y1 receptor, although a cyclic structure appears to be important for receptor activation, and the acyclic approach to the design of P2 receptor antagonists is valid.
- Kim, Yong-Chul,Gallo-Rodriguez, Carola,Jang, Soo-Yeon,Nandanan, Erathodiyil,Adams, Mary,Harden, T. Kendall,Boyer, José L.,Jacobson, Kenneth A.
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p. 746 - 755
(2007/10/03)
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