1398567-32-2Relevant academic research and scientific papers
Synthesis, molecular modeling and SAR study of novel pyrazolo[5,1-f][1,6]naphthyridines as CB2receptor antagonists/inverse agonists
Dore, Antonio,Asproni, Battistina,Scampuddu, Alessia,Gessi, Stefania,Murineddu, Gabriele,Cichero, Elena,Fossa, Paola,Merighi, Stefania,Bencivenni, Serena,Pinna, Gérard A.
, p. 5291 - 5301 (2016)
Pyrazolo[5,1-f][1,6]naphthyridine-carboxamide derivatives were synthesized and evaluated for the affinity at CB1and CB2receptors. Based on the AgOTf and proline-cocatalyzed multicomponent methodology, the ethyl 5-(p-tolyl)pyrazolo[5,1-f][1,6]naphthyridine-2-carboxylate (12) and ethyl 5-(2,4-dichlorophenyl)pyrazolo[5,1-f][1,6]naphthyridine-2-carboxylate (13) intermediates were synthesized from the appropriate o-alkynylaldehydes, p-toluenesulfonyl hydrazide and ethyl pyruvate. Most of the novel compounds feature a p-tolyl (8a–i) or a 2,4-dichlorophenyl (8j) motif at the C5-position of the tricyclic pyrazolo[5,1-f][1,6]naphthyridine scaffold. Structural variation on the carboxamide moiety at the C2-position includes basic monocyclic, terpenoid and adamantine-based amines. Among these derivatives, compound 8h (N-adamant-1-yl-5-(p-tolyl)pyrazolo[5,1-f][1,6]naphthyridine-2-carboxamide) exhibited the highest CB2receptor affinity (Ki?=?33?nM) and a high degree of selectivity (KiCB1/KiCB2?=?173:1), whereas a similar trend in the near nM range was seen for the bornyl analogue (compound 8f, Ki?=?53?nM) and the myrtanyl derivative 8j (Ki?=?67?nM). Effects of 8h, 8f and 8j on forskolin-stimulated cAMP levels were determined, showing antagonist/inverse agonist properties for such compounds. Docking studies conducted for these derivatives and the reference antagonist/inverse agonist compound 4 (SR144528) disclosed the specific pattern of interactions probably related to the pyrazolo[5,1-f][1,6]naphthyridine scaffold as CB2inverse agonists.
Synthetic Access to Functionalized Dipolarophiles of Lewis Basic Complexant Scaffolds through Sonogashira Cross-Coupling
Chaudhuri, Sauradip,Carrick, Jesse D.
, p. 10261 - 10271 (2018)
Soft Lewis basic complexants that facilitate selective removal of discrete ions resident in spent nuclear fuel can decrease repository volume and radiotoxicity and are of significant interest. Optimization of chelation efficacy is predicated on modular access to synthons to rapidly evaluate structure-activity relationships. The following work highlights efficient access to functionalized synthons for use as potential dipolarophiles in subsequent cycloaddition processes via Sonogashira coupling of 3-(6-bromo-pyridin-2-yl)-[1,2,4]triazine scaffolds. The 41 examples explored during method development evaluated electrophile and nucleophile diversity affording the desired coupled products in 31-96% isolated yield. Method optimization, substrate scope, a scale-up reaction, and downstream product functionalization are reported herein.
One-pot Synthesis of Isoquinoline-Fused Isoquinolines via Intramolecular Hydroamination/Aza-Claisen Type Rearrangement Cascade
Chiu, Wei-Jung,Chen, Jin-Yu,Liu, Shih-I,Barve, Indrajeet J.,Huang, Wan-Wen,Sun, Chung-Ming
, p. 2834 - 2842 (2021/04/26)
A one-pot, two-step synthesis of isoquinoline-fused isoquinolines from α-amino acid esters and 2-alkynyl benzaldehydes are reported. The strategy comprises an unconventional Pictet-Spengler reaction between α-amino acid esters and 2-alkynyl benzaldehydes to give isoquinoline intermediates. Subsequent gold-catalyzed intramolecular hydroamination furnishes isoquinoline-fused isoquinolines. The scope of this strategy is further extended to prepare multisubstituted isoquinoline-fused isoquinolines via subjecting the N-allylated isoquinoline intermediates to gold-catalyzed intramolecular hydroamination followed by aza-Claisen type rearrangement. (Figure presented.).
Synthesis of cyclopentaquinolinone and cyclopentapyridinone from: Ortho-alkynyl-N-arylaldehyde via superbase-promoted C-N, C-O and C-C bond formation
Saini, Kapil Mohan,Saunthwal, Rakesh K.,Sushmita,Verma, Akhilesh K.
supporting information, p. 5594 - 5601 (2020/08/21)
An environmentally benign, transition metal-free, superbase-mediated intramolecular annulation of o-alkynylaldehydes with primary amines forms highly functionalized amino-substituted cyclopentaquinolinones and cyclopentapyridinones via C-N, C-C, and CO bond formation. Contrary to the traditional approaches of ring closures, a different mode of annulation is disclosed. The protocol involves the in situ generations of imine intermediate followed by potassium hydroxide-promoted intramolecular cyclization and subsequent dimethyl sulfoxide induced dehydrogenation leads to the formation of N-heterocycles. X-ray crystallographic studies support the assigned structures of the amino-fused N-heterocycles.
Silver-catalyzed tandem synthesis of naphthyridines and thienopyridines via three-component reaction
Verma, Akhilesh K.,Kotla, Siva K. Reddy,Choudhary, Deepak,Patel, Monika,Tiwari, Rakesh K.
, p. 4386 - 4401 (2013/06/05)
An efficient approach for the silver-catalyzed regioselective tandem synthesis of highly functionalized 1,2-dihydrobenzo[1,6]naphthyridines 6a-z and 7a-e by the reaction of ortho-alkynylaldehydes 3a-n with amines 4a-d and ketones 5a-c/active methylene com
On water: Silver-catalyzed domino approach for the synthesis of benzoxazine/oxazine-fused isoquinolines and naphthyridines from o-alkynyl aldehydes
Verma, Akhilesh K.,Choudhary, Deepak,Saunthwal, Rakesh K.,Rustagi, Vineeta,Patel, Monika,Tiwari, Rakesh K.
, p. 6657 - 6669 (2013/07/26)
An operationally simple domino approach for the silver-catalyzed synthesis of oxazine/benzoxazine-fused isoquinolines 5a-q and naphthyridines 6a-v by the reaction of o-alkynyl aldehydes 3a-aa with amines having embedded nucleophiles 4a-d under mild reacti
Cyclizations of phenylethyl-substituted pyridinecarboxaldehydes
Naredla, Rajasekhar Reddy,Klumpp, Douglas A.
, p. 2137 - 2141 (2013/03/14)
Several phenylethyl-substituted pyridinecarboxaldehydes were prepared from 2-bromo-3-pyridine-carboxaldehyde and these substances are found to undergo cyclization reactions in acidic media. In the absence of added nucleophile, acid-promoted cyclization and oxidation (MnO2) provide an efficient route to 10,11-dihydro-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-ones. Arene nucleophiles may also be added to the acidic mixture to provide good yields of triarylmethane products. Mechanisms are proposed involving dicationic superelectrophilic intermediates.
