Novel tricyclic pyrazolopyrimidines as potent and selective GPR119 agonists

Azimioara, Mihai; Alper, Phil B.; Cow, Christopher; Mutnick, Daniel; Nikulin, V. I.; Lelais, Gérald; Mecom, John; McNeill, Matthew; Michellys, Pierre‐Yves; Wang, Zhiliang; Reding, Esther; Paliotti, Michael; Li, Jing; Bao, Dingjiu; Zoll, Jocelyn; Kim, Young; Zimmerman, Matthew C.; Groessl, Todd; Tuntland, Tove; Joseph, Sean B.; McNamara, Peter; Seidel, H. Martin; Epple, Robert

doi:10.1016/j.bmcl.2014.10.010

Cited by 10 publications

(8 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The compound 3e is known; however, no analytical data were reported . Title compound was prepared according the general procedure from pyrazole 1a and 4-(trifluoromethyl)phenylboronic acid 2e .…”

Section: Methodsmentioning

confidence: 99%

“…The compound 3e is known; however, no analytical data were reported. 40 Title compound was prepared according the general procedure from pyrazole 1a and 4-(trifluoromethyl)phenylboronic acid 2e. Purification via column chromatography afforded title product as a pale yellow solid (0.072 g, 30%); mp 114−119 °C (DCM− hexanes), 1 H NMR (400 MHz, DMSO-d 6 ) δ (ppm) = 7.68 (d, J = 8.2 Hz, 2H), 7.57 (d, J = 8.2 Hz, 2H), 2.21 (s, 3H); 13 C NMR (100 MHz, DMSO-d 6 ) δ (ppm) = 151.1, 138.8, 138.0, 127.9, 125.3 (q, J = 4 Hz), 124.9 (q, J = 32 Hz), 124.6 (q, J = 272 Hz), 102.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

See 1 more Smart Citation

The Suzuki–Miyaura Cross-Coupling Reaction of Halogenated Aminopyrazoles: Method Development, Scope, and Mechanism of Dehalogenation Side Reaction

et al. 2016

View full text Add to dashboard Cite

The efficient Suzuki-Miyaura cross-coupling reaction of halogenated aminopyrazoles and their amides or ureas with a range of aryl, heteroaryl, and styryl boronic acids or esters has been developed. The method allowed incorporation of problematic substrates: aminopyrazoles bearing protected or unprotected pyrazole NH, as well as the free amino or N-amide group. Direct comparison of the chloro, bromo, and iodopyrazoles in the Suzuki-Miyaura reaction revealed that Br and Cl derivatives were superior to iodopyrazoles, as a result of reduced propensity to dehalogenation. Moreover, the mechanism and factors affecting the undesired dehalogenation side reaction were revealed.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: ■ Experimental Sectionmentioning

confidence: 99%

The Suzuki–Miyaura Cross-Coupling Reaction of Halogenated Aminopyrazoles: Method Development, Scope, and Mechanism of Dehalogenation Side Reaction

et al. 2016

View full text Add to dashboard Cite

show abstract

“…92 Alternatively, the distance between the central piperidine ring and the heterocycle cap can also be lengthened by one methylene group to afford potent GPR119 agonists such as oxadiazole 62 (Figure 7.13). 93 GNF has also claimed GPR119 agonists that are structurally distinct from previously reported chemical classes. In one series, the common pharmacophore contained the familiar phenyl methylsulfone moiety linked at the para position to a pyrrolidine nitrogen.…”

Section: Novartismentioning

confidence: 93%

Chapter 7. Recent Advances in the Discovery of GPR119 Agonists

Shah¹,

Edmondson²,

Szewczyk³

2012

Drug Discovery

View full text Add to dashboard Cite

“…An original method for the construction of pyrazolo[5,1-с][1,2,4]triazepine derivatives is Wittig reaction with the participation of hydrazones 70а,b [144]. There is an interesting method for obtaining 3-unsubstituted pyrazolo[5,1-c]-as-triazines by reacting the salts 1 with γ-bromo-substituted β-keto ester 74 [149]. The reaction involves a СН 2 group activated with bromine from one side and a keto group from the other side.…”

Section: Intermolecular Azo Couplingmentioning

confidence: 99%

Chemistry of Pyrazole-3(5)-Diazonium Salts (Review)*

Ledenyova

Didenko

Shikhaliev

2014

Chem Heterocycl Comp

View full text Add to dashboard Cite

The methods of synthesis, structure, reactivity, and synthetic utility of pyrazole-3(5)-diazonium salts are reviewed here for the first time, with emphasis on heterocyclization reactions of these compounds.More than one hundred years have passed since α-diazo derivatives of pyrazole were discovered. A substantial amount of knowledge has been accumulated over this time regarding the stability, structure, and transformations of these compounds. However, the chemistry of pyrazole-3(5)-diazonium salts developed rapidly only in the second half of the 20th century, with many studies performed in various countries, in particular Germany, Egypt, Russia, and Japan. Unfortunately, no systematic review has been compiled for the wide range of data about pyrazole-3(5)-diazonium salts. Some aspects regarding the properties of these compounds have been discussed in reviews and monographs on other topics [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17].

show abstract

Novel tricyclic pyrazolopyrimidines as potent and selective GPR119 agonists

Cited by 10 publications

References 12 publications

The Suzuki–Miyaura Cross-Coupling Reaction of Halogenated Aminopyrazoles: Method Development, Scope, and Mechanism of Dehalogenation Side Reaction

The Suzuki–Miyaura Cross-Coupling Reaction of Halogenated Aminopyrazoles: Method Development, Scope, and Mechanism of Dehalogenation Side Reaction

Chapter 7. Recent Advances in the Discovery of GPR119 Agonists

Chemistry of Pyrazole-3(5)-Diazonium Salts (Review)*

Contact Info

Product

Resources

About