Parallel synthesis of 7-heteroaryl-pyrazolo[1,5-a]pyrimidine-3-carboxamides

Ahmetaj, Sizana; Velikanje, Nina; Grošelj, Uroš; Šterbal, Ines; Prek, Benjamin; Golobič, Amalija; Kočar, Drago; Dahmann, Georg; Stanovnik, B.; Svete, Jurij

doi:10.1007/s11030-013-9469-3

Cited by 21 publications

(5 citation statements)

References 24 publications

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“…For the final amidation step 1,1'-carbonyldiimidazole (CDI), 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ), and bis(pentafluorophenyl) carbonate (BPC) were tested as the reagents for the activation of the carboxy group of 4. As we already experienced previously in amidation of related hetarenecarboxylic acids, [22][23][24][25][26] BPC proved to be the most suitable reagent, because it gave the corresponding carboxamides 5 reproducibly and in good yields. Thus, upon activation of 4 with BPC to form the intermediate pentafluorophenyl ester 4', further treatment with 1:1 mixtures of amines and triethylamine for 12 h furnished the target carboxamides 5a-h in 55-87% yields upon chromatographic workup (Scheme 1).…”

Section: Resultsmentioning

confidence: 56%

Synthesis of Novel 5-(N-Boc-N-Benzyl-2-aminoethyl)-7-oxo- 4,7-dihydropyrazolo[1,5-a]pyrimidin-3-carboxamides and Their Inhibition of Cathepsins B and K

Lukić¹,

Grošelj

Novinec

et al. 2017

ACSi

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Eight novel 5-(N-Boc-N-benzyl-2-aminoethyl)-7-oxo-4,7-dihydropyrazolo[1,5-a]pyrimidin-3-carboxamides were prepa red in three steps from methyl 3-amino-1H-pyrazole-4-carboxylate and methyl 5-(benzyl(tert-butoxycarbonyl)amino)-3-oxopentanoate. The synthetic procedure comprises cyclocondensation of the above starting compounds, hydrolysis of the ester, and bis(pentafluorophenyl) carbonate (BPC)-mediated amidation. Title carboxamides were tested for inhibition of cathepsins K and B. The N-butylcarboxamide 5a exhibited appreciable inhibition of cathepsin K (IC 50 ~ 25 µM), while the strongest inhibition of cathepsin B was achieved with N-(2-picolyl)carboxamide 5c (IC 50 ~ 45 µM).

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Section: Resultsmentioning

confidence: 56%

Synthesis of Novel 5-(N-Boc-N-Benzyl-2-aminoethyl)-7-oxo- 4,7-dihydropyrazolo[1,5-a]pyrimidin-3-carboxamides and Their Inhibition of Cathepsins B and K

Lukić¹,

Grošelj

Novinec

et al. 2017

ACSi

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“…Following our previous successful applications of BPC as an activating agent for acids, i.e. for the formation of activated pentafluorophenyl esters for the peptide bond formation [18][19][20], 1 was treated with BPC in the presence of Et 3 N in anhydrous MeCN. The in situ formed reactive ester 11 was coupled with a variety of aliphatic amines 12a-k, thus furnishing the corresponding amides 13a-k in 59-91 % isolated yields.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and preliminary biological evaluations of (+)-isocampholenic acid-derived amides

et al. 2016

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The synthesis of two novel (+)-isocampholenic acid-derived amines has been realized starting from commercially available (1S)-(+)-10-camphorsulfonic acid. The novel amines as well as (+)-isocampholenic acid have been used as building blocks in the construction of a library of amides using various aliphatic, aromatic, and amino acid-derived coupling partners using BPC and CDI as activating agents. Amide derivatives have been assayed against several enzymes that hold potential for the development of new drugs to battle bacterial infections and Alzheimer's disease. Compounds 20c and 20e showed promising selective sub-micromolar inhibition of human butyrylcholinesterase [Formula: see text] ([Formula: see text] values [Formula: see text] and [Formula: see text], respectively).

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“…Ahmetaj et al [ 105 ] described a simple and efficient protocol for the synthesis of 7-heteroarylpyrazolo[1,5- a ]pyrimidine-3-carboxamides 166 from the reaction of 5-aminopyrazole 161 with ( E )-3-(dimethylamino)-1-(heteroaryl)prop-2-en-1-one 162 in aqueous ethanol at ambient temperature through the intermediacy of methyl 7-heteroarylpyrazolo[1,5- a ]pyrimidine-3-carboxylates 163 which was subsequently hydrolyzed to give the corresponding carboxylic acids 164 followed by coupling with various primary and secondary amines 165 in presence of bis(pentafluorophenyl) carbonate (BPC) as activating agent ( Scheme 46 ).…”

Section: Reviewmentioning

confidence: 99%

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

Aggarwal

Kumar

2018

Beilstein J. Org. Chem.

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The condensation of 5-aminopyrazole with various bielectrophilic moieties results in the formation of pyrazoloazines, an interesting array of fused heterocyclic systems. The development of new synthetic routes towards pyrazoloazines for their biological and medicinal exploration is an attractive area for researchers throughout the world. The present review focuses on various synthetic methods developed in the last decade for the synthesis of differently substituted pyrazoloazines by a broad range of organic reactions by means of 5-aminopyrazole as a precursor. ReviewPyrazole and its derivatives are known to exhibit significant biological and pharmacological activities such as: anticancer [1,2], anti-inflammatory [3,4], antioxidant [5], antibacterial [6][7][8], analgesic [9], antiviral [10,11], antimicrobial [12,13], antifungal [6], antiglycemic [14], antiamoebic [15] and antidepressive [16,17]. Considering the immense biological properties pyrazole is one of the most widely studied nitrogen-containing heterocyclic nuclei. Fused pyrazole derivatives are composed of the pyrazole nucleus attached to other heterocyclic moieties which enable them to exhibit improved pharmacological activities compared to the isolated fragments. These compounds are currently used in several marketed drugs like cartazolate (1), zaleplon (2), sildenafil (3), allopurinol (4), indiplon (5), etazolate (6) etc. (Figure 1). Fused pyrazole derivatives, especially pyrazoloazines have been reported to mimic purine bases, present in DNA and RNA, due to close structural resemblance.In addition to the immense biological potential related to fused pyrazoles, their synthetic potential needs to be reviewed for further improvements and extension of interests. Various efforts have been developed for the synthesis of pyrazole-based fused heterocycles. 5-Aminopyrazoles have been extensively employed as useful synthons in designing and constructing a Beilstein J. Org. Chem. 2018, 14, 203-242. 204 A number of review articles have been published by us and others highlighting the synthetic and biological aspects of 5-aminopyrazoles [26][27][28] as well as on the synthesis of fused pyrazole derivatives [25]. However, a perusal of literature reveals that the importance of 5-aminopyrazoles as synthetic precursors for fused heterocycles has not been reported till now to the best of our knowledge. Recent literature shows resurgence of interest in the chemistry and bioactivity of 5-aminopyrazole derivatives leading to improvements in several already known reactions and syntheses of various fused heterocyclic derivatives with various biological activities. Considering the synthetic importance of 5-aminopyrazoles and synthesis of fused pyrazole derivatives with the need for a more general collection, herein we report an exhaustive overview of the main developments in the last decade in the chemistry of 5-aminopyrazoles for the design and synthesis of fused pyrazoloazines.The typical reactivity of 5-aminopyrazoles 5-Aminopyrazoles are polyfunctional co...

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Parallel synthesis of 7-heteroaryl-pyrazolo[1,5-a]pyrimidine-3-carboxamides

Cited by 21 publications

References 24 publications

Synthesis of Novel 5-(N-Boc-N-Benzyl-2-aminoethyl)-7-oxo- 4,7-dihydropyrazolo[1,5-a]pyrimidin-3-carboxamides and Their Inhibition of Cathepsins B and K

Synthesis of Novel 5-(N-Boc-N-Benzyl-2-aminoethyl)-7-oxo- 4,7-dihydropyrazolo[1,5-a]pyrimidin-3-carboxamides and Their Inhibition of Cathepsins B and K

Synthesis and preliminary biological evaluations of (+)-isocampholenic acid-derived amides

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

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