Synthesis and Structure-Activity Relationship of a New Series of Potent Angiotensin II Receptor Antagonists: Pyrazolo(1,5-a)pyrimidine Derivatives.

Shiota, Takeshi; Yamamori, Teruo; Sakai, K.; Kiyokawa, Mitsugu; Honma, Teruki; Ogawa, Masayoshi; Hayashi, Kunio; Ishizuka, Natsuki; Matsumura, Ken‐ichi; Hara, Mariko; Fujimoto, Masafumi; Kawabata, Tomoji; Nakajima, Shōichi

doi:10.1248/cpb.47.928

Cited by 30 publications

(6 citation statements)

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“…Similarly, replacing the arylmethyl amines with the corresponding ether analogue 22 was not tolerated. Replacement of the 2-pyridyl moiety with other heterocyclic systems such as imidazoles (24 and 25), methylpyridinyl (26), furan (27), thiophene (28), thiazole (29) and quinoline (30) generally resulted in a lack of antimycobacterial activity at the highest concentration tested (MIC 99 > 160 µM). The exception was the methylimidazole analogue 23, which displayed good (MIC 99 = 5 µM) activity.…”

Section: Modifications To the 7-positionmentioning

confidence: 99%

“…Pyrazolo [1,5-a]pyrimidines are of chemical and pharmacological importance as purine analogues, and derivatives have been applied in various therapeutic areas such as antitumor, [15][16][17][18][19] antidepressant, [20][21] antibacterial, 22 antiviral, 23 antidiabetic 24 and antihypertensive agents. 25,26 Representatives of the SFK29 series (1-6, Figure 1) were selected for resynthesis based on their activities (MIC 99 < 5 µM) and confirmatory testing Based on its structural novelty, broad activity, and acceptable potencies, the aminopyrazolo[1,5-a]pyrimidine series was selected for a medicinal chemistry optimisation campaign. Herein, we present the synthesis, structure activity relationship (SAR), and in vitro Absorption, Distribution, Metabolism, Excretion (ADME) studies.…”

Section: Introductionmentioning

confidence: 99%

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Aminopyrazolo[1,5-a]pyrimidines as potential inhibitors of Mycobacterium tuberculosis: Structure activity relationships and ADME characterization

Melo

Feng

Westhuyzen

et al. 2015

Bioorganic & Medicinal Chemistry

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Whole-cell high-throughput screening of a diverse SoftFocus library against Mycobacterium tuberculosis (Mtb) generated a novel aminopyrazolo[1,5-a]pyrimidine hit series. The synthesis and structure activity relationship studies identified compounds with potent antimycobacterial activity. The SAR of over 140 compounds shows that the 2-pyridylmethylamine moiety at the C-7 position of the pyrazolopyrimidine scaffold was important for Mtb activity, whereas the C-3 position offered a higher degree of flexibility. The series was also profiled for in vitro cytotoxicity and microsomal metabolic stability as well as physicochemical properties. Consequently liabilities to be addressed in a future lead optimization campaign have been identified.

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Section: Modifications To the 7-positionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Aminopyrazolo[1,5-a]pyrimidines as potential inhibitors of Mycobacterium tuberculosis: Structure activity relationships and ADME characterization

Melo

Feng

Westhuyzen

et al. 2015

Bioorganic & Medicinal Chemistry

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“…In addition, reaction of aminopyrazole 5 with ethyl acetoacetate 16a and ethyl 2‐methyl‐3‐oxobutanoate 16b afforded two possible isomeric products 17 and 18 . Structure 18 was excluded on the basis of spectral data and analogy with previous work . The formation of 17 is assumed to proceed through the condensation of the oxocyclic amino group in 5 with the carbonyl of acetyl moiety followed by in situ heterocyclization through elimination of ethanol (Scheme ).…”

Section: Resultsmentioning

confidence: 99%

Synthesis, Antimicrobial Activity and Molecular Modeling of Some Novel 5‐Aminopyrazole, Pyrazolo[1,5‐a]pyrimidine, Bispyrazole and Bispyridone Derivatives Containing Antipyrinyl Moiety

Helal

Salem

Aly

2017

Journal of Heterocyclic Chem

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2‐Cyano‐N‐(antipyrin‐4‐yl)‐3‐(ethylthio)‐3‐(naphthalen‐1‐ylamino)acryl‐amide 4 was achieved via a one‐pot, three‐component reactions of cyanoacetamide derivative 2, 2‐naphthyl isothiocyanate, and diethyl‐sulphate. The cyano acrylamide derivative 4 was hydrazinolysis to furnish 5‐aminopyrazole 5; many pyrazolo[1,5‐a]pyrimidines 10a,b, 14, 15, 16, 18, and 20 have been synthesized via treatment of 5 with some electrophilic reagents. Also, ternary condensation of cyanoacetamide derivative 2, terephthalaldehyde, and active methylene derivatives afforded bispyridone derivatives 21a,b. The structures of the new compounds were confirmed on the basis of elemental analysis and spectral data. Representative compounds of the synthesized products were tested and evaluated as antimicrobial. In general, the novel‐synthesized compounds showed a good antimicrobial activity against Gram‐positive bacteria, Gram‐negative bacteria, and antifungal activity against Azithromycin and Ketoconazole. The molecular modeling of the 21a and 21b as representative examples of the synthesized compounds has been drawn, and their molecular parameters were calculated.

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“…The structural activity studies showed the methyl substituent at the 3-position to be essential for potent in vitro activity. We present the design syntheses and biological data of a series of pyrazolo (1,5a) pyrimidine derivatives, which are orally active, receptor antagonists [12].…”

Section: Angiotensin Receptor Antagonistsmentioning

confidence: 99%

The Therapeutic Journey of Tetrazoles: A Review

Sekar¹,

Rajendran²,

Battala³

et al. 2015

JCP

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Since the beginning of the search of medicinally important synthetic compounds heterocyclic chemistry always remained the point of attraction because of their diverse biological properties. Compounds containing tetrazole moiety possess interesting biological activity. A series of tetrazole compounds were synthesized in order to obtain new compounds with potent antimicrobial, anti-inflammatory, anticancer, anticonvulsant, antibacterial activity etc. This review provides brief summary on the biological activities of various tetrazole derivatives that can helps in developing new tetrazole derivatives with better efficacy and more safety.

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Synthesis and Structure-Activity Relationship of a New Series of Potent Angiotensin II Receptor Antagonists: Pyrazolo(1,5-a)pyrimidine Derivatives.

Cited by 30 publications

References 0 publications

Aminopyrazolo[1,5-a]pyrimidines as potential inhibitors of Mycobacterium tuberculosis: Structure activity relationships and ADME characterization

Aminopyrazolo[1,5-a]pyrimidines as potential inhibitors of Mycobacterium tuberculosis: Structure activity relationships and ADME characterization

Synthesis, Antimicrobial Activity and Molecular Modeling of Some Novel 5‐Aminopyrazole, Pyrazolo[1,5‐a]pyrimidine, Bispyrazole and Bispyridone Derivatives Containing Antipyrinyl Moiety

The Therapeutic Journey of Tetrazoles: A Review

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