Recent developments in the synthesis of azaindoles from pyridine and pyrrole building blocks

Reddy, Motatipally Damoder; Amaradhi, Radhika; Ganesh, Thota

doi:10.1039/d0qo01079k

Cited by 38 publications

(20 citation statements)

References 191 publications

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“…Being structurally different from indole only by one additional nitrogen in the six-membered pyridine ring, the azaindole moiety exhibits interesting biochemical and pharmacological activities. 1,2 Scientists identified that methylated azaindole chromophores could serve as blue or even green fluorescence protein markers. 3 Among various structural isomers of n-azaindole, 7-azaindole derivatives (see Figure 1 for the atom numbering) are excellent blue emitters for organic light-emitting diodes (OLEDs).…”

Section: Introductionmentioning

confidence: 99%

Weak Dewar bond modulates protonated azaindole photodynamics

Mansour

Mukherjee

Pinheiro

et al. 2022

Preprint

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Recent experimental work revealed that the lifetime of the S3 state of protonated 7-azaindole is about ten times slower than that of protonated 6-azaindole. We simulated the nonradiative decay pathways of these molecules using trajectory surface hopping dynamics after photoexcitation into S3 to elucidate the reason for this difference. Both isomers mainly follow a common pp* relaxation pathway involving multiple state crossings while coming down from S3 to S1 in the subpicosecond time scale. However, the simulations reveal that the excited-state topographies are such that while the 6-isomer can easily access the region of nonadiabatic transitions, the internal conversion of the 7-isomer is delayed by a pre-Dewar bond formation with a boat conformation.

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Section: Introductionmentioning

confidence: 99%

Weak Dewar bond modulates protonated azaindole photodynamics

Mansour

Mukherjee

Pinheiro

et al. 2022

Preprint

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“…The Bartoli protocol was successfully extended to the preparation of 4- and 6-azaindoles from the respective nitro-substituted pyridines, as summarized in Scheme 15 [ 44 – 46 ]. A prototype reaction was conducted on 2-methoxy-3-nitropyridine ( 136 ) which was exposed to a 3-fold excess of 127 in THF at −78 °C before warming the mixture to −20 °C and stirring for 8 h to afford the 6-azaindole 137 in 20% yield after chromatographic purification.…”

Section: Introductionmentioning

confidence: 99%

“…A second approach to access azaindoles relied upon the two-step Leimgruber–Batcho reaction protocol which was known to deliver 4- and 6-azaindoles [ 44 , 47 , 48 ]. In this process, a 2-methyl-substituted nitropyridine 141 was dissolved in DMF-dimethyl acetal ( 142 ) and the mixture heated at 115 °C for 14 h to afford the enamine 143 (Scheme 16 ) [ 49 ].…”

Section: Introductionmentioning

confidence: 99%

Innovation in the discovery of the HIV-1 attachment inhibitor temsavir and its phosphonooxymethyl prodrug fostemsavir

Wang¹,

Kadow²,

Meanwell

2021

Med Chem Res

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The discovery and development of fostemsavir (2), the tromethamine salt of the phosphonooxymethyl prodrug of temsavir (1), encountered significant challenges at many points in the preclinical and clinical development program that, in many cases, stimulated the implementation of innovative solutions in order to enable further progression. In the preclinical program, a range of novel chemistry methodologies were developed during the course of the discovery effort that enabled a thorough examination and definition of the HIV-1 attachment inhibitor (AI) pharmacophore. These discoveries helped to address the challenges associated with realizing a molecule with all of the properties necessary to successfully advance through development and this aspect of the program is the major focus of this retrospective. Although challenges and innovation are not unusual in drug discovery and development programs, the HIV-1 AI program is noteworthy not only because of the serial nature of the challenges encountered along the development path, but also because it resulted in a compound that remains the first and only example of a mechanistically novel class of HIV-1 inhibitor that is proving to be very beneficial for controlling virus levels in highly treatment-experienced HIV-1 infected patients.

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“…Fostemsavir has recently been approved for HIV treatment. Drugs containing a pyrrolopyridine scaffold such as Vemurafenib or Pexidartinib are used in anticancer therapy [ 3 ]. Pyrrolo[3,2- c ]pyridine derivatives show inhibitory effect against FMS kinase and are promising candidates for anticancer and antiarthritic drug development [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…As a topoisomerase I inhibitor, it has found application in cancer treatment and is active against HIV-1 [1]. Other alkaloids containing the pyrrolopyridine system in their structure include pumiloside 2a, deoxypumiloside 2b isolated from Ophiorrhiza pumila [2], and variolin B 3a, deoxyvariolin B 3b isolated from an antarctic sponge Kirkpatrickia variolosa [3], and the antiviral alkaloid mappicin 4, which was isolated from Mappia foetida [4], and anticancer meriolin derivatives 5a-b [3] (Figure 2). Due to their structure containing two important pharmacophores, i.e., pyrrole and pyridine, pyrrolopyridines have been the subject of many pharmacological studies over the last hundred years.…”

Section: Introductionmentioning

confidence: 99%

An Overview of the Biological Activity of Pyrrolo[3,4-c]pyridine Derivatives

Wójcicka

Redzicka

2021

Pharmaceuticals

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Pyrrolo[3,4-c]pyridine is one of the six structural isomers of the bicyclic ring system containing a pyrrole moiety fused to a pyridine nucleus. The broad spectrum of pharmacological properties of pyrrolo[3,4-c]pyridine derivatives is the main reason for developing new compounds containing this scaffold. This review presents studies on the biological activity of pyrrolo[3,4-c]pyridines that have been reported in the scientific literature. Most of these derivatives have been studied as analgesic and sedative agents. Biological investigations have shown that pyrrolo[3,4-c]pyridines can be used to treat diseases of the nervous and immune systems. Their antidiabetic, antimycobacterial, antiviral, and antitumor activities also have been found.

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Recent developments in the synthesis of azaindoles from pyridine and pyrrole building blocks

Abstract: Azaindole chemical scaffold is represented in many biologically active natural products and synthetic derivatives. Recently, this chemical scaffold yielded several therapeutic agents for variety of diseases. Due to the interesting...

Cited by 38 publications

References 191 publications

Weak Dewar bond modulates protonated azaindole photodynamics

Weak Dewar bond modulates protonated azaindole photodynamics

Innovation in the discovery of the HIV-1 attachment inhibitor temsavir and its phosphonooxymethyl prodrug fostemsavir

An Overview of the Biological Activity of Pyrrolo[3,4-c]pyridine Derivatives

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