A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications

Abstract

The analogs of nitrogen-based heterocycles occupy an exclusive position as a valuable source of therapeutic agents in medicinal chemistry. More than 75% of drugs approved by the FDA and currently available in the market are nitrogen-containing heterocyclic moieties. In the forthcoming decade, a much greater share of new nitrogen-based pharmaceuticals is anticipated. Many new nitrogen-based heterocycles have been designed. The number of novel N-heterocyclic moieties with significant physiological properties and promising applications in medicinal chemistry is ever-growing. In this review, we consolidate the recent advances on novel nitrogen-containing heterocycles and their distinct biological activities, reported over the past one year (2019 to early 2020). This review highlights the trends in the use of nitrogen-based moieties in drug design and the development of different potent and competent candidates against various diseases.

Keywords: biological activities; current trends; nitrogen-based heterocycles; structure-activity relationship.

Figure 1

Publications on nitrogen-based heterocycles between 2009 to early 2020 (Source Scopus) [26].

Figure 2

β-Lactam clinical drugs.

Figure 3

Anti-inflammatory (compound 1a) and anti-cancer activity (compound 1b) of the most active chromeno-β-lactam hybrids.

Figure 4

Antiproliferative activity of most potent β-lactam derivative 2a.

Figure 5

Most potent antibacterial β-lactam-anthraquinone hybrid 3a.

Figure 6

The antimicrobial activity of the most potent β-lactam analog 4a.

Figure 7

A 1,2,3-triazole-containing clinical drug.

Figure 8

Most significant antitubercular activity phenothiazine-1,2,3-triazole conjugate 5a.

Figure 9

The anti-HIV activity of the most potent phenylalanine-1,2,3-triazole conjugate 7a.

Figure 10

Antiproliferative activity of the most active 1,2,3-triazole scaffold 8a.

Figure 11

Most active anticancer agent chalcone conjugate with 1,2,3-triazole 9a.

Figure 12

Most active 1,2,3-triazole-coumarin hybrids 10a and 10b as α-glucosidase inhibitors.

Figure 13

α-Glucosidase inhibitor activity of the most active 1,2,3-triazole-quinazolinone hybrid 11a.

Figure 14

Most active 1,2,3-triazole-imidazole hybrids 12a and 12b as α-glucosidase inhibitors.

Figure 15

Cytotoxic activity of the most-active naphthoquinone-1,2,3-triazole conjugate 13a.

Figure 16

Imidazole clinical drugs.

Figure 17

Cytotoxic activity of the most active benzoimidazole-quinazolinone hybrid 14a.

Figure 18

Antiproliferative activity of the most active 2-arylimidazole derivative 15a.

Figure 19

Most active imidazole flavonoid conjugate 16a as a PTP1B inhibitor.

Figure 20

ALK5 inhibitory activity of the most active benzthiadiazole-imidazole scaffold (17a).

Figure 21

Antiproliferative activity of the most active benzo[d]imidazole conjugate 18a.

Figure 22

Most active pyrazole-imidazole hybrids 19a and 19b as α-glucosidase inhibitors.

Figure 23

Pyrazole-based clinical drugs.

Figure 24

Anti-inflammatory activity of the most active pyrazole fused triazole hybrid 20a.

Figure 25

Anti-inflammatory activity of the most active pyrazole sulfonamide conjugate 21a.

Figure 26

ALK5 kinase inhibitory activity of the most active pyridine-pyrazole derivative 22a.

Figure 27

Anti-inflammatory activity of the most active pyrazole-thiohydantoin conjugate 23a.

Figure 28

Antiproliferative activity of the most active pyrazole-benzothiazole-β-naphthol hybrid 24a.

Figure 29

The antitubercular activity of the most active thiazole-pyrazole hybrid 25a.

Figure 30

PTP1B inhibitory activity of most active pyrazole conjugate 26a.

Figure 31

KDM5B inhibitory activity of the most active pyrazole conjugate 27a.

Figure 32

ROS inhibitory activity of the most active pyrazole conjugate 28a.

Figure 33

Quinoline clinical drugs.

Figure 34

Antiproliferative activity of the most active quinoline conjugate 29a.

Figure 35

Antiproliferative activity of the most active quinoline conjugate 30a.

Figure 36

Antiproliferative activity of most active tetrahydrobenzo-quinoline scaffold 31a.

Figure 37

Antiproliferative activity of the most active indole-quinoline hybrid 32a.

Figure 38

The antitubercular activity of the most active quinoline-triazole hybrid 33a.

Figure 39

The most active quinoline with Schiff base analog 34a as an α-glucosidase inhibitor.

Figure 40

Antiproliferative activity of the most active quinoline-pyrazole-thiazole hybrid 35a.

Figure 41

The antileishmanial potential of the most active quinoline-thiadiazole hybrid 36a.

Figure 42

Quinazoline clinical drugs.

Figure 43

Antitumor activity of the most active quinazoline conjugate 37a.

Figure 44

Antitumor activity of the most active quinazoline conjugate 38a.

Figure 45

Carbonic anhydrase inhibitory activity of the most active quinazoline conjugate 39a.

Figure 46

EGFR tyrosine kinase inhibitory activity of the most active quinazoline-1,2,3-triazole hybrids 40a.

Figure 47

EGFR tyrosine kinase inhibitory activity of the most active quinazoline scaffold 41a.

Figure 48

Pyrimidine and pyrimidinone clinical drugs.

Figure 49

Xanthine oxidase (XO) inhibitory activity of the most active dihydropyrimidine-5-carboxylic acid analog 42a.

Figure 50

Antiproliferative activity of the most active dihydropyrimidinone conjugate 43a.

Figure 51

Antiproliferative activity of the most active thieno[3,2-d]pyrimidine conjugate 44a.

Figure 52

Most active pyrimidine scaffold 45a as a JAK3 inhibitor.

Figure 53

Anticancer activity of the most active pyrimidine-benzothiazole hybrid 46a.

Figure 54

The antitubercular activity of the most active pyrimidine -fused pyrazole hybrid 47a.

Figure 55

Antiproliferative activity of the most active 1,2,4-triazole-pyrimidine hybrid 48a.

Figure 56

Antiproliferative activity of the most potent pyrimidine-linked nitroxide derivative 49a.