Environmentally benign synthesis, molecular properties prediction and anti-inflammatory activity of novel isoxazolo[5,4-d]isoxazol-3-yl-aryl-methanones via vinylogous Henry nitroaldol adducts as synthons.

Synthesis of novel 6-methylisoxazolo[5,4-d]isoxazol-3-yl-aryl-methanones 5 has been achieved via nitro-nitrite rearrangement by utilizing vinylogous nitroaldol adducts as synthons under mild conditions. Furthermore, the new series of compounds 5a-i were assessed for molecular properties prediction, drug-likeness by Molinspiration (Molinspiration, 2008) & MolSoft (MolSoft, 2007) softwares, lipophilicity and solubility parameters using ALOGPS 2.1 program. The new series of compounds 5a-i were screened for their anti-inflammatory activity.

A facile synthesis, anti-inflammatory and analgesic activity of isoxazolyl-2,3-dihydrospiro[benzo[f]isoindole-1,3'-indoline]-2',4,9-triones.

A new series of isoxazolyl-2,3-dihydrospiro[benzo[f]isoindole-1,3'-indoline]-2',4,9-triones (14) were synthesized by reaction of 4-amino-3-methyl-5-styrylisoxazole 10 with chloroacetic acid followed by a three component reaction with substituted isatins 12 and 1,4-naphthoquinone 13 using Ceric ammonium nitrate (CAN) catalyst under aerial oxidation condition. Structures of these compounds were established on the basis of IR, (1)H NMR, (13)C NMR and mass spectral data. The title compounds 14a-j were evaluated for their anti-inflammatory and analgesic activity. Compounds 14d, 14e and 14f exhibited potent anti-inflammatory and analgesic activity as that of standard drugs.

Synthesis and in vitro and in vivo anticancer activity of novel 3-methyl-5H-isoxazolo[5',4':5,6]pyrido[2,3-b]indoles.

A series of novel isoxazolo[5',4':5,6]pyrido[2,3-b]indoles 7a-h were synthesized and tested for their in vitro and in vivo anticancer activities. The analogs 7d and 7g have shown potential anticancer activity as compared with the reference compound Cisplatin.

Design, synthesis, antimicrobial, anti-inflammatory and analgesic activity of novel isoxazolyl pyrimido[4,5-b]quinolines and isoxazolyl chromeno[2,3-d]pyrimidin-4-ones.

Novel series of 2-methyl-3-{3-methyl-5-[(E)-2-phenyl-1-ethenyl]-4-isoxazolyl}-3,4-dihydropyrimido[4,5-b]quinolin-4-ones 5 and 3-{3-methyl-5-[(E)-2-phenyl-1-ethenyl]-4-isoxazolyl}-3,4-dihydro-2H-chromeno[2,3-d]pyrimidin-4-ones 7 have been synthesized from isoxazolyl cyanoacetamide synthon 2. Compound 2 was obtained by reaction of 4-amino-3-methyl-5-styrylisoxazole 1 with ethyl cyanoacetate. Isoxazolyl pyrimido[4,5-b]quinolin-4-ones 5 were obtained from compounds 2 by condensation with o-nitro benzaldehyde followed by treatment with SnCl(2) and subsequent tandem N-acetylation and cyclodehydration with acetic anhydride. Compounds 2 were converted to isoxazolyl chromeno[2,3-d]pyrimidin-4-ones 7 by reaction with salicylaldehydes and subsequent cyclization with formaldehyde. Compounds 2-7 were characterized by IR, (1)H NMR, (13)C NMR, and Mass spectral data. The title compounds 5a-f and 7a-g were evaluated for their antimicrobial, anti-inflammatory and analgesic activity. Compounds 5d and 7e exhibited significant antimicrobial activity, potent anti-inflammatory and analgesic activities as that of standard drugs.

Multi-component synthesis and in vitro and in vivo anticancer activity of novel arylmethylene bis-isoxazolo[4,5-b]pyridine-N-oxides.

A three component one-pot protocol has been investigated for the synthesis of arylmethylene bis-isoxazolo[4,5-b]pyridine-N-oxides 1 from the commercially available materials. The title compounds 1 were also synthesized by a step-wise method and found to be identical with one-pot synthesis by spectral and analytical data. The newly synthesized compounds were evaluated for their in vitro anticancer activity against human cancer cell lines and in vivo anticancer activity on EAC-bearing mice. Compound 1a was found to be the most active both in in vitro and in vivo cytotoxic studies.

Design, synthesis, in vitro antimicrobial and anticancer activity of novel methylenebis-isoxazolo[4,5-b]azepines derivatives.

A series of novel methylene bis-isoxazolo[4,5-b]azepines have been synthesized by reaction of 3,5-dimethyl-4-nitroisoxazole 6 with an appropriate methylene bis-chalcones 7 to obtain various Michael adducts 8a-i, which on treatment with SnCl(2)-MeOH underwent reductive cyclization to afford the title compounds 9a-i. Structure of these compounds were established on the basis of IR, (1)H NMR, (13)C NMR and mass spectral data. The title compounds 9a-i were evaluated for their in vitro antimicrobial and anticancer activities. Compounds 9h and 9i exhibited potent antimicrobial and anticancer activities as that of standard drugs.

Synthesis and in vitro and in vivo anticancer activity of novel phenylmethylene bis-isoxazolo[4,5-b]azepines.

A series of novel phenylmethylene bis-isoxazolo[4,5-b]azepine derivatives (10) have been synthesized from 3-methyl-4-nitro-5-styrylisoxazoles 6. The reaction of 6 with 3,5-dimethyl-4-nitroisoxazole (7) in piperidine afforded the Michael type adducts 8, which on treatment with different substituted chalcones in the presence of piperidine gave the Michael adducts 9. Compounds 9 underwent reductive cyclization on treatment with SnCl(2)-MeOH to afford the title compounds 10. Structure of these compounds was established on the basis of IR, (1)H NMR, (13)C NMR and Mass spectral data. The title compounds 10a-j were evaluated for in vitro and in vivo anticancer activity. Compound 10j exhibited good anticancer activity as that of standard drug Cisplatin.

Synthesis, antimicrobial, and mosquito larvicidal activity of 1-aryl-4-methyl-3,6-bis-(5-methylisoxazol-3-yl)-2-thioxo-2,3,6,10b-tetrahydro-1H-pyrimido[5,4-c]quinolin-5-ones.

A series of 1-aryl-4-methyl-3,6-bis-(5-methylisoxazol-3-yl)-2-thioxo-2,3,6,10b-tetrahydro-1H-pyrimido[5,4-c]quinolin-5-ones (6a-h) have been synthesized by cyclization of ethyl-3-aryl-4-(2-chlorophenyl)-6-methyl-1-(5-methylisoxazol-3-yl)-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates 4a-h with 3-amino-5-methylisoxazole 5. Compounds 4a-h were obtained by Biginelli reaction, by condensation of aromatic aldehyde 1, ethyl acetoacetate 2, and isoxazolyl thioureas 3 in a one-pot reaction catalyzed by ceric ammonium nitrite (CAN). Compounds 6a-h were tested for their antibacterial and antifungal activities against various bacterial and fungal strains. The results showed that these compounds exhibited good antibacterial and antifungal activity compared with that of standard antibiotics. Mosquito larvicidal activity of the newly synthesized compounds 6a-h is also studied against fourth instar larvae Culex quinquefasciatus. Some of the compounds are proved to be lethal for mosquito larvae.