Back to Search
Start Over
Imidazo[1,5-b]pyridazine-d4T conjugates: synthesis and anti-human immunodeficiency virus evaluation.
- Source :
-
Antiviral chemistry & chemotherapy [Antivir Chem Chemother] 1998 May; Vol. 9 (3), pp. 205-23. - Publication Year :
- 1998
-
Abstract
- In an attempt to combine the human immunodeficiency virus type 1 (HIV-1)-inhibitory capacity of 2',3'-dideoxy-2',3'-didehydronucleoside analogues [nucleoside reverse transcriptase (RT) inhibitors; NRTI] and non-nucleoside RT inhibitors (NNRTI), we have designed, synthesized and evaluated for their anti-HIV activity several heterodimers of the general formula [d4T]-NH-(CH2)n-NH-[imidazo[1,5-b]pyridazine]. The synthesis of these heterodimers was conducted in three parts. The first part focused on the synthesis of the NRTI. The second part was devoted to the NNRTI and the NNRTI linked to appropriate spacers: [NNRTI]-NH-(CH2)n-NH2. In the third part, the condensation between the NRTI and the [NNRTI]-NH-(CH2)n-NH2 was performed. The in vitro inhibitory activities against HIV-1 of the [d4T]-NH-(CH2)n-NH-[imidazo[1,5-b]pyridazine] heterodimers were found to be comparable to that of d4T (stavudine) in HIV-infected cells. Moreover, the heterodimers were endowed with anti-HIV-2 activity and with anti-nevirapine-resistant HIV-1 activity. None of the heterodimers proved markedly cytotoxic to CEM-SS or MT-4 cells. There was not a clear trend toward antiviral potency on lengthening the methylene spacer in the [d4T]-NH-(CH2)n-NH-[imidazo[1,5-b]pyridazine] heterodimers.
- Subjects :
- Antiviral Agents pharmacology
Cell Line
Drug Resistance
Enzyme Inhibitors
HIV-2 drug effects
Imidazoles pharmacology
Molecular Structure
Nevirapine pharmacology
Nucleosides chemical synthesis
Nucleosides pharmacology
Protein Conformation
Pyridazines pharmacology
Reverse Transcriptase Inhibitors chemical synthesis
Reverse Transcriptase Inhibitors pharmacology
Stavudine pharmacology
Virus Replication drug effects
Antiviral Agents chemical synthesis
HIV-1 drug effects
Imidazoles chemical synthesis
Pyridazines chemical synthesis
Stavudine analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 0956-3202
- Volume :
- 9
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Antiviral chemistry & chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 9875400
- Full Text :
- https://doi.org/10.1177/095632029800900302