Imidazo[2′-3′-:6,5]dipyrido[3,2-b:2′,3′-e]-1,4-diazepines: non-nucleoside HIV-1 reverse transcriptase inhibitors with greater enzyme affinity than nevirapine

Terrett, Nicholas T.; Bojanic, Dejan; Merson, James; Stephenson, Peter T.

doi:10.1016/s0960-894x(00)80468-0

Cited by 29 publications

(17 citation statements)

References 15 publications

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“…HINT Calculated Total Interaction Constants and Experimental IC50 Values for HIV1-RT Activity a Data taken from Terrett et al9 Group A: 10 methoxysubstituted imidazodipyridodiazepines. Group B: methyl-substituted imidazodipyridodiazepines.…”

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confidence: 99%

All-Atom Models for the Non-Nucleoside Binding Site of HIV-1 Reverse Transcriptase Complexed with Inhibitors: A 3D QSAR Approach

et al. 1996

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Several molecular modeling techniques were used to generate an all-atom molecular model of a receptor binding site starting only from Ca atom coordinates. The model consists of 48 noncontiguous residues of the non-nucleoside binding site of HIV-1 reverse transcriptase and was generated using a congeneric series of nevirapine analogs as structural probes. On the basis of the receptor-ligand atom contacts, the program HINT was used to develop a 3D quantitative structure activity relationship that predicted the rank order of binding affinities for the series of inhibitors. Electronic profiles of the ligands in their docked conformations were characterized using electrostatic potential maps and frontier orbital calculations. These results led to the development of a 3D stereoelectronic pharmacophore which was used to construct 3D queries for database searches. A search of the National Cancer Institute's open database identified a lead compound that exhibited moderate antiviral activity.

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confidence: 99%

All-Atom Models for the Non-Nucleoside Binding Site of HIV-1 Reverse Transcriptase Complexed with Inhibitors: A 3D QSAR Approach

et al. 1996

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“…Since substitution at the 2-position of tricyclic 6a leads to an enhancement of enzyme inhibition,2•4 we expected that substitution at the corresponding 3-position of 5a should have a similar effect. A modest 2-fold increase in potency over the unsubstituted parent 5a (entry 2) is seen for the 3-chloro analog 5e (Table 1, entry 9) which mirrors the effect of this substituent in the dipyrido [3,[2][3][4][5][6]diazepinone series (compare entries 2a and 9a). In contrast, the 3-(3-aminophenyl) derivative 5p (entry 10) is inactive even though the corresponding dipyrido[3,2-fe]diazepinone analog 6p4•12 (entry 10a) is more potent than the parent 6a.…”

Section: Biologymentioning

confidence: 82%

“…Anal. (C15H13CIN4O) C, , N. 5c: NMR (CDC13) ó 8.32 (1H, dd, =7 = 2, 5), 8.07 (1H, dd, =7=2, 8), 7.34 (1H, d, =7 = 8), 6.99 (1H, dd, =7=5, 8), 6.95 (1H, d, =7 = 8), 4.2 (1H, br), 3.62 (3H, s), 3.55 (1H, br), 2.47 (3H, s), 1.22 (3H, t, =7 = 7); MS (Cl) 269 (MH+). Anal.…”

Section: Methodsmentioning

confidence: 99%

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Novel Non-nucleoside Inhibitors of HIV-1 Reverse Transcriptase. 3. Dipyrido[2,3-b:2',3'-e]diazepinones

Proudfoot

Patel²,

Kapadia³

et al. 1995

J. Med. Chem.

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We have explored the potential of derivatives of the dipyrido[2,3-b:2',3'-e][1,4]diazepinone ring system as inhibitors of HIV-1 reverse transcriptase (RT). These compounds are isomeric to the potent RT inhibitor nevirapine and are available via a novel Smiles rearrangement on intermediates used for the synthesis of nevirapine analogs. Derivatives of this isomeric series are weaker inhibitors of RT than corresponding nevirapine analogs, although with appropriate substitution of the A- and C-pyridine rings activity can be improved.

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“…[22][23] Although many methods for synthesising benzodiazepine ring systems have been reported, they continue to receive a great deal of attention. [24][25]…”

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Synthesis of Benzonaphtho[1,4]Diazepine Derivatives via the Reaction of 2-Aminoarylbenzimidamides with 2,3-Dichloro-1,4-Naphthoquinone

El‐Shaieb

2010

Journal of Chemical Research

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A series of (Z)-13-(arylimino)-12,13-dihydro-5H-benzo[e]naphtho [2,3-b][1,4]diazepine-6,11-dione derivatives have been synthesised by one pot cyclisation in good yield via electron donor-acceptor complexes by reacting 2-aminoarylbenzimidamides with 2,3-dichloro-1,4-naphthoquinone. The high yield and simplified workup procedure in addition to the mild and neutral reaction conditions are the main advantages of this approach.

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Imidazo[2′-3′-:6,5]dipyrido[3,2-b:2′,3′-e]-1,4-diazepines: non-nucleoside HIV-1 reverse transcriptase inhibitors with greater enzyme affinity than nevirapine

Cited by 29 publications

References 15 publications

All-Atom Models for the Non-Nucleoside Binding Site of HIV-1 Reverse Transcriptase Complexed with Inhibitors: A 3D QSAR Approach

All-Atom Models for the Non-Nucleoside Binding Site of HIV-1 Reverse Transcriptase Complexed with Inhibitors: A 3D QSAR Approach

Novel Non-nucleoside Inhibitors of HIV-1 Reverse Transcriptase. 3. Dipyrido[2,3-b:2',3'-e]diazepinones

Synthesis of Benzonaphtho[1,4]Diazepine Derivatives via the Reaction of 2-Aminoarylbenzimidamides with 2,3-Dichloro-1,4-Naphthoquinone

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