- Microwave assisted synthesis of pyrrolo[2,1-c][1,4]benzodiazepine-5,11- diones
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In a simple microwave assisted and environmentally benign approach isatoic anhydride reacts readily with proline to afford pyrrolo[2, 1- c][1,4]benzodiazepines-5,11-diones under solvent-free conditions.
- Kamal, Ahmed,Reddy, B.S. Narayan,Reddy, G. Suresh Kumar
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- Influence of temperature for the azide displacement in benzodiazepine derivatives: Experimental and DFT study of competing SN1, SN2 and double SN2 reaction pathways
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Molecules carrying the azido functionality are widely used as intermediates in medicinal chemistry. Pyrrolobenzodiazepines are molecules with a broad range of interesting pharmacological properties. Due to the wide importance of azido-PBD as a key interme
- Evangelista, Tereza Cristina Santos,Delarmelina, Maicon,Addla, Dinesh,All?o, Rafael A.,Kaiser, Carlos Roland,Carneiro, José Walkimar de M.,Silva-Jr, Floriano Paes,Ferreira, Sabrina Baptista
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- Synthesis of a novel C2-aryl pyrrolo[2,1-c][1,4]benzodiazepine-5,11-dione library: Effect of C2-aryl substitution on cytotoxicity and non-covalent DNA binding
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A 23-member C2-aryl pyrrolo[2,1-c][1,4]benzodiazepine-5,11-dione (PBD dilactam) library has been synthesized using Suzuki coupling, and the effect of base upon racemisation at the C11a-position during the cross-coupling reaction studied. Three library members (21, 30 and 33) were sufficiently cytotoxic in the NCI's preliminary screen to warrant further evaluation, and one (30, R = p-Br) was found to be cytotoxic at the sub-micromolar level in the A498 renal cancer cell line. DNA thermal denaturation studies suggested that this activity may be associated with non-covalent DNA interaction, and also demonstrated that introductin of C2-C3 unsaturation and addition of C2-aryl functionalities to the PBD dilactam skeleton significantly enhanced helix stabilisation compared to the unsubstituted PBD dilactam (6).
- Antonow, Dyeison,Jenkins, Terence C.,Howard, Philip W.,Thurston, David E.
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- One-Step Preparation of Pyrrolo[1,4]benzodiazepine Dilactams: Total Synthesis of Oxoprothracarcin, Boseongazepines B and C
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A one-step synthesis of pyrrolo[1,4]benzodiazepine dilactams has been developed. The high yielding method involves direct coupling of unprotected anthranilic acids with proline esters. This transformation was successfully applied in the first total syntheses of boseongazepines B and C as well as oxoprothracarcin and limazepine E.
- Smits, Gints,Zemribo, Ronalds
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p. 2272 - 2276
(2015/09/28)
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- Design, synthesis and evaluation of novel 2-hydroxypyrrolobenzodiazepine-5, 11-dione analogues as potent angiotensin converting enzyme (ACE) inhibitors
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A series of novel 10-substituted 2-hydroxypyrrolobenzodiazepine-5,11-diones designed through structure based rational hybridization approach, synthesized by the cyclodehydration of isotonic anhydride with (2S,4R)-4-hydroxypyrrolidine- 2-carboxylic acid followed by N-substitution, were evaluated as angiotensin converting enzyme (ACE) inhibitors. Among all the new compounds screened (2R,11aS)-10-((4-bromothiophen-2-yl)methyl)-2-hydroxy-2,3-dihydro-1H-benzo[e] pyrrolo[1,2-a][1,4]diazepine-5,11(10H,11aH)dione, 5v (IC50: 0.272 μM) emerged as most active non-carboxylic acid ACE inhibitor with minimal toxicity comparable to clinical drugs Lisinopril, Benazepril and Ramipril. Favorable binding characteristics in docking studies also supported the experimental results.
- Addla, Dinesh,Jallapally, Anvesh,Kanwal, Abhinav,Sridhar, Balasubramanian,Banerjee, Sanjay K.,Kantevari, Srinivas
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p. 4485 - 4493
(2013/07/26)
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- One-pot microwave-assisted selective azido reduction/tandem cyclization in condensed and solid phase with nickel boride
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An efficient and inexpensive method using microwave-assisted irradiation with Ni2B for the syntheses of aromatic amines, pyrrolobenzodiazepines as well as pyrroloquinazolinones was developed. This protocol was applied in the tandem resin-cleavage, azido reduction, and cyclization of compounds 3 and 5 that afforded substituted pyrrolo[2,1-c][1,4] benzodiazepines 4 and 6 in a one-pot manner. The microwave-assisted irradiation reactions enhanced yields with very short reaction times in contrast to the conventional thermal reactions. Georg Thieme Verlag Stuttgart.
- Shankaraiah, Nagula,Markandeya, Nagula,Espinoza-Moraga, Marlene,Arancibia, Claudia,Kamal, Ahmed,Santos, Leonardo Silva
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experimental part
p. 2163 - 2170
(2009/12/31)
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- Chemoselective aromatic azido reduction with concomitant aliphatic azide employing Al/Gd Triflates/Nal and ESI-MS mechanistic studies
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Aluminium and gadolinium inflates catalyze the chemoselective reduction of aromatic azides to the corresponding amines in combination with sodium iodide. This mild chemoselective method has been applied to the synthesis of various aryl amines, C2azido-substituted pyrrolo[2,1-c]-[1,4]benzodiazepines, and fused[2,1b]quinazolinones by an intramolecular azido reduction tandem cyclization reaction. Interestingly, this methodology selectively reduces aryl azides with enhanced yields and proceeds in shorter reaction times than previous strategies. The mechanistic aspects have been investigated and the intermediates associated with this selective transformation have been intercepted and characterized by online monitoring of the reaction by ESI-MS.
- Kamal, Ahmed,Markandeya, Nagula,Shankaraiah, Nagula,Ratna Reddy,Prabhakar,Sanjeeva Reddy,Eberlin, Marcos N.,Santos, Leonardo Silva
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experimental part
p. 7215 - 7224
(2010/03/05)
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- Design, synthesis, and in vitro activity of peptidomimetic inhibitors of myeloid differentiation factor 88
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We describe the design and synthesis of a peptidomimetic library derived from the heptapeptide AC-RDVLPGT-NH2, belonging to the Toll/IL-1 receptor (TIR) domain of the adaptor protein MyD88 and effective in inhibiting its homodimerization. The a
- Fantò, Nicola,Gallo, Grazia,Ciacci, Andrea,Semproni, Mauro,Vignola, Davide,Quaglia, Marco,Bombardi, Valentina,Mastroianni, Domenico,Zibella, M. Pia,Basile, Giancarlo,Sassano, Marica,Ruggiero, Vito,De Santis, Rita,Carminati, Paolo
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p. 1189 - 1202
(2008/09/20)
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- An efficient selective reduction of aromatic azides to amines employing BF3·OEt2/NaI: Synthesis of pyrrolobenzodiazepines
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A selective and facile method for the reduction of aromatic azides to amines by employing borontrifluoride diethyl etherate and sodium iodide. This methodology has been applied towards the preparation of biologically important imine-containing pyrrolobenzodiazepines and their dilactams through intramolecular reductive-cyclization process. In this protocol the reagent systems are amenable for the generation of solution-phase combinatorial synthesis. Georg Thieme Verlag Stuttgart.
- Kamal, Ahmed,Shankaraiah,Markandeya,Reddy, Ch. Sanjeeva
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experimental part
p. 1297 - 1300
(2009/04/06)
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- Selective reduction of aromatic azides in solution/solid-phase and resin cleavage by employing BF3·OEt2/EtSH. Preparation of DC-81
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An efficient method for the reduction of aromatic azides in both solution and solid-phase has been developed by employing BF3·OEt2/EtSH. This report also describes resin cleavage employing this reagent system. Further, this protocol has been utilized for the solution as well as the solid-phase synthesis of pyrrolo[2,1-c][1,4]benzodiazepines, including the naturally occurring antibiotic DC-81 and fused [2,1-b]quinazolinones.
- Kamal, Ahmed,Shankaraiah,Reddy, K. Laxma,Devaiah
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p. 4253 - 4257
(2007/10/03)
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- Facile and efficient solid-phase synthesis of DNA-interactive pyrrolo[2,1-c] [1,4]benzodiazepines
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The solid-phase synthesis of pyrrolo[2,1-c][1,4]benzodiazepines is described. Isatoic anhydrides attached to chloromethyl Wang resin are coupled with proline and the polymer-bound tricyclic compounds are reduced using very mild conditions, and successivel
- Kamal, Ahmed,Reddy, K. Laxma,Devaiah,Shankaraiah
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p. 1841 - 1843
(2007/10/03)
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- New benzo[h][1,6]naphthyridine and azepino[3,2-c]quinoline derivatives as selective antagonists of 5-HT4 receptors: Binding profile and pharmacological characterization
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A series of benzo[h] [1,6] naphthyridine and azepino[3,2-c] quinoline derivatives were prepared and evaluated to determine the necessary requirements for high affinity on the 5-HT4 receptors and high selectivity versus other receptors. The compounds were synthesized by substituting the chlorine atom of benzonaphthyridines and azepinoquinolines with various N-alkyl-4-piperidinylmethanolates. They were evaluated in binding assays with [3H]GR 113808 as the 5-HT4 receptor radioligand. The affinity values (Ki or inhibition percentages) depended upon the substituent on the aromatic ring on one hand and the substituent on the lateral piperidine chain on the other hand. A chlorine atom produced a marked drop in activity while a N-propyl or N-butyl group gave compounds with nanomolar affinities (1 i 4(a) receptor. Derivative 4a also showed in vivo potent analgesic activity in the writhing test at very low doses.
- Hinschberger, Antoine,Butt, Sabrina,Lelong, Véronique,Boulouard, Michel,Dumuis, Aline,Dauphin, Fran?cois,Bureau, Ronan,Pfeiffer, Bruno,Renard, Pierre,Rault, Sylvain
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p. 138 - 147
(2007/10/03)
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- Facile reduction of aromatic nitro/azido functionality on solid support employing Al/NiCl2·6H2O and Al/NH4Cl: Synthesis of pyrrolo[2,1-c][1,4]benzodiazepines
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An efficient and mild method for the reduction of aromatic nitro and azido groups on solid support using Al/NiCl2·6H2O and Al/NH4Cl is described. This solid phase reduction technique has been applied towards the synthesis
- Kamal, Ahmed,Reddy, K. Laxma,Devaiah,Reddy, G. Suresh Kumar
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p. 4741 - 4745
(2007/10/03)
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- Approach to the synthesis of (+)-ifforestine. Model studies directed at the tetracyclic framework
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In order to design an effective asymmetric synthesis of (+)-ifforestine, model approaches to the construction of the tetracyclic ring system have been investigated. These studies have identified two key synthons, a functionalized isatoic anhydride and a p
- Roos, Gregory H. P.,Dastlik, Kim A.
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p. 2023 - 2044
(2007/10/03)
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- Efficient solid-phase synthesis of DNA-interactive pyrrolo[2,1-c][1,4]benzodiazepine antitumour antibiotics
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The solid-phase synthesis of DNA-interactive pyrrolo[2,1-c][1,4]benzodiazepine (PBD) imines and biologically important pyrrolo[2,1-c][1,4]benzodiazepine-5,11-diones on Wang resin using a reduction/cyclization procedure is reported.
- Kamal, Ahmed,Reddy, G.Suresh Kumar,Reddy, K.Laxma,Raghavan, Sadagopan
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p. 2103 - 2106
(2007/10/03)
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- Biphenyl derivatives and drug composition
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A biphenyl derivative represented by the following general formula (1) and a pharmaceutically acceptable salt thereof: [In the formula (1), A represents a single bond, —CH2—, —CO—, —CS— or —SO2—; B represents a single bond or —CH2—; R1represents a hydrogen atom, —OH, —NR11R12(wherein R11and R12each independently represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms), —OCOCH3, or a halogen atom; R2represents a hydrogen atom or R1and R2form a group ═O together; R3represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms; provided that in the formula, the absolute configuration of the position a may be either R or S]. The compound of the present invention has considerably high safety and efficacy and is useful as, in particular, a vasopressin receptor antagonist.
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- Efficient reduction of aromatic nitro/azido groups on solid support employing indium: Synthesis of pyrrolo[2,1-c][1,4]benzodiazepine-5,11-diones
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An efficient method for the reduction of aromatic nitro and azido compounds on solid support using indium/NH4Cl is described. This solid-phase reduction technique has been applied to the synthesis of pyrrolo[2,1-c][1,4]benzodiazepine-5,11-dione
- Kamal, Ahmed,Reddy, G.Suresh Kumar,Reddy
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p. 6969 - 6971
(2007/10/03)
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- An efficient reduction of azides to amines: Synthesis of DNA interactive pyrrolo[2, 1-c][1,4]benzodiazepines
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Reaction of a variety of azido compounds with FeSO4·7H2O/NH3 results in quantitative yields of the corresponding amino compounds. This reductive methodology has been extended towards the synthesis of pyrrolo[2,1-c][1,4]benzodiazepine antibiotics. (C) 2000 Elsevier Science Ltd.
- Kamal,Laxman,Arifuddin
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p. 7743 - 7746
(2007/10/03)
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- Novel rearrangement of pyrrolo[2,1-c][1,4]benzodiazepines into pyrrolo[2,1-b]quinazolinones, analogous of alkaloid, vasicinone
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Tetrahydropyrrolo[2,1-c][1,4]benzodiazepin-5,11-diones (4) and (22-24) in concentrated hydrochloric acid rearranged after 30 min into new oxohexahydropyrrolo[2,1-b][1,4]quinazolinecarboxylic acids (5) and (25-27) in good yields. Quinazolinone (5) was then
- Jolivet-Fouchet, Sandrine,Fabis, Frederic,Bovy, Philippe,Ochsenbein, Philippe,Rault, Sylvain
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p. 1257 - 1273
(2007/10/03)
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- Building blocks for peptide and carbamate libraries
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A building block containing the 1,4-benzodiazepine-2,5-diazepine pharmacophore has been synthesized for use in constructing both peptide and carbamate combinatorial libraries.
- Bi, Yingzhi,Schultz, Peter G.
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p. 2299 - 2300
(2007/10/03)
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- Synthesis of pyrrolo[2,1-c][1,4]benzodiazepines via an intramolecular aza-Wittig reaction. Synthesis of the antibiotic DC-81
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A new and efficient synthesis of the pyrrolo[2,1-c][1,4]benzodiazepine ring system has been carried out using, as a key step, an intramolecular aza-Wittig reaction of the appropriately substituted N-(2-azidobenzoyl)pyrrolidine-2-carboxaldehydes. The paren
- Molina, Pedro,Diaz, Isidora,Tarraga, Alberto
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p. 5617 - 5630
(2007/10/02)
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- Pyrrolo[2,1-c][1,4]benzodiazepines: A mild conversion of thiolactam into amidine
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Reaction of 2-hydoxy pyrrolo [2,1-c] [1,4] benzodiazepines-5-one-thione or 5,11-dithiones with ammonia in presence of mercuric chloride affords new amidines in high yield.
- Foloppe, Mari P.,Rault, Sylvain,Robba, Max
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p. 2803 - 2804
(2007/10/02)
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- A total synthesis of anthramycin: Application of palladium-catalyzed coupling reactions for the attachment of the acrylic side chain
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Utilization of the palladium-catalyzed reactions of vinyl triflates 8 obtained from model N-substituted (11aS)-2,3,5,10,11,11a-hexahydro-2,5,11-trioxo-1H-pyrrolo[2,1-c][1,4] enzodiazepines (5, 6) either with β-(tributylstannyl)acrylates or acrylic esters
- Pena,Stille
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p. 5417 - 5424
(2007/10/02)
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- ATTACHMENT OF THE ANTHRAMYCIN ACRYLAMIDE SIDE CHAIN BY THE PALLADIUM CATALYZED COUPLING REACTION OF A VINYL TRFLATE
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Conversion of the 2-keto group in the pyrrolo ring of pyrrolo(1,4)benzodiazepines to the vinyl triflate takes place regiospecifically to yield the enamine.The triflate undergoes palladium catalyzed coupling reactions to attach the acrylamide side chain.
- Pena, Michael R.,Stille, J. K.
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p. 6573 - 6576
(2007/10/02)
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- Total Syntheses of Prothracarcin and Tomaymycin by Use of Palladium Catalyzed Carbonylation
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Total syntheses of optically active prothracarcin (1) and pretomaymycin (2), which is readily convertible to tomaymycin (3), were achived via a palladium catalyzed carbonylation developed by us.The structure of prothracarcin (1) was determined to be (11aS
- Mori, Miwako,Uozumi, Yasuhiro,Kimura, Masaya,Ban, Yoshio
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p. 3793 - 3806
(2007/10/02)
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