24919-40-2

Upstream product

• 118-48-9 isatoic anhydride 
• 609-36-9 rac-Pro-OH 
• 147-85-3 L-proline 
• 201230-82-2 carbon monoxide 
• 2133-40-6 L-proline methyl ester monohydrochloride 
• 615-36-1 2-bromoaniline 
• 142114-82-7 methyl (2S)-N-(2-azidobenzoyl)pyrrolidine-2-carboxylate 
• 552-16-9 ortho-nitrobenzoic acid 
• 1233669-19-6 (S)-10-(2-nitrobenzoyl)-2,3-dihydro-1H-benzopyrrolo[1,2][1,4]diazepine-5,11(10H,11aH)-dione 
• 118-92-3 anthranilic acid 
• 105089-64-3 N-(2-nitrobenzoyl)-L-proline methyl ester 
• 67900-22-5 5,10,11,11a-tetrahydropyrrolo[2,1-c][1,4]benzodiazepin-5,11-dione 

Downstream Products

• 125299-58-3 (+)-(11aS)-1,2,3,10,11,11a-hexahydro-10-(benzyloxycarbonyl)-5H-pyrrolo<2,1-c><1,4>benzodiazepin-5,11-dione 
• 1233669-19-6 (S)-10-(2-nitrobenzoyl)-2,3-dihydro-1H-benzopyrrolo[1,2][1,4]diazepine-5,11(10H,11aH)-dione 
• 1271450-08-8 C₃₀H₂₅N₃O₄S₂ 
• 1271450-22-6 C₃₀H₂₄N₄O₆S₂ 
• 1271450-54-4 C₃₀H₂₅N₃O₄S 
• 1271450-25-9 (Z)-11-(2-oxo-2-phenylethylidene)-2,3,11,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-5(10H)-one 
• 1271450-28-2 (Z)-11-(2-(biphenyl-4-yl)-2-oxoethylidene)-2,3,11,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-5(10H)-one 

Relevant academic research and scientific papers

Identification of an Orally Bioavailable, Brain-Penetrant Compound with Selectivity for the Cannabinoid Type 2 Receptor

Modulation of the endocannabinoid system (ECS) is of great interest for its therapeutic relevance in several pathophysiological processes. The CB2 subtype is largely localized to immune effectors, including microglia within the central nervous system, where it promotes anti-inflammation. Recently, a rational drug design toward precise modulation of the CB2 active site revealed the novelty of Pyrrolo[2,1-c][1,4]benzodiazepines tricyclic chemotype with a high conformational similarity in comparison to the existing leads. These compounds are structurally unique, confirming their chemo-type novelty. In our continuing search for new chemotypes as selective CB2 regulatory molecules, following SAR approaches, a total of 17 selected (S,E)-11-[2-(arylmethylene)hydrazono]-PBD analogs were synthesized and tested for their ability to bind to the CB1 and CB2 receptor orthosteric sites. A competitive [3H]CP-55,940 binding screen revealed five compounds that exhibited >60% displace-ment at 10 μM concentration. Further concentration-response analysis revealed two compounds, 4k and 4q, as potent and selective CB2 ligands with sub-micromolar activities (Ki = 146 nM and 137 nM, respectively). In order to support the potential efficacy and safety of the analogs, the oral and intravenous pharmacokinetic properties of compound 4k were sought. Compound 4k was orally bioavailable, reaching maximum brain concentrations of 602 ± 162 ng/g (p.o.) with an elimination half-life of 22.9 ± 3.73 h. Whether administered via the oral or intravenous route, the elimination half-lives ranged between 9.3 and 16.7 h in the liver and kidneys. These compounds represent novel chemotypes, which can be further optimized for improved affinity and selectivity toward the CB2 receptor.

First in class (S,E)-11-[2-(arylmethylene)hydrazono]-PBD analogs as selective CB2 modulators targeting neurodegenerative disorders

Newly designed pyrrolo[2,1-c][1,4]benzodiazepines tricyclic skeleton has shown potential clusters of cannabinoid receptors CB1/CB2 selective ligands. CB2 plays a critical role in microglial-derived neuroinflammation, where it modulates cell proliferation,

The synthesis and anti-inflammatory evaluation of 1,2,3-triazole linked isoflavone benzodiazepine hybrids

Copper catalyzed azide-alkyne cycloaddition was used for the first time to access a small series of eight novel 1,2,3-triazole linked isoflavone benzodiazepine hybrids. As part of this work, a previously unreported alkyne substituted pyrrolo[1,4]benzodiaz

Low-valent titanium-mediated enantioselective synthesis of quinazolinone alkaloids circumdatins F, H, and analogs

We report the concise and protecting-group-free enantioselective total syntheses of circumdatins F and H. In view of the extreme importance of analogs of quinazolinone alkaloids in drug research and discovery, four analogs of bioactive quinazolinobenzodiazepine alkaloids, including demethoxycircumdatin H (12) and N-demethylbenzomalvin A (13), have been synthesized. The method is based on the low-valent titanium-promoted intramolecular reductive coupling of imides with o-nitrobenzimides, which yielded quinazolino[3,2-a][1,4]benzodiazepines under mild conditions. In addition, heptacyclic dehydraasperlicin E (16) has been synthesized from asperlicin C by a NCS-mediated dehydra-cyclization reaction.

One-Step Preparation of Pyrrolo[1,4]benzodiazepine Dilactams: Total Synthesis of Oxoprothracarcin, Boseongazepines B and C

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.

Synthesis and cytotoxicity testing of new amido-substituted triazolopyrrolo[2,1-c][1,4]benzodiazepine (PBDT) derivatives

A series of amido-substituted triazolopyrrolo[2,1-c][1,4]benzodiazepine (PBDT) derivatives was synthesized from isatoic anhydride, and their cytotoxicity against the MRC-5 and Mahlavu cell lines was evaluated. The results suggest that compound PBDT-7i with the meta-trifluoromethylbenzoyl substituent can selectively inhibit the growth of Mahlavu cells and has low toxicity towards MRC-5 cells.

Palladium catalyzed synthesis of quinazolino [1,4] benzodiazepine alkaloids and analogous

A concise synthesis of enantiopure quinazolino [1,4] benzodiazepine was accomplished by palladium-catalyzed N-arylation of amidines with o-bromobenzoates followed by intra molecular cyclization. The strategy was successfully applied to the total synthesis of pyrrolo quinazolino [1,4] benzodiazepine alkaloids such as circumdatin H, J and other analogues.

One-pot eschenmoser episulfide contractions in DMSO: Applications to the synthesis of fuligocandins A and B and a number of vinylogous amides

Practical total syntheses of the natural products fuligocandin A (2a) and fuligocandin B (3) have been achieved through a convergent strategy depending on the Eschenmoser episulfide contraction as a key step. Conducting the reaction in DMSO proved to be an efficient and general method for the synthesis of a variety of vinylogous amides, such as azepan-2- ylidenepropan-2-one. 2011 American Chemical Society.

Sugar-based enantiomeric and conformationally constrained pyrrolo[2,1- c ][1,4]-benzodiazepines as potential GABAA ligands

Synthesis of a library of pyrrolo[2,1-c][1,4]-benzodiazepines derived from spiro bicyclic d- or l-proline analogues containing a d- or l-fructose moiety was developed. The l-fructose moiety was obtained by using a new synthetic pathway starting from l-arabinose through a six steps synthesis in 18% overall yield. Molecular modeling calculations and DNMR studies showed that d- and l-fructose-based pyrrolobenzodiazepines exhibit a rigid (P)- and (M)-helical conformation, respectively, in which the C-11a substituent was always pseudoequatorial. Additionally, pyrrolobenzodiazepines functionalized with a chloride, bromide, nitro, or amino group in the benzene ring, with or without N-methylation and with or without protection of sugar alcohol groups, allowed a relationship between the molecular structure and biological activity to be established. The conformation of the diazepam ring was not the sole key player influencing binding affinities, and the sugar moiety can in some cases increase the binding activity, possibly by participating in the binding event. Finally, these compounds have increased the understanding of the differential recognition of (M)-/(P)-helical benzodiazepines on GABAA receptor.

Synthesis and biological evaluation of oxadiazole derivatives as inhibitors of soluble guanylyl cyclase

Soluble guanylyl cyclase (sGC) is an ubiquitously expressed enzyme that generates the second messenger cGMP and hence, leads to a number of physiological responses including vasodilation, inhibition of platelet aggregation and neurotransmission. Whilst ma