TrkB-enhancer Facilitates Functional Recovery After Traumatic Brain Injury

Brain-derived neurotrophic factor (BDNF), a key player in regulating synaptic strength and learning, is dysregulated following traumatic brain injury (TBI), suggesting that stimulation of BDNF signaling pathways may facilitate functional recovery. This study investigates whether CN2097, a peptidomimetic ligand which targets the synaptic scaffold protein, postsynaptic density protein 95, to enhance downstream signaling of tropomyosin-related kinase B, a receptor for BDNF, can improve neurological function after TBI. Moderate to severe TBI elicits neuroinflammation and c-Jun-N-terminal kinase (JNK) activation, which is associated with memory deficits. Here we demonstrate that CN2097 significantly reduces the post-traumatic synthesis of proinflammatory mediators and inhibits the posttraumatic activation of JNK in a rodent model of TBI. The recordings of field excitatory post-synaptic potentials in the hippocampal CA1 subfield demonstrate that TBI inhibits the expression of long-term potentiation (LTP) evoked by high-frequency stimulation of Schaffer collaterals, and that CN2097 attenuates this LTP impairment. Lastly, we demonstrate that CN2097 significantly improves the complex auditory processing deficits, which are impaired after injury. The multifunctionality of CN2097 strongly suggests that CN2097 could be highly efficacious in targeting complex secondary injury processes resulting from neurotrauma

Palladium-Catalyzed Intramolecular Cross-Dehydrogenative Coupling: Synthesis of Fused Imidazo[1,2a]pyrimidines and Pyrazolo[1,5a]pyrimidines

A palladium-catalyzed intramolecular dehydrogenative coupling reaction was developed for the synthesis of fused imidazo[1,2-a]pyrimidines and pyrazolo[1,5-a]- pyrimidines. The developed protocol provides a practical approach for the synthesis of biologically important substituted pyrimidines from easily available substrates, with a broad substrate scope under mild reaction conditions

Palladium-Catalyzed Intramolecular Cross-Dehydrogenative Coupling: Synthesis of Fused Imidazo[1,2‑a]pyrimidines and Pyrazolo[1,5‑a]pyrimidines

A palladium-catalyzed intramolecular dehydrogenative coupling reaction was developed for the synthesis of fused imidazo[1,2-a]pyrimidines and pyrazolo[1,5-a]- pyrimidines. The developed protocol provides a practical approach for the synthesis of biologically important substituted pyrimidines from easily available substrates, with a broad substrate scope under mild reaction conditions

Silver-Catalyzed Tandem Synthesis of Naphthyridines and Thienopyridines via Three-Component Reaction

An efficient approach for the silver-catalyzed regioselective tandem synthesis of highly functionalized 1,2-dihydrobenzo­[1,6]­naphthyridines <b>6a</b>–<b>z</b> and <b>7a</b>–<b>e</b> by the reaction of <i>ortho</i>-alkynylaldehydes <b>3a</b>–<b>n</b> with amines <b>4a</b>–<b>d</b> and ketones <b>5a</b>–<b>c</b>/active methylene compounds <b>5d</b>–<b>g</b>, under mild reaction conditions, is described. The scope of the developed chemistry was successfully extended for the direct synthesis of 1,2-dihydrobenzo­[4,5]­thieno­[2,3-<i>c</i>]­pyridines <b>8a</b>–<b>e</b>, which is known as the sulfur analogue of β-carbolines. Naphthyridines <b>6a</b>–<b>z</b> and thienopyridines <b>8a</b>–<b>e</b> were obtained via dual activation concept using l-proline as organocatalyst; however, naphthyridines <b>7a</b>–<b>e</b> were synthesized without using organocatalyst. The reaction shows selective N–C bond formation on the more electrophilic alkynyl carbon, resulting in the regioselective 6-<i>endo</i>-<i>dig</i>-cyclized products. Reactivity behavior of electron-deficient and electron-rich <i>ortho</i>-alkynylaldehydes in the synthesis of naphthyridines and thienopyridine by three-component reaction is supported by the control experiment

Silver-Catalyzed Tandem Synthesis of Naphthyridines and Thienopyridines via Three-Component Reaction

An efficient approach for the silver-catalyzed regioselective tandem synthesis of highly functionalized 1,2-dihydrobenzo­[1,6]­naphthyridines <b>6a</b>–<b>z</b> and <b>7a</b>–<b>e</b> by the reaction of <i>ortho</i>-alkynylaldehydes <b>3a</b>–<b>n</b> with amines <b>4a</b>–<b>d</b> and ketones <b>5a</b>–<b>c</b>/active methylene compounds <b>5d</b>–<b>g</b>, under mild reaction conditions, is described. The scope of the developed chemistry was successfully extended for the direct synthesis of 1,2-dihydrobenzo­[4,5]­thieno­[2,3-<i>c</i>]­pyridines <b>8a</b>–<b>e</b>, which is known as the sulfur analogue of β-carbolines. Naphthyridines <b>6a</b>–<b>z</b> and thienopyridines <b>8a</b>–<b>e</b> were obtained via dual activation concept using l-proline as organocatalyst; however, naphthyridines <b>7a</b>–<b>e</b> were synthesized without using organocatalyst. The reaction shows selective N–C bond formation on the more electrophilic alkynyl carbon, resulting in the regioselective 6-<i>endo</i>-<i>dig</i>-cyclized products. Reactivity behavior of electron-deficient and electron-rich <i>ortho</i>-alkynylaldehydes in the synthesis of naphthyridines and thienopyridine by three-component reaction is supported by the control experiment

Palladium-Catalyzed Intramolecular Cross-Dehydrogenative Coupling: Synthesis of Fused Imidazo[1,2‑<i>a</i>]pyrimidines and Pyrazolo[1,5‑<i>a</i>]pyrimidines

A palladium-catalyzed intramolecular dehydrogenative coupling reaction was developed for the synthesis of fused imidazo­[1,2-<i>a</i>]­pyrimidines and pyrazolo­[1,5-<i>a</i>]­pyrimidines. The developed protocol provides a practical approach for the synthesis of biologically important substituted pyrimidines from easily available substrates, with a broad substrate scope under mild reaction conditions

Tandem Synthesis of Pyrroloacridones via [3 + 2] Alkyne Annulation/Ring-Opening with Concomitant Intramolecular Aldol Condensation

An efficient cascade strategy for the direct synthesis of pyrrolo­[3,2,1-<i>de</i>]­acridones <b>4a</b>–<b>v</b>, <b>5a</b>–<b>h</b> from iodo-pyranoquinolines <b>2a</b>–<b>i</b> by the palladium-catalyzed regioselective [3 + 2] alkyne annulation/ring-opening followed by intramolecular aldol condensation under microwave irradiation is described. The chemistry involves the in situ formation of pyrroloquinolines <b>Y</b>, via palladium-catalyzed selective [3 + 2] annulation of iodopyranoquinolines and internal akynes with ring-opening and successive intramolecular cross-aldol condensation. Both the symmetrical and unsymmetrical internal alkynes were reacted smoothly to provide the desired pyrroloacridones in good yields. This methodology provides the facile conversion of easily accessble iodopyranoquinoline into highly functionalized biologically important pyrroloacridones in a single process

Copper-Catalyzed Tandem Synthesis of Indolo‑, Pyrrolo[2,1‑<i>a</i>]isoquinolines, Naphthyridines and Bisindolo/Pyrrolo[2,1‑<i>a</i>]isoquinolines via Hydroamination of <i>ortho</i>-Haloarylalkynes Followed by C‑2 Arylation

An efficient approach for the copper-catalyzed regioselective tandem synthesis of diversely substituted indolo­[2,1-<i>a</i>]­isoquinolines <b>11a</b>–<b>r</b>, pyrrolo­[2,1-<i>a</i>]­isoquinolines <b>12a</b>–<b>d</b>, and indolo-, pyrrolo­[2,1-<i>f</i>]­[1,6]­naphthyridines <b>14a</b>–<b>f</b> via preferential addition of the heterocyclic amines onto the <i>ortho</i>-haloarylalkynes over <i>N</i>-arylation followed by intramolecular C-2 arylation is described. The scope of the developed chemistry was successfully extended for the direct synthesis of bisindolo-, pyrrolo­[2,1-<i>a</i>]­isoquinolines <b>15a</b>–<b>g</b>, a regioisomer of the bisindolo­[1,2-<i>a</i>]­quinolines used as organic single-crystal field-effect transistor. Hydroxymethyl benzotriazole, which is an inexpensive and air stable compound, has been used as a ligand to carry out this one-step conversion of simple, readily available starting materials into an interesting class of heterocyclic compounds

Copper-Catalyzed Tandem Synthesis of Indolo‑, Pyrrolo[2,1‑<i>a</i>]isoquinolines, Naphthyridines and Bisindolo/Pyrrolo[2,1‑<i>a</i>]isoquinolines via Hydroamination of <i>ortho</i>-Haloarylalkynes Followed by C‑2 Arylation

An efficient approach for the copper-catalyzed regioselective tandem synthesis of diversely substituted indolo­[2,1-<i>a</i>]­isoquinolines <b>11a</b>–<b>r</b>, pyrrolo­[2,1-<i>a</i>]­isoquinolines <b>12a</b>–<b>d</b>, and indolo-, pyrrolo­[2,1-<i>f</i>]­[1,6]­naphthyridines <b>14a</b>–<b>f</b> via preferential addition of the heterocyclic amines onto the <i>ortho</i>-haloarylalkynes over <i>N</i>-arylation followed by intramolecular C-2 arylation is described. The scope of the developed chemistry was successfully extended for the direct synthesis of bisindolo-, pyrrolo­[2,1-<i>a</i>]­isoquinolines <b>15a</b>–<b>g</b>, a regioisomer of the bisindolo­[1,2-<i>a</i>]­quinolines used as organic single-crystal field-effect transistor. Hydroxymethyl benzotriazole, which is an inexpensive and air stable compound, has been used as a ligand to carry out this one-step conversion of simple, readily available starting materials into an interesting class of heterocyclic compounds

Copper-Catalyzed Tandem Synthesis of Indolo‑, Pyrrolo[2,1‑<i>a</i>]isoquinolines, Naphthyridines and Bisindolo/Pyrrolo[2,1‑<i>a</i>]isoquinolines via Hydroamination of <i>ortho</i>-Haloarylalkynes Followed by C‑2 Arylation

An efficient approach for the copper-catalyzed regioselective tandem synthesis of diversely substituted indolo­[2,1-<i>a</i>]­isoquinolines <b>11a</b>–<b>r</b>, pyrrolo­[2,1-<i>a</i>]­isoquinolines <b>12a</b>–<b>d</b>, and indolo-, pyrrolo­[2,1-<i>f</i>]­[1,6]­naphthyridines <b>14a</b>–<b>f</b> via preferential addition of the heterocyclic amines onto the <i>ortho</i>-haloarylalkynes over <i>N</i>-arylation followed by intramolecular C-2 arylation is described. The scope of the developed chemistry was successfully extended for the direct synthesis of bisindolo-, pyrrolo­[2,1-<i>a</i>]­isoquinolines <b>15a</b>–<b>g</b>, a regioisomer of the bisindolo­[1,2-<i>a</i>]­quinolines used as organic single-crystal field-effect transistor. Hydroxymethyl benzotriazole, which is an inexpensive and air stable compound, has been used as a ligand to carry out this one-step conversion of simple, readily available starting materials into an interesting class of heterocyclic compounds