Day: November 21, 2022

Solum, Eirik published the artcileNew CDK8 inhibitors as potential anti-leukemic agents – Design, synthesis and biological evaluation, Product Details of C9H8BNO2, the publication is Bioorganic & Medicinal Chemistry (2020), 28(10), 115461, database is CAplus and MEDLINE.

Cyclin-dependent kinase 8 (CDK8) plays a vital role in regulating cell transcription either through its association with the mediator complex or by the phosphorylation of transcription factors. CDK8-mediated activation of oncogenes has proved to be important in a variety of cancer types including hematol. malignancies. We have designed and synthesized a series of new synthetic steroids. The compounds were evaluated as CDK8 inhibitors in vitro. The three most potent compounds exhibit K_d-values towards CDK8 in the low nanomolar range (3.5-18 nM). Furthermore, the compounds displayed selectivity for CDK8 in a panel of 465 different kinases. The cell studies indicated a selectivity to kill AML-cancer cell lines compared to normal cell lines.

Bioorganic & Medicinal Chemistry published new progress about 371766-08-4. 371766-08-4 belongs to isoquinoline, auxiliary class Isoquinoline,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is Isoquinolin-5-ylboronic acid, and the molecular formula is C37H30ClIrOP2, Product Details of C9H8BNO2.

Referemce:
https://en.wikipedia.org/wiki/Isoquinoline,
Isoquinoline | C9H7N – PubChem

Goldfogel, Matthew J. published the artcileAdvancing Base-Metal Catalysis: Development of a Screening Method for Nickel-Catalyzed Suzuki-Miyaura Reactions of Pharmaceutically Relevant Heterocycles, Application In Synthesis of 371766-08-4, the publication is Organic Process Research & Development (2022), 26(3), 785-794, database is CAplus.

Interest in replacing palladium catalysts with base metals resulted in the development of a 24-reaction screening platform for identifying nickel-catalyzed Suzuki-Miyaura reaction conditions. This method was designed to be directly applicable to process scale-up by employing homogeneous reaction conditions alongside stable and inexpensive nickel(II) precatalysts and has proven to be broadly suitable for complex heterocyclic substrates relevant to bioactive mols. These advances were enabled by the key discovery that a methanol additive greatly improves the reaction performance and enables the use of organic-soluble amine bases. The screening platform and scale-up workflow were applied to a representative cross-coupling using the antipsychotic perphenazine and enabled the rapid development of a gram-scale synthesis that highlighted the utility of this method and the advantages of nickel catalysis for metal remediation.

Organic Process Research & Development published new progress about 371766-08-4. 371766-08-4 belongs to isoquinoline, auxiliary class Isoquinoline,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is Isoquinolin-5-ylboronic acid, and the molecular formula is C9H8BNO2, Application In Synthesis of 371766-08-4.

Referemce:
https://en.wikipedia.org/wiki/Isoquinoline,
Isoquinoline | C9H7N – PubChem

Du, Wei published the artcileEnantioselective Palladium-Catalyzed Oxidative Cascade Cyclization of Aliphatic Alkenyl Amides, Synthetic Route of 2058236-53-4, the publication is Organic Letters (2017), 19(2), 316-319, database is CAplus and MEDLINE.

The catalyst system of Pd(TFA)₂/(S,S)-diPh-pyrox is reported to promote the highly efficient enantioselective oxidative cascade cyclization of alkene-tethered aliphatic acrylamides under mild aerobic conditions. Pyrrolizidine derivatives were synthesized in good yield and excellent enantioselectivity. D-labeling experiments revealed that the reaction proceeded through an anti-aminopalladation (anti-AP) pathway with high selectivity. The transition states for the anti-AP step account for the observed enantioselectivity.

Organic Letters published new progress about 2058236-53-4. 2058236-53-4 belongs to isoquinoline, auxiliary class Mono-oxazoline Ligands, name is (S)-2-(Isoquinolin-1-yl)-4-phenyl-4,5-dihydrooxazole, and the molecular formula is C18H14N2O, Synthetic Route of 2058236-53-4.

Referemce:
https://en.wikipedia.org/wiki/Isoquinoline,
Isoquinoline | C9H7N – PubChem

Bensch, Lisa published the artcile5-(Hetero)aryl-Substituted 9-Hydroxyphenalenones: Synthesis and Electronic Properties of Multifunctional Donor-Acceptor Conjugates, Category: isoquinoline, the publication is Chemistry – A European Journal (2017), 23(44), 10551-10558, database is CAplus and MEDLINE.

5-(Hetero)aryl-substituted 9-hydroxyphenalenones (9-HP) can be readily synthesized by Suzuki coupling of 5-bromo 9-HP with (hetero)aryl boronic acid (derivatives) without protection of the hydroxyl functionality in moderate to excellent yields (57-94 %). A library of 5-(hetero)aryl substituted 9-HP with broad substituent variation was studied with respect to their electronic properties (absorption and emission spectroscopies and cyclic voltammetry) and their computed electronic structures. All compounds show reversible reductive potentials between -1230 and -1110 mV and the donor-substituted representatives possess irreversible oxidation potentials around 600 mV. Compounds with electron-rich donors even show reversible oxidation potentials. Especially the donor-substituted 9-HPs display emission bands between 466 and 567 nm with quite large Stokes shifts (up to 4100 cm^-1). TD-DFT calculations nicely reproduce the spectroscopic data and Hammett correlations underline a pronounced resonance substituent influence on the photophys. properties.

Chemistry – A European Journal published new progress about 371766-08-4. 371766-08-4 belongs to isoquinoline, auxiliary class Isoquinoline,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is Isoquinolin-5-ylboronic acid, and the molecular formula is C9H8BNO2, Category: isoquinoline.

Referemce:
https://en.wikipedia.org/wiki/Isoquinoline,
Isoquinoline | C9H7N – PubChem

Coombs, John R. published the artcileAdvances in Base-Metal Catalysis: Development of a Screening Platform for Nickel-Catalyzed Borylations of Aryl (Pseudo)halides with B₂(OH)₄, Recommanded Product: Isoquinolin-5-ylboronic acid, the publication is Organometallics (2019), 38(1), 157-166, database is CAplus.

Investigations into nickel-catalyzed borylation reactions have led to the development of an exptl. design of 24 reaction conditions for rapid lead identification. A case study on the borylation of a model aryl bromide with B₂(OH)₄ prompted a series of mechanistic and stability studies to better understand the catalytic cycle and factors that affect robustness. HTEx was employed to study the effect of a series of scavengers on the remediation of nickel from the reaction stream. These combined results have generated an increased understanding of nickel-catalyzed borylation reactions and set the stage for their expanded use in process chem.

Organometallics published new progress about 371766-08-4. 371766-08-4 belongs to isoquinoline, auxiliary class Isoquinoline,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is Isoquinolin-5-ylboronic acid, and the molecular formula is C9H8BNO2, Recommanded Product: Isoquinolin-5-ylboronic acid.

Referemce:
https://en.wikipedia.org/wiki/Isoquinoline,
Isoquinoline | C9H7N – PubChem

Le Manach, Claire published the artcileMedicinal Chemistry Optimization of Antiplasmodial Imidazopyridazine Hits from High Throughput Screening of a SoftFocus Kinase Library: Part 1, Safety of Isoquinolin-5-ylboronic acid, the publication is Journal of Medicinal Chemistry (2014), 57(6), 2789-2798, database is CAplus and MEDLINE.

A novel class of imidazopyridazines identified from whole cell screening of a SoftFocus kinase library was synthesized and evaluated for antiplasmodial activity against K1 (multidrug resistant strain) and NF54 (sensitive strain). Structure-activity relationship studies led to the identification of highly potent compounds against both strains. Compound I was highly active (IC₅₀: K1 = 6.3 nM, NF54 = 7.3 nM) and comparable in potency to artesunate, and I exhibited 98% activity in the in vivo P. berghei mouse model (4-day test by Peters) at 4 × 50 mg/kg po. Compound I was also assessed against P. falciparum in the in vivo SCID mouse model where the efficacy was found to be more consistent with the in vitro activity. Furthermore, I displayed high (78%) rat oral bioavailability with good oral exposure and plasma half-life. Mice exposure at the same dose was 10-fold lower than in rat, suggesting lower oral absorption and/or higher metabolic clearance in mice.

Journal of Medicinal Chemistry published new progress about 371766-08-4. 371766-08-4 belongs to isoquinoline, auxiliary class Isoquinoline,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is Isoquinolin-5-ylboronic acid, and the molecular formula is C9H8BNO2, Safety of Isoquinolin-5-ylboronic acid.

Referemce:
https://en.wikipedia.org/wiki/Isoquinoline,
Isoquinoline | C9H7N – PubChem

Beveridge, Ramsay E. published the artcileA direct copper-catalyzed route to pyrrolo-fused heterocycles from boronic acids, Application of Isoquinolin-5-ylboronic acid, the publication is Tetrahedron Letters (2012), 53(5), 564-569, database is CAplus.

A convenient route to prepare azaindoles and related pyrrolo-fused heterocycles from boronic acids, DBAD (di-tert-Bu diazodicarboxylate), and enolizable aldehydes and ketones is presented. E.g., reaction of 6-methoxy-3-pyridineboronic acid, DMAD, and PhCH₂CHO, catalyzed by Cu(OAc)₂, gave 70% azaindole derivative I. The reaction proceeds via a one-pot four-step cascade sequence with key steps involving a copper-catalyzed boronic acid coupling to DBAD and a Fischer indolization providing access to a variety of pharmaceutically interesting heterocycles including pyrrolopyridines, -pyrimidines, -quinolines, and -isoquinolines from readily available aza-aryl boronic acid precursors.

Tetrahedron Letters published new progress about 371766-08-4. 371766-08-4 belongs to isoquinoline, auxiliary class Isoquinoline,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is Isoquinolin-5-ylboronic acid, and the molecular formula is C9H8BNO2, Application of Isoquinolin-5-ylboronic acid.

Referemce:
https://en.wikipedia.org/wiki/Isoquinoline,
Isoquinoline | C9H7N – PubChem

Engers, Darren W. published the artcileSynthesis and structure-activity relationships of a novel and selective bone morphogenetic protein receptor (BMP) inhibitor derived from the pyrazolo[1.5-a]pyrimidine scaffold of Dorsomorphin: The discovery of ML347 as an ALK2 versus ALK3 selective MLPCN probe, Computed Properties of 371766-08-4, the publication is Bioorganic & Medicinal Chemistry Letters (2013), 23(11), 3248-3252, database is CAplus and MEDLINE.

A structure-activity relation of the 3- and 6-positions of the pyrazolo[1,5-a]pyrimidine scaffold of the known BMP inhibitors dorsomorphin, 1, LDN-193189, 2, and DMH1, 3, led to the identification of a potent and selective compound for ALK2 vs. ALK3. The potency contributions of several 3-position substituents were evaluated with subtle structural changes leading to significant changes in potency. From these studies, a novel 5-quinoline mol. was identified and designated an MLPCN probe mol., ML347, which shows >300-fold selectivity for ALK2 and presents the community with a selective mol. probe for further biol. evaluation.

Bioorganic & Medicinal Chemistry Letters published new progress about 371766-08-4. 371766-08-4 belongs to isoquinoline, auxiliary class Isoquinoline,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is Isoquinolin-5-ylboronic acid, and the molecular formula is C9H8BNO2, Computed Properties of 371766-08-4.

Referemce:
https://en.wikipedia.org/wiki/Isoquinoline,
Isoquinoline | C9H7N – PubChem

Yu, Wensheng published the artcileDiscovery of macrocyclic HDACs 1, 2, and 3 selective inhibitors for HIV latency reactivation, Safety of 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-1(2H)-one, the publication is Bioorganic & Medicinal Chemistry Letters (2021), 128168, database is CAplus and MEDLINE.

A series of unique macrocyclic HDACs 1, 2, and 3 selective inhibitors were identified with good enzymic activity and high selectivity over HDACs 6 and 8. These macrocyclic HDAC inhibitors used an Et ketone as the zinc-binding group. Compounds I and II stood out as leads due to their low double-digit nM EC₅₀s in the 2C4 cell-based HIV latency reactivation assay. The PK profiles of these macrocyclic HDAC inhibitors still needed improvement.

Bioorganic & Medicinal Chemistry Letters published new progress about 1219130-56-9. 1219130-56-9 belongs to isoquinoline, auxiliary class Isoquinoline,Boronic acid and ester,Amide,Boronic Acids,Boronate Esters, name is 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-1(2H)-one, and the molecular formula is C19H36BNO2Si, Safety of 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-1(2H)-one.

Referemce:
https://en.wikipedia.org/wiki/Isoquinoline,
Isoquinoline | C9H7N – PubChem

Visseq, Alexia published the artcilePyridin-2(1H)one derivatives: A possible new class of therapeutics for mechanical allodynia, Synthetic Route of 371766-08-4, the publication is European Journal of Medicinal Chemistry (2020), 111917, database is CAplus and MEDLINE.

A series of 3,5-disubstituted pyridin-2(1H)-ones I [R = 1H-indol-4-yl, (1,1-biphenyl)-4-yl, 3-chlorophenyl, etc.] was designed, synthesized and evaluated in vivo toward a rat model of inflammatory mech. allodynia. The series rapidly and strongly prevented the development of mech. allodynia. The compound I (R = 2-bromophenyl (A)), a most active compound of the series, which was also able to quickly reverse neuropathic MA in rats, was founded. Next, when compound (A) was evaluated toward a panel of 50 protein kinases (PK) in order to identify its potential biol. target(s), it was found that compound (A) is a p38α MAPK inhibitor, a PK known to contribute to pain and hypersensitivity in animal models. 3,5-Disubstituted pyridin-2(1H)-ones I thus could represent a novel class of analgesic for the treatment of mech. allodynia.

European Journal of Medicinal Chemistry published new progress about 371766-08-4. 371766-08-4 belongs to isoquinoline, auxiliary class Isoquinoline,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is Isoquinolin-5-ylboronic acid, and the molecular formula is C12H10O4S, Synthetic Route of 371766-08-4.

Referemce:
https://en.wikipedia.org/wiki/Isoquinoline,
Isoquinoline | C9H7N – PubChem