Synthesis, Crystal Structure, Hirshfeld Surface Analysis, and Computational Approach of a New Pyrazolo[3,4-]isoquinoline Derivative as Potent against Leucine-Rich Repeat Kinase 2 (LRRK2).

Ethyl-2-((8-cyano-3,5,9a-trimethyl-1-(4-oxo-4,5-dihydrothiazol-2-yl)-4-phenyl-3a,4,9,9a-tetrahydro-1-pyrazolo[3,4-]isoquinolin-7-yl)thio)acetate () was synthesized, and its structure was characterized by IR, MS, and NMR (H and C) and verified by a single-crystal X-ray structure determination. Compound adopts a "pincer" conformation. In the crystal, the hydrogen bonds of -H···O, C-H···O, and O-H···S form thick layers of molecules that are parallel to (101).

New tetrahydroisoquinoline-4-carbonitrile derivatives as potent agents against cyclin-dependent kinases, crystal structures, and computational studies.

The synthesis of two new hexahydroisoquinoline-4-carbonitrile derivatives ( and ) is reported along with spectroscopic data and their crystal structures. In compound , the intramolecular O-H···O hydrogen bond constraints the acetyl and hydroxyl groups to be . In the crystal, inversion dimers are generated by C-H···O hydrogen bonds and are connected into layers parallel to (10-1) by additional C-H···O hydrogen bonds.

Pyridine Derivatives as Insecticides─Part 4: Synthesis, Crystal Structure, and Insecticidal Activity of Some New Thienylpyridines, Thienylthieno[2,3-]pyridines, and Related Heterocyclic Derivatives.

The reaction of ethyl 5-cyano-2-methyl-4-(thiophen-2-yl)-6-thioxo-1,6-dihydropyridine-3-carboxylate () with 2-chloroacetamide or its -aryl derivatives gave ethyl 6-((2-amino-2-oxoethyl)thio)-5-cyano-2-methyl-4-(thiophen-2-yl) nicotinate () or its -aryl derivatives -, respectively. Cyclization of - into their isomers - was carried out by heating in absolute ethanol in the presence of a catalytic amount of sodium ethoxide. The -aminoamide was reacted with some aryl aldehydes in refluxing ethanol containing a few drops of conc.

Synthesis, structural and X-ray analysis evaluations and computational studies of newly tetrahydroisoquinoline derivatives as potent against microsomal prostaglandin E synthase 1.

Tetrahydroisoquinolines (THIQs) are a significant class within the broad range of natural compounds known as isoquinoline alkaloids. Natural and manmade drugs based on THIQ have a variety of biological effects that protect against different infectious pathogens and neurological diseases. In this study, two new THIQ derivatives were synthesized and characterized using by X-ray crystallographic analysis.

Thieno[2,3-c]isoquinolines: A novel chemotype of antiproliferative agents inducing cellular apoptosis while targeting the G2/M phase and Tubulin.

In the era of modern synthetic methodology and advanced bio-evaluation techniques and considering the notorious history of hepatocellular carcinoma (HCC), hopeful expectations regarding novel bioactive chemotypes have grown dramatically. Among the widely versatile motifs in drug discovery studies are isoquinoline and thieno[2,3-b]pyridine. Herein, the molecular merging of both motifs evoked thieno[2,3-c]isoquinoline as a novel antiproliferative chemotype being hardly studied against HCC.

Exploration of Dihydrothieno[2,3-] Isoquinolines As Luminescent Materials and Corrosion Inhibitors.

The reaction of the starting compound, 7-acetyl-4-cyano-1,6-dimethyl-8-phenyl-7,8-dihydroisoquinoline-3(2)-thione, with some -aryl-2-chloroacetamides or chloroacetonitrile, in the presence of sodium acetate trihydrate, gave the corresponding substituted 3-methylsulfanyl-7-acetyl-4-cyano-1,6-dimethyl-8-phenyl-7,8-dihydroisoquinolines. Upon heating of the latter compounds with sodium methoxide in methanol, they underwent intramolecular Thorpe-Zeigler cyclization, affording the target isomers 1-amino-2-(substituted)-5,8-dimethyl-6-phenyl-6,7-dihydrothieno[2,3]isoquinolines (DHTIQs). The chemical structures of all produced substances were characterized by elemental and spectral analyses.

Pyridine Derivatives as Insecticides. Part 3. Synthesis, Crystal Structure, and Toxicological Evaluation of Some New Partially Hydrogenated Isoquinolines against (, 1887).

Three new series of isoquinolines, that is, 7-acetyl-3-acetonylsulfanyl-8-aryl-1,6-dimethyl-6-hydroxy-5,6,7,8-tetrahydroisoquinoline-4-carbonitriles (-); 3-acetonylsulfanyl-8-aryl-1,6-dimethyl-7,8-dihydroisoquinoline-4-carbonitriles (-); and 7-acetyl-8-aryl-1,6-dimethyl-3-ethylsulfanyl-7,8-dihydroisoquinoline-4-carbo-nitriles (,) were carefully synthesized. Also, pyrazoloisoquinoline was used as a precursor for synthesis of 7-ethylsulfanyl-4-phenyl-1-thiocarbamoyl-3,5,9a-trimethyl-3a,4,9,9a-tetrahydro-1-pyrazolo[3,4-g]isoquinoline-8-carbonitrile (); 7-benzyl-sulfanyl-4-phenyl-1-thiocarbamoyl-3,5,9a-trimethyl-3a,4,9,9a-tetrahydro-1-pyrazolo[3,4-]isoquinoline-8-carbonitrile (); and 7-ethylsulfanyl-1-(4-oxo-4,5-dihydrothiazol-2-yl)-4-phenyl-3,5,9a-trimethyl-3a,4,9,9a-tetrahydro-1-pyrazolo[3,4-]isoquinoline-8-carbonitrile (). Moreover, the crystal structures of two representative compounds were determined.

Crystal structure and Hirshfeld surface analysis of 2-{[7-acetyl-4-cyano-6-hy-droxy-8-(4-meth-oxyphen-yl)-1,6-dimethyl-5,6,7,8-tetra-hydro-isoquinolin-3-yl-]sulfan-yl}acetic acid ethyl ester.

In the title mol-ecule, CHNOS, (alternative name ethyl 2-{[7-acetyl-4-cyano-6-hy-droxy-8-(4-meth-oxy-phen-yl)-1,6-dimethyl-5,6,7,8-tetra-hydro-isoquinolin-3-yl]sulfanyl}-acetate) the 4-meth-oxy-phenyl group is disposed on one side of the bicyclic core and the oxygen atoms of the hydroxyl and acetyl groups are disposed on the other side. In the crystal, a layered structure parallel to the plane is generated by O-H⋯O and C-H⋯O hydrogen bonds plus C-H⋯π(ring) inter-actions.

Crystal structure and Hirshfeld surface analysis of 2-{[7-acetyl-8-(4-chloro-phen-yl)-4-cyano-6-hy-droxy-1,6-dimethyl-5,6,7,8-tetra-hydro-isoquinolin-3-yl]sulfan-yl}--(4-chloro-phen-yl)acetamide.

In the title mol-ecule, CHClNOS, the heterocyclic portion of the tetra-hydro-iso-quinoline unit is planar while the cyclo-hexene ring adopts a twist-boat conformation. The two 4-chloro-phenyl groups extend away from one side of this unit while the hydroxyl and acetyl groups extend away from the opposite side and form an intra-molecular O-H⋯O hydrogen bond. The crystal packing consists of layers parallel to the plane.

Synthesis and Characterization of Novel Functionally Substituted Planar Pyrimidothienoisoquinolines and Nonplanar (3a, 4, 9a)-pyrazolo[3,4-]isoquinolines.

7-Acetyl-8-aryl-4-cyano-1,6-dimethyl-6-hydroxy-5,6,7,8-tetrahydroisoquinolin-3(2)-thiones , are prepared and dehydrated to give 7-acetyl-8-aryl-4-cyano-1,6-dimethyl-6-hydroxy-7,8-dihydrodroisoquinolin-3(2)-thiones , via a novel method by heating with acetyl chloride in acetic acid. The reaction of both compounds , and , with -aryl-2-chloroacetamides - under two different conditions gave the same corresponding products, 7-acetyl-8-aryl-3-(-aryl)carbamoylmethylsulfanyl-4-cyano-1,6-dimethyl-7,8-dihydroisoquinolines -, in high yields. On treatment of compounds ,, in methanol with a slightly excess molar amount of sodium methoxide, they underwent intramolecular Thorpe-Ziegler cyclization followed by spontaneous aromatization, providing the planar 7-acetyl-1-amino-6-aryl-2-(-aryl)carbamoyl-5,8-dimethyl-8,9-dihydrothieno[2,3-] isoquinolines ,, in good yield.

Synthesis, Characterization, and Crystal Structure of Some New Tetrahydroisoquinolines and Related Tetrahydrothieno[2,3-]isoquinolines.

The starting compounds 7-acetyl-8-aryl-4-cyano-1,6-dimethyl-6-hydroxy-5,6,7,8-tetrahydroisoquinoline(2)-3-thiones were synthesized and reacted with some -aryl-2-chloroacetamides in the presence of sodium acetate to produce 7-acetyl-8-aryl-3-(arylcarbamoylmethylsulfanyl)-4-cyano-1,6-dimethyl-6-hydroxy-5,6,7,8-tetrahydroisoquinolines . Upon heating in ethanol containing sodium ethoxide, they underwent intramolecular Thorpe-Zeigler cyclization, affording the corresponding 7-acetyl-1-amino-6-aryl-2-(-arylcarbamoyl)-5,8-dimethyl-8-hydroxy-6,7,8,9-tetrahydrothieno[2,3-]isoquinolines . Compounds were converted into the corresponding 1-(1-pyrrolyl) derivatives by heating with 2,5-dimethoxytetrahydrofuran in glacial acetic acid.