cas 34784-04-8, 5-Bromoisoquinoline | Articles data

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Acceptorless Dehydrogenation of N-Heterocycles and Secondary Alcohols by Ru(II)-NNC Complexes Bearing a Pyrazoyl-indolyl-pyridine Ligand
Ruthenium(II) hydride complexes bearing a pyrazolyl-(2-indol-1-yl)-pyridine ligand were synthesized and structurally characterized by NMR analysis and X-ray single crystal crystallographic determinations. These complexes efficiently catalyzed acceptorless dehydrogenation of N-heterocycles and secondary alcohols, respectively, exhibiting highly catalytic activity with a broad substrate scope. The present work has established a strategy to construct highly active transition metal complex catalysts and provides an atom-economical and environmentally benign protocol for the synthesis of aromatic N-heterocyclic compounds and ketones.
Wang, Qingfu,Chai, Huining,Yu, Zhengkun
p. 584 - 591
(2018)
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Synthesis of novel polyfunctional pyrrolo[2,1-a]isoquinolines based on 1,3-dipolar cycloaddition reactions
A series of 5-substituted 8-nitroisoquinolines was synthesized based on the reaction of 5-bromo-8-nitroisoquinohne with various nucleophiles. N-Alkylation products of 8-nitroisoquinolines were shown to undergo 1,3-dipolar cycloaddition to substituted alkenes and alkynes as dipolarophiles in the presence of a base to form new polyfunctional nitro-containing pyrrolo-[2,1-a]isoquinolines and their hydrogenated analogs.
Bastrakov,Starosotnikov
p. 1729 - 1734
(2019)
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Molecularly engineered Ru(II) sensitizers compatible with cobalt(II/III) redox mediators for dye-sensitized solar cells
Thiocyanate-free isoquinazolylpyrazolate Ru(II) complexes were synthesized and applied as sensitizers in dye-sensitized solar cells (DSCs). Unlike most other successful Ru sensitizers, Co-based electrolytes were used, and resulting record efficiency of 9.53% was obtained under simulated sunlight with an intensity of 100 mW cm-2. Specifically, dye 51-57dht.1 and an electrolyte based on Co(phen)3 led to measurement of a JSC of 13.89 mA cm-2, VOC of 900 mV, and FF of 0.762 to yield 9.53% efficiency. The improved device performances were achieved by the inclusion of 2-hexylthiophene units onto the isoquinoline subunits, in addition to lengthening the perfluoroalkyl chain on the pyrazolate chelating group, which worked to increase light absorption and decrease recombination effects when using the Co-based electrolyte. As this study shows, Ru(II) sensitizers bearing sterically demanding ligands can allow successful utilization of important Co electrolytes and high performance.
Wu, Kuan-Lin,Huckaba, Aron J.,Clifford, John N.,Yang, Ya-Wen,Yella, Aswani,Palomares, Emilio,Gr?tzel, Michael,Chi, Yun,Nazeeruddin, Mohammad Khaja
p. 7388 - 7395
(2016)
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Discovery of potent and practical antiangiogenic agents inspired by cortistatin A
The discovery that cortistatins A and J show noteworthy antiangiogenic activity prompted an investigation of the possibility that simpler and much more easily made compounds based on a steroid core might have useful bioactivity. These studies have led to
Czako, Barbara,Kuerti, Laszlo,Mammoto, Akiko,Ingber, Donald E.,Corey
p. 9014 - 9019
(2009)
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Blue-emitting copolymers of isoquinoline and fluorene
5,8-Linked copolymers of isoquinoline with fluorene were synthesized by Pd(0)-catalyzed Suzuki polycondensation reaction. The polymers showed good solubility in common organic solvents and the number average molecular weights determined from GPC analysis fall in the range of 7.03-8.08 × 10 3 g/mol. The photoluminescence spectra of these neutral materials in solution exhibit emission maxima in the range 408-426 nm. An X-ray diffraction study on a single crystal of a 5,8-di(9,9-dimethylfluoren-2-yl) isoquinoline model compound shows it to have a non-planar conformation and sheds light on the factors that drive the solid-state packing. The alkylation of the imine nitrogen was achieved by treatment with methyl iodide and the alkylated products were characterized by 1H NMR, 13C NMR and UV-vis spectroscopy. The absorption maxima of model compounds and polymers were red shifted by 46-70 nm upon N-alkylation.
Scaria, Renchu,Lucas, Nigel T.,Müllen, Klaus,Jacob, Josemon
p. 849 - 856
(2011)
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(+)-Dinapsoline: An efficient synthesis and pharmacological profile of a novel dopamine agonist
A highly convergent synthesis was developed for the novel dopamine agonist dinapsoline (12) (Ghosh, D.; Snyder, S. E.; Watts, V. J.; Mailman, R. B.; Nichols, D. E. 8,9-Dihydroxy-2,3,7, 11b-tetrahydro-1H-naph[1,2,3-de]isoquinoline: A Potent Full Dopamine D1 Agonist Containing a Rigid β-Phenyldopamine Pharmacophore. J. Med. Chem. 1996, 39 (2), 549-555). The crucial step in the new synthesis was a free radical-initiated cyclization to give the complete dinapsoline framework. The improved synthesis required half as many steps as the original procedure (Nichols, D. E.; Mailman, R.; Ghosh, D. Preparation of novel naphtho[1,2,3-de]isoquinolines as dopamine receptor ligands. PCT Int. Appl. WO 9706799 A1, Feb 27, 1997). One of the late-stage intermediates (11) was resolved into a pair of enantiomers. From there, the (R)-(+)-12 (absolute configuration by x-ray) of dinapsoline was identified as the active enantiomer. In unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats, (+)-dinapsoline showed robust rotational behavior comparable to that of an external benchmark, trans- 4,5,5a,6,7,11b-hexahydro-2-propylbenzo[f]thieno[2,3-c]quinoline-9,10-diol, hydrochloride 18 (Michaelides, M. R.; Hong, Y. Preparation of heterotetracyclic compounds as dopamine agonists. PCT Int. Appl. WO 9422858 A1, Oct 13, 1994).
Sit, Sing-Yuen,Xie, Kai,Jacutin-Porte, Swanee,Taber, Matthew T.,Gulwadi, Amit G.,Korpinen, Carolyn D.,Burris, Kevin D.,Molski, Thaddeus F.,Ryan, Elaine,Xu, Cen,Wong, Henry,Zhu, Juliang,Krishnananthan, Subramaniam,Gao, Qi,Verdoorn, Todd,Johnson, Graham
p. 3660 - 3668
(2002)
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Highly Chemoselective Deoxygenation of N-Heterocyclic N-Oxides Using Hantzsch Esters as Mild Reducing Agents
Herein, we disclose a highly chemoselective room-temperature deoxygenation method applicable to various functionalized N-heterocyclic N-oxides via visible light-mediated metallaphotoredox catalysis using Hantzsch esters as the sole stoichiometric reductant. Despite the feasibility of catalyst-free conditions, most of these deoxygenations can be completed within a few minutes using only a tiny amount of a catalyst. This technology also allows for multigram-scale reactions even with an extremely low catalyst loading of 0.01 mol %. The scope of this scalable and operationally convenient protocol encompasses a wide range of functional groups, such as amides, carbamates, esters, ketones, nitrile groups, nitro groups, and halogens, which provide access to the corresponding deoxygenated N-heterocycles in good to excellent yields (an average of an 86.8% yield for a total of 45 examples).
An, Ju Hyeon,Kim, Kyu Dong,Lee, Jun Hee
supporting information
p. 2876 - 2894
(2021/02/01)

Discovery of Benzopyridone-Based Transient Receptor Potential Vanilloid 1 Agonists and Antagonists and the Structural Elucidation of Their Activity Shift
Among a series of benzopyridone-based scaffolds investigated as human transient receptor potential vanilloid 1 (TRPV1) ligands, two isomeric benzopyridone scaffolds demonstrated a consistent and distinctive functional profile in which 2-oxo-1,2-dihydroquinolin-5-yl analogues (e.g., 2) displayed high affinity and potent antagonism, whereas 1-oxo-1,2-dihydroisoquinolin-5-yl analogues (e.g., 3) showed full agonism with high potency. Our computational models provide insight into the agonist-antagonist boundary of the analogues suggesting that the Arg557 residue in the S4-S5 linker might be important for sensing the agonist binding and transmitting signals. These results provide structural insights into the TRPV1 and the protein-ligand interactions at a molecular level.
Thorat, Shivaji A.,Lee, Yoonji,Jung, Aeran,Ann, Jihyae,Ahn, Songyeon,Baek, Jisoo,Zuo, Dongxu,Do, Nayeon,Jeong, Jin Ju,Blumberg, Peter M.,Esch, Timothy E.,Turcios, Noe A.,Pearce, Larry V.,Ha, Hee-Jin,Yoo, Young Dong,Hong, Sunhye,Choi, Sun,Lee, Jeewoo
p. 370 - 384
(2021/02/05)

Iridium(III)-Catalyzed C(3)-H Alkylation of Isoquinolines via Metal Carbene Migratory Insertion
An Ir(III)-catalyzed C(3)-H alkylation of N-acetyl-1,2-dihydroisoquinolines with diverse acceptor-acceptor diazo compounds has been achieved under a single catalytic system via metal carbene migratory insertion. Moreover, further synthetic transformations of the alkylated products such as aromatization, selective decarboxylation, and decarbonylation lead to the formation of several synthetically viable isoquinoline derivatives having immense potentials.
Jha, Neha,Singh, Roushan Prakash,Saxena, Paridhi,Kapur, Manmohan
supporting information
p. 8694 - 8698
(2021/11/24)

Structure-activity relationships, biological evaluation and structural studies of novel pyrrolonaphthoxazepines as antitumor agents
Microtubule-targeting agents (MTAs) are a class of clinically successful anti-cancer drugs. The emergence of multidrug resistance to MTAs imposes the need for developing new MTAs endowed with diverse mechanistic properties. Benzoxazepines were recently identified as a novel class of MTAs. These anticancer agents were thoroughly characterized for their antitumor activity, although, their exact mechanism of action remained elusive. Combining chemical, biochemical, cellular, bioinformatics and structural efforts we developed improved pyrrolonaphthoxazepines antitumor agents and their mode of action at the molecular level was elucidated. Compound 6j, one of the most potent analogues, was confirmed by X-ray as a colchicine-site MTA. A comprehensive structural investigation was performed for a complete elucidation of the structure-activity relationships. Selected pyrrolonaphthoxazepines were evaluated for their effects on cell cycle, apoptosis and differentiation in a variety of cancer cells, including multidrug resistant cell lines. Our results define compound 6j as a potentially useful optimized hit for the development of effective compounds for treating drug-resistant tumors.
Brindisi, Margherita,Ulivieri, Cristina,Alfano, Gloria,Gemma, Sandra,de Asís Balaguer, Francisco,Khan, Tuhina,Grillo, Alessandro,Chemi, Giulia,Menchon, Grégory,Prota, Andrea E.,Olieric, Natacha,Lucena-Agell, Daniel,Barasoain, Isabel,Diaz, J. Fernando,Nebbioso, Angela,Conte, Mariarosaria,Lopresti, Ludovica,Magnano, Stefania,Amet, Rebecca,Kinsella, Paula,Zisterer, Daniela M.,Ibrahim, Ola,O'Sullivan, Jeff,Morbidelli, Lucia,Spaccapelo, Roberta,Baldari, Cosima,Butini, Stefania,Novellino, Ettore,Campiani, Giuseppe,Altucci, Lucia,Steinmetz, Michel O.,Brogi, Simone
p. 290 - 320
(2018/11/24)

Visible-Light Photocatalyzed Deoxygenation of N-Heterocyclic N-Oxides
A scalable and operationally simple method is described that allows for the chemoselective deoxygenation of a wide range of N-heterocyclic N-oxides (a total of 36 examples). This visible-light-induced protocol features the use of only commercially available reagents, room-temperature conditions, and unprecedented chemoselective removal of the oxygen atom in a quinoline N-oxide in the presence of a pyridine N-oxide in the same molecule through the judicious selection of a photocatalyst.
Kim, Kyu Dong,Lee, Jun Hee
supporting information
p. 7712 - 7716
(2019/01/03)

CEREBLON LIGANDS AND BIFUNCTIONAL COMPOUNDS COMPRISING THE SAME
The description relates to cereblon E3 ligase binding compounds, including bifunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present disclosure. In particular, the description provides compounds, which contain on one end a ligand which binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.
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Paragraph 1054; 1055; 1056; 10567

(2018/08/20)

Regioexhaustive Functionalization of the Carbocyclic Core of Isoquinoline: Concise Synthesis of Oxoaporphine Core and Ellipticine
A general and versatile strategy has been developed for the functionalization of the carbocyclic core of the isoquinoline. This regioexhaustive approach employs electrophilic halogenation as a toolbox methodology and delivers highly decorated intermediates that can be further elaborated toward medicinally relevant building blocks or natural products.
Horváth, Dániel Vajk,Domonyi, Frigyes,Palkó, Roberta,Lomoschitz, Andrea,Soós, Tibor
p. 2181 - 2190
(2018/03/21)

Dehydrogenation of Nitrogen Heterocycles Using Graphene Oxide as a Versatile Metal-Free Catalyst under Air
Graphene oxide (GO) has been developed as an inexpensive, environmental friendly, metal-free carbocatalyst for the dehydrogenation of nitrogen heterocycles. Valuable compounds, such as quinoline, 3,4-dihydroisoquinoline, quinazoline, and indole derivatives, have been successfully used as substrates. The investigation of various oxygen-containing molecules with different conjugated systems indicated that both the oxygen-containing groups and large π-conjugated system in GO sheets are essential for this reaction. (Figure presented.).
Zhang, Jingyu,Chen, Shiya,Chen, Fangfang,Xu, Wensheng,Deng, Guo-Jun,Gong, Hang
supporting information
p. 2358 - 2363
(2017/07/22)

One substrate, two modes of C-H functionalization: A metal-controlled site-selectivity switch in C-H arylation reactions
A unique site-selectivity switch has been achieved in the ruthenium-catalyzed C-H arylation reaction of N-acetyl-1,2-dihydroisoquinolines. This metal-mediated switch is antipodal to the previous report on the palladium-mediated C-4 C-H arylation on the same substrate. Mechanistic details reveal interesting aspects of the reaction pathway, and kinetic studies bring out the difference in the modes of C-H activation adopted by the two catalytic systems.
Tiwari, Virendra Kumar,Kamal, Neha,Kapur, Manmohan
supporting information
p. 262 - 265
(2017/11/27)

A 8-nitro -1, 2, 3, 4-isoquinoline method for the preparation of (by machine translation)
This invention has offered a kind of 8-nitro -1, 2, 3, 4-isoquinoline method for preparing, comprising the following steps: a) isoquinoline and bromizing to the bromination reaction in a strong acid solution, to obtain 5-bromo-isoquinoline; b) the nitrate and step a) the obtained 5-bromo-isoquinoline in the nitration reaction carried out in concentrated sulfuric acid, to obtain 8-nitro-5-bromo-isoquinoline; c) under the conditions of the hydrogen gas, the step b) of 8-nitro-5-bromo-isoquinoline in the solvent under the action of the catalyst to the catalytic hydrogenation Debrominative reaction, to obtain 8-nitro-isoquinoline; d) the step c) of the 8-nitro-isoquinoline with sodium borohydride in acetic acid in the reduction reaction, to obtain 8-nitro -1, 2, 3, 4-isoquinoline. Compared with the prior art, the present invention provides the preparation method of the isoquinoline uses the bromine first 5-C positioning, the subsequent nitration reaction only in 8-C to on, and then sequentially through the catalytic hydrogenation of less impurities are Debrominative and the reduction reaction, the obtained 8-nitro -1, 2, 3, 4-isoquinoline high yield. (by machine translation)
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Paragraph 0076; 0077

(2016/10/10)

The fight against the influenza A virus H1N1: Synthesis, molecular modeling, and biological evaluation of benzofurazan derivatives as viral RNA polymerase inhibitors
The influenza RNA polymerase complex, which consists of the three subunits PA, PB1, and PB2, is a promising target for the development of new antiviral drugs. A large library of benzofurazan compounds was synthesized and assayed against influenza virus A/WSN/33 (H1N1). Most of the new derivatives were found to act by inhibiting the viral RNA polymerase complex through disruption of the complex formed between subunits PA and PB1. Docking studies were also performed to elucidate the binding mode of benzofurazans within the PB1 binding site in PA and to identify amino acids involved in their mechanism of action. The predicted binding pose is fully consistent with the biological data and lays the foundation for the rational development of more effective PA-PB1 inhibitors. In the fight against influenza virus A/WSN/33 (H1N1), the PA-PB1 protein-protein interaction is emerging as a new drug target. To identify small molecules able to inhibit the viral RNA polymerase complex, the benzofurazan scaffold was explored by synthesizing a large library of derivatives. Some compounds showed high anti-H1N1 activity and emerged as effective inhibitors of the PA-PB1 interaction, with IC50 values in the micromolar range. Copyright
Pagano, Mafalda,Castagnolo, Daniele,Bernardini, Martina,Fallacara, Anna Lucia,Laurenzana, Ilaria,Deodato, Davide,Kessler, Ulrich,Pilger, Beatrice,Stergiou, Lilli,Strunze, Stephan,Tintori, Cristina,Botta, Maurizio
p. 129 - 150
(2014/01/17)

ANGIOGENESIS INHIBITORS
Compounds of Structural Formula I or pharmaceutically acceptable salts thereof, are effective inhibitors of angiogenesis:
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Page/Page column 68

(2010/11/05)

ALKYL-SUBSTITUTED 3' COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I): wherein R1, R2, Ar, m and n are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 25

(2010/02/17)

CONDENSED HETEROCYCLIC COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I) wherein R1, A, B, D, E, G, Q, Ar, n, m, and p are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 68

(2010/04/03)

ACYCLIC COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I): wherein R1, R2, R5, Q, G, Ar, m, and n are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 52

(2010/03/02)

4'-AMINO CYCLIC COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I): formula (I) wherein Cy is selected from formula (Il) and wherein R1, R2, R3, Q, G, Ar, m, n and p are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 86; 87

(2010/04/06)

PYRROLIDINE-SUBSTITUTED AZAINDOLE COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I): wherein R1, R2, A, B, D, E, G, Ar, and n are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 35; 36

(2010/02/17)

PYRROLE ANTIFUNGAL AGENTS
The invention provides compounds of formula (I), and pharmaceutically and agriculturally acceptable salts thereof; wherein: R1, R2, R3, R4, R5, R6, A1, L1 and n are as defined herein. These compounds and their pharmaceutically acceptable salts are useful in prevention or treatment of a fungal disease. Compounds of formula (I), and agriculturally acceptable salts thereof, may also be used as agricultural fungicides.
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Page/Page column 142

(2009/12/05)

3' SUBSTITUTED COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I): wherein Q, R1, R4, m and Ar are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 105-106

(2009/04/25)

4' SUBSTITUTED COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I): wherein R1, R2, R5, R6, B, D, E, G, Q, x and n are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 22

(2009/01/24)

6' SUBSTITUTED COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I): wherein R1—R4 A, B, D, E, and G are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 45; 45-46

(2008/12/08)

COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
The present disclosure provides compounds having affinity for the 5HT6 receptor which are of the formula (I), wherein R1-R3 A, B, D, E, G, Q, and x are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 127-128

(2010/11/28)

Co-administration of dopamine-receptor binding compounds
Methods for treating a patient having neurological, psychotic, and psychiatric disorders are described comprising the steps of administering to the patient an effective amount of a partial and/or full dopamine D1 receptor agonist, and administering to the patient an effective amount of a dopamine D2 receptor antagonist. Pharmaceutical compositions comprising a dopamine D1 receptor agonist and a dopamine D2 receptor antagonist are also described. The D1 dopamine receptor agonist and the D2 dopamine receptor antagonist can be administered to the patient in the same or in a different composition or compositions.
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Page/Page column 24

(2010/11/27)

METHOD OF ADMINISTRATION OF DOPAMINE RECEPTOR AGONISTS
Methods for treating a patient having pulmonary edema are described. The methods include administering to the lung endobronchial space of the airways of the patient an effective amount of a dopamine D1 receptor agonist. Dopamine D1 receptor agonists, including hexahydrobenzophenanthridine, hexahydrothienophenanthridine, phenylbenzodiazepine, chromenoisoquinoline, naphthoisoquinoline dopamine receptor agonists, and their pharmaceutically acceptable salts, formulated as aerosols and dry powders are also described.
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Page/Page column 52

(2008/06/13)

MODULATORS OF THE GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-KB ACTIVITY AND USE THEREOF
A class of novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-?B activity including obesity, diabetes, inflammatory and immune diseases, and have the structure of formula (I) its stereoisomers thereof, or a solvate thereof, or a prodrug thereof, or a pharmaceutically acceptable salt thereof, where Z is CONR1R2 or CH2NR1R2 and where at least one of X1 - X8 is N, and R, Ra, Rb, Rc and Rd are defined herein. Also provided are pharmaceutical compositions and methods of treating obesity, diabetes and inflammatory or immune associated diseases comprising said compounds.
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Page/Page column 61

(2008/06/13)

Efficient one-pot transformation of aminoarenes to haloarenes using halodimethylisulfonium halides generated in situ
Halodimethylsulfonium halide 1, which is readily formed in situ from hydrohaloic acid and DMSO, is a good nucleophilic halide. This activated nucleophilic halide rapidly converts aryldiazonium salt prepared in situ by the same hydrohaloic acid and nitrite ion to aryl chlorides, bromides, or iodides in good yield. The combined action of nitrite ion and hydrohaloic acid in DMSO is required for the direct transformation of aromatic amines, which results in the production of aryl halides within 1 h. Substituted compounds with electron-donating or -withdrawing groups or sterically hindered aromatic amines are also smoothly transformed to the corresponding aromatic halides. The only observed by-product is the deaminated arene (usually 7%). The isolated aryldiazonium salts can also be converted to the corresponding aryl halides using 1. The present method offers a facile, one-step procedure for transforming aminoarenes to haloarenes and lacks the environmental pollutants that usually accompany the Sandmeyer reaction using copper halides.
Baik, Woonphil,Luan, Wanqiang,Lee, Hyun Joo,Yoon, Cheol Hun,Koo, Sangho,Kim, Byeong Hyo
p. 213 - 219
(2007/10/03)

Synthesis and SAR of highly potent dual 5-HT1A and 5-HT 1B antagonists as potential antidepressant drugs
Novel 5-HT1 autoreceptor ligands based on the N-4-aryl-piperazinyl-N′-ethyl-5,6,7,8-tetrahydropyrido[4′, 3′:4,5]thieno[2,3-d]pyrimidin-4(3H)-one core are described. Aiming at antidepressants with a novel mode of action our objective was to identify potent antagonists showing balanced affinities and high selectivity for the 5-HT 1A and 5-HT1B receptors. Strategies for the development of dual 5-HT1A and 5-HT1B antagonists based on 1 and 2 as leads and the corresponding results are discussed. Isoquinoline analogue 33 displayed high affinity and an antagonistic mode of action for the 5-HT 1A and the 5-HT1B receptors and was characterized further with respect to selectivity, electrically stimulated [3H]5-HT release and in vivo efficacy.
Kling, Andreas,Lange, Udo E. W.,Mack, Helmut,Bakker, Margot H. M.,Drescher, Karla U.,Hornberger, Wilfried,Hutchins, Charles W.,Moeller, Achim,Mueller, Reinhold,Schmidt, Martin,Unger, Liliane,Wicke, Karsten,Schellhaas, Kurt,Steiner, Gerd
p. 5567 - 5573
(2007/10/03)

Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor
Compounds of formula (I) are novel VR1 antagonists that are useful in treating pain, inflammatory thermal hyperalgesia, urinary incontinence and bladder overactivity.
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Page/Page column 29

(2010/02/11)

Synthesis of 5-bromoisoquinoline and 5-bromo-8-nitroisoquinoline: (Isoquinoline, 5-bromo- and isoquinoline, 5-bromo-8-nitro-)
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Brown, William Dalby,Gouliaev, Alex Haahr,Wolff, Steven,Burger, Walter
p. 96 - 104
(2017/09/08)

SUBSTITUTE ISOQUINOLINES USEFUL IN THE TREATMENT OF DISEASES SUCH AS CANCER AND ATHEROSCLEROSIS
A compound of Formula (I) wherein: One of R1 and R2 is H and the other represents - NHCONHR4 wherein R4 represents a phenyl or naphthyl group (which may be optionally substituted by one or more substituents independently selected from -C1-6 alkyl, -C1-6 haloalkyl, - CH2CH2CH2-, halogen, C1-6 alkoxy, C1-6 haloalkoxy, OH, NO2), C3-7 cycloalkyl or R4 together with the NH to which it is bonded forms a morpholino group and R3 is H or NHR5 wherein R5 is H, -quinolinyl or -isoquinolinyl, -(CONH)p phenyl (wherein p is 0 or 1 and the phenyl is optionally substituted by one or more substituents independently selected from halogen, -C1-6 alkyl, -C1-6 haloalkyl, -morpholino, -SO2NH2, benzothiazole (substituted by methyl)) or a salt, solvate, or physiologically functional derivative thereof.
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Page/Page column 27

(2008/06/13)

1-AMINO-ISOQUINOLINE DERIVATIVES FOR THE TREATMENT OF DISEASES ASSOCIATED WITH INAPPROPRIATE ALK5
A compound of Formula (I) wherein R1 represents a phenyl or napthyl group (each of which is optionally substituted by one or more substituents independently selected from -OH, -C1-6alkyl, C1-6haloalkyl, -OCH2OCH3, -C1-6alkoxy, -halogen,), or a mono or bicyclic heteroaryl group comprising 1, 2 or 3 nitrogen atoms, optionally substituted by -C1-6alkoxy, -C1-6alkyl, C1-6haloalkyl or =0; R2 represents H, benzoimidazolyl, benzothiazolyl, isoquinolinyl, or quinolinyl group or phenyl (said phenyl being optionally substituted by -NR3R4, -C1-4alkoxy, -C1-6alkyl, -CONR3R4, -SO2NR3R4, -NHCONR3R4, -NHCOC1-6alkyl, -C1-6haloalkyl, -OCH2O-, -phenoxy (wherein the phenyl moiety is optionally substituted by NH2 ), -C1-3alkyl, -C1-3alkoxy, -CF3, -5 membered heteroaryl group comprising one or two nitrogen atoms). R3 and R4 are independently selected from H, -C1-6alkyl, -C1-3alkylNR5R6; R5 and R6 are independently H or C1-3alkyl; or a salt, solvate, or physiologically functional derivative thereof.
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Page/Page column 28

(2008/06/13)

Synthesis and radioligand binding studies of C-5- and C-8-substituted 1-(3,4-dimethoxybenzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinoliniums as SK channel blockers related to N-methyl-laudanosine and N-methyl-noscapine
The synthesis and the 125I-apamin binding studies of original C-5- and C-8-substituted 1-(3,4-dimethoxy-benzyl)-2,2-dimethyl-1,2,3,4- tetrahydroisoquinoliniums and 1-(3,4-dimethoxy-benzyl)-6,6-dimethyl-4,5,6,7- tetrahydrothieno[2,3-c]pyridiniums were performed in order to find a reversible and selective SK channel blocker structurally related to N-methyl-laudanosine and N-methyl-noscapine. A bulky alkyl substituent in the C-8 position of the tetrahydroisoquinoline produces a clear increase in the affinity for the apamin sensitive binding sites. The presence of an electron-withdrawing group in the C-5 and C-8 positions is not a suitable substitution for the affinity of drugs structurally related to N-methyl-laudanosine. Thiophenic analogues and 8-methoxy derivatives possess a poor affinity for the apamin sensitive binding sites. Electrophysiological studies performed with the most effective compound showed a blockade of the apamin sensitive afterhyperpolarization in rat dopaminergic neurons.
Graulich, Amaury,Scuvée-Moreau, Jacqueline,Seutin, Vincent,Liégeois, Jean-Fran?ois
p. 4972 - 4982
(2007/10/03)

Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor
Compounds of formula (I) are novel VR1 antagonists that are useful in treating pain, inflammatory thermal hyperalgesia, urinary incontinence and bladder overactivity, wherein X1, X2, X3, X4, X5, R5, R6, R7, R8a, R8b, R9, Z1, Z2 and L are as defined in the description.
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(2008/06/13)

Tetrahydroisoquinolinyl derivatives of quinazoline and isoquinoline
The invention pertains to substituted quinazoline and isoquinoline compounds that serve as effective phosphodiesterase (PDE) inhibitors. In particular, the invention relates to said compounds which are selective inhibitors of PDE-10. The invention also relates to intermediates for preparation of said compounds; pharmaceutical compositions comprising said compounds; and the use of said compounds in a method for treating certain central nervous system (CNS) or other disorders.
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Page/Page column 17

(2010/02/13)

Novel transient receptor potential vanilloid 1 receptor antagonists for the treatment of pain; Structure-activity relationships for ureas with quinoline, isoquinoline, quinazoline, phthalazine, quinoxaliue, and cinnoline moieties
Novel transient receptor potential vanilloid 1 (TRPV1) receptor antagonists with various bicyclic heteroaromatic pharmacophores were synthesized, and their in vitro activity in blocking capsaicin activation of TRPV1 was assessed. On the basis of the contribution of these pharmacophores to the in vitro potency, they were ranked in the order of 5-isoquinoline > 8-quinoline = 8-quinazoline > 8-isoquinoline ≥ cinnoline ≈ phthalazine ≈ quinoxaline ≈ 5-quinoline. The 5-isoquinoline-containing compound 14a (hTRPV1 IC50 = 4 nM) exhibited 46% oral bioavailability and in vivo activity in animal models of visceral and inflammatory pain. Pharmacokinetic and pharmacological properties of 14a are substantial improvements over the profile of the high-throughput screening hit 1 (hTRPV1 IC50 = 22 nM), which was not efficacious in animal pain models and was not orally bioavailable.
Gomtsyan, Arthur,Bayburt, Erol K.,Schmidt, Robert G.,Guo, Zhu Zheng,Perner, Richard J.,Didomenico, Stanley,Koenig, John R.,Turner, Sean,Jinkerson, Tammie,Drizin, Irene,Hannick, Steven M.,Macri, Bryan S.,McDonald, Heath A.,Honore, Prisca,Wismer, Carol T.,Marsh, Kennan C.,Wetter, Jill,Stewart, Kent D.,Oie, Tetsuro,Jarvis, Michael F.,Surowy, Carol S.,Faltynek, Connie R.,Lee, Chih-Hung
p. 744 - 752
(2007/10/03)

Substituted tetrahydroisoquinolines and uses thereof
The invention provides compounds of the formula: and pharmaceutically acceptable salts or prodrugs thereof, wherein, n, X, Y, R1, R2, R3, R4 and R5 are as defined herein. The invention also provides methods for preparing, compositions comprising, and methods for using compounds of formula I.
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Page/Page column 18-19

(2008/06/13)

Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor
Compounds of formula (I) are novel VR1 antagonists that are useful in treating pain, inflammatory thermal hyperalgesia, urinary incontinence and bladder overactivity.
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(2008/06/13)

Synthesis of imidazole intermediates
The invention provides a method for synthesis of compounds of formula wherein R1 and R19 are as defined. Compounds of formula 12 are useful as intermediates for synthesizing compounds having pharmacological activity inhibiting cdk5, cdk2, and GSK-3.
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(2008/06/13)

NOVEL QUINOXALINEDIONE DERIVATIVES, THEIR PREPARATION AND USE
A compound having the formula or a pharmaceutically acceptable salt thereof wherein R is hydrogen or hydroxy; R1 is hydrogen, alkyl, arylalkyl, (CH2)nOH, or (CH2) NR7R8; R5 and R6 are each independently hydrogen, halogen, NO2, CN, CF3, SO2NR7R8, PO3R9R10, alkyl, alkenyl, alkynyl, (CH2)nCONR7R8, (CH2)nCO2R10, NHCOR11, wherein R7 and R8 are each independently hydrogen or alkyl or together R7 and R8 form a ring of from three to seven atoms, R9 is hydrogen or alkyl, R10 is hydrogen or alkyl, R11 is hydrogen or alkyl, and n is an integer of from zero to four; A is a ring of five to seven atoms fused with the benzo ring at the positions marked a and b, and formed by the following bivalent radicals: a-NR12—CHR13—CHR14-b, a-CHR13—CHR14—NR12-b, a-CHR13—NR12—CHR14-b, a-CHR14—CH2—NR12—CHR13-b, a-CHR13—NR12—CH2—CHR14-b, a-CH2—CH2—CHR13—NR12-b, a-NR12—CHR12—CHR13—CH2—CH2-b, a-CH2—CH2—NR12—CH2—CH2-b, a-CH2—CH2—CH2NR12—CH2-b, a-CH2—NR12—CH2—CH2-b a-CH2—CH2—CH2—CH2—NR12-b, a-NR12—CH2—CH2—CH2—CH2-b, wherein R12 is hydrogen, CH2CH2OH, or alkyl, and R13 and R14 are each independently hydrogen, CN, CONH2, CH2NH2, CH2OH, alkyl, arylalkyl, alkenyl, or CO2R15, wherein R15 is hydrogen or alkyl. The compounds are useful in the treatment of disorders of mammals, responsive to the blockade of glutamic and aspartic acid receptors. Processes for preparing the compounds and novel intermediate useful in the processes are also included.
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(2008/06/13)

Kinase inhibitors
Compounds having the formula are useful for inhibiting protein kinases. Also disclosed are compositions which inhibit protein kinases and methods of inhibiting protein kinases in a patient.
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Page/Page column 34

(2010/01/31)

KINASE INHIBITORS
The present invention provides kinase inhibitors of Formula (I)
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Page/Page column 27

(2010/02/07)

PURINE DERIVATIVES AS KINASE INHIBITORS
The present invention provides kinase inhibitors of Formula I.
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Page/Page column 40

(2008/06/13)

Kinase inhibitors
Compounds having the formula are useful for inhibiting protein kinases. Also disclosed are compositions which inhibit protein kinases and methods of inhibiting protein kinases in a patient.
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(2008/06/13)

Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor
Compounds of formula (I) are novel VR1 antagonists that are useful in treating pain, inflammatory thermal hyperalgesia, urinary incontinence and bladder overactivity.
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(2008/06/13)

Synthesis of 5- or 8-bromoisoquinoline derivatives
The present invention is directed to a method of preparing bromoisoquinoline derivatives, in particular 5- or 8-bromoisoquinoline derivatives. Bromoisoquinoline derivatives, and in particular 5-bromoisoquinoline and 5-bromo-8-nitroisoquinoline derivatives, are key intermediates in the synthesis of pharmaceutical compounds.
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(2008/06/13)