Category: 58142-46-4

On March 15, 2004, Grubbs, Russell A.; Lewis, Mechelle M.; Owens-Vance, Connie; Gay, Elaine A.; Jassen, Amy K.; Mailman, Richard B.; Nichols, David E. published an article.HPLC of Formula: 58142-46-4 The title of the article was 8,9-Dihydroxy-1,2,3,11b-tetrahydrochromeno[4,3,2,-de]isoquinoline (dinoxyline), a high affinity and potent agonist at all dopamine receptor isoforms. And the article contained the following:

The synthesis and preliminary pharmacol. evaluation of 8,9-dihydroxy-1,2,3,11b-tetrahydrochromeno[4,3,2,-de]isoquinoline (5, now named dinoxyline) is described. This mol. was designed as a potential bioisostere that would conserve the essential elements of our β-phenyldopamine D1 pharmacophore (i.e., position and orientation of the nitrogen, hydroxyls, and Ph rings). Previously, we have rigidified these elements using alkyl bridges, as exemplified in the dopamine D1 full agonist mols. dihydrexidine (1) and dinapsoline (2). This approach has been modified and we now show that it is possible to tether these elements using an ether linkage. Preliminary pharmacol. has revealed that 5 is a potent full D1 agonist (K0.5 <10 nM; EC50=30 nM), but also has high affinity for brain D2-like and cloned D2 and D3 receptors. Interestingly, whereas 1 and 2 and their analogs have only moderate affinity for the human D4 receptor, 5 also has high affinity for this isoform. Moreover, although N-alkylation of 1 and 2 increases D2 affinity, the N-allyl (15) and N-Pr (17) derivatives of 5 had decreased D2 affinity. Therefore, 5 may be engaging different amino acid residues than do 1 and 2 when they bind to the D2 receptor. This is the first example of a ligand with high affinity at all dopamine receptors, yet with functional characteristics similar to dopamine. These rigid ligands also will be useful tools to determine specific residues of the receptor transmembrane domains that are critical for agonist ligand selectivity for the D4 receptor. The experimental process involved the reaction of 4-Bromo-5-nitroisoquinoline(cas: 58142-46-4).HPLC of Formula: 58142-46-4

The Article related to dinoxyline analog preparation dopamine receptor agonist, Pharmacology: Structure-Activity and other aspects.HPLC of Formula: 58142-46-4

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

On April 9, 2004, D’Orchymont, Hugues; Van Hijfte, Luc; Zimmermann, Andre published a patent.Reference of 4-Bromo-5-nitroisoquinoline The title of the patent was Preparation of indazolecarboxamides as CDK1, CDK2, and CDK4 inhibitors for treating CDK-related diseases, in particular cancer. And the patent contained the following:

Title compounds I [R1 = H, halo, NH2, NHR2, NHCOR2, NO2, CN, CH2NH2, CH2NHR2, (un)substituted Ph, heteroaryl; Ar = (un)substituted Ph, heteroaryl; R2 = Ph, heteroaryl, (un)substituted alkyl (substituent = Ph or heteroaryl); n = 0, 1, 2, or 3; PG = protecting group selected from trimethylsilylethoxymethyl, mesitylenesulfonyl; their free bases, addition salts with acids, solvates and hydrates; with the exclusion of certain compounds] were prepared as cyclin-dependent kinase (CDK)-1, CDK2, and CDK4 inhibitors for treating cdk-related diseases, in particular cancer. For instance, reacting indazole-3-carboxylic acid with N-phenyl-1,4-phenylenediamine in the presence of DCC gave 58% II. I displayed IC50 values < 20 μM for the inhibition of CDK2, CDK1, and CDK4 in a test for measuring the enzymic activity of CDK2/Cyclin A, CDK1/Cyclin B, and CDK4/Cyclin D1, resp. I are useful for treating cancers, autoimmune diseases, inflammations, cardiovascular diseases, viral and fungal infections, hematol. diseases, and degenerative diseases of muscular system. The experimental process involved the reaction of 4-Bromo-5-nitroisoquinoline(cas: 58142-46-4).Reference of 4-Bromo-5-nitroisoquinoline

The Article related to indazolecarboxamide preparation cdk1 cdk2 cdk4 inhibitor antitumor, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazoles and other aspects.Reference of 4-Bromo-5-nitroisoquinoline

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

On May 7, 2020, Lee, Matthew Randolph; Varano, Anthony Joseph, Jr. published a patent.Product Details of 58142-46-4 The title of the patent was Sulfonylisoquinolinone derivatives as ROCK kinase inhibitors and their preparation. And the patent contained the following:

The invention relates to compounds of formulas I and II that inhibit ROCK activity. The invention relates to compounds of formulas I and II, pharmaceutical compositions and methods of use, such as methods of inhibiting ROCK activity and methods for treating, for example cerebral cavernous malformation syndrome (CCM) and cardiovascular diseases using the compounds and pharmaceutical compositions of the invention. Compounds of formulas I and II wherein ring X is partially saturated aza-containing heteroaryl; Y is CH and N; m is 0, 1, 2 and 3; each R1 is independently CN, OH, hydroxyalkyl, halo, etc.; R2 is H and halo; R3 is H, halo and C1-3 alkyl; and with provisions; and pharmaceutically acceptable salts thereof, are claimed. Example compound III was prepared by sulfonylation of 1-chloroisoquinoline with chlorosulfonic acid; the resulting 1-chloroisoquinoline-5-sulfonyl chloride underwent hydrolysis to give 1-hydroxyisoquinoline-5-sulfonic acid, which underwent chlorination to give the corresponding sulfonyl chloride, which underwent amidation with 4-methylisoindoline to give compound III. The invention compounds were evaluated for their ROCK kinase inhibitory activity. From the assay, it was determined that compound III exhibited IC50 value in the range of 1,000 nM to ≤ 10,000 nM. The experimental process involved the reaction of 4-Bromo-5-nitroisoquinoline(cas: 58142-46-4).Product Details of 58142-46-4

The Article related to sulfonylisoquinolinone preparation rock kinase inhibitor, Heterocyclic Compounds (One Hetero Atom): Quinolines and Isoquinolines and other aspects.Product Details of 58142-46-4

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

On May 14, 2021, Lee, Matthew Randolph; Varano, Anthony Joseph; Bobinski, Thomas P. published a patent.Safety of 4-Bromo-5-nitroisoquinoline The title of the patent was Sulfonylisoquinolinone derivatives as ROCK kinase inhibitors and their preparation. And the patent contained the following:

The present invention relates to compounds that inhibit ROCK activity. In particular, the present invention relates to compounds, pharmaceutical compositions and methods of use, such as methods of inhibiting ROCK activity and methods for treating, for example cerebral cavernous malformation syndrome (CCM) and cardiovascular diseases using the compounds and pharmaceutical compositions of the present invention. Example compound I was prepared by sulfonylation of 1-chloroisoquinoline with chlorosulfonic acid; the resulting 1-chloroisoquinoline-5-sulfonyl chloride underwent hydrolysis to give 1-hydroxyisoquinoline-5-sulfonic acid, which underwent chlorination to give the corresponding sulfonyl chloride, which underwent amidation with 4-methylisoindoline to give compound I. The invention compounds were evaluated for their ROCK kinase inhibitory activity. From the assay, it was determined that compound I exhibited IC50 value in the range of 1,000 nM to ≤ 10,000 nM. The experimental process involved the reaction of 4-Bromo-5-nitroisoquinoline(cas: 58142-46-4).Safety of 4-Bromo-5-nitroisoquinoline

The Article related to sulfonylisoquinolinone preparation rock kinase inhibitor, Heterocyclic Compounds (One Hetero Atom): Quinolines and Isoquinolines and other aspects.Safety of 4-Bromo-5-nitroisoquinoline

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

On August 20, 2020, Lee, Matthew Randolph; Varano Jr., Anthony Joseph; Bobinski, Thomas P. published a patent.SDS of cas: 58142-46-4 The title of the patent was Sulfonylisoquinolinone derivatives as ROCK kinase inhibitors and their preparation. And the patent contained the following:

The present invention relates to compounds that inhibit ROCK activity. In particular, the present invention relates to compounds, pharmaceutical compositions and methods of use, such as methods of inhibiting ROCK activity and methods for treating, for example cerebral cavernous malformation syndrome (CCM) and cardiovascular diseases using the compounds and pharmaceutical compositions of the present invention. Example compound I was prepared by sulfonylation of 1-chloroisoquinoline with chlorosulfonic acid; the resulting 1-chloroisoquinoline-5-sulfonyl chloride underwent hydrolysis to give 1-hydroxyisoquinoline-5-sulfonic acid, which underwent chlorination to give the corresponding sulfonyl chloride, which underwent amidation with 4-methylisoindoline to give compound I. The invention compounds were evaluated for their ROCK kinase inhibitory activity. From the assay, it was determined that compound I exhibited IC50 value in the range of 1,000 nM to ≤ 10,000 nM. The experimental process involved the reaction of 4-Bromo-5-nitroisoquinoline(cas: 58142-46-4).SDS of cas: 58142-46-4

The Article related to sulfonylisoquinolinone preparation rock kinase inhibitor, Heterocyclic Compounds (One Hetero Atom): Quinolines and Isoquinolines and other aspects.SDS of cas: 58142-46-4

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

On June 6, 2013, Aebi, Johannes; Amrein, Kurt; Chen, Wenming; Hornsperger, Benoit; Kuhn, Bernd; Liu, Yongfu; Maerki, Hans P.; Mayweg, Alexander V.; Mohr, Peter; Tan, Xuefei; Wang, Zhanguo; Zhou, Mingwei published a patent.Application of 58142-46-4 The title of the patent was New bicyclic dihydroisoquinolin-1-one derivatives as aldosterone synthase inhibitors and their preparation. And the patent contained the following:

The invention provides compounds having formula I, compositions including the compounds and methods of using the compounds as aldosterone synthase (CYP11B2 or CYP11B1) inhibitors for the treatment or prophylaxis of chronic kidney disease, congestive heart failure, hypertension, primary aldosteronism and Cushing syndrome. Compounds of formula I wherein E is absent and CR3R4; A1 is CR8 and N; A2 is CR9 and N; A3 is CR10 and N; A4 is CR11 and N; A5 is CR6 and N; R1, R2, R3 and R4 are independently H, alkyl, cycloalkyl, haloalkyl, etc.; R2R4 can be taken together to form a double bond, then R5 is H; R1R2, R3R4 or R1R3 can be taken together to form substituted cycloalkyl and heterocycloalkyl; R5, R6, R7 and R8 are independently halo, CN, alkoxy, hydroxyalkoxy, etc.; R9 is H, halo, OH, CN, alkyl, etc.; R10 is (un)substituted alkoxy and substituted alkyl; R11 is H; and with proviso; and pharmaceutically acceptable salts thereof, are claimed. Example compound II was prepared by N-arylation of 6-chloro-3,4-dihydroisoquinolin-1(2H)-one with 3-bromopyridine. The invention compounds were evaluated for their aldosterone synthase inhibitory activity. From the assay, it was determined that compound II exhibited EC50 values of 0.0860 μM and 4.6072 μM towards CYP11B2 and CYP11B1, resp. The experimental process involved the reaction of 4-Bromo-5-nitroisoquinoline(cas: 58142-46-4).Application of 58142-46-4

The Article related to dihydroisoquinolinone preparation aldosterone synthase inhibitor, Heterocyclic Compounds (One Hetero Atom): Quinolines and Isoquinolines and other aspects.Application of 58142-46-4

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

On October 31, 1978, Hamada, Yoshiki; Sugiura, Michiharu; Hirota, Minoru published an article.Related Products of 58142-46-4 The title of the article was Studies on nitrogen-containing heterocyclic compounds. XXXIII. Syntheses of 3-alkoxyisoquinolines and 7-,8-substituted-1,6-naphthyridines from isoquinoline and 1,6-naphthyridine. And the article contained the following:

1,3-Dialkoxy-4-bromo-2-cyano-1,2,3,4-tetrahydroisoquinolines are obtained quant. by the addition of BrCN to isoquinoline dissolved in the corresponding alc., followed by application of Br and saturated sodium carbonate solution These products are a mixture of stereoisomers with the H atoms in 3- and 4-positions in cis (main) and trans configuration. Dehydrobromination of the cis-type compounds with KCN easily gives 3-alkoxyisoquinolines. Hydrolysis with HCl affords 4-bromoisoquinoline from cis-type compounds and 4-chloroisoqinoline from trans-type compounds 4-Bromo-5-nitroisoquinoline was obtained from 5-nitroisoquinoline by the application of the above reaction but 3-methoxy-5-nitroisoquinoline could not be obtained. Application of this reaction to 1,6-naphthyridine easily gave 8-bromo-1,6-naphthyridine and 7-methoxy-1,6-naphthyridine. The experimental process involved the reaction of 4-Bromo-5-nitroisoquinoline(cas: 58142-46-4).Related Products of 58142-46-4

The Article related to isoquinoline alkoxy, naphthyridine methoxy, cyanoisoquinoline alkoxy, Heterocyclic Compounds (One Hetero Atom): Quinolines and Isoquinolines and other aspects.Related Products of 58142-46-4

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

On August 8, 2001, Peglion, Jean-louis; Dessinges, Aimee; Poitevin, Christophe; Vilaine, Jean-paul; Villeneuve, Nicole; Thollon, Catherine; Bourguignon, Marie-pierre published a patent.Formula: C9H5BrN2O2 The title of the patent was Preparation of N-piperidinyl(alkyl)isoquinolinesulfonamides and analogs for treatment of vascular disease. And the patent contained the following:

RSO2NR1Z1ZZ2R2 [I; R = (un)substituted (hetero)aryl; R1 = H or alkyl; R2 = (un)substituted 2- or 3-indenyl or -benzofuranyl; Z = (4-hydroxy)piperidine-4,1-diyl; Z1 = bond or alkylene; Z2 = (un)substituted alk(en)ylene] were prepared Thus, Et 4-piperidinecarboxylate was converted in 5 steps to title compound II. Data for biol. activity of 1 prepared I were given. The experimental process involved the reaction of 4-Bromo-5-nitroisoquinoline(cas: 58142-46-4).Formula: C9H5BrN2O2

The Article related to piperidinylalkylisoquinolinesulfonamide preparation vascular disease treatment, Heterocyclic Compounds (One Hetero Atom): Quinolines and Isoquinolines and other aspects.Formula: C9H5BrN2O2

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

On January 29, 2004, Yamada, Rintaro; Seto, Minoru published a patent.Safety of 4-Bromo-5-nitroisoquinoline The title of the patent was Preparation of 5-substituted isoquinoline derivatives as myosin regulatory light-chain phosphorylation inhibitors. And the patent contained the following:

The title compounds I [wherein R1 = H, halo, OH, NH2, or alkoxy; R2 = H, halo, alkenyl, alkynyl, alkoxy,alkylthio, alkyl-SO, alkylsulfonyl, CN, (un)substituted alkyl, amino, etc.; R3 = (un)substituted OH, SO2NH2, or NH2] or salts thereof are prepared as myosin regulatory light-chain phosphorylation inhibitors. For example, N-(tert-butoxycarbonyl)-1,3-propanediamine was reacted with isoquinoline-5-sulfonyl chloride in CH2Cl2 in the presence of NEt3 to give the sulfonamide. The sulfonamide was reacted with 3-phenyl-1-propanol in THF in the presence of 1,1′-azobis(N,N-dimethylformamide) and Bu3P, followed by hydrolysis to provide II•xHCl. II showed inhibitory activity with IC50 of 0.8 μM against human myosin regulatory light-chain phosphorylation. The experimental process involved the reaction of 4-Bromo-5-nitroisoquinoline(cas: 58142-46-4).Safety of 4-Bromo-5-nitroisoquinoline

The Article related to isoquinoline myosin regulatory light chain phosphorylation inhibitor preparation human, Heterocyclic Compounds (One Hetero Atom): Quinolines and Isoquinolines and other aspects.Safety of 4-Bromo-5-nitroisoquinoline

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

On May 14, 2020, Lee, Matthew Randolph; Varano, Anthony Joseph published a patent.Reference of 4-Bromo-5-nitroisoquinoline The title of the patent was Sulfonylisoquinoline derivatives as Rock kinase inhibitors and their preparation. And the patent contained the following:

The invention relates to compounds of formula I as Rho-associated protein kinases (ROCK) inhibitors useful for treatment of cerebral cavernous malformation syndrome and cardiovascular diseases. Compounds of formulas I and II wherein ring X is partially saturated aza-containing heteroaryl; Y is CH or N; m is 0, 1, 2 and 3; each R1 is independently CN, OH, hydroxyalkyl, halo, etc.; R2 is H and halo; R3 is H, halo and C1-3 alkyl; with provisions; and pharmaceutically acceptable salts thereof, are claimed. Example compound III was prepared by sulfonylation of 1-chloroisoquinoline with chlorosulfonic acid; the resulting 1-chloroisoquinoline-5-sulfonyl chloride underwent hydrolysis to give 1-hydroxyisoquinoline-5-sulfonic acid, which underwent chlorination to give the corresponding sulfonyl chloride, which underwent amidation with 4-methylisoindoline to give compound III. Exemplified I were evaluated for selective ROCK kinase inhibitory activity from which III demonstrated IC50 values in the range of >1000 nM and ≤10,000 nM for both ROCK1 and ROCK2 compared to IC50 values of >10,000 for PKACA, AKT1, and PKG, resp. The experimental process involved the reaction of 4-Bromo-5-nitroisoquinoline(cas: 58142-46-4).Reference of 4-Bromo-5-nitroisoquinoline

The Article related to sulfonylisoquinoline derivative preparation rock kinase inhibitor cavernous malformation syndrome, selective rock1 rock2 inhibitor cardiovascular disease, Heterocyclic Compounds (One Hetero Atom): Quinolines and Isoquinolines and other aspects.Reference of 4-Bromo-5-nitroisoquinoline

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem