105627-79-0

Basic information

• Product Name: Isoquinoline-5-sulphonyl chloride hydrochloride
• Synonyms: 5-(Chlorosulphonyl)isoquinoline hydrochloride;5-Isoquinolinesulfonyl chloride, hydrochloride;isoquinolin-5-sulfonyl chloride HCl;Isoquinoline-5-sulphonyl chloride, HCl;5-(Chlorosulphonyl)isoquinoline hydrochloride, 5-(Chlorosulphonyl)-2-azanaphthalene hydrochloride;isoquinolin-5-ylsulphonyl chloride hydrochloride;5-Isoquinolinesulfonylchloride, hydrochloride (1:1);ISOQUINOLINE-5-SULPHONYL CHLORIDE HYDROCHLORIDE
• CAS NO: 105627-79-0
• Molecular Formula: C₉H₆ClNO₂S*ClH
• Molecular Weight: 264.13
• EINECS: 1312995-182-4
• Product Categories: Sulfonyl Chlorides;Sulfur & Selenium Compounds;Quinolines, Isoquinolines & Quinoxalines;Sulphonyl Chlorides;Quinolines, Isoquinolines & Quinoxalines;Sulphonyl Chlorides;Aromatics
• Mol File: 105627-79-0.mol

Chemical Properties

• Melting Point: 173-183°C
• Appearance: /
• Storage Temp.: -20°C Freezer
• Stability: Moisture Sensitive; Store in Freezer
• CAS DataBase Reference: Isoquinoline-5-sulphonyl chloride hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: Isoquinoline-5-sulphonyl chloride hydrochloride(105627-79-0)
• EPA Substance Registry System: Isoquinoline-5-sulphonyl chloride hydrochloride(105627-79-0)

Safety Data

• Hazard Codes: Xi
• Statements: 36
• Safety Statements: 26
• Hazardous Substances Data: 105627-79-0(Hazardous Substances Data)

Usage

Uses

Used in Organic Synthesis:
Isoquinoline-5-sulphonyl chloride hydrochloride is used as a synthetic building block for the creation of various organic compounds. Its application is primarily due to its reactivity and ability to form new chemical entities, which can be further utilized in the development of pharmaceuticals, agrochemicals, and other specialty chemicals.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, Isoquinoline-5-sulphonyl chloride hydrochloride is used as a key intermediate in the synthesis of various drug molecules. Its application is driven by its potential to form diverse chemical structures, which can be optimized for specific therapeutic targets, leading to the development of novel drugs with improved efficacy and safety profiles.
Used in Chemical Research:
Isoquinoline-5-sulphonyl chloride hydrochloride is also employed in chemical research as a versatile reagent for exploring new reaction pathways and understanding the fundamental aspects of organic chemistry. Its application in this context is due to its unique chemical properties, which allow researchers to investigate various reaction mechanisms and develop innovative synthetic strategies.

InChI:InChI=1/C9H6ClNO2S.ClH/c10-14(12,13)9-3-1-2-7-6-11-5-4-8(7)9;/h1-6H;1H

Upstream product

• 27655-40-9 isoquinoline-5-sulfonic acid 
• 119-65-3 isoquinoline 

Downstream Products

• 116970-50-4 N-(2-aminoethyl)-5-isoquinoline-sulphonamide hydrochloride 
• 116970-54-8 Isoquinoline-5-sulfonic acid benzyl-(2-hydroxy-ethyl)-amide 
• 116970-82-2 Isoquinoline-5-sulfonic acid benzyl-(2-benzylamino-ethyl)-amide; hydrochloride 
• 842136-05-4 (2S,4S)-2-(4-chlorobenzyloxymethyl)-4-[isoquinoline-5-sulfonyl(2-trimethylsilylethoxymethyl)amino]pyrrolidine-1-carboxylic acid tert-butyl ester 
• 655224-08-1 [2-({2-[2-amino-3-(4-benzoyl-phenyl)-propionylamino]-ethyl}-tert-butoxycarbonyl-amino)-ethyl]-[2-(isoquinoline-5-sulfonylamino)-ethyl]-carbamic acid tert-butyl ester 
• 655224-13-8 [2-({2-[2-(6-amino-hexanoylamino)-3-(4-benzoyl-phenyl)-propionylamino]-ethyl}-tert-butoxycarbonyl-amino)-ethyl]-[2-(isoquinoline-5-sulfonylamino)-ethyl]-carbamic acid tert-butyl ester 
• 655224-12-7 [5-(2-(4-benzoyl-phenyl)-1-{2-[tert-butoxycarbonyl-(2-{tert-butoxycarbonyl-[2-(isoquinoline-5-sulfonylamino)-ethyl]-amino}-ethyl)-amino]-ethylcarbamoyl}-ethylcarbamoyl)-pentyl]-carbamic acid 9H-fluoren-9-ylmethyl ester 
• 129305-12-0 Toluene-4-sulfonic acid 2-(isoquinoline-5-sulfonylamino)-ethyl ester 
• 116970-62-8 N-[2-(methylamino)ethyl]-5-isoquinoline sulfonamide hydrochloride 
• 116970-88-8 Isoquinoline-5-sulfonic acid (2-amino-ethyl)-benzyl-amide; hydrochloride 
• 116970-70-8 Isoquinoline-5-sulfonic acid (2-cyclohexylamino-ethyl)-amide; hydrochloride 
• 116970-75-3 Isoquinoline-5-sulfonic acid [2-(cyclohexyl-methyl-amino)-ethyl]-amide; hydrochloride 
• 116970-71-9 Isoquinoline-5-sulfonic acid (2-benzylamino-ethyl)-amide; hydrochloride 
• 116970-74-2 Isoquinoline-5-sulfonic acid (2-phenethylamino-ethyl)-amide; hydrochloride 

Relevant articles and documents

Rationally designed PKA inhibitors for positron emission tomography: Synthesis and cerebral biodistribution of N-(2-(4-bromocinnamylamino)ethyl)-N-[11C]methyl-isoquinoline-5-sulfonamide

Protein kinase A (PKA) is an important signal transduction target for drug development because it influences critical cellular processes implicated in neuropsychiatric illnesses such as major depressive disorder. The goal of the present study was to develop the first imaging agent for measuring the levels of PKA with positron emission tomography (PET). By rational derivatization of 5-isoquinoline sulfonamides, it was found that the introduction of a methyl group to the sulphonamidic nitrogen on the known PKA inhibitors N-(2-aminoethyl)isoquinoline-5-sulfonamide (H-9, 1) and N-(2-(4-bromocinnamylamino)ethyl)isoquinoline-5-sulfonamide (H-89, 2), (yielding N-(2-aminoethyl)-N-methyl-isoquinoline-5-sulfonamide (4) and N-(2-(4-bromocinnamylamino)ethyl)-N-methyl-isoquinoline-5-sulfonamide (5), respectively) does not appreciably reduce in vitro potency toward PKA. We have facilitated the synthesis of 4 by reacting isoquinoline-5-sulfonyl chloride with N-methylethylenediamine (20% yield). Several techniques were used to thoroughly characterize 4 including multi (1H, 13C and 15N) NMR spectroscopy and X-ray crystallography. Compound 4 and 1-(4-bromophenyl)-1-propen-3-yl bromide were reacted to produce 5 in 16% yield. Compound 2 was reacted with [11C]CH3I to prepare N-(2-(4-bromocinnamylamino) ethyl)-N-[11C]methyl-isoquinoline-5-sulfonamide ([11C]5), with a decay-corrected radiochemical yield of 32%, based on [11C]CO2. [11C]5 was produced with >98% radiochemical purity and 1130 mCi/μmol specific activity after 40 min (end of synthesis). Conscious rats were administered [11C] 5 and sacrificed at 5, 15, 30 and 60 min after injection. Radioactivity from all excised brain regions was 11C]5 may limit its use for studying PKA in the central nervous system.

Method for preparing isoquinoline hydrochloride intermediate and Rho kinase inhibitor by using BTC/Ph3PO chlorination system

The invention discloses a method for preparing an isoquinoline hydrochloride intermediate and an Rho kinase inhibitor by using a BTC/Ph3PO chlorination system, which comprises the following steps: putting an isoquinoline 5-sulfonic acid compound, BTC and a catalytic amount of Ph3PO into a reaction bottle, adding an organic solvent A, uniformly mixing all the components, and heating the mixture toreact; after the reaction is finished, carrying out suction filtration and drying to obtain a white solid isoquinoline hydrochloride intermediate, which is the isoquinoline 5-sulfonylchloride hydrochloride compound; concentrating a mother liquor part of the filtrate for separating out Ph3PO at a low temperature, and washing Ph3PO with a low-polarity solvent for recycling use. The method has the advantages of few side reactions, high product quality, less three-waste pollution, high atom economy and the like, the invention also provides a method for further preparing the Rho kinase inhibitor byutilizing the prepared isoquinoline hydrochloride intermediate; the impurities in the Rho kinase inhibitor prepared by the method are obviously lower than those in medicines obtained by a traditionalmethod.

Small-molecule inhibitor of protein kinase A as well as preparation method and application thereof

The invention discloses a small-molecule inhibitor of histone kinase A. The small-molecule inhibitor comprises an H89 isoquinoline precursor structure, the specific molecular formula is CxHyAzNmOnS, and in the molecular formula, x is 20 or 21, y is 20 or 22, A is F, z is 0 or 1, m is 3 or 4, and n is 2 or 4. The invention further provides small-molecule inhibitors HF89, HFC and HN89, and a PET tracer [ C] HF. The invention also provides a preparation method and an application of the related small-molecule inhibitor. A new feasible scheme is provided for early diagnosis, treatment, curative effect evaluation and the like of tumors.

Preparation method of Fasudil hydrochloride

The invention belongs to the technical field of preparation of heterocyclic compounds, and particularly relates to a preparation method of Fasudil hydrochloride. The preparation method includes the following steps: 1) reacting isoquinoline-5-sulfonyl chloride hydrochloride, homopiperazine and liquid ammonia in an organic solvent at the temperature of 10-15 DEG C for 2-4 hours, subjecting a reactedreaction system to water extraction separation, and concentrating an oil-phase separation product to obtain an intermediate; 2) subjecting the intermediate obtained in the step 1) and hydrochloric acid to a salt formation reaction to obtain the Fasudil hydrochloride. The preparation method has the advantages that the isoquinoline-5-sulfonyl chloride hydrochloride as a raw material directly reactswith the homopiperazine to obtain the intermediate, so that the operation steps are reduced and the preparation process is simple.

Paradoxically, Most Flexible Ligand Binds Most Entropy-Favored: Intriguing Impact of Ligand Flexibility and Solvation on Drug-Kinase Binding

Biophysical parameters can accelerate drug development; e.g., rigid ligands may reduce entropic penalty and improve binding affinity. We studied systematically the impact of ligand rigidification on thermodynamics using a series of fasudil derivatives inhibiting protein kinase A by crystallography, isothermal titration calorimetry, nuclear magnetic resonance, and molecular dynamics simulations. The ligands varied in their internal degrees of freedom but conserve the number of heteroatoms. Counterintuitively, the most flexible ligand displays the entropically most favored binding. As experiment shows, this cannot be explained by higher residual flexibility of ligand, protein, or formed complex nor by a deviating or increased release of water molecules upon complex formation. NMR and crystal structures show no differences in flexibility and water release, although strong ligand-induced adaptations are observed. Instead, the flexible ligand entraps more efficiently water molecules in solution prior to protein binding, and by release of these waters, the favored entropic binding is observed.

Discovery of novel 2,5-dioxoimidazolidine-based P2X7 receptor antagonists as constrained analogues of KN62

Novel 2,5-dioxoimidazolidine-based conformationally constrained analogues of KN62 (1) were developed as P2X7 receptor (P2X7R) antagonists using a rigidification strategy of the tyrosine backbone of 1. SAR analysis of the 2,5-dioxoimidazolidine scaffold indicated that piperidine substitution at the N3 position and no substitution at N1 position were preferable. Further optimization of the substituents at the piperidine nitrogen and the spacer around the skeleton resulted in several superior antagonists to 1, including 1-adamantanecarbonyl analogue 21i (IC50 = 23 nM in ethidium uptake assay; IC50 = 14 nM in IL-1β ELISA assay) and (3-CF3-4-Cl)benzoyl analogue (-)-21w (54 nM in ethidium uptake assay; 9 nM in IL-1β ELISA assay), which was more potent than the corresponding (+) isomer. Compound 21w displayed potent inhibitory activity in an ex vivo model of LTP-induced pain signaling in the spinal cord and significant anti-inflammatory activity in in vivo models of carrageenan-induced paw edema and type II collagen-induced joint arthritis.

5-Substituted isoquinoline derivatives

A compound represented by the following formula (1) or a salt thereof: wherein R1 represents hydrogen atom, a halogen atom and the like; R2 represents hydrogen atom, a halogen atom, a C1-6 alkyl group and the like; and R3 represents —O—X—C(A1)(A11)—C(A2)(A2l)—N(A3l)(A3)(X represents propylene group etc., A11 and A21 represent hydrogen atom, or a C1-6 alkyl group, A31 represents a C1-6 alkyl group substituted with hydroxyl group, or hydrogen atom, and A1, A2, and A3 represent hydrogen atom, a C1-6 alkyl group and the like) and the like, which has an inhibitory activity on the phosphorylation of myosin regulatory light chain, and is useful for treatment of diseases relating to contraction of various cells and the like.

De novo design and synthesis of HIV-1 integrase inhibitors

Existing AIDS therapies are out of reach for most HIV-infected people in developing countries and, where available, they are limited by their toxicity and their cost. New anti-HIV agents are needed urgently to combat emerging viral resistance and reduce the side effects associated with currently available drugs. Toward this end, LeapFrog, a de novo drug design program was used to design novel, potent, and selective inhibitors of HIV-1 integrase. The designed compounds were synthesized and tested for in vitro inhibition of HIV-1 integrase. Out of the 25 compounds that were designed, and synthesized, four molecules (compounds 23, 26, 43, and 59) showed moderate to low inhibition of HIV-1 integrase for 3′-processing and 3′- strand transfer activities. Nonetheless, these compounds possess structural features not seen in known HIV-1 integrase inhibitors and thus can serve as excellent leads for further optimization of anti-HIV-1 integrase activity.

ISOQUINOLINE-5-SULFONIC ACID AMIDES AS INHIBITORS OF AKT (PROTEIN KINASE B)

The present invention relates to compounds Formula (I): as inhibitors of AKT activity, which are useful for the treatment of susceptible neoplasms and viral infections.

5-Isoquinolinesulfonamide derivatives. 1. Synthesis and vasodilatory activity of N-(2-guanidinoethyl)-5-isoquinolinesulfonamide derivatives

Two novel series of N-(2-guanidinoalkyl)-5-isoquinolinesulfonamides, 2 and 3, were prepared. Many of the compounds possessed vasodilatory activity when injected locally into the femoral artery of dogs. The most potent compound, 1-amidino-4-(5-isoquinolylsulfonyl)-1,4-perhydrodiazepine, 33, was comparable to diltiazem, which is used clinically as a vasodilator.