4205-90-7

Usage

Uses

Used in Pharmaceutical Industry:
CLONIDINE (200 MG) is used as an antihypertensive agent for the treatment of high blood pressure. It helps to lower blood pressure by reducing the heart rate and relaxing blood vessels, thus allowing for better blood flow and decreased strain on the heart.
Used in Pain Management:
CLONIDINE (200 MG) is used as an analgesic enhancer for increasing the duration and potency of analgesia provided by epidural opioid or local anesthetic drugs. It is particularly effective when administered epidurally at a dosage of 1–2μgkg –1.
Used in Treatment of Acute Opioid Withdrawal:
CLONIDINE (200 MG) is used as a therapeutic agent for managing acute opioid withdrawal symptoms. It helps to alleviate the discomfort and cravings associated with opioid withdrawal, making it a valuable tool in the treatment of opioid addiction.
Brand Name:
Clonidine is available under the brand name Catapres, manufactured by Boehringer Ingelheim.

Pharmacokinetics

Clonidine is lipid soluble and rapidly absorbed after oral administration, with a peak plasma concentration occurring in 60–90min. O ral, intravenous and intramuscular routes may be used for sedation or analgesia. I n addition, epidural and intrathecal clonidine is used to augment regional anaesthesia, but perineural administration is of limited or no effect. The elimination halflife is 9–13h and is prolonged in renal failure. Fifty percent of an administered dose is excreted unchanged by the kidneys, and 50% is metabolised in the liver to inactive metabolites.

Physiological effects

CNS effects Clonidine produces sedation, anxiolysis and analgesia. I t also has a MA Csparing effect, but there is a ceiling to the reduction because of the potential for activity at α1 receptors when used at higher doses. CVS effects The cardiovascular effects of clonidine probably involve α1 receptors and imidazoline receptors as with dexmedetomidine. Clonidine lowers the set point around which arterial pressure is regulated. Respiratory effects Clonidine has minor respiratory effects, causing only a small reduction in minute ventilation.

Physiological effects

Clonidine has some effects at α1-receptors (α2/ α1 > 200 : 1). Clonidine reduces the MA C of inhalational anaesthetic agents by up to 50%. I t has a synergistic analgesic effect with opioids which may be partly pharmacokinetic because the elimination half-life of opioids is also increased.

Metabolic pathway

Clonidine is well absorbed orally, with peak plasma concentrations after 60–90min. I t is highly lipid soluble, and approximately 50% is metabolised in the liver to inactive metabolites; the rest is excreted unchanged via the kidneys, with an elimination half-life of 9–12h.

InChI:InChI=1S/C9H9Cl2N3/c10-6-2-1-3-7(11)8(6)14-9-12-4-5-13-9/h1-3H,4-5H2,(H2,12,13,14)

Upstream product

• 107-15-3 ethylenediamine 
• 21709-18-2 N-(2,6-dichlorophenyl)-1,1-dichloromethanimine 
• 65295-68-3 1-(2-aminoethyl)-3-(2,6-dichlorophenyl)thiourea 
• 6590-95-0 2,6-dichlorophenylisothiocyanate 
• 10468-16-3 2-chloro-N-hydroxybenzenamine 
• 109384-39-6 N-(o-chlorophenyl)formohydroxamic acid 
• 608-31-1 2,6-Dichloroaniline 
• 4205-91-8 clonidine hydrochloride 
• 10113-35-6 N-(2,6-dichlorophenyl)-formamide 
• 14034-59-4 ethylene diamine mono-p-toluenesulfonic acid salt 
• 87-69-4 tartaric acid 
• 57647-79-7 1-benzoyl-2-(2,6-dichloro-anilino)-4,5-dihydro-1H-imidazole 
• 141-43-5 ethanolamine 
• 111225-65-1 amino(2,6-dichlorophenylimino)methanesulfonic acid 

Downstream Products

• 75465-87-1 7-Chlor-2,6-dihydro-4-methyl-5,6-ethano-1H-<1,4>diazepino<1,7-a>benzimidazol-monohydrochlorid 
• 70909-36-3 5-<(2,6-Dichlorphenyl)(2-imidazolin-2-yl)amino>-2-pentanon 
• 87235-71-0 1-(p-methylsulfonylbenzoyl)-2-(2,6-dichlorophenylimino)-imidazolidine 
• 87235-72-1 1-p-ethoxybenzoyl-2-(2,6-dichlorophenylimino)-imidazolidine 
• 70993-54-3 2-[(2,6-dichlorophenyl)imino]-1-hydroxylimidazolidine 
• 86861-34-9 2,6-dichloro-3-nitro-N-(2-imidazolidinylidene)-benzamine 
• 4205-91-8 clonidine hydrochloride 
• 33178-86-8 alinidine 
• 66541-90-0 cyclopropylmethyl-(2,6-dichloro-phenyl)-(4,5-dihydro-1H-imidazol-2-yl)-amine 
• 1848-75-5 N-phenyl-N-(4,5-dihydro-1H-imidazol-2-yl)amine 
• 80026-76-2 1-(quinolin-2-oyl)-2-(2',6'-dichlorophenylamino)-2-imidazoline 
• 80026-34-2 1-(pyrid-3-oyl)-2-(2',6'-dichlorophenylamino)-2-imidazoline 

Relevant academic research and scientific papers

Molecular structure of clonidine: Gas-phase electron diffraction, single-crystal X-ray diffraction and quantum chemical studies

This study presents the first determination of the molecular structure of the antihypertensive drug clonidine in the gas phase using gas electron diffraction (GED). The refinement was supported by quantum chemical calculations (QCs). The tautomeric and conformational distribution was investigated theoretically, providing an explanation for the presence of the single conformer in the gas phase. The molecular conformation of clonidine has been shown to have a nearly perpendicular arrangement of the phenyl and imidazolidine rings as described by the torsion angle C2-N6-C7-C8 = -72(6)°. The following structural parameters were obtained (bond lengths in Angstroms and bond angles in degrees with 3σ in parentheses): r(CHH-CHH) = 1.549(7), r(CHH-NH)av = 1.470(7), r(NH-C)av = 1.388(2), r(CN) = 1.286(7), r(C-N) = 1.388(2), r(CzC)av = 1.403(2), r(C-Cl)av = 1.737(2); ∠(NH-C-NH) = 108.1(11), ∠(CHH-NH-C)av = 109.7(12), ∠(CHH-CHH-NH)av = 100.9(12), ∠(C-NC) = 122.5(12), ∠(CClzCzCCl) = 114.9(2), and ∠(CHzCClzC)av = 123.1(2). The standard enthalpy of formation of clonidine in the gas phase was calculated using G4 theory with both atomisation and isodesmic reaction approaches, yielding the corresponding value of. The molecular structure of clonidine in the solid phase was determined using X-ray diffraction (XRD). Clonidine crystallizes in the monoclinic space group P21/c as a twinned crystal. The imino-tautomer, as an equimolar mixture of the two conformers with geometries close to the enantiomeric pair, is present in the solid phase. The identical conformers are linked into centrosymmetric dimers by paired N-H?N hydrogen bonds. The geometries of gaseous and solid clonidine differ especially in the immediate vicinity of the intermolecular hydrogen bonds formed in the crystal.

Heterocyclic compounds as FGFR4 inhibitors

The present invention provides heterocyclic compounds as selective inhibitors of fibroblast growth factor receptor 4 (FGFR4), pharmaceutical compositions containing the compounds, methods of preparingthe compounds, and methods of treating cell proliferative diseases, such as cancer, using the compounds of the invention.

A preparation method of the clonidine hydrochloride

The invention discloses a method for preparing the clonidine hydrochloride, including intermediates 1 synthesis, intermediate 2 synthesis and clonidine hydrochloride synthetic three steps, the present invention in order to 2, 6 - dichloroaniline as raw materials, through the hydroformylation reaction get intermediate 1, "one-pot" get clonidine free base, finally with hydrogen chloride ethanol solution into salt clonidine hydrochloride. By processing the raw material synthetic process, by utilizing the free alkali in the course of refining into salt after adjusting pH, and the clonidine hydrochloride is used for purification of the pulping process control such as ethyl acetate, to obtain a high-purity clonidine hydrochloride preparation method. The method not only improves the product purity and yield, impurity can also effectively control, but also greatly reducing the cost, simplifying the process, is more suitable for industrial production.

Efficient synthesis of 2-arylamino-2-imidazolines and 2-aminobenzimidazoles with aminoiminomethanesulfonic acid derivatives

A highly efficient synthesis of 2-arylamino-2-imidazolines and 2-aminobenzimidazoles from aminoiminomethanesulfonic acid derivatives is described. The method is simple and practical, generating imidazoline and benzimidazoline derivatives in excellent isolated yields.

A convenient method for the synthesis of 2-amino substituted aza-heterocycles from N,N′-disubstituted thioureas using TsCl/NaOH

p-Toluenesulfonyl chloride (TsCl)/NaOH has been introduced as reagent combination for the synthesis of 2-amino-oxa- or 2-amino-thiazolidines from N-(2-hydroxyethyl)-thioureas, but its general application in heterocycle synthesis has not been investigated. In this paper the convenient and efficient synthesis of a variety of 2-amino-substituted 1-aza 3-(aza, oxo or thio) heterocycles of different substitution and ring sizes is described. The application of polymer-supported TsCl facilitates work-up and renders the reaction conditions very suitable for parallel or robot synthesis. Graphical Abstract

Process for synthesizing heterocyclic compounds

The invention provides the process illustrated in scheme 1 for synthesizing heterocyclic compounds of formula I. In the process, an isothiocyanate of formula II is initially reacted with a primary amine of formula III to give a thiourea of formula IV. Subsequently, the thiourea of formula IV is converted to the corresponding heterocycle of formula I using a base and a sulfonyl chloride.

TREATMENT OF URINARY INCONTINENCE BY ADMINISTRATION OF ALPHA 1L-ADRENOCEPTOR AGONISTS

The present invention relates to the use of α lL-agonists for treating urinary incontinence.

Process for making 2-amino-2-imidazoline, guanidine and 2-amino-3,4,5,6-tetrahydropyrimidine derivatives

The present invention provides a process for making 2-amino-2-imidazoline, guanidine, and 2-amino-3,4,5,6-tetrahydroyrimidine derivatives by preparing the corresponding activated 2-thio-subsituted-2-derivative in a two-step, one-pot procedure and by further reacting yields this isolated derivative with the appropriate amine or its salts in the presence of a proton source. The present process allows for the preparation of 2-amino-2-imidazolines, quanidines, and 2-amino-3,4,5,6-tetrahydropyrimidines under reaction conditions that eliminate the need for lengthy, costly, or multiple low yielding steps, and highly toxic reactants. This process allows for improved yields and product purity and provides additional synthetic flexibility.

N-Nitroso Compounds. Part 2. The Synthesis of N-Nitrosoclonidine and its Decomposition in Aqueous Acidic Media

Clonidine, a 2-arylaminoimidazoline, undergoes nitrosation in aqueous nitrous acid to form N-nitrosoclonidine. 1H NMR spectroscopy reveals that the nitroso group resides on one of the imidazoline nitrogen atoms.N-Nitrosoclonidine decomposes in aqueous acidic media to form quantitatively clonidine and nitrous acid.The reaction is acid catalysed and involves rate-limiting protonation of the substrate, as revealed by a solvent deuterium isotope effect, k2H/k2D, of 1.2 and the independence of the rate of denitrosation upon the presence of Cl- or SCN-.The Broensted α exponent for general acid-catalysis is 0.5.The mechanism is contrasted to that for analogous 2-arylimidazolines, which suffer acid-catalysed hydrolysis via a rapid pre-equilibrium protonation of the substrate followed by rate-limiting attack of the nucleophile to effect denitrosation or amidine hydrolysis.The present results are interpreted in terms of a protonation of the imidazoline nitroso nitrogen of N-nitrosoclonidine which results in an intermediate that decomposes by loss of the nitroso group.

Feed additive for improving growth in agricultural animals

By using α-mimetics, particularly compounds of general formulae I to III and the compounds listed in Table I, as feed additives in fattening animals, it has surprisingly been possible to improve the daily weight gain, the utilisation of fodder and the ratio of muscle to fat in favor of the proportion of muscle and protein.