57775-29-8 Usage
Uses
Used in Medical Imaging:
Carazolol HCL is used as a high-affinity beta-adrenergic receptor ligand for the noninvasive determination of beta receptor status using Positron Emission Tomography (PET). This application aids in the diagnosis and monitoring of conditions related to the adrenergic system, such as hypertension, heart failure, and certain types of cancer.
Used in Pharmaceutical Industry:
As a high-affinity, lipophilic, non-selective ligand of the β-adrenergic receptors, Carazolol HCL is used in the development of drugs targeting these receptors. It has potential applications in the treatment of various conditions, including cardiovascular diseases, asthma, and other disorders related to the adrenergic system.
Used in Research and Development:
Carazolol HCL serves as a valuable tool in research and development for studying the function and regulation of beta-adrenergic receptors. Its ability to act as an antagonist, inverse agonist, or agonist, depending on the receptor type, makes it a versatile compound for investigating receptor signaling pathways and developing new therapeutic strategies.
Originator
Conducton,Klinge,W. Germany,1980
Manufacturing Process
The 4-(2,3-epoxypropoxy)carbazole used as starting material is prepared as
follows. A solution of 16.3 g 4-hydroxycarbazole in a mixture of 190 ml dioxan
and 98 ml 1 N sodium hydroxide is, after the addition of 66 ml
epichlorohydrin, stirred for 2 hours at 40°C to 45°C. The reaction mixture is then diluted with water and shaken out with methylene chloride. The
methylene chloride phase is washed with water, dried over anhydrous sodium
sulfate and evaporated. There are obtained 16.8 g 4-(2,3-
epoxypropoxy)carbazole.A solution of 3.5 g 4-(2,3-epoxypropoxy)carbazole in 50 ml absolute alcohol is
mixed with 30 ml isopropylamine and heated for 3 hours under reflux. When
the reaction is finished, the reaction mixture is evaporated to dryness. The
residue obtained is taken up in methylene chloride and chromatographed over
an aluminum oxide column (300 g basic aluminum oxide, activity stage IV;
eluent methylene chloride). The eluted fractions are evaporated and the
residue is dissolved in methanol and acidified with 2 N ethereal hydrochloric
acid.The precipitate obtained is filtered off and recrystallized from methanol. There
are obtained 3.1 g (62% of theory) 4-(3-isopropylamino-2-hydroxypropoxy)
carbazole hydrochloride; MP 234°C to 235°C.
Therapeutic Function
Beta-adrenergic blocker
Biological Activity
carazolol is a high-affinity, lipophilic, and non-selective ligand of the β-adrenergic receptors [1,2].β-adrenergic receptors have been involved in mediating the physiological responses of the catecholamines, epinephrine and norepinephrine and modulating a myriad of physiological functions, such as relaxation of smooth muscle, chronotropic and inotropic cardiac responses, and lipolysis in adipose tissue. the β-adrenergic receptors exist in nearly all mammalian tissues. until now, three β-adrenergic receptors have been identified, β1-, β2- and β3-adrenergic receptors [3].in cho cells expressing the human β3-adrenoceptor, the ki value of carazolol was 2.0 ± 0.2 and the ic50 was 11.3 ± 1.2 nm. carazolol exhibited an ecs0 of 25 nm and behaved as a full agonist (intrinsic activity = 0.97) towards the murine β3-adrenoceptor. in murine 3t3-f442a-derived adipocytes express the β3-adrenoceptor, carazolol stimulated lipolysis [1]. carazolol bound to cortical β-receptors with a kd value of 0.15 nm. carazolol showed equal displacements constants when binding with calf cerebral cortex (which contained mainly β1 receptors) and calf cerebellum (which contained mainly β2 receptors), indicating that carazolol bound with equal affinity to β1 and β2 receptors [2].
references
[1] méjean a, guillaume j l, strosberg a d. carazolol: a potent, selective β3-adrenoceptor agonist[j]. european journal of pharmacology: molecular pharmacology, 1995, 291(3): 359-366.[2] innis r b, corrêa f m a, snyder s h. carazolol, an extremely potent β-adrenergic blocker: binding to β-receptors in brain membranes [j]. life sciences, 1979, 24(24): 2255-2264.[3] pellegrino s m, lee n h, fraser c m. β-adrenergic receptors[j]. biomembranes: a multi-volume treatise, 1996, 2: 245-279.
Check Digit Verification of cas no
The CAS Registry Mumber 57775-29-8 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 5,7,7,7 and 5 respectively; the second part has 2 digits, 2 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 57775-29:
(7*5)+(6*7)+(5*7)+(4*7)+(3*5)+(2*2)+(1*9)=168
168 % 10 = 8
So 57775-29-8 is a valid CAS Registry Number.
InChI:InChI=1/C18H22N2O2.ClH/c1-12(2)19-10-13(21)11-22-17-9-5-8-16-18(17)14-6-3-4-7-15(14)20-16;/h3-9,12-13,19-21H,10-11H2,1-2H3;1H
57775-29-8Relevant articles and documents
Development of Highly Potent Carbazole Amphiphiles as Membrane-Targeting Antimicrobials for Treating Gram-Positive Bacterial Infections
Lin, Shuimu,Liu, Jiayong,Li, Hongxia,Liu, Ying,Chen, Yongzhi,Luo, Jiachun,Liu, Shouping
, p. 9284 - 9299 (2020/10/19)
The development of new antimicrobial agents capable of curing drug-resistant bacteria-induced infections is becoming a major challenge to the global healthcare system. To develop antimicrobials with new molecular entities, a series of novel carbazole-based compounds were designed and synthesized by biomimicking the structural properties and biological function of antimicrobial peptides. Compound 29 was selected as a lead compound from the structure-activity relationship analyses and biological activity evaluation. Compound 29 showed excellent antimicrobial activity against Gram-positive bacteria (MICs = 0.78-1.56 μg/mL), poor hemolytic activity (HC50 > 200 μg/mL), and low cytotoxicity to mammalian cells. Compound 29 had fast bactericidal properties and effectively prevented bacterial resistance in laboratory simulations. Antibacterial mechanism studies revealed that compound 29 directly destroyed bacterial cell membranes, leading to bacterial deaths. Importantly, compound 29 displayed an excellent efficacy in a murine bacterial keratitis model caused by Staphylococcus aureus ATCC29213.
THERAPY FOR COMPLICATIONS OF DIABETES
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, (2009/07/02)
A method for enhancing glycemic control and/or insulin sensitivity in a human subject having diabetic nephropathy and/or metabolic syndrome comprises administering to the subject a selective endothelin A (ETA) receptor antagonist in a glycemic control and/or insulin sensitivity enhancing effective amount. A method for treating a complex of comorbidities in an elderly diabetic human subject comprises administering to the subject a selective ETA receptor antagonist in combination or as adjunctive therapy with at least one additional agent that is (i) other than a selective ETA receptor antagonist and (ii) effective in treatment of diabetes and/or at least one of said comorbidities other than hypertension. A therapeutic combination useful in such a method comprises a selective ETA receptor antagonist and at least one antidiabetic, anti-obesity or antidyslipidemic agent other than a selective ETA receptor antagonist.
ANTIHYPERTENSIVE THERAPY
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, (2009/09/08)
A new use of darusentan is provided in preparation of a pharmaceutical composition for lowering blood pressure in a patient exhibiting resistance to a baseline antihypertensive therapy with one or more drugs. The composition comprises darusentan in an amount providing a therapeutically effective daily dose; wherein (a) the composition is orally deliverable and/or (b) the daily dose of darusentan is effective to provide a reduction of at least about 3 mmHg in one or more blood pressure parameters selected from trough sitting systolic, trough sitting diastolic, 24-hour ambulatory systolic, 24-hour ambulatory diastolic, maximum diurnal systolic and maximum diurnal diastolic blood pressures. Further provided is a new use of darusentan in preparation of a pharmaceutical composition for lowering blood pressure in a patient exhibiting resistance to a baseline antihypertensive therapy, wherein the composition is administered adjunctively with at least one diuretic and at least one antihypertensive drug selected from ACE inhibitors, angiotensin II receptor blockers, beta-adrenergic receptor blockers and calcium channel blockers.
Method for treating resistant hypertension
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, (2008/06/13)
A method is provided for lowering blood pressure in a patient having clinically diagnosed resistant hypertension. The method comprises administering darusentan to the patient adjunctively with a baseline antihypertensive regimen that comprises administration of at least one diuretic and at least two antihypertensive drugs selected from at least two of (a) ACE inhibitors and angiotensin II receptor blockers, (b) beta-adrenergic receptor blockers and (c) calcium channel blockers. The darusentan is orally administered at a dose and frequency effective, in combination with the baseline regimen, to provide a reduction of at least about 3 mmHg in one or more blood pressure parameters selected from trough sitting systolic, trough sitting diastolic, 24-hour ambulatory systolic, 24-hour ambulatory diastolic, maximum diurnal systolic and maximum diurnal diastolic blood pressures.
Use of D,L-and D-carazolol as anti-glaucoma agent
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, (2008/06/13)
The present invention is concerned with the topical use of D,L- and D-carazolol and of the pharmacologically acceptable salts in the therapy of glaucoma. The present invention is also concerned with eye drops containing these active materials.
