116666-63-8

Basic information

• Product Name: MIBEFRADIL
• Synonyms: (1s-cis)-orid;2-(2-((3-(1h-benzimidazol-2-yl)propyl)methylamino)ethyl)-aceticaci;6-fluoro-1,2,3,4-tetrahydro-1-(1-methylethyl)-2-naphthalenylester,dihydrochl;ro40-5967/001;Mibefradil diHCl;Mibefradil hydrate dihydrochloride;Ro 40-5967 hydrate, (1S,2S)-2-[2[[3-(2-Benzimidazolylpropyl]methylamino]ethyl]-6-fluoro-1,2,3,4-tetrahydro-1-isopropyl-2-naphthyl methoxyacetate hydrate dihydrochloride;Acetic acid, methoxy-, 2-(2-((3-(1H-benzimidazol-2-yl)propyl)methylamino)ethyl)-6-fluoro-1,2,3,4-tetrahydro-1-(1-methylethyl)-2-naphthalenyl ester, dihydrochloride, (1S-cis)-
• CAS NO: 116666-63-8
• Molecular Formula: C29H40Cl2FN3O3
• Molecular Weight: 568.5506032
• Mol File: 116666-63-8.mol

Chemical Properties

• Melting Point: 128℃
• Boiling Point: 647.6°Cat760mmHg
• Flash Point: 345.5°C
• Appearance: white/solid
• Density: g/cm³
• Vapor Pressure: 1.17E-16mmHg at 25°C
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility: H2O: 24 mg/mL, soluble
• PKA: 4.8; 5.5(at 25℃)
• Stability: Hygroscopic
• CAS DataBase Reference: MIBEFRADIL(CAS DataBase Reference)
• NIST Chemistry Reference: MIBEFRADIL(116666-63-8)
• EPA Substance Registry System: MIBEFRADIL(116666-63-8)

Safety Data

• WGK Germany: 3
• RTECS: AI8977250
• Hazardous Substances Data: 116666-63-8(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
MIBEFRADIL is used as a vasodilator for the treatment of hypertension. It is effective in lowering blood pressure and has been launched in various countries for this purpose.
Used in Cardiovascular Applications:
MIBEFRADIL is used as a T-type calcium channel blocker in various cells, playing a role in cardiovascular health by managing calcium channel activity.
Used in Neuroprotection:
MIBEFRADIL has been used to reduce apoptosis of retinal ganglion cells (RGC) in EphB2-Fc, providing a neuroprotective effect.

Originator

Roche (Switzerland)

Therapeutic Function

Coronary vasodilator

Biochem/physiol Actions

Mibefradil is a tetralol derivative and nondihydropyridine calcium channel blocker. It blocks long-type (L-type) calcium channels. It blocks mildly the Purkinje-type (P-type) calcium channels in Purkinje neurons.

InChI:InChI=1/C29H38FN3O3.2ClH/c1-20(2)28-23-12-11-22(30)18-21(23)13-14-29(28,36-27(34)19-35-4)15-17-33(3)16-7-10-26-31-24-8-5-6-9-25(24)32-26;;/h5-6,8-9,11-12,18,20,28H,7,10,13-17,19H2,1-4H3,(H,31,32);2*1H/t28-,29-;;/m0../s1

Upstream product

• 38870-89-2 Methoxyacetyl chloride 
• 116666-60-5 (1S,2S)-2-[2-{[3-(1H-benzimidazol-2-yl)propyl]methylamino}ethyl]-6-fluoro-1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-ol 

Relevant articles and documents

THERAPY FOR COMPLICATIONS OF DIABETES

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

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

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.

Preparation of mibefradil via a naphthalenylacetic acid

A method of preparing 2-?2-{?3-(1H-benzimidazol-2-yl)propyl!methylamino}ethyl!-6-fluoro-1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-yl methoxyacetate comprises contacting (6-fluoro-2-hydroxy-1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-yl)acetic acid or an activated derivative of (6-fluoro-2-hydroxy-1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-yl)acetic acid with ?3-(1H-benzimidazol-2-yl)propyl!methylamine to form N-?3-(1H-benzimidazol-2-yl) propyl!-2-(6-fluoro-2-hydroxy-1-isopropyl-1,2,3 ,4-tetrahydronaphthalen-2-yl)-N-methylacetamide, reducing this to 2-?2-{?3-(1H-benzimidazol-2-yl)propyl!methylamino}ethyl!-6-fluoro-1-isopropyl-1, 2,3,4-tetrahydronaphthalen-2-ol, and treating the 2-?2-{?3-(1H-benzimidazol-2-yl) propyl!-methylamino}ethyl!-6-fluoro-1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-ol with methoxyacetic acid or an activated derivative of methoxyacetic acid. The invention is particularly applicable to the preparation of mibefradil, (1S,2S)-2-?2-{?3-(1H-benzimidazol-2-yl)propyl!methylamino}-ethyl!-6-fluoro-1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-yl methoxyacetate, and its dihydrochloride salt. N-?3-(1H-benzimidazol-2yl)propyl!-2-(6-fluoro-2-hydroxy-1-isopropyl-1, 2,3,4-tetrahydronaphthalen-2-yl)-N-methylacetamide is new.

Tetrahydronaphthalene derivatives as calcium antagonists

Compounds of the formula STR1 wherein R is lower-alkyl, R1 is halogen, R2 is C1 -C12 -alkyl, R3 is hydroxy, lower-alkoxy, lower-alkyl-carbonyloxy, lower-alkoxy-lower-alkylcarbonoyloxy, lower-alkylamin