52468-60-7

Usage

Uses

Vasodilator.

Therapeutic Function

Vasodilator

World Health Organization (WHO)

Flunarizine, an antihistaminic and vasodilator agent, was introduced into medicine in 1970. It is indicated for the treatment of central and peripheral vascular disorders. However, its effectiveness in these conditions has not been convincingly demonstrated, and its use has been associated with adverse reactions involving the central nervous system, including extrapyramidal disturbances and depression. This has led several regulatory authorities to restrict the approved indications for products containing flunarizine.

InChI:InChI=1/C26H26F2N2/c27-24-12-8-22(9-13-24)26(23-10-14-25(28)15-11-23)30-19-17-29(18-20-30)16-4-7-21-5-2-1-3-6-21/h1-15,26H,16-20H2

Upstream product

• 18903-01-0 trans-1-cinnamylpiperazine 
• 104-55-2 3-phenyl-propenal 
• 75145-31-2 sodium (E)-1-hydroxy-3-phenylprop-2-ene-1-sulfonate 
• 27469-60-9 1-(4-fluorophenyl)methyl-piperazine 
• 104-54-1 3-Phenylpropenol 
• 27064-94-4 4,4'-difluorobenzhydryl chloride 
• 18903-01-0 1-(3-phenyl-2-propenyl)piperazine 
• 352-34-1 4-fluoro-1-iodobenzene 
• 459-57-4 4-fluorobenzaldehyde 
• 100-59-4 phenylmagnesium chloride 
• 100-58-3 phenylmagnesium bromide 
• 369-57-3 benzenediazonium tetrafluoroborate 
• 1522375-84-3 1-[bis(4-fluorophenyl)methyl]-4-(2,2-dimethoxyethyl)piperazine 
• 1522375-87-6 1-(4,4’-difluorophenylmethyl)-4-(2-acetaldehyde)piperazine 

Relevant academic research and scientific papers

Bisulfite Addition Compounds as Substrates for Reductive Aminations in Water

Highly valued products resulting from reductive aminations utilizing shelf-stable bisulfite addition compounds of aldehydes can be made under aqueous micellar catalysis conditions. Readily available α-picolineborane serves as the stoichiometric hydride source. Recycling of the aqueous reaction medium is easily accomplished, and several applications to targets in the pharmaceutical industry are documented.

A Simple, Broad-Scope Nickel(0) Precatalyst System for the Direct Amination of Allyl Alcohols

The preparation of allylic amines is traditionally accomplished by reactions of amines with reactive electrophiles, such as allylic halides, sulfonates, or oxyphosphonium species; such methods involve hazardous reagents, generate stoichiometric waste streams, and often suffer from side reactions (such as overalkylation). We report here the first broad-scope nickel-catalysed direct amination of allyl alcohols: An inexpensive NiII/Zn couple enables the allylation of primary, secondary, and electron-deficient amines without the need for glove-box techniques. Under mild conditions, primary and secondary aliphatic amines react smoothly with a range of allyl alcohols, giving secondary and tertiary amines efficiently. This “totally catalytic” method can also be applied to electron-deficient nitrogen nucleophiles; the practicality of the process was demonstrated in an efficient, gram-scale preparation of the calcium antagonist drug substance flunarizine (Sibelium).

Ni-Catalyzed Carbon-Carbon Bond-Forming Reductive Amination

This report describes a three-component, Ni-catalyzed reductive coupling that enables the convergent synthesis of tertiary benzhydryl amines, which are challenging to access by traditional reductive amination methodologies. The reaction makes use of iminium ions generated in situ from the condensation of secondary N-trimethylsilyl amines with benzaldehydes, and these species undergo reaction with several distinct classes of organic electrophiles. The synthetic value of this process is demonstrated by a single-step synthesis of antimigraine drug flunarizine (Sibelium) and high yielding derivatization of paroxetine (Paxil) and metoprolol (Lopressor). Mechanistic investigations support a sequential oxidative addition mechanism rather than a pathway proceeding via α-amino radical formation. Accordingly, application of catalytic conditions to an intramolecular reductive coupling is demonstrated for the synthesis of endo- and exocyclic benzhydryl amines.

ADENYLYL CYCLASE INHIBITORS FOR NEUROPATHIC AND INFLAMMATORY PAIN

The invention generally relates to adenylyl cyclase inhibitor compounds and methods for treating neuropathic or inflammatory pain by using those compounds.

Palladium-catalyzed regio- and stereoselective β-arylation of tertiary allylic amines: Identification of potent adenylyl cyclase inhibitors

Substituted allylic amines and their derivatives are key structural motifs of many drug molecules and natural products. A general, mild, and practical palladium-catalyzed β-arylation of tertiary allylic amines, one of the most challenging Heck arylation substrates, has been developed. The β-arylation products were obtained in excellent regio- and stereoselectivity. Moreover, novel and potent adenylyl cyclase inhibitors with the potential for treating neuropathic and inflammatory pain have been identified from the β-arylation products.

Stereoselective synthesis of (z)-1-benzhydryl-4-cinnamylpiperazines via the wittig reaction

A synthetic method of producing (E)- and (Z)-isomers of 1-benzhydryl-4-cinnamylpiperazines in a specific ratio from corresponding benzhydrylpiperazine is described. Of the three compounds synthesized (5a-c), the ratio of E/Z-isomers remained around 15:85. The key intermediates, 1-benzhydryl-4-(2,2-dimethoxyethyl)piperazine derivatives (3a-c), were prepared by nucleophilic substitution reaction of benzhydrylpiperazines (2a-c) with chloroacetaldehyde dimethylacetal in good yield (up to 88%). Hydrolysis of 3a-c gave the corresponding aldehydes 4a-c, which when subjected to the Wittig reaction followed by column purification to afford 1a-c (E-isomers) and 6a-c (Z-isomers) in pure form. The isolated compounds were characterized by NMR and mass spectral analysis. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications for the following free supplemental resource(s): Full experimental and spectral details.] Copyright

An efficient and convenient palladium catalyst system for the synthesis of amines from allylic alcohols

A novel catalyst system for efficient amination of allylic alcohols with aryl and alkyl amines is presented. By applying a convenient combination consisting of Pd(OAc)2/1,10-phenanthroline, a variety of allylic alcohols reacted smoothly to give the corresponding secondary and tertiary amines in good to excellent yields with high regioselectivity. The usefulness of our protocol is demonstrated in the one-step synthesis of the antifungal drug naftifine and the calcium channel blocker flunarizine. One pot is all it takes: By applying a convenient combination consisting of Pd(OAc)2/1,10- phenanthroline, a variety of allylic alcohols reacts smoothly to give the corresponding secondary and tertiary amines in good to excellent yields with high regioselectivity (see picture).

Compositions of a cyclooxygenase-2 selective inhibitor and a sodium ion channel blocker for the treatment of pain, inflammation or inflammation mediated disorders

The present invention provides compositions and methods for the treatment of pain, inflammation or inflammation-mediated disorders in a subject. More particularly, the invention provides a combination therapy for the treatment of pain, inflammation or inflammation mediated disorders comprising the administration to a subject of a sodium ion channel blocker in combination with a cyclooxygenase-2 selective inhibitor.