1668-19-5

Usage

Uses

Used in Pharmaceutical Industry:
DOXEPIN is used as an antidepressant for treating anxiety and depression. It is effective in managing the symptoms of these conditions by regulating the levels of neurotransmitters in the brain, such as serotonin and norepinephrine.
Brand names for DOXEPIN include Apo-doxepin, Co dox, Deptran, Doksapan, Dolat, Doxal, Doxedyn, Doxepin hcl, Gilex, Novo-doxepin, Novoxapin, Sinequan, Sinquan concentrate, Sinquane, Tolllluan, Triadapin, and Zonalon. These brand names represent various formulations and dosages of DOXEPIN available in the market, catering to the specific needs of patients and healthcare providers.

Therapeutic Function

Tranquilizer

World Health Organization (WHO)

Doxepin, a tricyclic antidepressant was introduced in 1964 for the management of endogenous depression. Much of the adverse effects are caused by its antimuscarinic actions. These include dry mouth, cardiac arrhythmias, central nervous system disturbances, blood disorders and risk of suicide. The risk of suicide and dangers related to overdosage led the Norwegian Medicines Control Authority to put the higher strength formulation under prescribing restriction in 1992. The risk of death following overdosage is apparently higher for products containing tricyclic compounds as compared with nontricyclic products.

Biological Activity

Highly potent H 1 histamine receptor antagonist (K d = 310 pM) and tricyclic antidepressant. Also binds to the H 4 histamine receptor (pK i = 6.79).

Contact allergens

This benzoxepin tricylcic drug has antidepressant, anticholinergic, antiitching, and antihistamine properties. After oral use, it has been developed as a topical antiitching agent. Allergic contact dermatitis is not infrequent.

InChI:InChI=1/C19H21NO/c1-20(2)13-7-11-17-16-9-4-3-8-15(16)14-21-19-12-6-5-10-18(17)19/h3-6,8-12H,7,13-14H2,1-2H3/p+1/b17-11-

Upstream product

• 1229-29-4 doxepin hydrochloride 
• 1221-23-4 11-(3-chloropropylidene)-6,11-dihydrodibenzo-[b,e]-oxepine 
• 124-40-3 dimethyl amine 
• 724-98-1 2-(phenoxymethyl)benzoic acid 
• 108-95-2 phenol 
• 87-41-2 2-benzofuran-1(3H)-one 
• 4504-87-4 6,11-dihydrodibenz[b,e]oxepin-11-one 
• 109-54-6 3-(Dimethylamino)propyl chloride 
• 25127-31-5 doxepin hydrochloride 
• 83300-00-9 chlorure de N,N-dimethylamino-3 propyltriphenylphosphonium 
• 79333-82-7 diethyl 3-(N,N-dimethylamino)propylphosphonate 
• 4504-88-5 11-[3-(dimethylamino)propyl]-6,11-dihydrodibenz[b,e]oxepin-11-ol 
• 612-20-4 2-(hydroxymethyl)benzoic acid 
• 39244-78-5 11-(3-bromopropylidene)-6,11-dihydrodibenz[b,e] oxepine 

Downstream Products

• 135718-71-7 ((2R,3R,4S,5S,6S)-6-Carboxy-3,4,5-trihydroxy-tetrahydro-pyran-2-yl)-{3-[6H-dibenzo[b,e]oxepin-(11E)-ylidene]-propyl}-dimethyl-ammonium; chloride 
• 145919-96-6 ((2R,3R,4S,5S,6S)-6-Carboxy-3,4,5-trihydroxy-tetrahydro-pyran-2-yl)-{3-[6H-dibenzo[b,e]oxepin-(11E)-ylidene]-propyl}-dimethyl-ammonium; chloride 
• 22684-91-9 doxepin N-oxide 
• 4698-39-9 Doxepin hydrochloride 
• 25127-31-5 doxepin hydrochloride 
• 67035-76-1 (E)-Desmethyldoxepin 
• 58534-46-6 (Z)-Desmethyldoxepin 
• 1229-29-4 doxepin hydrochloride 

Related news

Research paperAntidepressant polypharmacy and the potential of pharmacokinetic interactions: DOXEPIN (cas 1668-19-5) but not mirtazapine causes clinically relevant changes in venlafaxine metabolism10/01/2019

BackgroundTo uncover pharmacokinetic interactions between venlafaxine and doxepin or mirtazapine in a naturalistic sample.detailed

Physicochemical evaluation and non-isothermal kinetic study of the drug–excipient interaction between DOXEPIN (cas 1668-19-5) and lactose09/27/2019

In this study, the incompatibility of doxepin in solid physical mixtures with lactose (monohydrate and anhydrous) was investigated. The compatibility testing was made using various physicochemical techniques, such as differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) spec...detailed

Original Research ArticleHighly sensitive LC–MS/MS method to estimate DOXEPIN (cas 1668-19-5) and its metabolite norDOXEPIN (cas 1668-19-5) in human plasma for a bioequivalence study09/25/2019

A selective, sensitive and rugged liquid chromatography–tandem mass spectrometry (LC–MS/MS) assay has been developed for the simultaneous determination of doxepin (Dox) and its pharmacologically active metabolite, nordoxepin (NDox) in human plasma. The analytes and their internal standards (IS...detailed

Document headingTherapeutic rationale for low dose DOXEPIN (cas 1668-19-5) in insomnia patients09/24/2019

Histamine is an excitatory neurotransmitter in central nervous system. It plays an important role in the regulation of the sleep-wake cycle. Antidepressant with sleep-promoting effects, for example, doxepin, promotes sleep not through a sedative action but through resynchronisation of circadian ...detailed

Comparing DOXEPIN (cas 1668-19-5) cream to oral antihistamines for the treatment of itch in burn patients: A multi-center triple-blind randomized controlled trial09/10/2019

BackgroundDoxepin cream, an antihistaminic agent, has shown promising results in the treatment of pruritus in burn patients. However, its effectiveness has not been studied comprehensively.detailed

Relevant academic research and scientific papers

Improved synthesis method of doxepin hydrochloride

The invention relates to an improved synthesis method of doxepin hydrochloride. The method comprises the following steps: (1) reacting triphenylphosphine with 3 - chlorine -1 - (N, N - dimethyl) propylamine to prepare (3 - (dimethylamino) propyl) triphenyl phosphine chloride. (2) Reaction of (3 - (dimethylamino) propyl) triphenyl phosphine chloride and 6, 11 -dihydrodibenzo [b, e] oxepin -11 - ketone under a strong base condition to Wittig prepare a doxorubicin. (3) The multi-plug is subjected to salt formation reaction with hydrochloric acid to prepare the doxorubicin hydrochloride. The second Reaction is adopted in Wittig-step reaction, so that the reaction is simpler, the requirements for water and reaction equipment of the solvent and the raw materials are lower, and the repetition rate is higher. Compared with the prior art, the method has the advantages of simple process, low production cost, less process steps and the like.

Synthesis method of doxepin hydrochloride

The invention relates to a synthetic method of doxepin hydrochloride. The method comprises the following steps: (1) phosphites react with 3 - chlorine -1 - (N, N - dimethyl) propylamine to obtain 3 - (N, N - dimethyl) propyl phosphate, or a salt thereof with hydrochloric acid to obtain 3 - (N, N - dimethyl) propyl phosphate hydrochloride. (2) Reaction of 3 - (N, N -dimethyl) propyl phosphate or its hydrochloride with 6, 11 -dihydrodibenzo [b, e] oxepin -11 - ketone under strong base conditions Wittig to obtain doxorubicin. (3) The multi-plug is subjected to salt formation reaction with hydrochloric acid to prepare the doxorubicin hydrochloride. In 1st-step reaction step, the yield of the alkyl phosphate product prepared by adopting the reaction is high, thereby ensuring the yield and purity of the final product hydrochloride. Compared with the prior art, the method has the advantages of simple process, low production cost, less process steps and the like.

Refining method of doxepin hydrochloride

The invention belongs to the field of medicine synthesis, and relates to a refining method of doxepin hydrochloride. The refining method of doxepin hydrochloride comprises the following steps: adding a doxepin hydrochloride crude product into water, adjusting the pH value with alkali liquor, extracting with dichloromethane, and spin-drying an organic phase to obtain free doxepin. The method comprises the following steps: dissolving free doxepin in a mixed solvent of diethyl ether and ethanol, adding maleic acid in a controlled temperature range, and stirring to separate out doxepin maleate; adding doxepin maleate into water, adjusting the pH value with alkali liquor, extracting with dichloromethane, and spin-drying an organic phase to obtain free doxepin; dropwise adding isopropyl ether hydrogen chloride into the free doxepin, stirring and crystallizing to obtain doxepin hydrochloride. The Z-configuration doxepin hydrochloride content of the product obtained by the method is 17%-18.5%.

Synthetic method of doxepin hydrochloride

The invention discloses a synthetic method of doxepin hydrochloride. The synthetic method comprises the following steps: using N, N-dimethyl-3-chloropropylamine as an initial raw material, carrying out Grignard reaction, carrying out addition reaction on the reaction product and 6, 11-dihydrodibenzo [b, e] oxepine-11-ketone, and sequentially carrying out elimination reaction and salifying reactionto synthesize the final product. According to the method, high-purity doxepin hydrochloride can be obtained through four-step synthesis, a substitution reaction is not needed, and the yield of the prepared product is high. Compared with the existing synthesis process, the method has the advantages of few synthesis steps, simple process, short production period, low cost and the like.

Iron(II) promoted direct synthesis of dibenzo[b,e]oxepin-11(6H)-one derivatives with biological activity. A short synthesis of doxepin

A novel and efficient synthesis of dibenzo[b,e]oxepin-11(6H)-ones by direct intramolecular ortho-acylation from readily available 2-(phenoxymethyl)benzoic acids was developed. The method takes advantage of a newly developed cooperative system consisting of sustainable FeCl2 and Cl2CHOCH3 as the key components. This methodology is compatible with a wide variety of functional groups in good to excellent yields and high regioselectivity. The synthetic application of new protocol was extended to the synthesis of known tricyclic drug doxepin as well as a small library of oxepin based derivatives. For the first time, the obtained dibenzo[b,e]oxepinone derivatives were evaluated for their biological activities on the free-living nematode Caenorhabditis elegans as an effective and cost-efficient model system for anthelmintic discovery.

A to phthaldialdehyde as the raw material to synthesize method of doxepin hydrochloride (by machine translation)

This invention discloses in a to phthaldialdehyde as the raw material to synthesize method of doxepin hydrochloride. The method comprises in a wide range of sources phthaldialdehyde as the starting material, reaction by sequentially connie Zha Luo, intramolecular esterification, substituted, cyclized, nucleophilic addition, elimination reactions, nucleophilic substitution, pro-nuclear substituted, and in the reaction, to obtain liu Danhuang pyridine. In section 8 step in the nucleophilic substitution reaction steps, yu Mi using organic lithium compound in the solvent, so that the organic compound forming ammonium lithium salt with dimethylamine , Then this ammonium lithium salt for carrying out the alkylation reaction with halo, improve the yield of the addition, the ultimate so as to guarantee the yield and purity of doxepin hydrochloride. Phthaldialdehyde cheap, so as to reduce the production cost. (by machine translation)

Method for preparing doxepin hydrochloride using o-halogen methyl methyl benzoate as raw material

The present invention discloses a method for preparing doxepin hydrochloride using o-halogen methyl methyl benzoate as a raw material. In the method, o-halogen methyl methyl benzoate which is wide in source is used as a starting raw material, and sulfasalazine is obtained through substitution, hydrolysis, cyclization, nucleophilic addition, elimination reaction, nucleophilic substitution and neutralization reaction. The method comprises: during a nucleophilic substitution reaction obtained in the seventh step, using an organic lithium compound in an ether solution, so that the organic lithium compound and dimethylamine form an ammonium lithium salt (the formula is as shown in the description); then conducting an alkylation reaction on the ammonium lithium salt and a halide to improve the yield of tertiary amine, thereby ensuring the yield and purity of doxepin hydrochloride.

A chemoselective deoxygenation of N-oxides by sodium borohydride-Raney nickel in water

A simple and convenient protocol for deoxygenation of aliphatic and aromatic N-oxides to the corresponding amines in good to excellent yield using sodium borohydride-Raney nickel in water is reported. Other functional moieties such as alkenes, halides, ethers, and amides are unaffected under the present reaction condition.

ULTRA LOW DOSE DOXEPIN AND METHODS OF USING THE SAME TO TREAT SLEEP DISORDERS

The invention relates to doxepin, pharmaceutically acceptable salts and prodrugs of doxepin; compositions containing the same, and the use of any of the aforementioned for the treatment of sleep disorders.

METHODS OF USING LOW-DOSE DOXEPIN FOR THE IMPROVEMENT OF SLEEP

Methods of treating sleep disorders by administration of low doses of doxepin in individuals seeking sustained efficacy or in need of avoiding weight gain, rebound insomnia, or sedative tolerance resulting from doxepin treatment.