- Simple and Efficient Process for the Large-Scale Preparation of Agomelatine: An Antidepressant Drug
-
A simple and efficient process for the large-scale preparation of agomelatine (1), an antidepressant drug is, described. Agomelatine was prepared in a linear manner starting from readily available, inexpensive 2-naphthol. Key steps in the synthesis are Friedel-Crafts acylation of 2-naphthyl acetate with chloroacetyl chloride, reduction of keto intermediate, and nucleophilic displacement of chloro intermediate with sodium diformylamide. A systemic approach was described to streamline the process into a robust scalable process by controlling the impurities.
- Vujjini, Satish Kumar,Vyala, Sunitha,Badarla, Krishna Rao,Kandala, Sreenatha Charyulu,Bandichhor, Rakeshwar,Kagga, Mukkanti,Cherukupalli, Praveen
-
-
Read Online
- A facile synthesis of melatonergic antidepressant agomelatine
-
Agomelatine was synthesized from 8-aminonaphthalen-2-ol by diazotization-iodination, formylation, C-C bond formation by nitroaldol and Pd/C hydrogenation of β-nitrovinylnaphthalene followed by N-acetylation. The route reported employs readily and commercially viable starting materials and reagents, and can potentially be utilized for process synthesis of agomelatine.
- Kandagatla, Bhaskar,Raju, Vetukuri Venkata Naga Kali Vara Prasada,Reddy, Ganta Madhusudhan,Rao, Sirigiri Chandrakanth,Iqbal, Javed,Bandichhor, Rakeshwar,Oruganti, Srinivas
-
-
Read Online
- A simple and efficient procedure for synthesis of agomelatine
-
A simple and efficient process for the large scale preparation of agomelatine, an antidepressant drug is described. Agomelatine was synthesized from 7-methoxy-1-tetralone in five steps. The route reported employs readily, commercially viable starting materials, reagents and potentially be utilized for the process of synthesis of agomelatine.
- Gurunadham,Raju, R. Madhusudhan,Venkateswarlu
-
-
Read Online
- Novel conformationally constrained analogues of agomelatine as new melatoninergic ligands
-
Novel conformationally restricted analogues of agomelatine were synthesized and pharmacologically evaluated at MT1 and MT2 melatoninergic receptors. Replacement of the N-Acetyl side chain of agomelatine by oxathiadiazole-2-oxide (compound 3), oxadiazole-5(4H)-one (compound 4), tetrazole (compound 5), oxazolidinone (compound 7a), pyrrolidinone (compound 7b), imidazolidinedione (compound 12), thiazole (compounds 13 and 14) and isoxazole moieties (compound 15) led to a decrease of the melatoninergic binding affinities, particularly at MT1. Compounds 7a and 7b exhibiting nanomolar affinity towards the MT2 receptors subtypes have shown the most interesting pharmacological results of this series with the appearance of a weak MT2-selectivity.
- Rami, Marouan,Landagaray, Elodie,Ettaoussi, Mohamed,Boukhalfa, Koussayla,Caignard, Daniel-Henri,Delagrange, Philippe,Berthelot, Pascal,Yous, Said
-
-
Read Online
- A novel synthesis of the antidepressant agomelatine
-
Agomelatine was synthesized from (2-methoxynaphthalene-8-yl)oxoacetic acid in a four-step approach involving borane reduction, semipinacol rearrangement of the resulting diol, ald-oxime formation, and Ra-Ni hydrogenation/acetylation in 51% overall yield. The reaction sequence includes a novel one-pot conversion of an aldoxime into an N-acetylamine. The synthetic route could be useful as a new approach towards N-acetylarylethyl-amines. Georg Thieme Verlag Stuttgart · New York.
- Markl, Christian,Zlotos, Darius P.
-
-
Read Online
- Total synthesis of agomelatine via Friedel-Crafts acylation followed by Willgerodt-Kindler reaction
-
Total synthesis of antidepressant drug, agomelatine is reported. Regio selective Friedel-Crafts acylation followed by Willgerodt-Kindler reactions is used as the key steps for the synthesis of agomelatine.
- Vujjini, Satish Kumar,Datla, V.R. Krishnam Raju,Badarla, Krishna Rao,Vetukuri, V.N.K.V. Prasada Raju,Bandichhor, Rakeshwar,Kagga, Mukkanti,Cherukupally, Praveen
-
-
Read Online
- Synthesis and structure-activity relationships of novel naphthalenic and bioisosteric related amidic derivatives as melatonin receptor ligands
-
A series of N-naphthylethyl amide derivatives were synthesized and evaluated as melatonin receptor ligands. The affinity of each compound for the melatonin receptor was determined by binding studies using [2- 125I]iodomelatonin on ovine pars tuberalis membrane homogenates. Structure-activity relationships led to the conclusion that naphthalene is a bioisostere of the indole moiety of melatonin. Moreover it appears that the affinity is strongly affected by the size of the substituent of the nitrogen of the amidic function. Many of these ligands give biphasic dose-response curves which suggests that there may be two melatonin receptor subtypes within the ovine pars tuberalis cells. The replacement of naphthalene by benzofuran or benzothiophene did not strongly alter the affinity for the melatonin receptor. In contrast, the benzimidazole analogue was a poor ligand. Compound 7, the naphthalenic analogue of melatonin, a selective ligand of the melatonin receptor and an agonist derivative, has been selected for clinical development.
- Depreux,Lesieur,Mansour,Morgan,Howell,Renard,Caignard,Pfeiffer,Delagrange,Guardiola,Yous,Demarque,Adam,Andrieux
-
-
Read Online
- PROCESS FOR THE PREPARATION OF AGOMELATINE IN CRYSTALLINE FORM
-
The present invention pertains to a process for the preparation of polymorph form X of agomelatine, which comprises providing agomelatine, and crystallizing agomelatine in the presence of at least one of an acid and a salt thereof, and to a polymorph form of agomelatine.
- -
-
Page/Page column 41
(2019/05/02)
-
- Preparation method of agomelatine
-
The invention provides a preparation method of agomelatine. According to the preparation method, 7-methoxy-1-naphthaldehyde is taken as a substrate, and three reaction steps including a condensation dehydration reaction, a reduction reaction and a acetylation reaction are respectively carried out. The preparation method disclosed by the invention has the beneficial effects that the process is simple and only comprises three reaction steps, the operation is convenient, and the industrial production is easily realized; secondly, synthetic raw materials are easily available and cheap, and the cost of the whole process is very low; thirdly, the agomelatine product prepared by virtue of the preparation method reaches up to 99.9%, and the quality of the agomelatine product meets the requirementsof European and the United States Pharmacopoeias; and finally, the agomelatine product prepared by virtue of the preparation method is high in yield, and the total yield reaches 64%.
- -
-
Paragraph 0039; 0043; 0051-0055; 0061-0065; 0071-0074
(2018/09/11)
-
- Preparation method of agomelatine
-
The invention discloses a preparation method of agomelatine. In the method, 1-methyl-7-methoxynaphthalene is used as an initial raw material and is successively subjected to a bromination reaction with N-bromosuccinimide, a substitution reaction with nitromethane, a nitro-reduction reaction, and an acetylation reaction to produce a final product of agomelatine. The preparation method has fewer steps and employs low-cost and easy-to-obtained raw materials. During the reactions, high-risk and high-cost hydrogenation catalysts, such as palladium-carbon and Raney nickel, are not employed, so that the reactions are more reliable and require lower energy. The method can reduce transfer loss of intermediates, is simpler in operation, occupies fewer operators, is stable in product quality and high in yield and is suitable for large-scale industrial stable production.
- -
-
-
- Synthesis method of Agomelatine
-
The invention relates to a preparation method of Agomelatine. The preparation method is characterized by comprising the following steps: halogenating 7-methoxy-naphthylamine, performing potassium vinyltrifluoroborate substituting and ammonifying and protecting acetyl, so as to obtain a product. The preparation method has the advantages of being easily available in raw materials, concise in processes, high in total yield, less in by-products and simple in aftertreatment, therefore, the preparation method is suitable for industrial production.
- -
-
-
- A compound and its preparation method and application
-
The invention provides a 1-cyan-1-(7-methoxyl-3, 4-dihdyro-1-naphthyl) methanol ester compound shown as a structural formula I described in the specification, wherein R is H, C1-C6 aliphatic groups or aryl. The invention further provides a preparation method of the compound and an application thereof in preparing agomelatine. The method of synthesizing agomelatine by the 1-cyan-1-(7-methoxyl-3, 4-dihdyro-1-naphthyl) methanol ester compound shown as the structural formula I is mild in condition, lower in production cost, higher in yield and fewer in impurities in end-products of reaction, and is more suitable for industrialized production.
- -
-
-
- New synthesis and purification method of agomelatine
-
The invention discloses a new method for synthesizing crystal form II agomelatine. The method comprises the following steps: performing reaction on a compound (I) serving as a raw material and hydrogen in an ammonia gas/ethanol system to obtain a compound (II); and performing reaction on a compound (II) and acetic anhydride in a sodium acetate/ethanol system to obtain a compound (III) crude product, and recrystallizing an absolute ethanol/ethyl acetate system to obtain the crystal form II agomelatine. The invention discloses a method (two-step method) for synthesizing the crystal form II agomelatine. The method is simple and safe in experimental condition, energy-saving, environment-friendly and simple in aftertreatment, the product is easily available, high in yield and high in purity, and the method is simple in process cost and suitable for industrialized mass production.
- -
-
Paragraph 0085; 0098; 0099
(2017/09/01)
-
- Preparation method of Agomelatine
-
The invention relates to a preparation method of Agomelatine. The preparation method comprises the steps of directly reducing a raw material 4-methylbenzenesulfonic acid 1-(cyano methyl)-7-methoxynaphthalene-2-estoral into 2-(7-methoxyl-1-naphthyl) ethylamine, and then further transforming into the Agomelatine. The preparation method of the Agomelatine provided by the invention is less in reaction step, high in yield/purity, and simple in aftertreatment.
- -
-
Paragraph 0034; 0035
(2017/08/30)
-
- PROCESS FOR THE SYNTHESIS OF AGOMELATINE
-
Process for the industrial synthesis of the compound of formula (I):
- -
-
-
- PROCESS FOR THE PREPARATION OF AGOMELATINE
-
The present invention relates to a method for economically and efficiently manufacturing agomelatine used as a medicine of depression, and a novel intermediate therefor. The manufacturing method comprises the steps of: (i) converting a hydroxy group of (7-methoxynaphthalene-1-yl)methanol of chemical formula II into a leaving group to obtain a compound of chemical formula III; (ii) coupling-reacting a compound of chemical formula IV or a compound of chemical formula V with the compound of chemical formula III, performing decarboxylation on the same, and obtaining 3-(7-methoxynaphthalene-1-yl)propanoic acid of chemical formula VI; (iii) performing Curtius rearrangement on the 3-(7-methoxynaphthalene-1-yl)propanoic acid of chemical formula VI, and obtaining 2-(7-methoxynaphthalene-1-yl)ethanamine of chemical formula VII; and (iv) performing an acetylization reaction on the 2-(7-methoxynaphthalene-1-yl)ethanamine of chemical formula VII.
- -
-
Paragraph 0080-0081
(2017/02/09)
-
- 1-CYAN-1-(7-METHOXYL-1-NAPHTYL) METHANOL ESTER COMPOUND AND PREPARATION METHOD AND USE THEREOF
-
Provided are a 1-cyan-1-(7-methoxyl-1-naphtyl) methanol ester compound, and preparation method and use thereof in the preparation of agomelatine intermediate 2-(7-methoxyl-1-naphtyl) ethylamine. Also provided is an agomelatine preparation method by using the 1-cyan-1-(7-methoxyl-1-naphtyl) methanol ester compound as an intermediate.
- -
-
-
- A NOVEL PROCESS FOR THE PREPARATION OF TETRALIN AND NAPHTHALENE DERIVATIVES
-
The present invention relates to a novel process for the preparation or tetralin and naphthalene derivatives, including Agomelatine and pharmaceutical acceptable salts thereof. Such compounds are considered to be interesting either as useful building blocks or due to their biological activity.
- -
-
-
- A scalable synthesis of the antidepressant agomelatine by a tandem allylic chlorination-isomerization process
-
A concise, scalable, and industrially applicable process for the synthesis of the antidepressant agomelatine is described. The process relies on a tandem allylic chlorination-isomerization sequence, on a tetralone-derived allyl carbinol, as the key transformation. The target compound is obtained in five steps from commercially available 7-methoxy-1-tetralone, in 52.3 % overall yield after final recrystallization. A tandem allylic rearrangement-isomerization sequence on a tetralone-derived allyl carbinol was applied for the preparation of agomelatine, a high-potential antidepressant agent with improved pharmacokinetic profile. The active pharmaceutical ingredient (API) was obtained in 52.3 % overall yield and excellent purity (> 99.5 %) by a simple process amenable to industrial-scale applications.
- Stathakis, Christos I.,Neokosmidis, Efstratios,Koftis, Theocharis V.
-
p. 6376 - 6379
(2016/02/18)
-
- AN IMPROVED PROCESS FOR PREPARATION OF AGOMELATINE
-
The present invention provides an improved process for preparing agomelatine of formula (I). The process comprises reacting 7-methoxy tetralone with cyanoacetic acid in an organic solvent to obtain (7-methoxy-3,4-dihydro- 1 -naphthalenyl)acetonitrile of Formula (B); treating compound of Formula (B) with a catalyst to obtain (7-methoxy- 1 - naphthyl)acetonitrile of Formula (C); reducing compound of formula (C) with hydrogen in presence of Raney nickel in ammoniacal methanol medium and subsequently converting to a salt using hydrochloric acid to obtain 2-(7-methoxy- 1 -naphthyI)ethanamine hydrochloride of formula (D); iv) reacting compound of formula (D) with acetic anhydride or acetic chloride in an organic solvent in presence of a base and a catalyst to obtain agomelatine of Formula (I); and optionally purifying agomelatine of Formula (I). The present invention also provides a process for preparing polymorphic Form-I of agomelatine of formula (I) comprising treating agomelatine of formula (I) in a suitable organic solvent; and isolating polymorphic Form-I of agomelatine of formula (I).
- -
-
Page/Page column 15; 16
(2014/05/24)
-
- PROCESSES FOR THE PREPARATION OF AGOMELATINE USING NOVEL INTERMEDIATES
-
Provided herein are novel, commercially viable and industrially advantageous processes for the preparation of Agomelatine or a salt thereof, in high yield and purity, using novel intermediates.
- -
-
-
- PROCESS FOR PREPARATION OF AGOMELATINE AND CRYSTALLINE FORM I THEREOF
-
An improved process for the preparation of agomelatine of formula (I) and a new process for the preparation of crystalline form I of agomelatine are provided.
- -
-
-
- PROCESS FOR THE PREPARATION OF AGOMELATINE
-
The present invention provides a process for the preparation of agomelatine and its intermediate compounds. The invention also provides an intermediate compound of agomelatine represented by Formula (V).
- -
-
Paragraph 0057; 0058; 0059
(2014/11/27)
-
- Process for the preparation of agomelatine
-
Disclosed is a process for the synthesis of Agomelatine (1), N-(2-(7-methoxynaphthalen-1-yl)ethyl)acetamide from ethyl 2-(7-methoxynaphthalen-1-yl)acetate (4). Said synthesis method is particularly advantageous compared with known procedures because it uses low-cost reagents under mild reaction conditions and allows the isolation of a product with excellent yields and quality.
- -
-
-
- PROCESS FOR THE PREPARATION OF CRYSTALLINE FORMS OF AGOMELATINE AND NOVEL POLYMORPH THEREOF
-
The invention concerns a new process for the preparation of two crystalline forms of agomelatine, in particular a process for preparation of form I and a new form of agomelatine, here called form VII.
- -
-
Paragraph 0053
(2014/08/19)
-
- PROCESS FOR THE SYNTHESIS OF AGOMELATINE
-
Process for the industrial synthesis of the compound of formula (I)
- -
-
-
- PROCESS FOR THE SYNTHESIS OF AGOMELATINE
-
Process for the industrial synthesis of the compound of formula (I)
- -
-
-
- PROCESS FOR THE PREPARATION OF AGOMELATINE
-
The present invention provides a process for the preparation of agomelatine and its intermediate compounds. The invention also provides intermediate compounds of agomelatine represented by Formula IV, Formula V and Formula VIII. Formula IV Formula V Formula VIII
- -
-
-
- PROCESS FOR THE PREPARATION OF AGOMELATINE
-
The present invention provides a process for the preparation of agomelatine and its intermediate compounds. The invention also provides an intermediate compound of agomelatine represented by Formula (V).
- -
-
Page/Page column 12; 13
(2013/06/27)
-
- Processes for the preparation of agomelatine and its intermediates
-
Aspects of the present application relate to processes for the preparation of agomelatine and its intermediates which are used in manufacturing process of agomelatine.
- -
-
Paragraph 0123
(2013/03/26)
-
- AGOMELATINE INTERMEDIATES AND PREPARATION METHOD THEREOF
-
The present invention relates to the intermediate compounds for preparation of agomelatine, as well as the preparation methods thereof. The intermediate of the present invention for preparation of agomelatine is compound A as shown in the following formula. Also provided are two novel intermediate compounds. When we use these new intermediate compounds to prepare agomelatine, it is simple to manipulate, well-controlled and with high purity, without complicated operations such as rectification and column chromatography separation, and suitable for industrial production. Meanwhile, the preparation methods of the two new intermediates themselves is simple and high yield, only using the most commonly-used 7-methoxy-tetralone as original starting material and undergoing one step of reaction to obtain the intermediates, followed by one more step of converting the intermediate compounds to desired product agomelatine. Said reaction processes are greatly simplified, with the reaction yield being improved and the difficulty in purification of previous method being overcome, as compare with the previous technique for preparation of agomelatine. Typically, the yield of the present invention is over 70%.
- -
-
Paragraph 0043; 0044
(2013/10/22)
-
- AGOMELATINE-UREA COMPLEX AND CRYSTALLINE FORMS THEREOF
-
The present invention provides an Agomelatine-urea complex, and a specific crystalline form thereof.
- -
-
Page/Page column 10
(2013/06/27)
-
- AGOMELATINE AND PHARMACEUTICAL COMPOSITIONS THEREOF
-
Agomelatine crystal, which is a drug for treating depression, and pharmaceutical compositions thereof are provided. The X-ray powder diffraction spectra of such agomelatine crystal, which is irradiated by Cu-Kα and showed by 20(degree), has characteristic diffraction peaks at 12.84, 13.84, 16.14, 18.56, 19.12, 20.86, 21.20, 23.84; its IR absorption pattern has characteristic absorption peaks at about 3234, 3060, 2940, 1638, 1511, 1436, 1249, 1215, 1184, 1032, 908, 828, 755, 588 cm-1; and its DSC endothermic transition temperature is 97.6°C. The use of the agomelatine crystal as an active ingredient in preparing a medicament for the treatment of depression is also provided.
- -
-
-
- Design, synthesis and pharmacological evaluation of new series of naphthalenic analogues as melatoninergic (MT1/MT2) and serotoninergic 5-HT2C dual ligands (I)
-
As part of our ongoing interest in developing new melatoninergic ligands bearing the same pharmacological profile as agomelatine, we focused our attention on this compound as a lead. Several chemical modifications have been performed on positions C-3 and 8 of the naphthalene ring determined as primary targets for the agomelatine metabolism. Herein we report the modulation of the positions C-3 and 7 in addition of the amide side chain because of this later prominent role in the affinity profile of such ligands. Synthesized compounds were then biologically evaluated at human cloned melatoninergic and serotoninergic receptors and showed different binding affinity and intrinsic activity profiles. Compounds bearing fluoroacetamide group (compounds 4 and 5) showed a high melatoninergic binding affinity particularly towards MT 1 receptor subtype. Thus, the fluoroacetamide 4 exhibited a good melatoninergic (MT1/MT2) binding affinity (70 pM) higher than the lead. Moreover, other compounds (10a, 10e, 16, 17 and 18) issued from these modulations behaved as MT1 and MT2 agonists and exhibited a sub-nanomolar binding affinity towards these receptors. However, only compounds 10e, 17 and 18 showed a sub-nanomolar binding affinity at 5-HT2C higher than the agomelatine.
- Ettaoussi, Mohamed,Sabaouni, Ahmed,Rami, Marouan,Boutin, Jean A.,Delagrange, Philippe,Renard, Pierre,Spedding, Michael,Caignard, Daniel-Henri,Berthelot, Pascal,Yous, Sa?d
-
experimental part
p. 310 - 323
(2012/04/10)
-
- PROCESSES FOR THE PREPARATION OF N-[2-(7-METHOXY-1-NAPHTHYL)ETHYL]ACETAMIDE
-
The present invention relates to processes for the synthesis of N-[2-(7-methoxy-l - naphthethyl] acetamide, amorphous form of N-[2-(7-methoxy-l -naphthethyl] acetamide and pharmaceutical compositions thereof.
- -
-
-
- PROCESS FOR THE PREPARATION OF N-[2- (7-METHOXY-L-NAPHTHYL) ETHYL] ACETAMIDE AND ITS NOVEL CRYSTALLINE FORMS
-
The present invention relates to a process for the preparation of N-[2-(7-methoxy-l-naphthyl)ethyl]acetamide compound of formula-1 and novel crystalline forms of its intermediates as well as the final compound.
- -
-
Page/Page column 26; 31; 32
(2012/04/23)
-
- PROCESSES FOR THE PREPARATION OF INTERMEDIATES OF N-[2-(7-METHOXY-1-NAPHTHYL) ETHYL] ACETAMIDE
-
The present invention provides processes for the preparation of intermediates of N-[2-(7-methoxy-1-naphthyl) ethyl] acetamide. More particularly the present invention relates to processes for the preparation of the compound of structural formula II. Also provides Isolated solid (7-Methoxy-l-naphthyl)ethanamine compound of structural formula VI as freebase.
- -
-
Page/Page column 11
(2012/10/08)
-
- PROCESS FOR THE PREPARATION OF AGOMELATINE
-
The present invention relates to a process for the manufacture of N-[2-(7-methoxy-1-naphthalenyl) ethyl]acetamide (Agomelatine) with improved yield and reduced level of N- acetyl-N-[2-(7-methoxy-1-naphthalenyl) ethyl]acetamide impurity.
- -
-
Page/Page column 11
(2012/06/15)
-
- PROCESS FOR THE PREPARATION OF CRYSTALLINE FORMS OF AGOMELATINE AND NOVEL POLYMORPH THEREOF
-
The invention concerns a new process for the preparation of two crystalline forms of agomelatine, in particular a process for preparation of form I and a new form of agomelatine, here called form VII.
- -
-
Page/Page column 6; 7
(2013/02/28)
-
- NEW PROCESS FOR THE PREPARATION OF N-[2-(7-METHOXY-1-NAPHTHYL)-ETHYL]ACETAMIDE AND NEW CRYSTALLINE FORM
-
A novel process for the preparation of N-[2-(7-methoxy-1-naphthyl)ethyl]acetamide, also known as agomelatine, Compound (I), from 7-methoxy-tetralone as starting material, and to a new crystalline form X of agomelatine.
- -
-
-
- AGOMELATINE INTERMEDIATES AND PREPARATION METHOD THEREOF
-
Intermediate compounds for preparation of agomelatine and preparation methods thereof are provided. Also provided are two novel intermediate compounds. The method is simple to manipulate, well-controlled, suitable for industrial production and has a high purity without complicated operations such as rectification and column chromatography separation. Meanwhile, preparation methods of the two new intermediates themselves are simple and have a high yield.
- -
-
Page/Page column 9
(2012/01/04)
-
- PROCESS FOR THE MANUFACTURE OF AGOMELATINE AND ITS INTERMEDIATE
-
A process for the manufacture of agomelatine and its intermediate N-[2-(7-methoxy-1-naphthyl)ethyl] phthalimide comprises: reacting 7-methoxy-1-naphthyl ethanol (III) with benzenesulfonyl chloride to obtain 7-methoxy-1-naphthylethyl benzene sulfonate (IV), which is reacted with potassium phthalimide to produce N-[2-(7-methoxy-1-naphthyl)ethyl] phthalimide (II); and subjecting N-[2-(7-methoxy-1-naphthyl)ethyl] phthalimide (II) to alkaline hydrolysis and acetylation, to obtain agomelatine.
- -
-
-
- Process for the synthesis of agomelatine
-
Process for the industrial synthesis of the compound of formula (I)
- -
-
Page/Page column 2
(2010/03/02)
-
- Process for the synthesis of agomelatine
-
Process for the industrial synthesis of the compound of formula (I)
- -
-
Page/Page column 2
(2010/03/02)
-
- Process for the synthesis of agomelatine
-
Process for the industrial synthesis of the compound of formula (I)
- -
-
Page/Page column 2
(2010/03/02)
-
- SUBSTITUTED NAPHTHALENES
-
Disclosed herein are substituted naphthalene-based melatonin (MT) receptor modulators and/or 5-HT receptor modulators of Formula I, process of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.
- -
-
Page/Page column 36
(2008/12/08)
-
- Process for the synthesis and crystalline form of agomelatine
-
A process for the industrial synthesis and a new crystalline form of the compound of formula (I): Medicinal products containing the same which are useful in treating disorders of the melatoninergic system.
- -
-
Page/Page column 6
(2008/06/13)
-
- Structure-activity relationships for substrates and inhibitors of pineal 5-hydroxytryptamine-N-acetyltransferase: Preliminary studies
-
Tryptamine, (1-naphthyl)ethylamine and phenethylamine derivatives were tested as substrates of ovine pineal serotonin-N-acetyl transferase (5-HT-NAT), a key enzyme involved in the synthesis of melatonin. Almost all of the indole derivatives possessed affinity similar to that of tryptamine (K(m) - 0.05 mM), while the substituted naphthalene and phenyl derivatives were less potent. However, the K, values seem be influenced by the steric hindrance and polar properties of the substituent. V(max) values for the naphthyl and phenyl derivatives were generally 10-20-fold higher than those of the indole derivatives and no clear structure-activity relationship was observed. Melatonin and several bioisoteric derivatives were shown to be inhibitors of 5-HT-N-acetyltransferase. Preliminary data suggested that over the 5-50-μM concentration range, melatonin was a competitive inhibitor (IC50 = 10 μM) with a concentration-dependent inhibitory effect on its own synthesis in the pineal gland. However, the bioisosteric naphthalene derivatives were characterized instead as mixed inhibitors. (1-Napthyl)ethylacetamido, a putative melatoninergic antagonist, was also shown to be an inhibitor of 5-HT-N-acetyltransferase (IC50 = 8 μM) and is a promising tool for the regulation of melatonin synthesis and the understanding of its role.
- Shen, Shuren,Bremont, Beatrice,Serraz, Isabelle,Andrieux, Jean,Poncet, Annie,Mathe-Allainmat, Monique,Chanut, Evelyne,Trouvin, Jean-Hugues,Langlois, Michel
-
p. 133 - 140
(2007/10/03)
-
- Compounds having a naphthalene structure
-
Compounds of general formula: STR1 in which A and R are defined in the description.
- -
-
-
