cas 53726-14-0, 2-Aminobutanamide | Articles data

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Method for synthesizing medicine for treating epilepsy by using L-2-aminobutanamide hydrochloride
The invention discloses a method for synthesizing a medicine for treating epilepsy by using L-2-aminobutanamide hydrochloride, and relates to the technical field of medicine synthesis, and the method comprises the following steps: under the protection of nitrogen, adding L-2-aminobutanamide hydrochloride and 4-chlorobutyrate into isopropyl alcohol, and reacting under the action of an alkaline substance and a catalyst, heating and refluxing to carry out nucleophilic substitution reaction and ring-closure reaction to prepare the levetiracetam. According to the method, the levetiracetam is synthesized by adopting a milder alkaline substance and a one-pot method, the operation is simple, the levetiracetam can be prepared without post-treatment, the levetiracetam obtained by the method is low in impurity content and high in chemical purity, the yield can reach 83.43% or above, and the purity reaches 99.6%.
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Paragraph 0048-0053; 0057-0061; 0064-0067; 0071-0074; ...

(2021/11/03)

Preparation method of L-2-aminobutanamide hydrochloride
The invention relates to the technical field of preparation of chiral drug intermediates, and discloses a preparation method of L-2-aminobutanamide hydrochloride, which comprises the following steps: dropwise adding ethyl 2-bromobutyrate into stronger ammonia water, and carrying out chemical reaction in a closed container to prepare a prefabricated mixture; According to the preparation method of the L-2-aminobutanamide hydrochloride, ethyl 2-bromobutyrate is used as an initial raw material, and the medical intermediate L-2-aminobutanamide hydrochloride is prepared through ammonolysis and chiral resolution. Compared with the traditional preparation method, the preparation method adopts a chiral reagent (+)-mandelic acid with low raw material price and racemic 2-aminobutanamide hydrochloride to form diastereoisomers, the L-2-aminobutanamide hydrochloride is obtained through resolution by utilizing the difference of the dissolving properties of the diastereoisomers in ethanol, the optical purity and the chemical purity of the product are high, and the technical scheme has the advantages of mild reaction conditions, short reaction steps, high yield, stable product quality and easy realization of industrial production.
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Paragraph 0020; 0026; 0029; 0035; 0038; 0044

(2021/06/21)

Method for splitting aminobutanamide by using ammonium hydrogen tartrate
The present invention relates to the technical field of aminobutanamide resolution, and discloses a method for resolving aminobutanamide by using ammonium hydrogen tartrate, and the method comprises the following steps: taking 10-20 parts of ammonium tartrate, placing ammonium tartrate in a reaction flask, adding 20-40 parts of purified water, and performing stirring for 0.5-1.5 h to obtain an ammonium tartrate solution. According to the method for resolving aminobutanamide by using ammonium hydrogen tartrate, the ammonium hydrogen tartrate is used as a reactant and is subjected to resolution reaction with racemic 2-aminobutanamide, and an L-2-aminobutanamide ammonium hydrogen tartrate wet product obtained after the reaction is reacted with methanol and ammonia gas, so L-2-aminobutanamide and ammonium hydrogen tartrate can be separated out; the L-2-aminobutanamide liquid can be obtained, the ammonium hydrogen tartrate can be converted into the ammonium tartrate solid for recovery and storage, and the L-2-aminobutanamide solid can be used for splitting the aminobutanamide in the next ammonium hydrogen tartrate preparation so as to achieve the recovery and reutilization of the reactants, such that the production cost is reduced, and the low cost purpose is achieved.
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Paragraph 0024; 0029-0031; 0036-0038; 0043-0044

(2021/06/09)

Preparation method of (S)-(+)-2-aminobutanamide hydrochloride
The invention discloses a preparation method of (S)-(+)-2-aminobutanamide hydrochloride, and relates to a preparation method of a levetiracetam key intermediate, and the method comprises the followingspecific steps: carrying out esterification reaction on L-2-aminobutyric acid serving as a starting material and thionyl chloride, and concentrating part of solvent after the reaction is finished; introducing ammonia gas to neutralize generated hydrogen chloride and residual thionyl chloride; and filtering, introducing ammonia gas, and carrying out an ammonolysis reaction to obtain the (S)-2-aminobutanamide hydrochloride after the treating is finished. According to the preparation method, the starting material is simple and easy to obtain, the one-pot method is adopted, the atom utilization rate is high, operation is easy and convenient, and the obtained product quality is high.
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Paragraph 0032; 0038-0043; 0049-0054; 0060-0065; 0071-0076

(2020/08/02)

Method for preparing levetiracetam
The invention relates to a method for preparing levetiracetam. The method comprises the following steps: reacting aminobutyric acid in lower alcohol and thionyl chloride to obtain an intermediate I; adding ammonia water to continue the reaction, and adding hydrochloric acid to adjust the pH value to about 3 to salify to obtain a salified intermediate II refined product; reacting the intermediate II in the presence of KOH in the presence of a catalyst and dichloromethane, and then adding 4-chlorobutyryl chloride to continuously react; adding water to hydrolyze, adjusting the pH to be weakly alkaline by using diluted hydrochloric acid, and crystallizing to obtain a levetiracetam crude product; decolorizing and crystallizing in ethyl acetate to obtain a refined product of levetiracetam. The invention also relates to the levetiracetam prepared by the method and pharmaceutical application thereof, for example, the levetiracetam can be used for treating or preventing epilepsy, Parkinson's disease, dyskinesia, migraine, tremor, idiopathic tremor, bipolar disorder, chronic pain, neuropathic pain, or bronchial, asthma or allergic diseases.
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Paragraph 0077; 0080; 0083; 0087; 0089; 0093; 0095; 0099

(2020/02/14)

Production system of 2-aminobutanamide
The utility model provides a production system of 2-aminobutanamide, which comprises a first reactor, a second reactor, a third reactor, a fourth reactor, a fifth reactor and a sixth reactor, the second reactor is communicated with the first reactor and is used for reacting 2-hydroxybutyronitrile with an ammonia source to prepare 2-aminobutyronitrile; the third reactor is communicated with the second reactor and is used for carrying out hydrolysis reaction on the 2-aminobutyronitrile and strong base to prepare the 2-aminobutyramide. The device effectively reduces waste water, waste gas and waste residues, effectively reduces the use amount of hydrogen cyanide, improves the content of target products, and reduces the production cost.
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Paragraph 0069; 0093-0113

(2020/04/17)

A Viedma ripening route to an enantiopure building block for Levetiracetam and Brivaracetam
A simple route to enantiomerically pure (S)-2-aminobutyramide-the chiral component of the anti-epileptic drugs Levetiracetam and Brivaracetam has been developed. This approach is based on the rational design and application of a Viedma ripening process. The practical potential of the process is demonstrated on a large scale.
Baglai, Iaroslav,Leeman, Michel,Kellogg, Richard M.,Noorduin, Willem L.
supporting information
p. 35 - 38
(2019/01/04)

Method for synthesizing L-2-aminobutanamide hydrochloride by asymmetric transformation
The invention belongs to the field of pharmaceutical synthesis, and discloses an asymmetric transformation synthesis method of L-2-aminobutanamide hydrochloride. The asymmetric transformation synthesis method comprises the following steps: dissolving DL-aminobutanamide in n-butyric acid; sequentially adding a racemizing agent n-butyraldehyde, L-tartaric acid and a small amount of acetic anhydride;reacting at 115-125 DEG C for 8-10 h to obtain an L-aminobutanamide tartrate complex salt; soaking the L-aminobutanamide tartrate complex salt in ethanol; introducing a hydrogen chloride gas; keepingthe temperature at 20-30 DEG C and reacting for 4 h; and filtering to obtain L-2-aminobutanamide hydrochloride. The method is simple in process operation and environmentally-friendly, the purity of afinal product is up to 99.72% and the yield is up to 95.25%, and industrial production is facilitated.
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Paragraph 0039; 0040; 0041; 0042; 0043; 0044

(2019/05/08)

Method for preparing levetiracetam
The invention relates to the technical field of drug synthesis, and provides a method for preparing levetiracetam. The method includes the following steps: taking L-2-aminobutyric acid as a starting material, and preforming esterification with thionyl chloride to obtain (S)-2-methyl aminobutyrate hydrochloride; performing aminolysis reaction between the (S)-2-methyl aminobutyrate hydrochloride andammonia water to generate (S)-2-aminobutylamine hydrochloride; preforming acylation reaction between the(S)-2-aminobutylamine hydrochloride and the mixed solution of 4-chlorobutyryl chloride and dichloromethane; directly performing cyclization reaction between the intermediate product with the dichloromethane and tetrabutyl ammonium bromide to obtain a crude product of levetiracetam; and recrystallizing the crude product to generate the levetiracetam. The preparation method uses the easily-obtained starting material to ensure good reproducibility of the synthesis route, simple unit operationand economic accounting. The reaction in each step is easy to purify, the quality is controllable, and the reaction yield is greatly improved.
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Paragraph 0112; 0117-0119; 0129; 0133-0134

(2019/01/23)

Continuous-flow protocol for the synthesis of enantiomerically pure intermediates of anti epilepsy and anti tuberculosis active pharmaceutical ingredients
Continuous-flow production of chiral intermediates plays an important role in the development of building blocks for Active Pharmaceutical Ingredients (APIs), being α-amino acids and their derivatives widely applied as building blocks. In this work we developed two different strategies for the synthesis of intermediates used on the synthesis of levetiracetam/brivaracetam and ethambutol. The results obtained show that methionine methyl ester can be continuously converted to the desired ethambutol intermediate by RANEY Nickel dessulfurization/reduction strategy whereas levetiracetam/brivaracetam intermediates could be synthesized by both RANEY Nickel (without H2) and Pd/C-H2 approach or by photochemical desulfurization.
Aguiar, Renata M.,Le?o, Raquel A. C.,Mata, Alejandro,Cantillo, David,Kappe, C. Oliver,Miranda, Leandro S. M.,De Souza, Rodrigo O. M. A.
supporting information
p. 1552 - 1557
(2019/02/14)

Preparation method and preparation system of 2-aminobutyramide
The invention provides a preparation method and a preparation system of 2-aminobutyramide. The preparation method comprises: (1) generating 2-hydroxybutyronitrile from hydrogen cyanide and n-propanalunder the action of a first catalyst; (2) adding an ammonia source and a second catalyst to the 2-hydroxybutyronitrile obtained in the step (1), and carrying out a reaction to generate 2-aminobutyronitrile; and (3) removing the excess ammonia from the reaction solution obtained in the step (2), adding a strong base and a third catalyst, and carrying out a hydrolysis reaction to obtain DL-2-aminobutanamide. According to the present invention, with the method and the system, the wastewater, the waste gas and the waste residue can be effectively reduced, the consumption of hydrogen cyanide can beeffectively reduced, the content of the target product can be increased, and the production cost can be reduced.
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Paragraph 0091; 0092-0110

(2019/10/01)

Preparation method of (S)-(+)-2-aminobutanamide hydrochloride
The invention discloses a synthetic process of a chiral drug (S)-alpha-ethyl-2-oxo-pyrrolidine acetamide (levetiracetam) intermediate (S)-(+)-2-aminobutanamide hydrochloride which has anti-epileptic function. The synthetic process comprises the following steps: performing condensation on acetone cyanohydrins and n-propanal as initial raw materials in the presence of a catalyst to obtain 2-hydroxybutyronitrile; then carrying out a reaction with ammonia to obtain 2-amino butyronitrile; then carrying out hydrolysis to obtain 2-aminobutanamide; then splitting and salifying the 2-aminobutanamide to obtain a target product. The synthetic process is high in yield, the raw materials are low in price and are easily purchased on a large scale, and the synthetic process overcomes the defects that several existing processes need highly toxic and highly polluting raw materials and is simple in process operation and low in cost. Mother liquor after splitting is further racemized and split and is recycled repeatedly, so that the synthetic process is suitable for industrial production.
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Paragraph 0038; 0039; 0040

(2019/01/23)

Preparation method of (S)-2-aminobutanamide as key intermediate for levetiracetam
The invention discloses a preparation method of (S)-2-aminobutanamide as a key intermediate for levetiracetam, which belongs to the technical field of drug intermediate synthesis. According to the preparation method disclosed by the invention, a compound 1 undergoes ammonolysis reaction in C1-C3 alkyl alcohol, vacuum concentration is carried out until a dry state is formed after the reaction is complete, an alcoholic solvent is added, ammonia is further injected for freeing, an alcoholic solvent is added for clarification by dissolution after filtration and concentration, crystals are grown after an acidic alcoholic solvent is dripped for salification, a compound 2 is obtained by preparation and purification, wherein X is hydrochloric acid, hydrobromic acid or methanesulfonic acid. The preparation method disclosed by the invention is simple and effective, yield and purity are greatly increased, molar yield is higher than 90 percent, purity is higher than 99.5 percent, a high-quality intermediate is provided for the subsequent preparation of the levetiracetam, the preparation method does not have the step of chiral resolution, and adopts only one type of solvent, recovery is simple,three types of wastes are fewer, and the preparation method meets the requirement of industrial production.
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Paragraph 0034; 0035; 0037; 0039

(2018/03/01)

A process for preparing L - 2 - amino ding amide hydrochloride
The invention discloses a method for efficiently preparing L-2-aminobutanamide hydrochloride. The method comprises the following steps of: (a) treating the L-2- aminobutanamide L-tartrate with a hydrogen chloride solution or hydrogen chloride gas in a ketones solvent; (b) filtering and separating to get the L-2- aminobutanamide hydrochloride. Meanwhile, the L-tartaric acid can be recycled from the mother solution. The method provided by the invention is simple to operate, convenient for after-treatment and beneficial for industrial production.
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Paragraph 0015-0017; 0018-0021

(2017/10/26)

PROCESS FOR PREPARING BRIVARACETAM
The present invention relates to a new process for preparing brivaracetam. (Ib)
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Page/Page column 7

(2017/06/23)

A 2 - amino Ding amide synthesis method
The invention discloses a method for synthesizing 2-aminobutanamide, and belongs to the field of organic chemistry. The method includes the steps of using 2-chlorobutyric acid as raw materials and reaction solvent, using phosphorus trichloride or phosphorus pentachloride as a catalyst, making 2-chlorobutyric acid and phosphorus trichloride or phosphorus pentachloride react with thionyl chloride at the temperature of 50-80 DEG C, introducing ammonia gas to 2-chlorobutyryl chloride in alcohol solvent, and obtaining 2-aminobutanamide through an ammonolysis reaction. The total yield of the product obtained through the method reaches up to 80%, the process is simple, cost is low, the method is environmentally friendly and safe, and industrialization can be easily achieved.
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Paragraph 0032

(2017/08/25)

Preparation method for levetiracetam intermediate L-2-aminobutanamide hydrochloride
The invention relates to a preparation method for a levetiracetam intermediate L-2-aminobutanamide hydrochloride. The method comprises the steps that n-propanal reacts with ammonia and hydrocyanic acid in a water solution under existing of ammonium chloride to prepare 2-amidogen butyronitrile, a certain amount of liquid ammonia and hydrocyanic acid are fed into mother liquor, and the mother liquor can be used indiscriminately for infinite times; the 2-amidogen butyronitrile is hydrolyzed in a 1% sodium hydroxide water solution to obtain 2-aminobutanamide, and water can be used indiscriminately for infinite times after being distilled; the 2-aminobutanamide is subjected to resolution to obtain L-2-aminobutanamide; salifying is carried out, and the L-2-aminobutanamide hydrochloride is obtained. The method has the advantages that the product quality is good, no waste water is produced in the production process, and the cost is low, and the preparation method is suitable for industrial production.
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Paragraph 0044; 0051; 0052; 0060; 0061; 0069; 0070

(2017/04/18)

A L-α-amido butyramide hydrochlorate method for the preparation of
The invention discloses a brand-new method for preparing L-alpha-aminobutanamide hydrochloride. The method comprises the following steps: (1) enabling L-alpha-aminobutyric acid to react with 2,2-dimethoxy propane under an acidic condition, so as to generate (S)-4-ethyl-2,2-dimethyl oxazolidine-5-ketone; and (2) carrying out ammonolysis on the (S)-4-ethyl-2,2-dimethyl oxazolidine-5-ketone to obtain L-alpha-amino butanamide, and then salifying in a hydrogen ethanol solution, so as to obtain the final product, namely the L-alpha-aminobutanamide hydrochloride. The method is simple and convenient to operate, mild in reaction condition, and easy to amplify. A reagent with hypertoxicity and strong acidity is avoided, and is friendly to environment. Meanwhile, the method is cheap in used raw material and high in yield, and the obtained product is high in purity.
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Paragraph 0040; 0041

(2017/06/02)

Processing technique of L-2-amino butyramide hydrochloride
The invention relates to a processing technique of L-2-amino butyramide hydrochloride. The processing technique includes: using 2-chlorobutyric acid as a raw material and hexamethylenetetramine as a catalyst to prepare 2-aminobutyric acid; using L-tartaric acid to resolve 2-aminobutyric acid to obtain L-2-aminobutyric acid, acrylating L-2-aminobutyric acid to obtain L-2-aminobutyryl compound, and obtaining L-2-amino butyramide hydrochloride under the condition of ammonia water. The processing technique has the advantages that by the processing technique, reaction yield is increased, and byproducts are few. In addition, the processing technique is mild in reaction condition, easy in reaction control, low in cost, high in yield, high in product purity, low in equipment requirement and suitable for industrial production, and technique safety is improved greatly.
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Paragraph 0017; 0018

(2017/02/02)

Preparation method of S-2-aminobutanamide
The invention provides a preparation method of S-2-aminobutanamide, comprising the steps of 1), reacting hydrogen cyanide, ammonia and n-propanal as materials to obtain 2-aminobutanenitrile; 2), separating a reacted liquid of step 1) by means of extraction to obtain an oil phase and a water phase, adding a catalyst and an alkali solution into the oil phase to carrying out hydrolysis, and reacting to obtain hydrolysate; 3), adding an acid or acid aqueous solution into the hydrolysate of step 2), separating to obtain an oil phase and a water phase, and separating the water phase to obtain S-2-aminobutanamide. The hydrogen cyanide, n-propanal and ammonia are reacted as materials to synthesize 2-aminobutanenitrile, the 2-aminobutanenitrile is hydrolyzed to directly obtain a target product, little byproducts are produced in reaction, and the content of the target product is high; little waste water and waste gas are produced in reaction, zero residue is produced, and there is no mass waste salts produced in the sodium cyanide process; the operation is simple, and product yield and purity are high.
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Paragraph 0024; 0027; 0029; 0032

(2017/02/09)

Synthesis process of levetiracetam intermediate
The invention relates to a synthesis process of a levetiracetam intermediate of L-2-aminoacid amide hydrochloride. According to the process, 2-chloro-butyric acid is used as initial raw materials; a 2-chlorobutyl ammonia intermediate is firstly prepared; the 2-chlorobutyl ammonia intermediate takes a reaction to generate dl-2-aminobutanamide; finally, the synthesis of the L-2-aminoacid amide hydrochloride is realized through salt formation through splitting. The synthesis path is shown as the accompanying drawing. The synthesis process provided by the invention has the advantages that the 2-chloro-butyric acid is used as raw materials in the synthesis process; the cost of the main raw materials is greatly reduced. Compared with the existing synthesis process, the synthesis process has the effects that the reaction yield is improved; in addition, by products are few; further, the purity of finished products is improved.
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Paragraph 0008; 0021; 0023

(2017/02/09)

An asymmetric synthesis of Levetiracetam
An asymmetric synthesis of (S)-levetiracetam has been developed through application of a Strecker reaction using [(1S)- 1-(4-methoxyphenyl)ethyl]amine hydrochloride as a chiral auxiliary. Addition of propanaldehyde to a solution of sodium cyanide and [(1S)-1-(4-methoxyphenyl)ethyl]amine hydrochloride in the mixture of methanol and water at 25-30°C afforded diastereomerically pure 2-[2-(4-methoxyphenyl)-(S)-methylethyl-amino]-( S )-butyronitrile hydrochloride compound 4 . In this reaction cyanide group attack at less hindered side that is re-face of the imine intermediate gave the diastereomerically pure nitrile 4. Which upon hydrolysis in the presence of 6 M aqueous hydrochloride solution obtained enantiomerically pure (S )-2- aminobutyric acid hydrochloride 5, is a key intermediate for the (S)-levetiracetam. This intermediate further react with SOCl2 in presence of methanol formed S-2-amino methyl butyrate as in situ intermediate which on further ammonalysis in the presence of methnaolic ammonia as a solvent under ammonia pressure provided S-2-amino butyramide hydrochloride 6 which further condensed with 4-chlorobutyryl chloride 7 and followed by cyclization in the presence of potassium hydroxide, dichloromethane solvent used catalytic amount of tetra butyl ammonium bromide afforded crude (S)-levetiracetam 1, further recrystalization in the presence of ethyl acetate obtained pure (S)-levetiracetam 1.
Raju, Veeramalla,Somaiah, Sripathi,Sashikanth, Suthrapu,Laxminarayan, Eppakayala,Mukkanti, Kagga
p. 1218 - 1221
(2014/12/10)

Process for the resolution of aminobutyramide
The present invention relates to a process for the resolution of Schiff bases of racemic (R,S)-2-aminobutyramide to give optically pure (S)-2-aminobutyramide, an intermediate in the synthesis of levetiracetam.
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Page/Page column 6

(2012/12/13)

Synthesis of tritium-labeled levetiracetam ((2S)-2-(2-oxopyrrolidin-1-yl) butanamide) with high specific activity
A method for the preparation of [A3H]levetiracetam with a high specific activity of 98Ci/mmol (3.6TBq/mmol) is described. The radioligand proved to be highly useful for the labeling of specific levetiracetam binding sites in rat brain membrane preparations.
Hildenbrand, Simone,Baqi, Younis,Mueller, Christa E.
experimental part
p. 48 - 51
(2012/06/29)

Dynamic kinetic resolution of α-aminonitriles to form chiral α-amino acids
We have succeeded in the enzymatic synthesis of (R)-α-aminobutyric acid from racemic α-aminobutyronitrile. This has been demonstrated by the use of non-stereoselective nitrile hydratase (NHase) from Rhodococcus opacus 71D, D-aminopeptidase from Ochrobactrum anthropi C1-38 and α-amino-ε- caprolactam (ACL) racemase from Achromobacter obae. Racemic α- aminobutyronitrile was completely converted in 6 h at 30 °C to (R)-α-aminobutyric acid whose optical purity was more than 99%. (S)-α-Aminobutyric acid was also synthesized from α- aminobutyronitrile by NHase, ACL racemase and L-amino acid amidase from Brevundimonas diminuta TPU 5720. In a similar manner, other (R)- or (S)-α-amino acids with more than 97.5% ee could be synthesized from the corresponding α-aminonitriles. This is the first report on the dynamic kinetic resolution (DKR) of α-aminonitriles to form chiral α-amino acids. The key enzyme in this DKR is non-stereoselective NHase, which had been newly screened from soil samples, and its gene cloned. Copyright
Yasukawa, Kazuyuki,Hasemi, Ryuji,Asano, Yasuhisa
supporting information; scheme or table
p. 2328 - 2332
(2011/10/19)

PREPARATION OF (S)-2-AMINOBUTYRIC ACID
Processes for the preparation of (S)-2-aminobutyric acid, embodiments including selective hydrolysis of racemic N-protected-2-aminobutyric acid using an acylase enzyme, such as one derived from Thermococcus litorolis or Aspergillus melleus.
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Page/Page column 9

(2010/04/03)

Preparation of amino acid amides
A process for making amino acid amides, comprising reacting an amino acid, or acid salt of an amino acid, with a halogenating agent, or with a substance that reacts with carboxylic acids to form a leaving group, to form an intermediate, then reacting the intermediate with ammonia. When the amino acid or acid salt is enantiomerically pure, the amide will be a stereoisomer. An amide made by the process can be used to form levetiracetam.
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Page/Page column 2

(2008/06/13)

PROCESS FOR PREPARING 2-OXO-1-PYRROLIDINE DERIVATIVES
The present invention relates to a new process for preparing 2-oxo- I -pyrrolidine derivatives of general formula (I) wherein the substituents are as defined in the specification.
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Page/Page column 7-8

(2008/06/13)

PROCESS FOR PREPARING 2-OXO-1-PYRROLIDINE DERIVATIVES BY INTRAMOLECULAR ALLYLATION
The present invention relates to a new process for preparing 2-oxo-1-pyrrolidine derivatives of general formula (I), comprising the cyclisation of an intermediate of general formula (II) wherein the substituents are as defined in the specification.
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Page/Page column 11-12

(2008/06/13)

Synthesis of an analogue of the substance P C-terminal hexapeptide with modification at the glutaminyl and methioninyl residues and increased activity in NK-2 receptor type: Structure-activity relationships
Analogues of [Orn6]-SP6-11 have been synthesized in which the Met11 residue is replaced by Hse(CH3), Hse(Bzl), Nva(5-OCH3), Nva(5-OBzl) and Abu. These analogues were tested in 3 in vitro preparations representative of NK-1, NK-2 and NK-3 receptor types. The Hse(Bzl) analogue is 16.6-fold more potent than the parent hexapeptide at the NK-2 receptor and 2.4-fold more potent at the NK-3 receptor. The Nva(5-OCH3) analogue showed weak antagonist activity in NK-2 and NK-3 receptor types, being a full agonist at NK-1. It is concluded from structure-activity correlations that the role of Met11 side chain in substance P is associated with activity and/or efficacy, as appropriate modifications in the side chain may result either in agonists with increased activity compared to the parent hexapeptide or selective agonists or may induce antagonism.
Manolopoulou,Poulos,Tsegenidis
p. 949 - 954
(2007/10/02)

Pharmaceutical compositions
Compounds of formula II: wherein n is 0, 1 or 2, R1, R2, R3 and R4 are each separately selected from hydrogen, unsubstituted acyclic aliphatic hydrocarbon groups having a maximum of six carbon atoms and C1 6 alkyl groups substituted by a hydroxy group or a C1 6 alkoxy group, or one of R1 and R2 and one of R3 and R4 is hydrogen and the others are a trimethylene, tetramethylene or pentamethylene bridging group, and R5 as hydrogen or an unsubstituted acyclic aliphatic hydrocarbon group having a maximum of six carbon atoms, but with the provisos that (a) when n is 0 the combinations R1 = R2 = R3 = R4 = R5 = H and R1 = R2 = R3 = R5 = H, R4 = methyl are excluded, and (b) when n is 0, R1, R3 and R5 are each hydrogen, and each of R2 and R4 is other than hydrogen the compound is in other than the mesoor erythroconfiguration, or a salt thereof formed with a physiologically acceptable inorganic or organic acid, are of use in therapy, particularly as cardioprotective agents.
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(2008/06/13)