Nihon Medi-Physics Company, Limited

Ge Healthcare Limited

Daisaku Nakamura

Shinya Takasaki

Shigeyuki Tanifuji

Yuki Okumura

Akio Hayashi

Masahito Toyama

Soichi Nakamura

Manabu Node

Naomi Sugimoto

Naoyuki Takano

Anthony Eamon Storey

Toshiyuki Shinmura

Denis Raymond Christophe Bouvet

Masato Kiriu

Emi Kaneko

Gota Tonoya

Hiroaki Ichikawa

Shinji Tokunaga

Soichi Takasaki

Shogo Ichihashi

Toshio Fujiwara

Soichi Nihon Medi-Physics K K Nakamura

Provided is a method for producing a radiohalogen-labeled compound, the method comprises: a step in which a radiohalogen-labeling precursor compound (S-L) having a leaving group (L) capable of being nucleophilically substituted by a radioactive halide ion (X) is subjected to a radiohalogenation reaction to obtain a reaction mixture RM1 which contains the radiohalogen-labeling precursor compound (S-L) and a reaction product (S&#x2014;X) resulting from the radiohalogenation reaction; a step in which the reaction mixture RM1 is mixed with a polyvalent acid or a salt thereof to obtain a reaction mixture RM2; and a step in which the reaction product (S&#x2014;X) is purified from the reaction mixture RM2 by a solid phase extraction method.

Method for producing radiohalogen-labeled compound and method for producing radiopharmaceutical

A composition including a radioactive fluorine-labeled amino acid compound is provided, which can be prevented from radiolysis. Disclosed is a composition which includes a solution containing a radioactive fluorine-labeled amino acid compound as an effective ingredient, in which the pH value of the solution is kept at 2.0-5.9, more preferably 2.0-4.9 in order to inhibit radiolysis. Also, it is possible to further inhibit radiolysis by adding thereto a pharmaceutical additive capable of inhibiting radiolysis, such as a sugar, a sugar alcohol and a sugar lactone, while the pH is kept at 2.0-5.9.

Radioactive diagnostic imaging agent

A method for producing a radioactive diagnostic imaging agent containing a radioactivefluorine-labeled organic compound represented by the following formula (1): as an effective ingredient in which radiolysis of the effective ingredient is inhibited, involves providing a solution containing the radioactivefluorine-labeled organic compound represented by the above formula (1), adding an acid to the solution obtained in the first step in an amount sufficient for the solution to be kept within a pH of 2.0-5.9 in the following third step, and diluting the solution obtained in the second step in order to adjust the solution to a desired radioactive concentration within a pH of 2.0-5.9.

Method for production of radiation diagnostic imaging agent

The present invention provides a compound which has affinity with amyloid, shows sufficiently rapid clearance from normal tissues and is suppressed in toxicity such as mutagencity. Provided is a compound represented by the following formula (1) or a salt thereof: wherein A, A, Aand Aindependently represents a carbon or nitrogen; Ris a halogen substituent; Ris a halogen substituent; and m is an integer of 0 to 2, provided that at least one of Rand Ris a radioactive halogen substituent, at least one of A, A, Aand Arepresents a carbon, and Rbinds to a carbon represented by A, A, Aor Aas well as a low-toxic diagnostic agent comprising a compound represented by the preceding formula or a salt thereof.

Compounds having affinity for amyloid

A compound effective as a probe targeting amyloid for image diagnosis and a reagent comprising the compound for detecting amyloid deposited on a biological tissue are provided. Provided are a compound represented by the following formula (1): wherein R, Rand Rindependently represent a group selected from the group consisting of a hydrogen, hydroxyl group, alkyl substituent with 1 to 4 carbon atoms, alkoxy substituent having alkyl chain with 1 to 4 carbon atoms and halogen substituent, excluding the case where two or more of the substituents R, Rand Rare hydrogen, Ris a group selected from the group consisting of a hydrogen, hydroxyl group, alkoxy substituent having alkyl chain with 1 to 4 carbon atoms and halogen substituent, and m is an integer of 1 to 4, provided that at least one of R, R, Rand Rrepresents a radioactive halogen substituent, and a reagent comprising the same.

Compound having affinity for amyloid

A method for producing a radioactive diagnostic imaging agent which contains a radioactive halogen-labeled amino acid compound as an effective ingredient and has a composition that can inhibit radiolysis of the effective ingredient, thereby further improving stability, is provided. Disclosed is a method for producing a radioactive diagnostic imaging agent, comprising a solution preparation step of preparing a solution containing a radioactive halogen-labeled amino acid compound, and a dilution step of diluting the solution containing the radioactive fluorine-labeled organic compound in order to adjust radioactive concentration thereof, which further comprises an acid addition step of adding an acid to the solution containing the radioactive fluorine-labeled organic compound, after the solution preparation step and before the dilution step, wherein the acid is added in the acid addition step in an amount sufficient to adjust the pH of the solution resulting from the dilution step to 2.0-5.9, for example, in an amount corresponding to 0.40-2.8 mmol per 1 L of the solution resulting from the dilution step.

Alkoxy substituted imidazo[1,2-a]pyridines having affinity for amyloid

A compound that has affinity with amyloid, exhibits sufficiently rapid clearance from normal tissues, and is suppressed in toxicity such as mutagenicity is provided, which is represented by the following formula (1): or a salt thereof,wherein Ris a group selected from hydrogen, hydroxyl group, carboxyl group, sulfate group, amino group, nitro group, cyano group, an alkyl substituent with one to 4 carbon atoms or an alkoxy substituent with one to 4 carbon atoms; Ris a radioactive halogen substituent; and m is an integer of 0 to 2, and a low-toxic diagnostic agent for Alzheimer's disease comprising a compound represented by the above formula or a salt thereof is also provided.

A compound represented by the following formula or a salt thereof: wherein each of A, A, Aand Aindependently represents a carbon or nitrogen, Ris a radioactive halogen substituent, Ris a group selected from the group consisting of hydrogen, a hydroxyl group, a methoxy group, a carboxyl group, an amino group, an N-methylamino group, an N,N-dimethylamino group and a cyano group, and p is an integer ofto, provided at least one of A, A, Aand Arepresents a carbon, and Rbinds to a carbon represented by A, A, Aor A, is effective as an image diagnosis probe targeting amyloid. A diagnostic agent for Alzheimer's disease contains the compound.

The invention relates to a compound which has affinity with amyloid, shows sufficiently rapid clearance from normal tissues and is suppressed in toxicity such as mutagenicity, and also relates to a low-toxic diagnostic agent for Alzheimer's disease containing the compound. The compound is represented by the following formula (1) or a salt thereof: wherein A, A, Aand Aindependently represent a carbon or a nitrogen, andRis a group represented by the following formula: wherein Ris a radioactive halogen substituent; m is an integer of 0 to 4; and n is an integer of 0 or 1, provided that at least one of A, A, Aand Arepresents a carbon, and Rbinds to a carbon represented by A, A, Aor A.

Compound having affinity to amyloid

There is disclosed a process for producing an amide compound, which process is characterized in that a compound having an amino group are reacted with a polyaminopolycarboxylic acid anhydride in the presence of the polyaminopolycarboxylic acid.

Process for producing an amide compound

An optically active tropinonemonocarboxylic acid ester derivative useful as an intermediate for synthesis of optically active tropane derivatives was obtained by reacting succindialdehyde with an organic amine and acetonedicarboxylic acid ester to obtain a tropinonedicarboxylic acid ester derivative, and then subjecting this derivative to enzyme-catalyzed asymmetric dealkoxy-carbonylation. Since anhydroecgonine methyl ester derived from the optically active tropinone-monocarboxylic acid ester derivative by reduction and dehydration had the same direction of optical rotation as in the case of anhydroecgonine methyl ester obtained from natural cocaine, it was proved that the obtained optically active tropinonemonocarboxylic acid ester derivative had the same absolute configuration as that of natural cocaine. The yield of the optically active tropinonemonocarboxylic acid ester derivative from the asymmetric dealkoxycarbonylation was 30 to 50 mol %, and its optical purity was 70 to 97% ee. In addition, it was found that a crystalline optically active anhydroecgonine carboxylic acid ester derivative can be obtained by reducing and then dehydrating the optically active tropinonemonocarboxylic acid ester derivative and that its optical purity can easily be increased by recrystallization.

Process for producing optically active tropinonemonocarboxylic acid derivative

The present invention relates to a method for synthesis of an optically active halopyridyl-azacyclo-pentane derivative and the intermediate thereof which comprises preparing an optically active allene-1,3-dicarboxylic acid ester derivative from an optically active acetonedicarboxylic acid ester derivative and then proceeding through a 7-azabicyclo&lsqb;2.2.1&rsqb;heptane derivative to obtain the objective product.

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Sodegaura, Japan

Daisaku Nakamura