159213-17-9

Upstream product

• 1239129-13-5 diethyl 2-benzyloxycarbonylamino-2-ethoxycarbonylsuccinate 
• 1239129-17-9 (R)-diethyl 2-benzyloxycarbonylamino-2-carbamoylsuccinate 
• 1239129-15-7 (R)-1-ethyl hydrogen 3-benzyloxycarbonylamino-3-ethoxycarbonylsuccinate 
• 3005-66-1 diethyl 2-benzyloxycarbonylaminomalonate 
• 1010807-62-1 ethyl (2R)-2-benzyloxycarbonylamino-2-carbamoyl-3-[(-)-menthyloxycarbonyl]propionate 
• 147194-08-9 (RS)-ethyl 2-(benzyloxycarbonylamino)-2-cyanoacetate 
• 147194-10-3 ethyl 3-benzyloxycarbonylamino-2,5-dioxopyrrolidine-3-carboxylate 

Downstream Products

• 159213-18-0 (R)-ethyl-3-amino-2,5-dioxopyrrolidine-3-carboxylate 
• 147254-64-6 ranirestat 

Relevant academic research and scientific papers

PROCESS FOR PRODUCING OPTICALLY ACTIVE SUCCINIMIDE DERIVATIVES AND INTERMEDIATES THEREOF

A process for producing optically active succinimide derivatives as key intermediates of (3R)-2′-(4-bromo-2-fluorobenzyl)spiro{pyrrolidine-3,4′(1′H)-pyrrolo[1,2-a]pyrazine}-1′,2,3′,5(2′H)-tetraone, which comprises the following reaction steps.

Method for producing optically active succinimide compound

There is provided a novel method for producing an optically active succinimide compound which is a useful compound utilized as an intermediate raw material for pharmaceutical products or the like. The method for producing an optically active succinimide c

SUCCINIC ACID DIESTER DERIVATIVE, PROCESS FOR PRODUCTION THEREOF, AND USE OF THE DERIVATIVE IN THE PRODUCTION OF PHARMACEUTICAL PREPARATION

The present invention provides with a process of preparing an optically active succinimide derivative, which is a key intermediate for production of ranirestat. A compound (3) is easily prepared by treating the derivative of succinic acid diester of the formula (2): wherein R1 is an amino group protected with a group removed by hydrogenolysis or a tert-butoxycarbonylamino group and R2 is an ethyl group optionally substituted with one or two methyl group(s) at α-position, provided that R2 is not a tert-butyl group when R1 is a tert-butoxycarbonylamino group; with alkali metal alkoxide and the compound (3) can be an important intermediate for production of ranirestat.

Novel, highly potent aldose reductase inhibitors: (R)-(-)-2-(4-bromo-2- fluorobenzyl)-1,2,3,4-tetrahydropyrrolo[1,2-α]pyrazine-4-spiro-3'- pyrrolidine-1,2',3,5'-tetrone (AS-3201) and its congeners

A series of novel tetrahydropyrrolo[1,2-α]pyrazine derivatives were synthesized and evaluated as aldose reductase inhibitors (ARIs) on the basis of their abilities to inhibit porcine lens aldose reductase (AR) in vitro and to inhibit sorbitol accumulation in the sciatic nerve of streptozotocin- induced diabetic rats in vivo. Of these compounds, spirosuccinimide-fused tetrahydropyrrolo-[1,2-α]pyrazine-1,3-dione derivatives showed significantly potent AR inhibitory activity. In the in vivo activity of these derivatives, 2-(4-bromo-2-fluorobenzyl)-1,2,3,4-tetrahydropyrrolo-[1,2-α]pyrazine-4- spiro-3'-pyrrolidine-1,2',3,5'-tetrone (23t) (SX-3030) showed the best oral activity. The enantiomers of 23t were synthesized, and the biological activities were evaluated. It was found that AR inhibitory activity resides in the (-)-enantiomer 43 (AS-3201), which was 10 times more potent in inhibition of the AR (IC50 = 1.5 x 10-8 M) and 500 times more potent in the in vivo activity (ED50 = 0.18 mg/kg/day for 5 days) than the corresponding (+)-enantiomer 44 (SX-3202). From these results, AS-3201 was selected as the candidate for clinical development. The absolute configuration of AS-3201 was also established to be (R)-form by single- crystal X, ray analysis. In this article we report the preparation and structure-activity relationship (SAR) of tetrahydropyrrolopyrazine derivatives including a novel ARI, AS-3201.