83507-88-4

Usage

InChI:InChI=1/C20H26N2O5S2/c1-13(21-15(18(24)25)8-7-14-5-3-2-4-6-14)17(23)22-12-20(28-9-10-29-20)11-16(22)19(26)27/h2-6,13,15-16,21H,7-12H2,1H3,(H,24,25)(H,26,27)

Upstream product

• 83552-43-6 (S)-7-[(S)-2-((S)-1-Ethoxycarbonyl-3-phenyl-propylamino)-propionyl]-1,4-dithia-7-aza-spiro[4.4]nonane-8-carboxylic acid methyl ester 
• 121209-29-8 7--(S)-alanyl>-1,4-dithia-7-azaspiro<4.4>nonane-8(S)-carboxylic acid 
• 64187-47-9 1-benzyloxycarbonyl-4-keto-L-proline 
• 90891-24-0 (R)-2-[(S)-1-(2,5-Dioxo-pyrrolidin-1-yloxycarbonyl)-ethylamino]-4-phenyl-butyric acid ethyl ester 
• 83507-90-8 N-<(phenylmethoxy)carbonyl>-1,4-dithia-7-azaspiro<4.4>nonane-8(S)-carboxylic acid ethyl ester 
• 83507-89-5 N-<(phenylmethoxy)carbonyl>-4-oxo-(S)-proline ethyl ester 
• 83552-44-7 1,4-dithia-7-azaspiro<4.4>nonane-8(S)-carboxylic acid 
• 84324-12-9 N-<1(R)-(ethoxycarbonyl)-3-phenylpropyl>-(S)-alanine 
• 83552-41-4 (S)-1,4-dithia-7-azaspiro[4.4]nonane-8-carboxylic acid, hydrochloride 
• 83552-42-5 1,4-dithia-7-diazaspiro<4.4>nonane-8-carboxylic acid methyl ester monohydrochloride 
• 89371-34-6 N-succinimidyl (2S)-2-{N-[(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]amino}propionate 
• 82717-96-2 [1(S)-(ethoxycarbonyl)-3-phenylpropyl]-(S)-alanine 
• 83647-97-6 spirapril 
• 75776-77-1 7-<(phenylmethoxy)carbonyl>-1,4-dithia-7-azaspiro<4.4>nonane-8(S)-carboxylic acid 

Relevant academic research and scientific papers

Angiotensin Converting Enzyme Inhibitors: Spirapril and Related Compounds

The synthesis of spirapril (5), spiraprilat (25), their RSS stereoisomers, and their glycyl (18b) and lysyl (36, 37) analogues is described.These compounds were evaluated in vivo for inhibition of angiotensin converting enzyme (ACE), and selected compounds were evaluated for in vitro ACE inhibition (spirapril ID50 16 μg/kg; spiraprilat IC50 0.8 nM, ID50 8 μg/kg).In anesthetized rats, iv, esters 5 and 36 are more potent than enalapril, and diacids 25 and 37 are more potent than enalaprilat in vitro.In the conscious rats, orally, 5 and enalapril (2) showed potent and sustained activity at doses of 0.03-1 and 0.1-1 mg/kg, respectively.From this work, spirapril was selected for clinical evaluation as an antihypertensive agent.

Angiotensin-converting enzyme inhibitors. Mercaptan, carboxyalkyl dipeptide, and phosphinic acid inhibitors incorporating 4-substituted prolines

Analogues of captopril, enalaprilat, and the phosphinic acid [[hydroxy(4-phenylbutyl)phosphinyl]acetyl)-L-proline incorporating 4-substituted proline derivatives have been synthesized and evaluated as inhibitors of angiotensin-converting enzyme (ACE) in vitro and in vivo. The 4-substituted prolines, incorporating alkyl, aryl, alkoxy, aryloxy, alkylthio, and arylthio substituents were prepared from derivatives of 4-hydroxy- and 4-ketoproline. In general, analogues of all three classes of inhibitors with hydrophobic substituents on proline were more potent in vitro than the corresponding unsubstituted proline compounds. 4-Substituted analogues of captopril showed greater potency and duration of action than the parent compound as inhibitors of the angiotensin I induced pressor response in normotensive rats. The S-benzoyl derivative of cis-4-(phenylthio)captopril, zofenopril, was found to be one of the most potent compounds of this class and is now being evaluated clinically as an antihypertensive agent. In the phosphinic acid series, the 4-ethylenethioketal and trans-4-cyclohexyl derivatives were found to be the most potent compounds in vitro and in vivo. A prodrug of the latter compound, fosinopril, is also being evaluated in clinical trials.

7-Carboxyalkylaminoacyl-1,4-dithia-7-azaspiro[4.4]-nonane-8-carboxylic acids

This invention relates to 7-carboxyalkyl-aminoacyl-1,4-adithia-7-azaspiro[4.4]nonane-8-carboxylic acids. The compounds of the invention are useful in the treatment of cardiovascular disorders and especially as antihypertensive agents.