74654-91-4

Usage

InChI:InChI=1/C11H11ClO2S/c1-8(10(12)13)7-15-11(14)9-5-3-2-4-6-9/h2-6,8H,7H2,1H3/t8-/m1/s1

Upstream product

• 74407-70-8 (R)-3-Benzoylsulfanyl-2-methyl-propionic acid 
• 72679-02-8 (2S)-3-(benzoylthio)-2-methylpropionic acid 
• 74431-50-8 (D)-3-(Benzoylthio)-2-methylpropanoic acid 

Downstream Products

• 78701-25-4 1-<(S)-3-(benzoylthio)-2-methyl-1-oxopropyl>indoline-2-carboxylic acid 
• 78779-26-7 (+)-(S)-1-<(R)-(3-benzoylthio)-2-methyl-1-oxopropyl>indoline-2-carboxylic acid 
• 86323-74-2 ethyl 1-<3-(benzoylthio)-2(S)-methylpropionyl>indoline-2(S)-carboxylate 
• 87022-29-5 (S)-2-((R)-3-Benzoylsulfanyl-2-methyl-propionyl)-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid benzyl ester 
• 86323-74-2 ethyl 1-<3-(benzoylthio)-2(S)-methylpropionyl>indoline-2(R)-carboxylate 
• 87022-29-5 (R)-2-((R)-3-Benzoylsulfanyl-2-methyl-propionyl)-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid benzyl ester 
• 84117-84-0 (S)-1-(3-Benzoylsulfanyl-2-methyl-propionyl)-5-ethyl-2,3-dihydro-1H-indole-2-carboxylic acid 
• 81872-10-8 zofenopril 
• 81814-84-8 (1S,4R)-1-<3-(benzoylthio)-2-methyl-1-oxopropyl>-4-hydroxy-L-proline 
• 80586-33-0 (1S,4R)-1-<3-(benzoylthio)-2-methyl-1-oxopropyl>-4-hydroxy-L-proline methyl ester 
• 113949-52-3 (4S)-1-[(S)-3-benzoylthio-2-methylpropanoyl]-4-phenylthio-L-proline methyl ester 
• 81814-75-7 (2S,4S)-1-((S)-3-Benzoylsulfanyl-2-methyl-propionyl)-4-(naphthalen-2-yloxy)-pyrrolidine-2-carboxylic acid methyl ester 
• 78779-28-9 (-)-(R)-1-<(S)-3-(benzoylthio)-2-methyl-1-oxopropyl>indoline-2-carboxylic acid 
• 84117-84-0 (S)-1-((S)-3-Benzoylsulfanyl-2-methyl-propionyl)-5-ethyl-2,3-dihydro-1H-indole-2-carboxylic acid 

Relevant academic research and scientific papers

An improved large scale procedure for the preparation of N-Cbz amino acids

A simple and scalable method for the preparation of N-Cbz protected amino acids is presented which uses a mixture of aqueous sodium carbonate and sodium bicarbonate to maintain the appropriate pH during the addition of benzyl chloroformate. The method has been extended to other N-protections and is amenable to large scale preparation of an intermediate toward Zofenopril, an ACE inhibitor.

1,1'-[DITHIOBIS(2-ALKYL-1-OXO-3,1-PROPANEDIYL)]-BIS[2,3-DIHYDRO-1H-INDOLE-2-CARBOXYLIC ACIDS AND DERIVATIVES

Disclosed herein are N-(3-mercapto-2-alkyl-1-oxopropyl)-2,3-dihydro-1H-indole-2-carboxylic acids and derivatives thereof which act as inhibitors of angiotensin converting enzyme and as anti-hypertensive agents. Derivatives include those in which the 3-mercapto group is substituted with phosphate derivatives or is replaced by a variously substituted amino group. The compounds of the invention (excluding disclosed intermediates) have the general formula: STR1 wherein: n is 1 or 0; R 1 is hydrogen, lower alkyl, aryl or aralkyl;R 2 is hydrogen or lower alkyl; R 3 is hydrogen, lower alkyl or aroyl; R. sub.5 is hydroxy, amino, or lower alkoxy;X is hydrogen, hydroxy, lower alkyl, lower alkoxy, or halogen;Y is hydrogen, lower alkyl, or aryl;R 4 is-SH, STR2 wherein L is O, NR 7 or S (where R 7 is hydrogen or lower alkyl); M is R 8, OR 8, SR 8, or NR 9 R 10 (where R 8 is hydrogen, lower alkyl, aryl, or aralkyl; and R 9 and R 10 are, independently, hydrogen, lower alkyl, or aryl); A is O, NR 13 or S;R 11 and R 12 are, independently, hydrogen, alkyl, aralkyl or aryl; R. sub. 13 is hydrogen or lower alkyl;m is 0, 1, 2, or 3; R 20 is hydrogen or aryl; andR. sub. 21 is hydroxy or lower alkoxy;or pharmaceutically acceptable salts thereof.

(Mercaptopropanoyl)indoline-2-carboxylic Acids and Related Compounds as Potent Angiotensin Converting Enzyme Inhibitors and Antihypertensive Agents

1-(3-Mercapto-2-methyl-1-oxopropyl)indoline-2-carboxylic acids (7b) and related compounds were synthesized in order to examine their ability to inhibit angiotensin converting enzyme (ACE) and to reduce the systolic blood pressure of spontaneously hypertensive rats (SHR).All four possible stereoisomers of the precursor 1-indoline-2-carboxylic acid (6b) were characterized with absolute stereochemical assigment.The removal of the benzoyl group of the precursor to give 7b was conveniently carried out by treatment with 2-methoxyethylamine.Three of the four stereoisomers of the benzoyl derivative 6 showed in vitro ACE inhibitory activity in the following order: 6b(S,S) > 6b(S,R) > 6b(R,S).The stereoisomer having the R,R configuration was essentialy inactive.The substitution at the C5 of the indoline nucleus with the Et or OMe group caused only marginal changes in the inhibitory activity.The mercaptan 7b(S,S) was the most active ACE inhibitor synthesized in this study, showing in vitro potency 3 times that of captopril.The augmentation of the potency may be due to the increased hydrophobicity of 7b (S,S) compared with captopril and suggests the presence of a hydrophobic pocket at the active site of ACE.When tested in spontaneously hypertensive rats, 7b(S,S) exhibited oral antihypertensive activity 27 times that of captopril.The corresponding benzoyl derivative 6b(S,S) was 24 times as potent as captopril.The thio lactone 10 obtained by cyclization of 7b(S,S) as a potential prodrug was less potent than the parent compound, 7b(S,S), in the ACE inhibitory and antihypertensive tests.

Studies on angiotensin-converting enzyme inhibitors. I. Syntheses and angiotensin-converting enzyme inhibitory activity of 2-(3-merecaptopropionyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives

(3S)-2-[(2S)-mercapto-2-methylpropionyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid [(3S), (2S)-6a] was prepared by the reaction of (3S)-1,2,3,4-tetrahydreoisoquinoline-3-carboxylic acid test-butyl ester [(3S)-2a) or benzyl ester [(3S)-2b] with 3-benzoylthio-2-methylpropionyl chloride (3a), followed by fractional crystallization and removal of the protective group. The absolute configuration of (3S), (2S)-6a was confirmed by X-ray diffraction analysis of the thiazepinol[4,3-b]isoquinoline compound (7) derived from 6a. Resolution of 3-benzoylthio-2-methylpropionic acid (8) was completed by using optically active phenylalanine amide as a resolving agent. The other optical isomers of (3S),(2S)-6a were prepared by the reaction of (3S)- or (3R)-2b with optically active 3a. The in vitro ACE inhibitory activity of each isomer of 6a was evaluated. Among them, (3S),(2S)-6a was found to be the most potent inhibitor with an IC50 value of 8.6X10-9M. Compound (3S),(2S)-6a induced a dose-dependent inhibition of the pressor response to angiotensin 1 after oral administration to normotensive anesthetized rats. Moreover, (3S),(2S)-6a markedly reduced the systolic blood pressure in renal hypertensive rats (RHR) and spontaneously hypertensive rats (SHR). The in vivo ACE inhibitory activity and the hypotensive effects of (3S),(2S)-6a were comparable to those of captopril.

N-(2-SUBSTITUTED-1-OXOALKYL)-2,3-DIHYDRO-1H-INDOLE-2-CARBOXYLIC ACID DERIVATIVES

Disclosed herein are 2,3-dihydro-1H-indole-2-carboxylic acids substituted on the nitrogen with 3-mercapto-2-alkyl-1-oxoalkyl, 3-phosphoryl-2-alkyl-1-oxopropyl, or 2-amino-2-alkyl-1-oxoalkyl derivatives which act as inhibitors of angiotensin converting enz

1H,5H-[1,4]THIAZEPINO[4,3-a]INDOLE-1,5-DIONES

Disclosed herein are N-(3-mercapto-2-alkyl-1-oxopropyl)-2,3-dihydro-1H-indole-2-carboxylic acids and derivatives thereof which act as inhibitors of angiotensin converting enzyme and as anti-hypertensive agents. Derivatives include those in which the 3-mer