New indolylalkyl esters of mercaptoalkanoic acids, and salts thereof, which have the general formula ##STR1## are useful as hypotensive agents.

BACKGROUND OF THE INVENTION 
The prior application relates to carboxymethyl esters of mercaptopropanoic 
acids which have the formula 
##STR2## 
wherein R is hydrogen or lower alkanoyl; R.sub.1 is hydrogen or lower 
alkyl; R.sub.2 is hydrogen, lower alkyl, phenyl, phenyl-lower alkyl, 
4-hydroxyphenyl-lower alkyl or indolyl-lower alkyl; and salts thereof. 
In the parent application those compounds of the above formula wherein 
R.sub.2 is indolyl-lower alkyl have been held to constitute a different 
invention. Upon additional experimentation, it has been found that a group 
of compounds of the above type, characterized by the presence of an 
indolyl-lower alkyl group, constitute a particularly interesting group as 
described below. 
SUMMARY OF THE INVENTION 
This invention relates to compounds which have the formula 
##STR3## 
wherein R is hydrogen, lower alkanoyl, benzoyl or 
##STR4## 
R.sub.1 is hydrogen, lower alkyl or phenyl-lower alkyl; R.sub.2 is 
hydrogen or lower alkyl; 
R.sub.3 is hydrogen, halogen, hydroxy, nitro, lower alkoxy or lower 
alkylthio; 
m and n each is 0, 1, 2 or 3 and to salts thereof. 
The above compounds are useful as hypotensive agents. 
DETAILED DESCRIPTION OF THE INVENTION 
The lower alkyl groups are straight or branched chain hydrocarbon radicals 
having up to seven carbon atoms, e.g., methyl, ethyl, propyl, isopropyl, 
butyl, sec. butyl and the like. The C.sub.1 -C.sub.4 and especially 
C.sub.1 -C.sub.2 alkyl groups are preferred. The phenyl-lower alkyl, lower 
alkoxy and lower alkylthio groups include lower alkyl groups of the same 
type (with the same preferences expressed above). 
The halogens are the four common halogens, chlorine and bromine being 
preferred. 
The lower alkanoyl groups are the acyl radicals of the lower (C.sub.2 
-C.sub.7) fatty acids, e.g., acetyl, propionyl, butyryl, isobutyryl and 
the like. The members mentioned, and especially acetyl, are preferred. 
Preferred members of the invention are those compounds of formula I wherein 
R is hydrogen or lower alkanoyl, especially hydrogen or acetyl; R.sub.1 is 
hydrogen or lower alkyl, especially hydrogen or methyl; R.sub.2 and 
R.sub.3 each is hydrogen; m is 1; and n is 1. 
The compounds of formula I are produced by acylation of an .alpha.-hydroxy 
acid having the formula 
##STR5## 
with an acid having the formula 
##STR6## 
by conventional esterification procedures. 
One method comprises activating the acid of formula III with 
carbodiimidazole to form the acylimidazole intermediate having the formula 
##STR7## 
which is used without isolation. It is also preferred to form a product 
wherein R is lower alkanoyl, then treat the acyl derivative with ammonia, 
ammonium hydroxide or sodium hydroxide to obtain the product wherein R is 
hydrogen. 
A preferred method comprises treating the acid of formula III, preferably 
wherein R is lower alkanoyl or benzoyl with an alkylchloroformate like 
methyl chloroformate in the presence of an organic base like triethylamine 
in an inert organic solvent like tetrahydrofuran, or the like then 
contacting this reaction mixture with the hydroxy acid of formula II. The 
acyl group can then be removed, if desired, as described above. 
Another preferred method comprises treating the acid of formula III with 
thionyl chloride to yield the corresponding acid chloride, then reacting 
the acid chloride with the hydroxy acid of formula II in an inert solvent 
such as tetrahydrofuran in the presence of an acid acceptor, such as 
pyridine. The acyl group can be removed as described above. 
The bis compounds or "dimers" formed when R is 
##STR8## 
are obtained by oxidation of a compound of formula I wherein R is 
hydrogen, e.g., with an alcoholic solution of iodine. 
The carbon atom marked with an asterisk in formula I is asymmetric if 
R.sub.1 is other than hydrogen. The carbon atom marked with a double 
asterisk is always asymmetric. Thus the compounds with the asymmetric 
carbons exist as diastereoisomers or in racemic mixtures thereof. All of 
these are within the scope of the invention. 
Some of the .alpha.-hydroxy acids of formula II are known compounds. Others 
may be prepared according to the following procedures. Other procedures 
are possible. 
PROCEDURE I (n=1 to 3) 
An R.sub.3 substituted indole having the formula 
##STR9## 
(wherein R.sub.2 is H) is acylated with an acyl chloride to give the acyl 
indole having the formula 
##STR10## 
in accordance with the teachings of Oddo et al., Gazz. Chim. Ital., 41 No. 
1,234 (1911). 
Treatment of VII with sulfur and morpholine [Willgerodt-Kindler reaction, 
Avramenko et al., Chem. Het. Cmpds., 698 (1973)] gives the terminal 
carboxy compound having the formula 
##STR11## 
The lower alkyl group of R.sub.2 may be optionally introduced by 
alkylating VI, VII or VIII (wherein R.sub.2 is H) with an alkyl halide in 
hexamethylphosphoramide [Casnati et al., Chem. Ind. (Milan) 49 172 (1967)] 
to give the corresponding compound 
wherein R.sub.2 is lower alkyl. 
The .alpha.-hydroxy group may be introduced by treatment with 2 equivalents 
of lithium diisopropyl amide followed by oxidation with air [Moersch et 
al., Synthesis, 647 (1971)] or by bromination with bromine and phosphorus 
tribromide [Hell-Volhard-Zelinsky Reaction] followed by barium hydroxide 
hydrolysis [Johne et al., Z. Chem. 6, 149 (1966)] or by conversion to the 
cyanophosphonic ester having the formula 
##STR12## 
and treatment of IX with potassium cyanide followed by hydrolysis 
according to the teachings of Okamoto et al., Kogyo Kagaku Zasshi 71 187 
(1968) (Chem. Abstr. 69 35342), or by other methods known in the art. 
In addition, many indolelactic acids may be prepared from the corresponding 
tryptophan compounds by fermentation with Geotrichum candida or by 
chemical means such as diazotization and hydrolysis or other procedures 
known in the art. 
PROCEDURE II (n=0) 
A procedure similar to that described in British Pat. No. 1,089,071 may be 
employed. The indole VI wherein R.sub.2 is hydrogen or lower alkyl is 
treated with oxalyl chloride and a lower alkanol or benzyl alcohol to give 
the glyoxylic ester. 
Reduction with sodium borohydride gives the glycolic ester; saponification 
of the ester under established conditions or catalytic hydrogenation (if 
it is a benzyl ester) gives the hydroxy acid. 
The mercaptopropanoic acids of formula III can be produced as described in 
U.S. Pat. No. 4,053,651, Oct. 11, 1977, and No. 4,105,776, Aug. 8, 1978, 
e.g., by reacting a thioacid of the formula (X) 
EQU R.sub.4 --CO--SH 
wherein R.sub.4 is lower alkyl, with an acrylic acid having the formula 
##STR13## 
Other procedures known in the art may also be employed. 
The R.sub.4 --CO group can be removed at this stage or later by treatment 
with ammonia or concentrated ammonium hydroxide as described above. 
The compounds of formula I form the common (basic) salts of carboxylic 
acids, e.g., by reaction with inorganic or organic bases. Such well known 
salts include ammonium salts, alkali metal salts like sodium and potassium 
salts, alkaline earth metal salts like calcium and magnesium salts, salts 
with organic bases, e.g., dicylcohexylamine, benzathine, hydrabamine and 
N-methyl-D-glucamine salts. Since some of the compounds of formula I are 
not readily obtainable as crystalline substances with well defined melting 
points, the salts (which are not necessarily physiologically acceptable) 
provide means to isolate and characterize the product by conventional 
techniques. 
Additional experimental details can be found in the illustrative examples 
below. 
The compounds of this invention are angiotensin converting enzyme 
inhibitors and are useful as hypotensive agents, particularly for the 
reduction of renin-angiotensin dependent hypertension. By administering a 
composition containing one or a combination of angiotensin converting 
enzyme inhibitors of this invention to a hypertensive mammal, e.g., rats, 
mice, cats, dogs, etc. it intervenes in the 
renin.fwdarw.angiotensinogen.fwdarw.angiotensin.fwdarw.angiotensin II 
sequence and the hypertension is reduced or alleviated. 
A single dose, or preferably two to four divided daily doses, provided on a 
basis of about 1 to 1000 mg. per kilogram per day and especially about 10 
to 100 mg. per kilogram per day is appropriate to bring about a reduction 
in elevated blood pressure. The animal model experiments described by 
Engel et al., Proc. Soc. Exp. Biol. Med. 143, 483 (1973) provide a 
valuable guide. 
The composition is preferably administered orally, but it can also be 
administered subcutaneously, intramuscularly, intravenously or 
intraperitoneally. The compound or compounds of formula I can be 
formulated as tablets, capsules or elixirs for oral administration. 
Sterile solutions or suspensions can be used for parenteral use. 
About 20 to 1000 mg. of a compound or compounds of formula I or 
physiologically acceptable salt thereof can be compounded with a 
physiologically acceptable vehicle, carrier, excipient, binder, 
preservative, stabilizer, flavor, etc., in a conventional unit dosage form 
as called for by accepted pharmaceutical practice. The amount of active 
substance is selected so as to provide a dosage in the range indicated.

The following examples are illustrative of the invention. The examples from 
the parent application are also included herein in order to provide 
additional details of experimental methodology. All temperatures are in 
degrees Celsius. 
EXAMPLE 1 
O-(3-Acetylthiopropanoyl)glycolic Acid 
3-(Acetylthio)propanoic acid (2.96 g.) and 1,1'-carbonyldiimidazole (3.24 
g.) are dissolved in 20 ml. of dry tetrahydrofuran with stirring at room 
temperature. After twenty minutes, a solution of glycolic acid (1.52 g.) 
and 2.80 ml. of triethylamine in 15 ml. of tetrahydrofuran are added. The 
reaction mixture is stored overnight at room temperature. The 
tetrahydrofuran is removed in vacuo, the crude residue taken up into ethyl 
acetate, washed with 1 N hydrochloric acid and three times with water, 
dried over magnesium sulfate and the O-(3-acetylthiopropanoyl)glycolic 
acid is concentrated to dryness in vacuo, yield 3.9 g. This is dissolved 
in ether and dicyclohexylamine is added. The dicyclohexylamine salt 
precipitates, yield 2.85 g., m.p. 150.degree.-157.degree.. The salt is 
converted to the free acid by adding to ethyl acetate and adding 10% 
potassium bisulfate solution, yield 1.5 g. 
EXAMPLE 2 
O-(3-Mercaptopropanoyl)glycolic Acid 
O-(3-acetylthiopropanoyl)glycolic acid from Example 1 (1.3 g.), under a 
blanket of argon is treated for fifteen minutes with a cold solution of 7 
ml. of water and 7 ml. of concentrated ammonium hydroxide. This is 
chilled, acidified with concentrated hydrochloric acid and extracted into 
ethyl acetate, yield: 1.2 g. This product O-(3-mercaptopropanoyl)-glycolic 
acid is chromatographed on DEAE Sephadex A25 (Polidextrane anion exchange 
resin) with a linear gradient of ammonium bicarbonate. The desired 
fractions (45-70; U.V. peak at 254 nm.) are pooled, concentrated and 
lyophilized. This ammonium salt of O-(3-mercaptopropanoyl)glycolic acid is 
converted to the free acid by treatment with Dowex 50WX2 cation exchange 
resin, yield 320 mg. The O-(3-mercaptopropanoyl)glycolic acid is converted 
to the dicyclohexylamine salt by dissolving in ether and precipitating by 
the addition of dicyclohexylamine, m.p. 143.degree.-144.degree.. 
EXAMPLE 3 
O-[3-(Acetylthio)-2-Methylpropanoyl]Glycolic Acid 
A mixture of thioacetic acid (50 g.) and methacrylic acid (40.7 g.) is 
heated on the steam bath for one hour and then stored at room temperature 
for 18 hours. After confirming by nmr spectrocopy that complete reaction 
of the methacrylic acid has been achieved, the reaction mixture is 
distilled in vacuo and the desired 3-acetylthio-2-methylpropanoic acid is 
separated in the fraction with boiling point 128.5.degree.-131.degree. 
(2.6 mmHg.), yield 64 g. 
3-Acetylthio-2-methylpropanoic acid (6.48 g.) is taken into 40 ml. of dry 
tetrahydrofuran. To this 1,1'-carbonyldiimidazole (0.48 g.) is added and 
stirred for 30 minutes at room temperature. Glycolic acid (6.08 g.) and 
11.2 ml. of triethylamine in 60 ml. of dry tetrahydrofuran are added. 
After several minutes, the imidazole salt of glycolic acid begins to come 
out of solution. The reaction is permitted to run overnight at room 
temperature. The crystalline salt is filtered and the filtrate 
concentrated to dryness in vacuo. The residue is taken up into ethyl 
acetate, washed with 1 N hydrochloric acid and three times with water, 
dried over magnesium sulfate and concentrated to dryness in vacuo. This 
product is converted to its dicyclohexylamine salt by dissolving in 
ether/hexane and precipitating by the addition of dicyclohexylamine. The 
salt is recrystallized from ether, m.p. 120.degree.-122.degree.. This salt 
is then converted to the free acid, 
O-[3-(acetylthio)-2-methylpropanoyl]glycolic acid, by adding to ethyl 
acetate, adding 10% potassium bisulfate solution, then crystallizing from 
ethyl/hexane, yield 2.96 g., m.p. 50.degree.-51.degree.. 
EXAMPLE 4 
O-(DL-3-Mercapto-2-Methylpropanoyl)Glycolic Acid 
O-[3-(Acetylthio)-2-methylpropanoyl]glycolic acid (1.5 g.) is placed under 
a blanket of argon. To this a cold solution of 7.5 ml. of concentrated 
ammonium hydroxide and 7.5 ml. of water is added and the mixture is stored 
for 15 minutes at room temperature. This is then acidified with 
concentrated hydrochloric acid and extracted with ethyl acetate, yield 1.3 
g. This product is dissolved in ether/hexane and dicyclohexylamine is 
added to precipitate the dicyclohexylamine salt, yield 2.24 g., m.p. 
96.degree.-98.degree.. A 1.9 g. aliquot of the salt is converted to the 
free O-(DL-3-mercapto-2-methylpropanoyl)glycolic acid by adding to ethyl 
acetate and adding 10% potassium bisulfate solution, yield 0.9 g. The 
product is a heavy oil which is chromatographed in silica gel (benzene 7:2 
acetic acid), R.sub.f =0.49, traces R.sub.f =0.32 and 0.57. 
EXAMPLE 5 
O-L-[3-(Acetylthio)propanoyl]-3-Phenyllactic Acid 
3-(Acetylthio)propanoic acid (1.48 g.) is added to 10 ml. of dry 
tetrahydrofuran with stirring. To this 1,1'-carbonyldiimidazole (1.62 g.) 
is added and the mixture stirred for twenty minutes at room temperature. 
L-(-)-3-phenyllactic acid (1.66 g.) is added in a solution of 7.5 ml. of 
dry tetrahydrofuran and 1.4 ml. of triethylamine. The reaction mixture is 
stored overnight at room temperature. The tetrahydrofuran is removed in 
vacuo, the residue is taken up into ethyl acetate, washed with 1 N 
hydrochloric acid, three times with water, dried over magnesium sulfate 
and concentrated to dryness in vacuo, yield 2.8 g. The 
O-L-[3-(acetylthio)propanoyl]-3-phenyllactic acid is purified on a silica 
gel column, eluting with benzene 7:1 acetic acid, yield 1.7 g. 
EXAMPLE 6 
O-L-(3-Mercaptopropanoyl)-3-Phenyllactic Acid 
To 1.5 g. of O-L-[3-(acetylthio)propanoyl]-3-phenyllactic acid a solution 
of 7.5 ml. of water and 7.5 ml. of concentrated ammonium hydroxide is 
added under an argon blanket. After fifteen minutes, the reaction mixture 
is chilled, acidified with concentrated hydrochloric acid and extracted 
into ethyl acetate, yield 1.1 g. The product, 
O-L-(3-mercaptopropanoyl)-3-phenyllactic acid is purified on a silica gel 
column, eluting with benzene 14:1 acetic acid, yield 357 mg. A small 
portion of the semi-solid product is converted to its dicyclohexylamine 
salt by dissolving in ether/hexane and precipitating with 
dicyclohexylamine, m.p. 100.degree.. 
EXAMPLE 7 
O-DL-(3-Acetylthiopropanoyl)-3-Indolelactic Acid 
By substituting DL-3-indolelactic acid for the L-.beta.-phenyllactic acid 
in the procedure of Example 5, O-DL-(3-acetylthiopropanoyl)-3-indolelactic 
acid is obtained. 
EXAMPLE 8 
O-DL-(3-Mercaptopropanoyl)-3-Indolelactic Acid 
By substituting O-DL-(3-acetylthiopropanoyl)-3-indolelactic acid for the 
O-L-(3-acetylthiopropanoyl)-3-phenyllactic acid in the procedure of 
Example 6, O-DL-(3-mercaptopropanoyl)-3-indolelactic acid is obtained. 
EXAMPLE 9 
O-DL-(3-Mercapto-2-Methylpropanoyl)-3-Indolelactic Acid 
By substituting 3-indolelactic acid for the glycolic acid in the procedure 
of Example 3 and then submitting the product to the procedure of Example 
4, O-DL-[3-(acetylthio)-2-methylpropanoyl]-3-indolelactic acid and 
O-DL-(3-mercapto-2-methylpropanoyl)-3-indolelactic acid are obtained. 
EXAMPLE 10 
O-L-(3-Mercaptopropanoyl)lactic Acid 
By substituting L-lactic acid for the glycolic acid in the procedure of 
Example 1 and then submitting the product to the procedure of Example 2, 
O-L-(3-acetylthiopropanoyl)lactic acid and O-L-(3-mercaptopropanoyl)lactic 
acid are obtained. 
EXAMPLE 11 
O-L-(3-Mercaptopropanoyl)-.alpha.-Hydroxyisocaproic Acid 
By substituting L-.alpha.-hydroxyisocaproic acid [Winitz, et al., J.Am. 
Chem. Soc. 78, 2423 (1956)] for the glycolic acid in the procedure of 
Example 1 and then submitting the product to the procedure of Example 2, 
O-L-(3-acetylthiopropanoyl)-.alpha.-hydroxy-isocaproic acid and 
O-L-(3-mercaptopropanoyl)-.alpha.-hydroxy-isocaproic acid are obtained. 
EXAMPLE 12 
O-L-(3-Acetylthiopropanoyl)-3-(p-tert-butoxyphenyl)-lactic Acid 
By substituting 3-(p-tert-butoxyphenyl)lactic acid [obtained from 
O-tert-butyl-L-tyrosine by the procedure described by H. D. Dakin and H. 
W. Dudley in J. Biol. Chem., 18, 29 (1914) for the preparation of 
3-L-phenyllactic acid] for the 3-L-phenyllactic acid in the procedure of 
Example 5, O-L-(3-acetylthiopropanoyl)-3-(p-tert-butoxyphenyl)lactic acid 
is obtained. 
EXAMPLE 13 
O-L-(3-Mercaptopropanoyl)-3-p-Hydroxyphenyllactic Acid 
O-L-(3-acetylthiopropanoyl)-3-(p-tert-butoxy-phenyl)lactic acid (1.8 g.) is 
dissolved in trifluoroacetic acid (15 ml.) and the solution is stored at 
room temperature for one hour. After removing the trifluoroacetic acid in 
vacuo, the residue is dissolved in a mixture of water (7.5 ml.) and 
concentrated ammonium hydroxide (7.5 ml.) under an argon blanket. After 
fifteen minutes, the reaction mixture is chilled, acidified with 
concentrated hydrochloric acid and extracted with ethyl acetate. The 
organic layer is concentrated in vacuo to yield 
O-L-(3-mercaptopropanoyl)-3-hydroxyphenyllactic acid. 
EXAMPLE 14 
O-(3-Mercaptopropanoyl)mandelic Acid 
By substituting mandelic acid for the L-3-phenyllactic acid in the 
procedure of Example 5, and then submitting the product to the procedure 
of Example 6, O-(3-acetylthiopropanoyl)mandelic acid and 
O-(3-mercaptopropanoyl)mandelic acid are obtained. 
EXAMPLE 15 
O-DL-(3-Acetylthiopropanoyl)-3-Indolelactic Acid 
To 6.66 g. (0.045 mol.) of 3-(acetylthio)-propanoic acid in 250 ml. of dry 
tetrahydrofuran in an ice/acetone (-5.degree.) bath is added 4.55 g. 
(0.045 mol.) of triethylamine followed by 4.25 g. (0.045 mol.) of methyl 
chloroformate (dropwise over 5 minutes). A copious precipitate of 
triethylamine hydrochloride forms immediately. After the mixture is 
stirred for 30 minutes, 6.0 g. (0.029 mol.) of DL-indolelactic acid in 50 
ml. of dry tetrahydrofuran is added all at once. The mixture is stirred 
for 3 hours at 0.degree., then allowed to stand in the refrigerator 
(0.degree.) overnight. The reaction mixture is poured into 1 liter of ice 
cold saturated sodium chloride solution, covered with 500 ml. of ethyl 
acetate and stirred. The layers are separated and the aqueous layer is 
washed with two 250 ml. portions of ethyl acetate (pH of aqueous is 5.5). 
The ethyl acetate portions are combined, dried (Na.sub.2 SO.sub.4) and 
stripped to yield 15 g. of residue. This material is then taken up in 500 
ml. of ethyl acetate and extracted with 3.times.100 ml. of cold saturated 
sodium bicarbonate solution. The aqueous solution is acidified with 
concentrated hydrochloric acid to pH 1 and reextracted with ethyl acetate. 
The organic solution is dried (Na.sub.2 SO.sub.4) and evaporated to 
dryness to yield 8.8 g. of residue. The 8.8 g. of material is 
chromatographed on 400 g. of silica gel with 8:2 benzene:acetic acid. The 
pure fractions are combined and stripped to yield 7.3 g (76%) of 
O-DL-(3-acetylthiopropanoyl)-3-indolelactic acid. 
EXAMPLE 16 
O-DL-(3-Mercaptopropanoyl)-3-Indolelactic Acid 
5.9 g. (0.018 mol.) of the product of Example 14 is dissolved in a mixture 
of 25 ml. of concentrated ammonium hydroxide and 25 ml. of water and 
stirred (under Argon) for 20 minutes. The mixture is acidified with 
concentrated hydrochloric acid and extracted with ethyl acetate, which is, 
in turn, dried (Na.sub.2 SO.sub.4) and stripped to yield 5.0 g. (97% 
crude) of residue. This material is chromatographed on 400 g. of silica 
gel with 9:1 benzene:acetic acid. The pure fractions are combined and 
stripped to yield 5.5 g of residue (containing some solvent) which 
solidifies (m.p. 54-56) on standing in the freezer. 3.86 g. (0.013 mol.) 
of the residue is dissolved in 300 ml. of ether and treated with 2.38 g. 
(0.0137 mol.) of dicyclohexylamine in 100 ml. of ether. The resulting 
clear solution is allowed to stand overnight under argon at room 
temperature. The resulting dicyclohexylamine salt (5.5 g., m.p. 
152-154.degree.) is filtered off and partitioned between water pH 1 and 
ethyl acetate. After 30 minutes, the layers are separated and the ethyl 
acetate layer is dried (Na.sub.2 SO.sub.4) and stripped to yield an oil 
that slowly solidifies after the addition of seed crystals. Drying 
overnight at room temperature (1 torr) gives a solid, m.p. 53-55.degree.. 
room temperature (1 torr) gives a solid, m.p. 53-55.degree.. Drying 
overnight at 40.degree. (1 torr) yields 3.3 g. of analytically pure 
O-DL-(3-mercaptopropanoyl)-3-indolelactic acid as a tacky, glassy solid. 
Anal. Calc'd. for C.sub.14 H.sub.15 NO.sub.4 S: C, 57.32; H, 5.15; N, 4.78; 
S, 10.93. Found: C, 57.35; H, 5.29; N, 4.60; S, 10.65; SH, 100%. 
The product is non-crystalline and has no melting point, but softens and 
starts to flow at 54-56.degree.. It forms crystalline or semicrystalline 
solvates with acetic acid and ethyl acetate and chloroform. They all melt 
in the 53-56.degree. range. 
An aliquot of free acid in ether is treated with one equivalent of 
dicyclohexylamine in ether, as above, to yield the dicyclohexylamine salt, 
m.p. 151.degree.-153.degree.. 
Anal. Calc'd for C.sub.26 H.sub.38 N.sub.2 O.sub.4 S: C, 65.79; H, 8.07; N, 
5.90; S, 6.75 Found: C, 65.57; H, 8.12; N, 5.72; S, 6.51. 
EXAMPLE 17 to 31 
By substituting the hydroxy acid shown in Column I of Table A set out below 
for DL-indolelactic acid and substituting the thio acid shown in Column II 
for 3-(acetylthio)propanoic acid in the procedure of Example 15, the final 
products shown in Column III are obtained. 
TABLE A 
__________________________________________________________________________ 
Column I Column II 
##STR14## 
##STR15## 
R.sub.3 
R.sub.2 
n R m R.sub.1 
__________________________________________________________________________ 
17 H H 3 CH.sub.3 CO 
1 H 
18 5-Cl H 1 
##STR16## 
0 H 
19 5-Br H 1 C.sub.4 H.sub.9 CO 
1 C.sub.2 H.sub.5 
20 5-OH C.sub.2 H.sub.5 
1 C.sub.2 H.sub.5 CO 
2 H 
21 5-OC.sub.2 H.sub.5 
H 1 C.sub.3 H.sub.7 CO 
3 H 
22 4-SCH.sub.3 
CH.sub.3 
1 CH.sub.3 CO 
1 H 
23 4-NO.sub.2 
H 1 C.sub.4 H.sub.9 CO 
0 H 
24 H H 1 CH.sub.3 CO 
2 H 
25 H CH.sub.3 
0 CH.sub.3 CO 
1 H 
26 H CH.sub.3 
2 C.sub.2 H.sub.5 CO 
1 H 
27 H CH.sub.3 
0 
##STR17## 
1 H 
28 H C.sub.2 H.sub.5 
1 CH.sub.3 CO 
1 C.sub.4 H.sub.9 
29 H H 1 CH.sub.3 CO 
1 
##STR18## 
30 5-F H 1 CH.sub.3 CO 
1 
##STR19## 
31 6-F H 1 C.sub.2 H.sub.5 CO 
1 
##STR20## 
__________________________________________________________________________ 
Column III 
##STR21## 
R.sub.3 
R.sub.2 
n R m R.sub.1 
__________________________________________________________________________ 
17 
H H 3 CH.sub.3 CO 
1 H 
18 
5-Cl H 1 
##STR22## 
0 H 
19 
5-Br H 1 C.sub.4 H.sub.9 CO 
1 C.sub.2 H.sub.5 
20 
5-OH C.sub.2 H.sub.5 
1 C.sub.2 H.sub.5 CO 
2 H 
21 
5-OC.sub.2 H.sub.5 
H 1 C.sub.3 H.sub.7 CO 
3 H 
22 
4-SCH.sub.3 
CH.sub.3 
1 CH.sub.3 CO 
1 H 
23 
4-NO.sub.2 
H 1 C.sub.4 H.sub.9 CO 
0 H 
24 
H H 1 CH.sub.3 CO 
2 H 
25 
H CH.sub.3 
0 CH.sub.3 CO 
1 H 
26 
H CH.sub.3 
2 C.sub.2 H.sub.5 CO 
1 H 
27 
H CH.sub.3 
0 
##STR23## 
1 H 
28 
H C.sub.2 H.sub.5 
1 CH.sub.3 CO 
1 C.sub.4 H.sub.9 
29 
H H 1 CH.sub.3 CO 
1 
##STR24## 
30 
5-F H 1 CH.sub.3 CO 
1 
##STR25## 
31 
6-F H 1 C.sub.2 H.sub.5 CO 
1 
##STR26## 
__________________________________________________________________________ 
EXAMPLES 32 to 46 
By submitting the products of Examples 17 to 31 shown in Column III of 
Table A to the procedure of Example 16, the final products corresponding 
to the products of Examples 17 to 31 wherein R is hydrogen are obtained. 
EXAMPLE 47 
Disulfide of O-DL-(3-Mercaptopropanoyl)-3-Indolelactic Acid 
O-DL-(3-Mercaptopropanoyl)-3-indolelactic acid from Example 16 (4 g.) is 
dissolved in 67 ml. of water and the pH adjusted to 6.5 with 1 N sodium 
hydroxide. To this a total of 27.8 ml. of 0.5 M iodine solution (95% EtOH) 
is added dropwise while maintaining a pH of 5.5 to 6.5 with 1 N sodium 
hydroxide. After 15 minutes a trace of excess iodine is discharged with 
dilute sodium thiosulfate. The reaction mixture is concentrated in vacuo, 
acidified with concentrated HCl and extracted with ethyl acetate. The 
organic layer is dried over magnesium sulfate and concentrated to dryness 
in vacuo to yield the compound of the title. 
EXAMPLE 48 
O-L-(D-3-Acetylthio-2-methylpropanoyl)-3-indolelactic acid 
Following the procedure of Example 15, but substituting L-indolelactic acid 
for DL-indolelactic acid and substituting D-3-acetylthio-2-methylpropanoic 
acid for 3-acetylthiopropanoic acid, the title compound is obtained. 
EXAMPLE 49 
O-L-(D-3-Mercapto-2-methylpropanoyl)-3-indolelactic acid 
Submitting the product of Example 48 to the procedure of Example 16, gives 
the title compound.