卡托普利

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Glutathione, L-cysteine, DL-homocysteine, D-penicillin, hemoglobin (bovine), methylene blue and Medium 199 sets were purchased from Sigma Chemical Co., St. Louis, Mo. N-acetylcysteine was obtained from Aldrich Chemical Co., Milwaukee, Wis. Captopril was kindly provided by Dr. Victor Dzau. Sodium nitrite, histamine and methacholine were purchased from Fisher Scientific, Fairlawn, N.J. Leukotriene D4 was purchased from Anaquest, BOC Inc., Madison, Wis. Antibiotic/antimycotic mixture (10,000 U/ml penicillin G sodium, 10,000 mg/ml, streptomycin sulfate, 25 mg/ml amphotericin B) was purchased from Gibco laboratories, Grand Island, N.Y. Radioimmunoassay kits for the determination of cyclic GMP were purchased from New England Nuclear, Boston, Mass.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Typical preparations of S-nitrosocaptopril involve the reaction of 50 mM captopril with 50 mM NaNO2 in 0.1 N acetic or sulfuric acid at room temperature for five minutes, after which the reaction solution is passed over a cation exchange resin, e.g., Dowex 50 in the protonated form, and the product eluted with water. The fractions that give positive reactions with N-(1-naphthyl)ethylenediamine, after exposure to 0.15% HgCl2 and diazotization with sulfanilamide, are lyophilized. Hygroscopic, bright red crystals were obtained that were the product eluted with water

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Glutathione, L-cysteine, DL-homocysteine, D-penicillin, hemoglobin (bovine), methylene blue and Medium 199 sets were purchased from Sigma Chemical Co., St. Louis, Mo. N-acetylcysteine was obtained from Aldrich Chemical Co., Milwaukee, Wis. Captopril was kindly provided by Dr. Victor Dzau. Sodium nitrite, histamine and methacholine were purchased from Fisher Scientific, Fairlawn, N.J. Leukotriene D4 was purchased from Anaquest, BOC Inc., Madison, Wis. Antibiotic/antimycotic m nxture (10,000 U/ml penicillin G sodium, 10,000 mg/ml, streptomycin sulfate, 25 mg/ml amphotericin B) was purchased from Gibco laboratories, Grand Island, N.Y. Radioimmunoassay kits for the determination of cyclic GMP were purchased from New England Nuclear, Boston, Mass.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: It has been found that the compound of the formula I can be prepared from L-proline in two reaction steps with a total yield of 67% through the acylation of L-proline, if L-proline is acylated with (R)-3-acetylthio-2-methylpropanoyl chloride of formula III: ##STR3## in the presence of KOH and potassium phosphate buffer at pH 7.5-8.5, and at a temperature of between about 0°-5° C. The resulting compound is 1-[3-acetylthio-2-(S)-methylpropanoyl]-L-proline, ##STR4## Compound IV, which also can be termed "S-acetyl captopril", can be acidified and then deblocked with sodium hydroxide to give captopril in yield of 67% relative to starting material of formula III, without any unwanted byproducts. of between about 0°-5° C

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: It has been found that the compound of the formula I can be prepared from L-proline in two reaction steps with a total yield of 67% through the acylation of L-proline, if L-proline is acylated with (R)-3-acetylthio-2-methylpropanoyl chloride of formula III: ##STR3## in the presence of KOH and potassium phosphate buffer at pH 7.5-8.5, and at a temperature of between about 0°-5° C. The resulting compound is 1-[3-acetylthio-2-(S)-methylpropanoyl]-L-proline, ##STR4## Compound IV, which also can be termed "S-acetyl captopril", can be acidified and then deblocked with sodium hydroxide to give captopril in yield of 67% relative to starting material of formula III, without any unwanted byproducts. of between about 0°-5° C

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Glutathione, L-cysteine, DL-homocysteine, D-penicillin, hemoglobin (bovine), methylene blue and Medium 199 sets were purchased from Sigma Chemical Co., St. Louis, Mo. N-acetylcysteine was obtained from Aldrich Chemical Co., Milwaukee, Wis. Captopril was kindly provided by Dr Victor Dzau. Sodium nitrite, histamine and methacholine were purchased from Fisher Scientific, Fairlawn, N.J. Leukotriene D4 was purchased from Anaquest, BOC Inc., Madison, Wis. Antibiotic/antimycotic mixture (10,000 U/ml penicillin G sodium, 10,000 mcg/ml, streptomycin sulfate, 25 mcg/ml amphotericin B) was purchased from Gibco Laboratories, Grand Island, N.Y. Radioimmunoassay kits for the determination of cyclic GMP were purchased from New England Nuclear, Boston, Mass.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Glutathione, L-cysteine, DL-homocysteine, D-penicillin, hemoglobin (bovine), methylene blue and Medium 199 sets were purchased from Sigma Chemical Co., St. Louis, Mo. N-acetylcysteine was obtained from Aldrich Chemical Co., Milwaukee, Wis. Captopril was kindly provided by Dr Victor Dzau. Sodium nitrite, histamine and methacholine were purchased from Fisher Scientific, Fairlawn, N.J. Leukotriene D4 was purchased from Anaquest, BOC Inc., Madison, Wis. Antibiotic/antimycotic mixture (10,000 U/ml penicillin G sodium, 10,000 mcg/ml, streptomycin sulfate, 25 mcg/ml amphotericin B) was purchased from Gibco Laboratories, Grand Island, N.Y. Radioimmunoassay kits for the determination of cyclic GMP were purchased from New England Nuclear, Boston, Mass.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Glutathione, L-cysteine, DL-homocysteine, D-penicillin, hemoglobin Coovine), methylene blue and Medium 199 sets were purchased from Sigma Chemical Co., St. Louis, MO. N-acetylcysteine was obtained from Aldrich Chemical Co., Milwaukee, WI. Captopril was kindly provided by Dr. Victor Dzau. Sodium nitrite, histamine and methacholine were purchased from Fisher Scientific, Fairlawn,. N.J. Leukotriene D4 was purchased from Anaquest, BOC Inc., Madison, WI. Antibiotic/antimycotic mixture (10,000 U/ml penicillin G sodium, 10,000 mg/ml, streptomycin sulfate, 25 mg/ml amphotericin B) was purchased from Gibco laboratories, Grand Island, NY. Radioimmunoassay kits for the determination of cyclic GMP were purchased from New England Nuclear, Boston, MA.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The product from Example 1 (0.3 g., 0.4 mmole) is dissolved in 50 ml. of argon purged sodium hydroxide (2.5%) and stirred at 25° for 3 hours. The solution is acidified with 10% potassium bisulfate and extracted with ethyl acetate. The organics are dried (Na2SO4) and evaporated. Trituration with ether gives a solid. Chromatography on 50 g. of LH-20 in methanol and pooling and evaporation of the product containing fractions gives a glass. Trituration with ether gives 0.2 g. of (S)-4-[[7-(aminosulfonyl)-6-chloro-3,4-dihydro-1,1-dioxo-2H-1,2,4-benzothiadiazin-3-yl]methyl]phenoxy]-1-[(S)-3-mercapto-2-methyl-1-oxopropyl]-L-proline as a white crystalline solid; m.p. 175°-185°; [α]D =-22° (c=0.1%, methanol). TLC (silica, methylene chloride:methanol:acetic acid; 8:1:1) Rf =0.32. of argon purged sodium hydroxide (2.5%) extracted with ethyl acetate The organics are dried (Na2SO4) evaporated Trituration with ether gives a solid of LH-20 in methanol and pooling and evaporation of the product containing fractions gives a glass

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Glutathione, L-cysteine, DL-homocysteine, D-penicillin, hemoglobin (bovine), methylene blue and Medium 199 sets were purchased from Sigma Chemical Co., St. Louis, Mo. N-acetylcysteine was obtained from Aldrich Chemical Co., Milwaukee, Wis. Captopril was kindly provided by Dr. Victor Dzau. Sodium nitrite, histamine and methacholine were purchased from Fisher Scientific, Fairlawn, N.J. Leukotriene D4 was purchased from Anaquest, BOC Inc., Madison, Wis. Antibiotic/antimycotic mixture (10,000 U/ml penicillin G sodium, 10,000 mg/ml, streptomycin sulfate, 25 mg/ml amphotericin B) was purchased from Gibco laboratories, Grand Island, N.Y. Radioimmunoassay kits for the determination of cyclic GMP were purchased from New England Nuclear, Boston, Mass.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Glutathione, L-cysteine, DL-homocysteine, D-penicillin, hemoglobin (bovine), methylene blue and Medium 199 sets were purchased from Sigma Chemical Co., St. Louis, Mo. N-acetylcysteine was obtained from Aldrich Chemical Co., Milwaukee, Wis. Captopril was kindly provided by Dr. Victor Dzau. Sodium nitrite, histamine and methacholine were purchased from Fisher Scientific, Fairlawn, N.J. Leukotriene D4 was purchased from Anaquest, BOC Inc., Madison, Wis. Antibiotic/antimycotic mixture (10,000 U/ml penicillin G sodium, 10,000 mg/ml, streptomycin sulfate, 25 mg/ml amphotericin B) was purchased from Gibco laboratories, Grand Island, N.Y. Radioimmunoassay kits for the determination of cyclic GMP were purchased from New England Nuclear, Boston, Mass.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Typical preparations of S-nitrosocaptopril involve the reaction of 50 mM captopril with 50 mM NaNO2 in 0.1 N acetic or sulfuric acid at room temperature for five minutes, after which the reaction solution is passed over a cation exchange resin, e.g., Dowex 50 in the protonated form, and the product eluted with water. The fractions that give positive reactions with N-(1-naphthyl)ethylenediamine, after exposure to 0.15% HgCl2 and diazotization with sulfanilamide, are lyophilized. Hygroscopic, bright red crystals were obtained that were the product eluted with water