(2S)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]pyrrolidine-2-carboxylic acid

• ChemBase ID: 1067
• Molecular Formular: C9H15NO3S
• Molecular Mass: 217.2853
• Monoisotopic Mass: 217.07726435
• SMILES: SC[C@H](C(=O)N1[C@@H](CCC1)C(=O)O)C
• Canonical SMILES: SC[C@H](C(=O)N1CCC[C@H]1C(=O)O)C
• InChI: InChI=1S/C9H15NO3S/c1-6(5-14)8(11)10-4-2-3-7(10)9(12)13/h6-7,14H,2-5H2,1H3,(H,12,13)/t6-,7+/m1/s1
• InChIKey: FAKRSMQSSFJEIM-RQJHMYQMSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (2S)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]pyrrolidine-2-carboxylic acid
• IUPAC Traditional name: captopril; (2S)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]pyrrolidine-2-carboxylic acid
• Brand Name: Acepress; Acepril; Alopresin; Apopril; Capoten; Captolane; Captoril; Cesplon; Dilabar; Garranil (discontinued); Hipertil; Hypertil; Lopirin; Lopril; Tenosbon; Tensoprel
• Synonyms: Captoprilum [INN-Latin]; Captopryl; L-Captopril; Captopril; Capoten; (S)-1-((S)-3-mercapto-2-methylpropanoyl)pyrrolidine-2-carboxylic acid; ([2S]-N-[3-Mercapto-2-methylpropionyl]-L-proline; SQ-14225; N-[(S)-3-Mercapto-2-methylpropionyl]-L-proline; Captopril; Acenorm; Acepril; Capace; (2S)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]pyrrolidine-2-carboxylic acid; N-[(S)-3-巯基-2-甲基丙酰基]-L-脯氨酸; 卡托普利

Database IDs

• CAS Number: 62571-86-2
• EC Number: 263-607-1
• MDL Number: MFCD00168073
• Beilstein Number: 477887
• PubChem SID: 46506879; 160964530; 24278149; 24893111
• PubChem CID: 44093
• CHEBI ID: 3380
• ATC CODE: C09AA01
• CHEMBL: 1560
• Chemspider ID: 40130
• DrugBank ID: DB01197
• KEGG ID: D00251
• Unique Ingredient Identifier: 9G64RSX1XD
• Wikipedia Title: Captopril
• Medline Plus: a682823

CALCULATED PROPERTIES

JChem

• Acid pKa: 4.018635
• H Acceptors: 3
• H Donor: 2
• LogD (pH = 5.5): -0.7646909
• LogD (pH = 7.4): -2.422175
• Log P: 0.72692126
• Molar Refractivity: 54.6349 cm^3
• Polarizability: 21.422962 Å^3
• Polar Surface Area: 57.61 Å^2
• Rotatable Bonds: 3
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 1.02
• LOG S: -1.68
• Solubility (Water): 4.52e+00 g/l

PROPERTIES

Physical Property

• Solubility: Chloroform; Dichloromethane; Ethanol; Freely soluble; H2O: soluble0.1 g/mL, very slightly hazy, colorless; Methanol
• Apperance: White Solid; white to off-white powder
• Melting Point: 103-104°C; 104-108 °C(lit.)
• Optical Rotation: [α]20/D -129°, c = 1.7 in ethanol
• Hydrophobicity(logP): 0.6; 0.89

Safety Information

• Storage Condition: -20°C; -20°C Freezer
• RTECS: UY0550000
• European Hazard Symbols: Harmful (Xn)
• German water hazard class: 3
• Risk Statements: 63-43
• Safety Statements: 36/37
• GHS Pictograms: GHS07; GHS08
• GHS Signal Word: Warning
• GHS Hazard statements: H317-H361
• GHS Precautionary statements: P280
• Personal Protective Equipment: Eyeshields, Faceshields, full-face particle respirator type N100 (US), Gloves, respirator cartridge type N100 (US), type P1 (EN143) respirator filter, type P3 (EN 143) respirator cartridges

Pharmacology Properties

• Target: Hormone
• Admin Routes: oral
• Bioavailability: 70–75%
• Excretion: renal
• Half Life: 1.9 hours
• Metabolism: hepatic
• Legal Status: Rx-only
• Pregnancy Category: D (Australia)
• Gene Information: human ... ACE(1636); human ... ACE(1636), AGTR1(185), AGTR2(186), ECE1(1889)rat ... Ace(24310); human ... ACE(1636), ECE1(1889)rat ... Ace(24310)
• Mechanism of Action: ACE inhibitor; angiotensin-antagonist; apparent primary action involves suppression of the renin-angiotensin-aldosterone-system; decrease in plasma-volume; decreases plasma-angiotensin-2 concentration; increased plasma-renin causes decrease in aldosterone-secretion resulting in: small increases in serum-potassium; increased sodium-excretion; increases plasma levels of PGE2 and PGE2-alpha metabolites.; increases plasma-renin activity resulting from loss of negative feedback on renin release due to reduced angiotensin-2 concentration; Increases urinary excretion of PGE2; May increase prostaglandin synthesis; May inhibit local angiotensin 2 at vascular and renal sites so attenuating catecholamine release

Product Information

• Purity: ≥98% (HPLC); ≥99.0% (HPLC); 95%; 97%
• Salt Data: Free Base
• Suitability: meets USP testing specifications
• Description: Diastereomers
• Application(s): Antihypertensive agent; Drug used for diagnosis and treatment of renin-dependent hypertension; Exp. drug for treatment of myocardial infarction; Smooth muscle relaxant
• Empirical Formula (Hill Notation): C9H15NO3S

DETAILS

DrugBank - DB01197

• Drug Groups: approved
• Description: Captopril is a potent, competitive inhibitor of angiotensin-converting enzyme (ACE), the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). Captopril may be used in the treatment of hypertension.
• Indication: For the treatment of essential or renovascular hypertension (usually administered with other drugs, particularly thiazide diuretics). May be used to treat congestive heart failure in combination with other drugs (e.g. cardiac glycosides, diuretics, β-adrenergic blockers). May improve survival in patients with left ventricular dysfunction following myocardial infarction. May be used to treat nephropathy, including diabetic nephropathy.
• Pharmacology: Captopril, an ACE inhibitor, antagonizes the effect of the RAAS. The RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from the granular cells of the juxtaglomerular apparatus in the kidneys. In the blood stream, renin cleaves circulating angiotensinogen to ATI, which is subsequently cleaved to ATII by ACE. ATII increases blood pressure using a number of mechanisms. First, it stimulates the secretion of aldosterone from the adrenal cortex. Aldosterone travels to the distal convoluted tubule (DCT) and collecting tubule of nephrons where it increases sodium and water reabsorption by increasing the number of sodium channels and sodium-potassium ATPases on cell membranes. Second, ATII stimulates the secretion of vasopressin (also known as antidiuretic hormone or ADH) from the posterior pituitary gland. ADH stimulates further water reabsorption from the kidneys via insertion of aquaporin-2 channels on the apical surface of cells of the DCT and collecting tubules. Third, ATII increases blood pressure through direct arterial vasoconstriction. Stimulation of the Type 1 ATII receptor on vascular smooth muscle cells leads to a cascade of events resulting in myocyte contraction and vasoconstriction. In addition to these major effects, ATII induces the thirst response via stimulation of hypothalamic neurons. ACE inhibitors inhibit the rapid conversion of ATI to ATII and antagonize RAAS-induced increases in blood pressure. ACE (also known as kininase II) is also involved in the enzymatic deactivation of bradykinin, a vasodilator. Inhibiting the deactivation of bradykinin increases bradykinin levels and may sustain its effects by causing increased vasodilation and decreased blood pressure.
• Toxicity: Symptoms of overdose include emesis and decreased blood pressure. Side effects include dose-dependent rash (usually maculopapular), taste alterations, hypotension, gastric irritation, cough, and angioedema.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic. Major metabolites are captopril-cysteine disulfide and the disulfide dimer of captopril. Metabolites may undergo reversible interconversion.
• Absorption: 60-75% in fasting individuals; food decreases absorption by 25-40% (some evidence indicates that this is not clinically significant)
• Half Life: 2 hours
• Protein Binding: 25-30% bound to plasma proteins, primarily albumin
• References: Atkinson AB, Robertson JI: Captopril in the treatment of clinical hypertension and cardiac failure. Lancet. 1979 Oct 20;2(8147):836-9. [Pubmed] ; Patchett AA, Harris E, Tristram EW, Wyvratt MJ, Wu MT, Taub D, Peterson ER, Ikeler TJ, ten Broeke J, Payne LG, Ondeyka DL, Thorsett ED, Greenlee WJ, Lohr NS, Hoffsommer RD, Joshua H, Ruyle WV, Rothrock JW, Aster SD, Maycock AL, Robinson FM, Hirschmann R, Sweet CS, Ulm EH, Gross DM, Vassil TC, Stone CA: A new class of angiotensin-converting enzyme inhibitors. Nature. 1980 Nov 20;288(5788):280-3. [Pubmed] ; Smith CG, Vane JR: The discovery of captopril. FASEB J. 2003 May;17(8):788-9. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Selleck Chemicals - S2051

Research Area: Cancer
Biological Activity:

InterBioScreen - BB_NC-2104

Diastereomers

Sigma Aldrich - C4042

Biochem/physiol Actions
Angiotensin converting enzyme inhibitor. Inhibits the formation of angiotensin II, a bioactive peptide that stimulates angiogenesis and increases microvessel density.
Packaging
5, 25 g in glass bottle

Sigma Aldrich - 441600

Biochem/physiol Actions
Angiotensin converting enzyme inhibitor. Inhibits the formation of angiotensin II, a bioactive peptide that stimulates angiogenesis and increases microvessel density.

Sigma Aldrich - 21751

Biochem/physiol Actions
Angiotensin converting enzyme inhibitor. Inhibits the formation of angiotensin II, a bioactive peptide that stimulates angiogenesis and increases microvessel density.

Sigma Aldrich - C8856

Biochem/physiol Actions
Angiotensin converting enzyme inhibitor. Inhibits the formation of angiotensin II, a bioactive peptide that stimulates angiogenesis and increases microvessel density.

Toronto Research Chemicals - C175750

Orally active angiotensin-converting enzyme (ACE) inhibitor.

REFERENCES

• Atkinson AB, Robertson JI: Captopril in the treatment of clinical hypertension and cardiac failure. Lancet. 1979 Oct 20;2(8147):836-9. Pubmed
• Smith CG, Vane JR: The discovery of captopril. FASEB J. 2003 May;17(8):788-9. Pubmed
• Patchett AA, Harris E, Tristram EW, Wyvratt MJ, Wu MT, Taub D, Peterson ER, Ikeler TJ, ten Broeke J, Payne LG, Ondeyka DL, Thorsett ED, Greenlee WJ, Lohr NS, Hoffsommer RD, Joshua H, Ruyle WV, Rothrock JW, Aster SD, Maycock AL, Robinson FM, Hirschmann R, Sweet CS, Ulm EH, Gross DM, Vassil TC, Stone CA: A new class of angiotensin-converting enzyme inhibitors. Nature. 1980 Nov 20;288(5788):280-3. Pubmed
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