82009-34-5 Usage
Description
Cilastatin is an inhibitor of dipeptidase (dehydropeptidase I), a renal dipeptidase. It inhibits human renal dipeptidase (Ki = 0.7 μM), porcine dipeptidase (IC50 = 0.11 μM), and bacterial metallo-β-lactamase CphA from A. hydrophila (IC50 = 178 μM). Cilastatin (200 μg/ml) protects primary porcine renal proximal tubular epithelial cells from nephrotoxicity and apoptosis induced by vancomycin . In a mouse model of systemic infection, cilastatin in combination with imipenem protects mice from S. aureus, E. coli, and P. aeruginosa infection. Cilastatin was designed to inhibit renal metabolism of imipenem and prolong its half-life. Formulations containing cilastatin in combination with imipenem have been used to treat susceptible bacterial infections.
Chemical Properties
White to Light-Yellow Crystalline Powder
Uses
Different sources of media describe the Uses of 82009-34-5 differently. You can refer to the following data:
1. Prevents renal metabolism of penem and carbapenem antibiotics by specific and reversible dehydropeptidase I inhibition. Antibacterial adjunct
2. spectrum antibiotic
3. Cilastatin is used for treating diseases caused by polyresistant Gram-negative microorganisms and serious complex infections, including infection of S. aureus. Because of its strong
activity against anaerobic bacteria, cilastatin is effective in monotherapy of intraabdominal infections. It is used for infectious diseases of the lower respiratory tract, urinary tract,
gynecological infections, bacterial septicemia, and infections of the bones, skin, and so on.
Synthesis
Cilastatin, (Z)-7-[(2-amino-2-carboethoxyethyl)thio]-2-[[2,2-dimethylcyclopropyl) carbonyl] amino]-2-heptenoic acid (32.1.3.6), is synthesized from the ethyl ester of
1,3-dithian-2-carboxylic acid (which is ethyl glyoxylate, protected at the aldehyde group
with 1,3-propanedithiol), which is alkylated by 1,5-dibromopentane in the presence of
sodium amide, forming the ethyl ester of 7-bromo-2-[2-(1,3-dithiano)]hepthanoic acid
(32.1.3.2). Oxidative hydrolysis of this product with N-bromosuccinimide in a mixture of
acetonitrile–water solvents leads to the formation of the ethyl ester of 7-bromo-α-ketoheptanoic acid (32.1.3.3). Acidic hydrolysis of this product using hydrogen bromide in acetic
acid gives 7-bromo-α-ketoheptanoic acid (32.1.3.4). This is reacted with 2,2-dimethylcyclopropancarboxylic acid amide to form the corresponding enamide, (Z)-7-bromo-2-(2,
2-dimethylcycloprotancarboxamido)-2-heptenoic acid (32.1.3.5). The resulting product is
used for S-alkylation of L-cysteine, which results in the production of the desired cilastatin
(32.1.3.6).
Check Digit Verification of cas no
The CAS Registry Mumber 82009-34-5 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 8,2,0,0 and 9 respectively; the second part has 2 digits, 3 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 82009-34:
(7*8)+(6*2)+(5*0)+(4*0)+(3*9)+(2*3)+(1*4)=105
105 % 10 = 5
So 82009-34-5 is a valid CAS Registry Number.
InChI:InChI=1/C16H26N2O5S/c1-16(2)8-10(16)13(19)18-12(15(22)23)6-4-3-5-7-24-9-11(17)14(20)21/h6,10-11H,3-5,7-9,17H2,1-2H3,(H,18,19)(H,20,21)(H,22,23)/b12-6-/t10-,11+/m1/s1
82009-34-5Relevant articles and documents
A Cilastatin ding Gai the crystal and its preparation method and application
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Paragraph 0090-0092, (2017/08/25)
The invention discloses a cilastatin calcium crystal, a preparation method and an application thereof. Under X-ray powder diffraction, the cilastatin calcium crystal has main characteristic peaks at positions with 2[theta] being 5.2+/-0.1 degree, 10.3+/-0.1 degree, 15.9+/-0.1 degree, 18.9+/-0.1 degree, 20.7+/-0.1 degree and 22.4+/-0.1 degree. The preparation method of the cilastatin calcium crystal includes following steps: (1) adding calcium chloride to an aqueous solution containing cilastatin or/and cilastatin salt; (2) regulating the pH value to 5-9 with an inorganic acid or an inorganic alkali; (3) adding an organic solvent which is mix-dissolvable with water to the system to perform stir-crystallization; and (4) filtering and drying an obtained crystal. By means of the cilastatin calcium crystal provided in the invention, cilastatin sodium being higher than 99.0% in HPLC purity can be conveniently prepared. The preparation method is simple in operation, is high in yield, is easy to carry out in large scale, and can provide an effective approach for preparing the cilastatin sodium being high in purity and stable in quality industrially in large scale.
Preparation method of cilastatin sodium active pharmaceutical ingredient
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Paragraph 0087; 0088; 0092; 0093; 0097; 0098; 0102-0163, (2017/06/02)
The invention provides a preparation method of a cilastatin sodium active pharmaceutical ingredient. The preparation method comprises the following steps: (1) mixing alkali and reaction solvent, adding a compound (Z)-7-chloro-2-((S)-2,2-dimethylcyclopropylformacyl)-2-heptenoic acid shown in Formula (V), then adding cysteine hydrochloride, reacting to obtain a reaction solution containing a compound cilastatin shown in Formula (VI); (2) purifying the reaction solution obtained in the step (1) through macroporous adsorption resin to obtain the compound cilastatin shown in Formula (VI); and (3) mixing sodium hydroxide and water, adding the cilastatin obtained in the step (2), regulating the pH value, and drying to obtain the compound cilastatin sodium shown in Formula (I). The preparation method is quick, efficient and suitable for industrial production; and the obtained cilastatin sodium active pharmaceutical ingredient is low in impurity content.
An improved process for the preparation of cilastatin acid
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, (2012/02/04)
The present invention relates to an improved process for the preparation of Cilastatin Sodium of formula (I). The present invention also provides an isolation technique for Cilastatin acid from the reaction mixture.
