Cefotiam

ChEBI: A cephalosporin with ({1-[2-(dimethylamino)ethyl]-1H-tetrazol-5-yl}sulfanyl)methyl and (2-amino-1,3-thiazol-4-yl)acetamido substituents at positions 3 and 7, respectively, of the cephem skeleton. A third generation beta-lactam cephalospo in antibiotic, it is active against a broad spectrum of both Gram positive and Gram negative bacteria.

Solid

Cefotiam is a cephalosporin with ({1-[2-(dimethylamino)ethyl]-1H-tetrazol-5-yl}sulfanyl)methyl and (2-amino-1,3-thiazol-4-yl)acetamido substituents at positions 3 and 7, respectively, of the cephem skeleton. A third generation beta-lactam cephalosporin antibiotic, it is active against a broad spectrum of both Gram positive and Gram negative bacteria. It has a role as an antibacterial drug. It is a cephalosporin, a semisynthetic derivative and a beta-lactam antibiotic allergen.|One of the cephalosporins that has a broad spectrum of activity against both gram-positive and gram-negative microorganisms.|Cefotiam is a third-generation, semi-synthetic, beta-lactam cephalosporin antibiotic with antibacterial activity. Cefotiam binds to penicillin-binding proteins (PBPs), transpeptidases that are responsible for crosslinking of peptidoglycan. By preventing crosslinking of peptidoglycan, cell wall integrity is lost and cell wall synthesis is halted.|One of the CEPHALOSPORINS that has a broad spectrum of activity against both gram-positive and gram-negative microorganisms.

Method 1: 0.824g of compound (I), 0.346g of 1-(2-dimethylaminoethyl)-1H-tetrazole-5-thiol and 0.168g of sodium bicarbonate are dissolved in 8ml of water and heated at 65 66°C for 1.5 h. After acidifying with lmol/L hydrochloric acid to Ph=3, filtering. The filtrate was adjusted to Ph=5.8 with 1mol/L sodium hydroxide, and chromatographed with XAD-2 column. The eluent was slowly changed from water to 40% methanol. The eluate containing the product was collected and lyophilized to obtain 0.151 g of cefotiam with a yield of 14%. 1-(2-dimethylaminoethyl)-1H-tetrazol-5-thiol can be obtained by heating N-(2-dimethylaminoethyl) isothiocyanate and sodium azide in aqueous ethanol . Method 2: Preparation of cefotiam hydrochloride. 1.83 g of cyclohexanol and 1.45 g of pyridine were dissolved in 30 ml of dichloromethane. Under dry ice cooling and stirring, 2 ml of 1-chloroethyl chloroformate was added dropwise. After the addition, the mixture was stirred at room temperature for 16h. It was washed with saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the remaining liquid was distilled under reduced pressure to obtain a colorless oily dichloroethyl carbonate cyclohexyl ester with a yield of 88% and a boiling point of 100-103°C (667 Pa). 1.56g of 1-chloroethyl carbonate cyclohexyl ester and 5g of sodium iodide were stirred in 50ml of acetonitrile at 60°C for 70min. It was concentrated under reduced pressure, and the residue was extracted with ether. The extract was concentrated under reduced pressure to obtain oily 1-iodoethyl carbonate cyclohexyl ester. 3.6g of Ceftiam potassium salt (CTM-K) was dissolved in 30ml of dimethylformamide, and under cooling and stirring in an ice bath, the resulting solution of 1-iodoethyl carbonate cyclohexyl ester in dimethylformamide was added . After stirring for 5 min, the reaction solution was poured into a mixture of 150 ml of 20% brine and 150 ml of ethyl acetate cooled with an ice bath. The organic layer was separated, washed with saturated brine, and then extracted with 40 ml of 1 mol/L hydrochloric acid. The aqueous extract was chromatographed on an MCI GELCHP 20P (75-150 μrn, Mitsubishi Kasei) column, eluting continuously with 0.01 mol/L hydrochloric acid and acetonitrile-0.01 mol/L hydrochloric acid (1:4). The eluate containing the product was collected, concentrated under reduced pressure after combining, and the residue was lyophilized to obtain cefotiam hydrochloride in a yield of 20%.

Antibacterial

Molecular Weight:525.6
XLogP3:-2.4
Hydrogen Bond Donor Count:3
Hydrogen Bond Acceptor Count:13
Rotatable Bond Count:10
Exact Mass:525.10351377
Monoisotopic Mass:525.10351377
Topological Polar Surface Area:251
Heavy Atom Count:34
Complexity:848
Defined Atom Stereocenter Count:2
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes