Derivatives piron, a pharmaceutical composition with anti-virus and antibacterial activity based on them and the method of treatment caused by rotavirus infection or disease

 

(57) Abstract:

Describes the new pyrone derivatives of the General formula I, where X, A, A1, W, W1- W3, R3, R4, m and n are specified in paragraph 1 of the claims of the values that can be an active ingredient of a pharmaceutical composition having antiviral and antibacterial activity. Also described is a method of treatment caused by rotavirus infection or disease by introducing a pyrone derivative of the above formula I in a therapeutically effective amount. 3 C. and 15 C. p. F.-ly, 3 PL.

The invention relates to a new oxygen-containing heterocyclic compounds with biological activity, in particular pyrone derivatives, pharmaceutical compositions with anti-virus and antibacterial activity on their basis and method of treatment caused by rotavirus infection or disease.

In the application WO 89/07939 describes coumarin derivatives, which possess biological activity, in particular antiviral and antibacterial activity.

Object of the invention is the expansion of the range of oxygen-containing heterocyclic compounds having the task is solved by the proposed pyrone derivatives of the General formula (I)

< / BR>
where X is a group of the formula OR1or CO2R1where R1has the following value, And and AND1independent from each other represent a chemical bond, unsubstituted or substituted phenyl, naphthyl, pyridinyl, coumarin, benzo[1,4]dioxines, benzodioxol, cycloalkyl with 3-12 carbon atoms, and the substituents are one or a few residues, selected from the group comprising fluorine, chlorine, bromine, OR1, CO2R1, CON(R1)2, COR1, R1, OCH2O, OCH2CH2O, C=N, where R1independently means hydrogen, substituted or unsubstituted alkyl with 1-12 carbon atoms or phenyl, substituted by one or more residues selected from the group comprising CO2R2, OR2, phenyl, naphthyl, morpholinyl, tetrazolyl, thienyl, isoxazolyl, pyridinyl or TRIFLUORIDE carbon, where R2independently denotes alkyl with 1-12 carbon atoms or hydrogen;

R4is hydrogen or alkyl with 1-12 carbon atoms,

R3independently means hydrogen, (CH2)pR1or (CH2)pA, where p is an integer of 0 to 2, R1and a have the above meanings;

W, W1and W3independent and mean chemical bond, oxygen, NR
W2means oxygen, NR3, S(O)p, SO2NR3where R3and R have the above values, m and n are independent and indicate an integer of 0 to 4, if the remains of W and W1both mean heteroatoms or if the W2and W3both mean heteroatoms, m means the number of 2-4, and a group of the formula R3W1(CH2)mW(CH2)nA means methyl or ethyl, and their pharmaceutically acceptable salts.

Preferred pyrone derivatives of the General formula (1) are compounds selected from the group including:

4-hydroxy-3-[(2-isopropylphenyl)thio]-6-phenyl-2H-Piran-2-it,

4-hydroxy-3-[[(2-methylpropyl " phenyl]thio]-6-phenyl-2H-Piran-2-it,

3-[((2-cyclopropylethyl)phenyl)thio]-4-hydroxy-6-phenyl-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-(2,3-dihydro-1,4-benzodioxin-6-yl)- 2H-Piran-2-it,

3-[(2,5-diisopropylphenyl)thio]-4-hydroxy-6-[(3-phenyl)phenyl]-2H-Piran-2-it,

6-phenyl-4-hydroxy-5-methyl-3-(phenylthio)-2H-Piran-2-it,

[4-[4-hydroxy-2-oxo-3-(phenylthio)-2H-Piran-6-yl]phenoxy]acetic acid,

[4-[4-hydroxy-5-methyl-2-oxo-3-(phenylthio)-2H-Piran-6 - yl] phenoxy]acetic acid,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[1-(2-methylpropyl " cyclopentyl]- 2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio]- 2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[1-(phenylmethyl)cyclopentyl] -2H - Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[1-(2-phenylethyl)cyclopentyl]-2H - Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[1-(3-phenylpropyl)cyclopentyl]- 2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[1-(2-methylpropyl " cyclopropyl]- 2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[1-(3-methylbutyl)cyclopropyl] - 2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[1-(4-methylpentyl)cyclopropyl]- 2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[1-(phenylmethyl)cyclopropyl] -2H - Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[1-(2-phenylethyl)cyclopropyl]-2H - Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[1-(3-phenylpropyl)cyclopropyl] -2H-Piran-2-it,

4-hydroxy-6-(3 oksifenil)-3-[(2-isopropylphenyl)thio]-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio]-6-(pyridin-4-yl)-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio]-6-(pyridin-2-yl)-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio]-6-(4-nitrophenyl)-2H-Piran-2 - it,

6-(4-forfinal)-4-hydroxy-3-[(2-isopropylphenyl)thio]-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio]-6-(2-were)-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio]-6-(2-methoxyphenyl)-2H-Piran - 2-it,

6-(2-chlorophenyl)-4-hydroxy-3-[(2-isopropylphenyl)thio]-2H-Piran-2-o is IO]-6-(3-triptoreline)-2H-Piran - 2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[4-(1-naphthalenyloxy)phenyl] - 2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[4-[2-(morpholine-4 - yl)ethoxy]phenyl] -2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[3-[2-(morpholine-4-yl)ethoxy] phenyl] -2H-Piran-2-it,

6-(4-benzyloxy-3-methoxyphenyl)-4-hydroxy-3-[(2-isopropylphenyl)thio] -2H - Piran-2-it,

6-(4-benzyloxy-3-chlorophenyl)-4-hydroxy-3-[(2-isopropylphenyl)thio] -2H - Piran-2-it,

4-[4-hydroxy-2-oxo-3-[(2-isopropylphenyl)thio] -2H-Piran-6-yl] -2 - methylphenoxyacetic acid,

4-hydroxy-6-[4-(2-acetoxy)phenyl] -3-[(2-isopropylphenyl)thio] -2H - Piran-2-it,

2-[3-[4-hydroxy-5-[(2-isopropylphenyl)thio]-6-oxo-6N-Piran-2-yl]phenoxy] -ndimethylacetamide,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[4-(2,3-pyrazinamidase)phenyl] - 2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[4-(pyridine-3 - ylethoxy)phenyl]-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[4-(pyridine-2-ylethoxy)-3-methyl - phenyl]-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[4-(pyridine-4-ylethoxy)phenyl]- 2H-Piran-2-it,

3-[(2-cyclopropylmethyl)thio] -4-hydroxy-6-[4-(pyridine-3-ylethoxy)phenyl] - 2H-Piran-2-it,

4-hydroxy-3-[(2,5-diisopropylphenyl)thio] -6-[4-(pyridine-3-ylethoxy) phenyl)-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[4-[2-(thiomorpholine-4 - yl)ethoxy]phenyl]-2H-Piran-2-he is enyl)thio] -6-[4-[2-(methylpiperazin-1-yl) ethoxy] -phenyl]-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[4-[2-(1,1 - diocletianopolis-4-yl)ethoxy]phenyl]-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio]-6-(1-phenyl-cyclopentyl)-2H - Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-(4-phenyl-piperidine - 4-yl)-2H-Piran-2-it,

complex 2-oxo-6-phenyl-3-[(2-isopropylphenyl)thio]-2H-Piran-2 - he-4-silt ether of isopentanol acid,

complex 2-oxo-6-phenyl-3-[(2-isopropylphenyl)thio]-2H - Piran-2-he-4-silt ester propanoic acid,

complex 2-oxo-6-phenyl-3-[(2-isopropylphenyl)thio]-2H-Piran-2-he - 4-silt ester of phenylacetic acid,

4-hydroxy-3-[(2-isopropyl-5-were)thio]-6-phenyl-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropyl-4-were)thio]-6-phenyl-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropyl-6-were)thio]-6-phenyl-2H-Piran-2-it,

3-[(4-chloro-2-isopropylphenyl)thio]-4-hydroxy-6-phenyl-2H-Piran-2-it,

4-hydroxy-3-[(4-hydroxy-2-isopropylphenyl)thio]-6-phenyl-2H-Piran-2-it,

3-[(2-cyclopropylmethyl)thio]-4-hydroxy-6-phenyl-2H-Piran-2-it,

3-[(2,5-diisopropylphenyl)thio]-4-hydroxy-6-phenyl-2H-Piran-2-it,

4-hydroxy-6-phenyl-3-[(2-tert.butylphenyl)thio]-2H-Piran-2-it,

3-[(2-cyclopropyl-5-isopropylphenyl)thio]-4-hydroxy-6-phenyl-2H - Piran-2-it,

3-[(2-cyclopentyl-5-isopropylphenyl)thio]-4-hydroxy-6 - phenyl-2H-Piran-2-it,

3-[(2-cyclohexyl-5-isopropylphenyl)thio]-4 - hydroxy-6-phenyl)thio]-4-hydroxy-6-phenyl-2H-Piran-2-it,

3-[(2-cyclopentylphenol)thio]-4-hydroxy-6-phenyl-2H-Piran-2-it,

3-[(2-cyclohexylphenol)thio]-4-hydroxy-6-phenyl-2H-Piran-2-it,

4-[[4-hydroxy-2-oxo-6-phenyl-2H-Piran-3-yl]thio]-2-hydroxy-indan,

4-hydroxy-3-[[2-isopropyl-4-(morpholine-4-ylmethyl)phenyl] thio]-6 - phenyl-2H-Piran-2-it,

4-hydroxy-3-[(6-isopropyl-indan-5-yl)thio]-6-phenyl-2H-Piran-2-it,

4-hydroxy-3-[(4-isopropyl-benzo[1,3] dioxol-5-yl)thio] -6-phenyl-2H - Piran-2-it,

3-[(2-tert. butyl-4-thiomorpholine-4-ylmethylene)thio]-4-hydroxy-6 - phenyl-2H-Piran-2-it,

4-hydroxy-6-[4-(pyridine-3-ylethoxy)phenyl] -3- [(2-tert. butylphenyl)thio]-2H-Piran-2-it,

3-[[(2-cyclopropyl-5-isopropyl)phenyl] thio] -4-hydroxy-6-[4-(pyridine-3 - ylethoxy)phenyl]-2H-Piran-2-it,

3-[[(2-cyclopentyl-5-isopropyl)phenyl] thio] -4-hydroxy-6-[4- (pyridin-3-yl-methoxy)phenyl]-2H-Piran-2-it,

3-[[(2-cyclohexyl-5-isopropyl)phenyl] thio] -4-hydroxy-6-[4-(pyridin - 3-yl-methoxy)phenyl]-2H-Piran-2-it,

4-hydroxy-6-[4-(pyridine-3-ylethoxy)phenyl] -3-[(2 - tert.butyl-5-isopropyl-phenyl)thio]-2H-Piran-2-it,

3-[(2,5-di-tert.butylphenyl)thio]-4-hydroxy-6-[4-(pyridine-3-ylethoxy) phenyl] -2H-Piran-2-it,

3-[(2-cyclopentylphenol)thio] -4-hydroxy-6-[4-(pyridine-3-ylethoxy)phenyl] - 2H-Piran-2-it,

3-[(2-cyclohexylphenol)thio] -4-hydroxy-6-[4-(pyridine-3 - ylethoxy)phenyl]-2H-Piran-2-it,

4-hydroxy-6-[4-(pyridine-3 - ylethoxy)phenyl]-3-[(6-Ethoxy)phenyl]-2H-Piran-2-it,

complex 3-[(2-isopropylphenyl)thio] -2-oxo-6-[4-(pyridine-3 - ylethoxy)phenyl]-2H-Piran-4-silt ether acetic acid,

complex 3-[(2-isopropylphenyl)thio] -2-oxo-6-[4-(pyridine-3 - ylethoxy)phenyl]-2H-Piran-4-silt ether somaclonal acid,

complex 3-[(2-isopropylphenyl)thio] -2-oxo-6-[4-(pyridine-3 - ylethoxy)phenyl]-2H-Piran-4-silt ether of 2,2-dimethylpropionic acid,

4-hydroxy-3-[(2-isopropylphenyl)sulfonyl]-6-[4-(pyridine-3-ylethoxy) phenyl] -2H-Piran-2-it,

3-[(2-tert.butylphenyl)sulfonyl]-4-hydroxy-6-phenyl-2H - Piran-2-it,

6-(1-benzylbutyl)-4-hydroxy-3-[(2-isopropylphenyl)sulfonyl] -2H - Piran-2-it,

6-(1-benzylbutyl)-4-hydroxy-3-[(2-isopropylphenyl)thio]-2H-Piran-2-it,

6-(1-benzylbutyl)-3-[(2-tert.butylphenyl)thio]-4-hydroxy-2H-Piran-2-it,

N-[3-[[6-(1-benzylbutyl)-4-hydroxy-2-oxo-2H-Piran-3-yl] thio] -2 - isopropyl-phenyl]benzosulfimide,

6-[1-cyclopropylmethyl-2-(tetrahydro-Piran-3-yl)ethyl] -4-hydroxy-3- [(2-isopropylphenyl)thio]-2H-Piran-2-it,

6-(1,1-dimethyl-3-phenylpropyl)-4-hydroxy-3-[(2-isopropylphenyl)thio] - 2H-Piran-2-it,

6-(benzo[1,3] -dioxol-5-yl)-4-hydroxy-3-[(2-isopropylphenyl)thio] - 2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[1-(phenylmethyl)cyclobutyl] -2H - Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[1-(2-phenylethyl)cyclobutyl] - 2H-Piran-2-it,
the Nile)thio]-6-(1-benzylcarbamoyl)- 2H-Piran-2-it,

4-hydroxy-3-[(2-isopropyl-5-were)thio] -6-[1-(2-phenylethyl) cyclopropyl)-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropyl-5-were)thio] -6-[1-(3-phenylpropyl) cyclopropyl)-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropyl-5-were)thio] -6-(1-benzylcarbamoyl)- 2H-Piran-2-it,

4-hydroxy-3-[(2-isopropyl-5-were)thio] -6-[1-(2-phenylethyl) cyclobutyl] -2H-Piran-2-it,

4-hydroxy-3-[(2-isopropyl-5-were)thio]-6-[1-(3- phenylpropyl)cyclobutyl]-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropyl-5-were)thio] -6-(1-benzyltoluenes)- 2H-Piran-2-it,

4-hydroxy-3-[(2-isopropyl-5-were)thio] -6-[1-(2-phenylethyl) cyclopentyl)-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropyl-5-were)thio] -6-[1-(3- phenylpropyl)cyclo-pentyl)-2H-Piran-2-it,

6-(1,1-dimethyl-3-phenylpropyl)-4-hydroxy-3-[(2-isopropylphenyl)thio] -2H - Piran-2-it,

6-(1,1-dimethyl-2-phenylethyl)-4-hydroxy-3-[(2-isopropylphenyl)thio] -2H - Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio]-6-(1-methyl-1 - phenylethyl)-2H-Piran-2-it,

6-(1,1-diethyl-3-phenylpropyl)-4-hydroxy-3- [(2-isopropylphenyl)thio]-2H-Piran-2-it,

6-(1-benzyl-1-ethylpropyl)-4-hydroxy-3-[(2-isopropylphenyl)thio] -2H - Piran-2-it,

6-(1-ethyl-1-phenylpropyl)-4-hydroxy-3-[(2-isopropylphenyl)thio] -2H - Piran-2-it,

6-[4-[(3,5-dimethyl-4-isoxazolyl)methoxy]phenyl]-4-hydroxy-3- [(2-phenyl-ethyl)thio]-2H-Piran-2-it,

4-hydroxy-3-[(2-what is it,

4-hydroxy-6-(3-phenoxyphenyl)-3-[(2-phenylethyl)thio]-2H-Piran-2-it,

4-hydroxy-6-[3-methoxy-4-(phenylmethoxy)phenyl]-3-[(2-phenylethyl)thio]- 2H-Piran-2-it,

4-hydroxy-3-[(2-oxo-2-phenylethyl)thio]-6-phenyl-2H-Piran-2-it,

4-hydroxy-6-phenyl-3-[(phenylmethyl)thio]-2H-Piran-2-it,

4-hydroxy-3-[(2-phenoxyethyl)thio]-6-phenyl-2H-Piran-2-it,

(E)-4-hydroxy-6-phenyl-3-[(3-phenyl-2-propenyl)thio]-2H-Piran-2-it,

ester 2-oxo-6-phenyl-3-[(phenylmethyl)thio] -2H-Piran-4-yl-3 - methyl-butane acid,

6-(3,4-dichlorophenyl)-4-hydroxy-3-[(phenylmethyl)thio]-2H-Piran-2-it,

6-(3-chlorophenyl)-4-hydroxy-3-[(phenylmethyl)thio]-2H-Piran-2-it,

ester 2-oxo-6-phenyl-3-[(phenylmethyl)thio] -2H-Piran-4-yl - propanoic acid,

4-hydroxy-6-(3-were)-3-[(phenylmethyl)thio]-2H-Piran-2-it,

4-hydroxy-6-(3 oksifenil)-3-[(phenylmethyl)thio]-2H-Piran-2-it,

4-hydroxy-6-(2-phenylethyl)-3-[(phenylmethyl)thio]-2H-Piran-2-it,

4-hydroxy-6-(4 oksifenil)-3-[(2-phenylethyl)thio]-2H-Piran-2-it,

4-hydroxy-3-[(2-phenylethyl)thio]-6-[4-(phenylmethoxy)phenyl]-2H - Piran-2-it,

4-hydroxy-6-[4-(2-phenylethane)phenyl]-3-[(2-phenylethyl)thio]-2H - Piran-2-it,

4-hydroxy-6-[3-(2-phenylethane)phenyl]-3-[(2-phenylethyl)thio]- 2H-Piran-2-it,

4-hydroxy-6-(2 oksifenil)-3-[(phenylmethyl)thio]-2H-Piran-2-it,

4-hydroxy-6-(3-methoxyphenyl)-3-[(phenylmethyl)thio]-2H-Piran-2-it,

6-(3-chlorophenyl)-4-o-chloro-4-methoxyphenyl)-4-hydroxy-3-[(phenylmethyl)thio]-2H-Piran-2-it,

4-hydroxy-3-[(2-phenylethyl)thio]-6-[3-(phenylmethoxy)phenyl]-2H-Piran-2-it,

4-hydroxy-3-[[2-(4-methoxyphenyl)ethyl]thio]-6-phenyl-2H-Piran-2-it,

3-[(cyclohexylmethyl)thio]-4-hydroxy-6-phenyl-2H-Piran-2-it,

4-hydroxy-3-[(phenylmethyl)thio]-6-[3-(trifluoromethyl)phenyl]- 2H-Piran-2-it,

4-hydroxy-3-[(2-phenylethyl)thio]-6-[3-(trifluoromethyl)phenyl]-2H - Piran-2-it,

6-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-hydroxy-3-[(phenylmethyl)thio]- 2H-Piran-2-it,

4-hydroxy-3-[(2-phenylethyl)thio] -6-[3-methyl-4-(3-pyridinylmethyl) phenyl]-2H-Piran-2-it,

[4-[4-hydroxy-2-oxo-3-[(2-phenylethyl)thio] -2H-Piran-6-yl] phenoxy] acetic acid,

complex ethyl ester [4-[4-hydroxy-2-oxo-3-[(2-phenylethyl)thio] - 2H-Piran-6-yl]phenoxy]acetic acid,

4-hydroxy-6-(4-phenoxyphenyl)-3-[(2-phenylethyl)thio]-2H-Piran-2-it,

4-hydroxy-3-[(2-phenylethyl)thio] -6-[4-(2-pyridinylmethyl)phenyl]-2H - Piran-2-it,

4-hydroxy-3-[(2-phenylethyl)thio] -6-[4-(3-pyridinylmethyl)phenyl]-2H - Piran-2-it,

4-hydroxy-6-[4-(2 - methoxyphenyl)methoxy] phenyl] -3-[(2-phenylethyl)thio]-2H-Piran-2-it,

4-hydroxy-3-[(2-phenylethyl)thio]-6-[4-(phenylthio)phenyl]-2H-Piran-2-it,

6-(1,3-benzodioxol-5-yl)-4-hydroxy-3-[(phenylmethyl)thio]-2H-Piran-2-it,

6-(3, 5dimethylphenyl)-4-hydroxy-3-[(phenylmethyl)thio]-2H-Piran-2-it,

4-hydroxy-6-(2-naphthalenyl)-3-[(phenylmethyl)thio]-2H-Piran-2-it,

4-hydroxy-6-(4 oksifenil)-3-[(f the l)phenyl]-3-[(phenylmethyl)thio]-2H-Piran-2-it,

6-(3, 5dimethylphenyl)-4-(oxymethyl)-3-[(phenylmethyl)thio]-2H-Piran-2-it,

[4-[4-hydroxy-5-(oxymethyl)-2-oxo-3-[(2-phenylethyl)thio] -2H-Piran-6-yl] - phenoxy]acetic acid,

4-hydroxy-6-[(4-methoxyphenyl)methyl] -3-[[1- (phenylmethyl)butyl] thio]-2H-Piran-2-it,

[[5-[2-oxo-4-hydroxy-3-[(3 - methyl-1-phenylbutyl)thio]-2H-Piran-6-yl]-2-pyridinyl]oxy]acetic acid,

[[4-[4-hydroxy-2-oxo-3-[(phenylmethyl)thio] -2H-Piran-6 - yl]cyclohexyl]oxy] acetic acid,

6-[4-(chicagocelebrex)phenyl] -4-hydroxy-3-[(2-phenylethyl)thio] - 2H-Piran-2-it,

4-hydroxy-3-[(2-phenylethyl)thio]-6-[4-(phenylsulfonyl)phenyl]-2H - Piran-2-it,

4-hydroxy-3-[(2-phenylethyl)thio]-6-[4-(benzoyloxy)phenyl]- 2H-Piran-2-it,

4-hydroxy-3-[(2-phenylethyl)thio]-6-[4-(phenylsulfinyl)phenyl]-2H - Piran-2-it,

4-hydroxy-3-[(2-phenylethyl)thio]-6-(4-pyridinyl)-2H-Piran-2-it,

4-hydroxy-6-(3-phenoxyphenyl)-3-[(2-phenylethyl)thio]-2H-Piran-2-it,

4-hydroxy-6-[3-methoxy-4-(phenylmethoxy)phenyl] -3-[(2-phenylethyl)thio]- 2H-Piran-2-it,

6-(3, 5dimethylphenyl)-4-hydroxy-3-[(2-phenylethyl)thio]-2H-Piran-2-it,

4-hydroxy-3-[[(3-methoxyphenyl)methyl]thio]-6-phenyl-2H-Piran-2-it,

4-hydroxy-6-phenyl-[[[3-(phenylmethoxy)phenyl]methyl]thio]-2H-Piran-2-it,

3-[(1,3-benzodioxol-5-ylmethyl)thio]-4-hydroxy-6-phenyl-2H-Piran-2-it,

4-hydroxy-3-[[(2-methoxyphenyl)methyl]thio]-6-phenyl-2H-Piran-2-it,

4 oaks is 4-hydroxy-3-[[(4-were)methyl]thio]-6-phenyl-2H-Piran-2-it,

6-[1,11-biphenyl]-3-yl-4-hydroxy-3-[(2-phenylethyl)thio]-2H - Piran-2-it,

4-hydroxy-3-[[(4-methoxyphenyl)methyl]thio]-6-phenyl-2H-Piran-2-it,

complex ethyl ester [4-[4-hydroxy-2-oxo-3-[(2-phenylethyl)thio] - 2H-Piran-6-yl]-2-methylphenoxy]acetic acid,

4-hydroxy-3-[(2-phenylethyl)thio] -6-[4-(4-pyridinylmethyl)phenyl]- 2H-Piran-2-it,

[4-[4-hydroxy-2-oxo-3-[(2-phenylethyl)thio] -2H-Piran-6-yl] -2 - methylphenoxy] -acetic acid,

4-hydroxy-6-(4-hydroxy-3, 5dimethylphenyl)-3-[(phenylmethyl)thio]-2H - Piran-2-it,

4-hydroxy-6-phenyl-3-[[[3-(2-phenylethane)phenyl]methyl]thio]-2H - Piran-2-it,

4-hydroxy-6-[4-(2-phenylethynyl)phenyl]-3-[(2-phenylethyl)thio]-2H - Piran-2-it,

4-hydroxy-6-[4-(2-phenylethyl)phenyl]-3-[(2-phenylethyl)thio]-2H - Piran-2-it,

4-hydroxy-3-[(2-phenylmethyl)thio]-6-[3-(triptoreline)phenyl]- 2H-Piran-2-it,

3-[(cyclohexylmethyl)thio]-4-hydroxy-6-phenyl-2H-Piran-2-it,

4-hydroxy-3-[(2-phenylethyl)thio] -6-[3-methyl-4-(3-pyridinylmethyl) phenyl]-2H-Piran-2-it,

6-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-hydroxy-3- [(phenylmethyl)thio]-2H-Piran-2-it,

4-hydroxy-3-[(2-phenylethyl)thio]-6-[3-(trifluoromethyl)phenyl]-2H - Piran-2-it,

4-hydroxy-3-[(phenylmethyl)thio]-6-[3-(trifluoromethyl)phenyl]-2H - Piran-2-it,

4-hydroxy-3-[(phenylmethyl)thio]-6-(2,3,4-trimethoxyphenyl)-2H - Piran-2-it,

N-[4-[4-hydroxy-2-oxo-3-[(2-phenylethyl)thio] -2H-Piran-6-yl] phenyl] benzene is iny methyl ester 2-[[(4-hydroxy-2-oxo-6-phenyl-2H-Piran-3 - yl)thio]-methyl]-benzoic acid,

methyl ester 2-[[4-(4-hydroxy-2-oxo-3-[(2-phenylethyl)thio]- 2H-Piran-6-yl]phenoxy]methyl]benzoic acid

4-hydroxy-3-[(2-phenylethyl)thio] -6-[4-(1H-tetrazol-5-ylethoxy) phenyl]-2H-Piran-2-it,

4-hydroxy-6-[3-methyl-4-(2-pyridinylmethyl)phenyl] -3-[(2-phenylethyl)thio] -2H-Piran-2-it,

methyl ester 4-[[4-hydroxy-2-oxo-3-[(2 - phenylethyl)thio]-2H-Piran-6-yl]phenoxy]methyl-benzoic acid,

methyl ester 3-[[4-[4-hydroxy-2-oxo-3-[(2-phenylethyl)thio]- 2H-Piran-6-yl]phenoxy]methyl]benzoic acid

6-[4-[(3,4-dichlorophenyl)methoxy] phenyl]-4-hydroxy-3-[(2-phenylethyl)thio]- 2H-Piran-2-it,

methyl ester 3-[[(4-hydroxy-2-oxo-6-phenyl-2H-Piran-3 - yl)thio]-methyl]benzoic acid

methyl ester 4-[[(4-hydroxy-2-oxo-6-phenyl-2H-Piran-3-yl) thio]-methyl]benzoic acid

6-[3,5-bis(trifluoromethyl)phenyl] -4-hydroxy-3-[(phenylmethyl)thio]-2H - Piran-2-it,

[4-[4-hydroxy-2-oxo-3-[(2-phenylethyl)thio] -2H-Piran-6 - yl] phenoxy] acetonitrile,

6-phenyl-4-hydroxy-3-[(cyclopropylmethyl)thio]-2H-Piran-2-it,

6-(3-chlorophenyl)-4-hydroxy-3-[(4-phenylbutyl)thio]-2H - Piran-2-it,

4-hydroxy-3-[(2-hydroxy-2-phenylethyl)thio]-6-phenyl-2H-Piran-2-it,

4-hydroxy-3-[(phenylmethyl)thio]-6-(3-pyridinyl)-2H-Piran-2-it,

6-(2,6-dimethyl-4-pyridinyl)-4-hydroxy-3-[(phenylmethyl)thio]-2H - Piran-2-it,

4-hydroxy-3-[(FeNi is-[4-(pyridine-3-ylethoxy)phenyl] - 2H-Piran-2-it,

4-hydroxy-3-(2-isopropyl-phenoxy)-6-phenyl-2H-Piran-2-it,

3-(2-tert.butyl-phenoxy)-4-hydroxy-6-[4-(pyridine-3-ylethoxy)phenyl]- 2H-Piran-2-it,

3-(2-tert. butyl-5-methyl-phenoxy)-4-hydroxy-6-[4-(pyridine-3 - ylethoxy)phenyl]-2H-Piran-2-it,

6-(1-benzylbutyl)-4-hydroxy-3-(2-isopropylphenoxy)-2H-Piran-2-it,

6-(1-benzylbutyl)-3-(2-tert.butylphenoxy)-4-hydroxy-2H-Piran-2-it,

3-benzyloxy-4-hydroxy-6-[4-(pyridine-3-ylethoxy)phenyl]-2H-Piran-2-it,

methyl ester 2-[4-hydroxy-2-oxo-6-[4-(pyridine-3-ylethoxy)- phenyl]-2H-Piran-3-intoximeter]benzoic acid

complex ethyl ester 2-[[[6-(1-benzylbutyl)-4-hydroxy-2-oxo-2H - Piran-3-yl]oxy]methyl]benzoic acid

6-(1-benzylbutyl)-4-hydroxy-3-(1-phenylmethoxy)-2H-Piran-2-it,

3-[bis(2-naphthalenyloxy)amino]-4-hydroxy-6-phenyl-2H-Piran-2-it,

6-(1-benzylbutyl)-3-(cyclopropylamino)-4-hydroxy-2H-Piran-2-it,

N-[3-[[6-(1-benzylbutyl)-4-hydroxy-2-oxo-2H-Piran-3-yl] cyclopropyl - amino]phenyl]benzosulfimide,

3-[cyclopropylamino]-4-hydroxy-6-(pyridine-3-ylethoxy)-2H-Piran-2-it,

3-(bis-cyclopentylmethyl-amino)-4-hydroxy-6-(pyridine-3 - ylethoxy)-2H-Piran-2-it,

3-[cyclopentylmethyl(cyclopropylmethyl)amino] -4-hydroxy-6-(pyridine-3 - ylethoxy)-2H-Piran-2-it,

6-[1-cyclopropylmethyl-2-(tetrahydro the EN-3-yl)- N'-(phenylmethyl)urea,

cyclopentylmethyl-[4-hydroxy-2-oxo-6-[(pyridine - 3-ylethoxy)phenyl] -2H-Piran-3-yl]amide cyclopropanecarboxylic acid,

cyclopentylmethyl-[4-hydroxy-2-oxo-6-[4-(pyridine-3 - ylethoxy)phenyl]-2H-Piran-3-yl]amide cyclopentanecarbonyl acid,

N-cyclopentylmethyl-N-[4-hydroxy-2-oxo-6-[4-(pyridine-3 - ylethoxy)phenyl]-2H-Piran-3-yl]cyclopentanecarbonyl.

Compounds according to the invention are non-toxic in concentrations equal to or greater than 100 microns.

Some compounds of General formula (I) are capable of forming pharmaceutically acceptable acid additive salts and/or pharmaceutically acceptable salts with bases.

Pharmaceutically acceptable acid additive salts of compounds of formula (I) include salts with non-toxic inorganic acids such as, for example, hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, Hydrobromic acid, todistava-burly acid, hydrofluoric acid, phosphoric acid, etc. and salts with non-toxic organic acids such as, for example, aliphatic mono - and dicarboxylic acids, substituted phenyl alcancarao acid, hydroxy-alcancarao acid, Alcantara clucalc sulfate, persulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, secondary phosphate, primary phosphate, metaphosphate, pyrophosphate, chloride, bromide, iodide, acetate, triptorelin, propionate, kaprilat, isobutyrate, oxalate, malonate, succinate, suberate, sebacate, fumarate, maleate, mandelate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, phthalate, bansilalpet, toluensulfonate, phenyl acetate, citrate, lactate, maleate, tartrate, methanesulfonate, etc., this invention also covered salt with amino acid such as, for example, Argent etc., and gluconate and galacturonic.

Acid additive salts of the basic compounds produced as a result of interaction of the free base with a sufficient amount of the desired acid to produce the salt of a standard technique.

Pharmaceutically acceptable salts with a base are salts with metals or amines, such as, for example, alkali metals or alkaline earth metals? or organic amines. As metals suitable for use as cations include, for example, sodium, potassium, magnesium, calcium, etc., as suitable amines include, for example, N, N'-dibenziletilendiaminom, chloroprocaine, choline, diethanol the cation produced by interaction of the free acid with a sufficient amount of the desired base to obtain a salt of a standard technique.

Some compounds of the present invention may be in resolutiony forms, and solvated forms, including hydrated forms. In General, the solvated forms, including hydrated forms, are the same activities that nonsolvated form of the proposed compounds. So they are also covered by the present invention.

Some of the proposed compounds have one or more chiral centers, each of which may be in the form of configuration R(D) or S(L). The present invention includes all enantiomeric and epimeria forms, and mixtures thereof.

The compounds of this invention can be applied in the form of various preparations suitable for oral or parenteral application. The proposed connection can be applicirovti by injection, i.e., intravenously, intramuscularly, intracutaneously, subcutaneously, intraduodenally or intraperitoneally. The proposed connection can also be applicirovti by inhalation, for example, through the nose. In addition, the proposed connection can be applicirovti transdermal.

Pharmaceutically acceptable carriers used for the manufacture of pharmaceutical compositions, soderjasimi are for example, powders, tablets, pills, capsules, suppositories, and dispersible granules. As a solid carrier can be used one or more substances which may also act as diluents, flavoring agents, binders, preservatives, dezintegriruetsja tablets of the substance or substances for encapsulation of the active agent.

In the case of the powder carrier is a finely ground substance present in a mixture with finely ground active early.

For the preparation of tablets, the active principle is mixed with a suitable carrier in suitable proportions, after which the mixture is compressed to obtain tablets of desired sizes and configurations.

The powders and tablets preferably contain from 5 or 10 to approximately 70% of the active principle. Suitable carriers are, for example, magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragakant, methylcellulose, carboxymethylcellulose sodium, low melting wax, cocoa butter, etc., the term "drug" refers also capsules are active early, alone or in mixtures with native speakers, this material, which is made from the capsules, pre is apsule and tortillas. Tablets, powders, capsules, pills, starch capsules and pellets are solid preparations suitable for oral testimony.

Suppositories can do due to the fact that the low-melting wax, such as, for example, a mixture of glycerides of fatty acids or cocoa butter, is first melted and stirring, to obtain a homogeneous melt is dispersed active principle. The resulting homogeneous melt is poured into molds of suitable size, where he is allowed to cool and cure.

As liquid preparations can be called solutions, suspensions and emulsions, for example aqueous solutions or solutions of water and propylene glycol. For parenteral injection, liquid preparations are a solution in aqueous polyethylene glycol.

Suitable for oral application of aqueous solutions can be obtained by dissolving the active agent in water and adding suitable target additives, such as dyes, flavoring agents, stabilizers, thickeners.

Suitable for oral application of aqueous suspensions can be obtained by dispersing finely ground active principle in water in the presence of viscous substances, such as, for example, natural elendira agents.

In the scope of the invention also include solid preparations intended for transferring in liquid preparations immediately prior to oral application. Such fluids are solutions, suspensions and emulsions. In addition to the active principle, these preparations may contain colouring agents, flavouring agents, stabilizers, buffers, natural or synthetic sweeteners, dispersants, thickeners, promoting solubilization agents, etc.

The pharmaceutical composition is preferably produced in the form of the drug, including dosing units, each of which contains the appropriate amount of active principle. The dosing unit can be a packaged preparation, the package contains a suitable quantity of the drug, for example Packed tablets, Packed capsules, powders shells or capsules. A dosage unit may also be a capsule or tablet as such or Packed appropriate number of tablets or capsules.

The amount of the active agent in a dosage unit may vary in the range of 0.1 - 100 mg, preferably 0.5 to 100 mg, depending on the specific purpose and effective the LASS="ptx2">

When used as an antagonist of the retroviral protease, the active agent for treatment caused by a retrovirus, including HIV infection, or as an active principle for the treatment of diseases caused by AIDS connection on the proposed method of treatment is first given in doses of about 0.01 to 100 mg/kg per day. The preferred daily dose of the active agent is about 0.01 to 10 mg/kg, However, from the above doses can deviate depending on the condition of the patient, the severity of the disease and appliciruemah connection. The person skilled in the art can determine the appropriate dosage in any specific case.

Usually do that at the beginning of treatment give small doses of proposed connections that are less than the optimum dose. Then gradually increase the dose to achieve the optimal therapeutic effect. If necessary, the total daily dose may be divided and portions to be given during the day.

New pyrone derivatives of the General formula (I) can be obtained with known methods, for example by the following methods.

Method a:

Example: Synthesis by interaction of simple selenology esters of 2-substituted esters Probenvorbereitung ketone in 100 ml of dry tetrahydrofuran at a temperature of 78oC add 11 mmol (1.1 equivalent) hexamethyldisilazide lithium. The reaction mixture is stirred for 1 hour at a temperature of -78oC and for a further 0.5 hours, at a temperature of -35oC . At a temperature of -78oC was added dropwise trimethylchlorosilane, and the resulting mixture is stirred for 1 hour at a temperature of -78oC and for a further 0.5 hours, at a temperature of 0oC. the Reaction is stopped by adding a saturated solution of sodium bicarbonate and the reaction mixture is extracted with ethyl acetate, taken in the amount of 300 ml of an ethyl acetate phase is washed with saturated sodium bicarbonate solution and brine and dried over anhydrous sodium sulfate. An ethyl acetate solution is concentrated under reduced pressure, and the selected substance is dried in vacuum for 1 hour and used without purification.

2. Condensation simple trimethylsilanol esters with complex dialkylamino esters of 2-substituted proponderance acid

11 mmol (1.1 equivalent) crude simple trimethylsilylacetamide ester, obtained as described above, together with 10 mmol (1.0 equivalent) complex dialkylamide ether 2-substituted proponderance acid, and the resulting mixture over night on clonney the mixture is cooled to room temperature and the product purified by chromatography on silica gel. By elution with a mixture of ethyl acetate and hexanol with the content of ethyl acetate, equal to 10 to 15%, remove neproreagirovavshimi starting material and other impurities, and by elution with a mixture of ethyl acetate, methylene chloride and hexanol with the content of ethyl acetate, 30 - 50%, and methylene chloride - 5%, carry out further purification to obtain the desired pyrone. The yield may vary from 20 to 75%. This method is illustrated by reaction scheme A (see the end of the description).

Method B:

Example: Sulfenimidovy 6-aryl-4-hydroxy-2H-Piran-2-it

1. Getting 6-aryl-4-hydroxy-2-pyrone

20 mmol (1 equivalent) simple trimethylsilylacetamide ether, obtained by a similar method As follows (or available in the form of trading of the product), served in anhydrous ethyl ether and cooled to a temperature of -78oC -40oC. To the mixture was added dropwise 30 - 40 mmol (1.5-2 EQ.) malonaldehyde. The reaction mixture was gradually warmed to room temperature and during the night stirred at room temperature. The resulting solid is filtered and washed with anhydrous diethyl ether.

2. Sulfenimidovy 6-aryl-4-hydroxy-2H-Piran-2-it

of 1.62 mmol (1 EQ.) 6-aryl-4-hydroxy-2-pyrone, obtained above about the Valens of triethylamine, and 1,72 mmol (1.04 EQ. the respective thiosulfonate. The reaction mixture is heated under reflux during the night. The solvents are evaporated, the reaction mixture was acidified with 1-N. hydrochloric acid and the product extracted with ethyl acetate. After evaporation of the solvents the crude product is purified by chromatography on silica gel with a particle size of 230 - 400 mesh using as eluent a mixture of ethyl acetate and hexanol with the content of ethyl acetate, 30 - 50%, to obtain the target product. The yield may vary from 40 to 80%.

This method is illustrated by the following reaction scheme B (see the end of the description).

Method:

Example: Obtaining (6-aryl-4-hydroxy-2-oxo-2H-Piran-3 - yl)alltimecase

To 2.16 mmol (1 EQ.) 6-aryl-4-hydroxy-2H-Piran-2-it in 10 ml of ethanol serves is 2.37 mmol (1.1 EQ.) the corresponding aldehyde, 5,62 mmol (2.6 EQ.) the corresponding thiol, and 0.50 ml of piperidine and 0.50 ml of acetic acid. The reaction mixture is kept at a temperature of 80oC for 24 hours. The ethanol is evaporated, the residue acidified with 1-N. hydrochloric acid, purified by chromatography on silica gel with a particle size of 230 - 400 mesh and get the target product. When this output can range from 35 to 60%.


Example: obtain the 6-aryl-3-alkylamino-4-hydroxy-2H-Piran-2-it

1.6-aryl-4-hydroxy-3-nitro-2H-Piran-2-he

In the suspension to 2.65 mmol of 6-aryl-4-hydroxy-2H-Piran-2-she 2,77 ml of acetic acid at room temperature serves 0,222 ml of fuming nitric acid. The reaction mixture is stirred for 5 minutes, cooled to a temperature of 0oC and the product filtered. The product was then purified by recrystallization from boiling acetic acid.1H-NMR (250 MHz, d-triptorelin): = 7,02 (s, 1 H), the 7.65 (s, 3 H), to 7.99 (m, 2H)

2.3-amino-6-aryl-4-hydroxy-2H-Piran-2-he

To a suspension of 10.5 mmol (1 EQ.) 6-aryl-4-hydroxy-3-nitro-2H-Piran-2-she's in 15 ml of acetic acid and 7,34 ml of concentrated hydrochloric acid added to 20.6 mmol (1,96 EQ.) fleecy tin. The resulting mixture is heated under reflux, you get a homogeneous mixture. The reaction mixture is heated under reflux for 7 minutes, after which it was cooled in an ice bath. Add concentrated hydrochloric acid, while the precipitated 3-amino-6 - aryl-4-hydroxy-2H-Piran-2-it is in the form of the hydrochloride, which is collected and dried.1H-NMR (250 MHz, D2O): = 6,74 (s, 1 H), 7,53 (m, 3 H), to 7.84 (m, 2 H).

3,3-alkylamino-6-aryl-4-hydroxy-2H-Piran-2-he

To a solution of 2 mmol (1 EQ.) 3-amino-6-aryl-4-hydroxy-2H-what Ino serves 2,1 - 4,2 mmol (1,05 - 2.1 EQ.) aldehyde and 2.1 - 4.2 mmol (1,05 - 2.1 EQ.) cyanoborohydride sodium.

The reaction mixture is stirred for 5 minutes, then mixed with water and concentrated in vacuum. The oily residue is diluted with 100 ml of ethyl acetate, sequentially washed with water and saturated sodium chloride and dried over anhydrous magnesium sulfate. The solvents are evaporated in vacuum and the crude product is purified either by column chromatography on silica gel with a particle size of 230 - 400 mesh, or by recrystallization to obtain the target product.

This method is illustrated by the following reaction scheme G (see the end of the description).

Method D.

Example: Obtaining 3-acylamino-6-aryl-4-hydroxy-2H-Piran-2-it

In a solution of 0.84 mmol (1.0 equiv.) 3-amino-6-aryl-4-hydroxy-2H-Piran-2-it is in the form of hydrochloride in 10 ml of tetrahydrofuran serves to 0.92 mmol (1.1 EQ.) 60% sodium hydride. Stirred for 30 minutes at room temperature. In another flask 1.67 mmol 2 EQ.) the corresponding carboxylic acid in 20 ml of tetrahydrofuran at -20 With consistently serves to 0.92 mmol (1.1 EQ.) N-methylmorpholine and 0.92 mmol (1.1 EQ.) 1-(3-dimethylaminopropyl)- 3-ethylcarbodiimide as hydrochloride. The reaction mixture is stirred of Priya-2H - Piran-2-it, then add another 0,918 mmol (1.1 EQ.) N - methylmorpholine. The reaction mixture was stirred at room temperature overnight. To the reaction mixture add the brine and diluted with ethyl acetate. The organic layer is successively washed with 1-N. hydrochloric acid, water and saturated sodium chloride, then dried over anhydrous magnesium sulfate. The solvents are evaporated in vacuum and the crude product purified by column chromatography on silica gel with a particle size of 230 - 400 mesh to obtain the target product.

This method is illustrated by the following reaction scheme D (see the end of the description).

Method D can also be carried out as follows.

Option 1

In the slurry, 0.83 mmol (1.0 equiv.) 3-amino-6-aryl-4-hydroxy-2H - Piran-2-it is in the form of monohydrochloride in 8 ml of methylene chloride successively served 3.3 mmol (4.0 EQ. ) of triethylamine, and a catalytic amount (0.08 mmol, 0.1 EQ. ) 4 - dimethylaminopyridine and 0.92 mmol (1.1 EQ.) the corresponding carboxylic acid. The reaction mixture was stirred at room temperature for 6 hours. To the mixture was added 1-N. hydrochloric acid, after which the reaction mixture is diluted with methylene chloride. The organic phase is washed in the crude product is recrystallized from boiling acetic acid.

Option 2

In the solution to 0.63 mmol (1.0 equiv.) 3-amino-6-aryl-4-hydroxy-2H - Piran-2-it is in the form of monohydrochloride in 6 ml of tetrahydrofuran at a temperature of 0oC serves 0.69 mmol (1.1 EQ.) 60% sodium hydride. The resulting mixture was stirred at room temperature for 15 minutes. In the reaction mixture serves 0.69 mmol (1.1 EQ.) the corresponding carboxylic acid. The reaction mixture for 1 hour, heated to a temperature of 50oC and during the night keep it at room temperature. To the reaction mixture was added 1-N. hydrochloric acid and diluted with ethyl acetate. The organic phase is washed with saturated sodium chloride and dried over anhydrous magnesium sulfate. The solvents are evaporated in vacuum and the crude product is recrystallized from boiling nitromethane to obtain the pure product.

Method E:

Example: Obtaining complex 4-acyloxy-ether 4-hydroxy - 3-aaltio-6 - aryl-2H-Piran-2-or 4-acyloxy-ether 4-hydroxy-3 - arylalkyl-6-aryl-2H-Piran-2-it

3 mmol (1 EQ.) 4-hydroxy-3-aaltio-6-aryl-2H-Piran-2-or 4-hydroxy-3-arylalkyl-6-aryl-2H-Piran-2-it was dissolved in 20 ml of tetrahydrofuran and cooled to a temperature of 0oC. the resulting mixture is slowly serves 3.3 mmol (1.1 EQ.) hydride sodium stuudio the carboxylic acid and the reaction mixture was stirred at room temperature overnight. To the reaction mixture is added a saturated solution of sodium chloride and diluted with ethyl acetate, taken in an amount of 100 ml Combined organic phase is washed with sodium bicarbonate solution and brine and dried over anhydrous sodium sulfate. The solvents are evaporated and the crude product purified by column chromatography on silica gel with a particle size of 230 - 400 mesh using as eluent a mixture of ethyl acetate and hexane in a ratio of 1:9. You get a complex enol ether. When this output can range from 70 to 85%.

This method is illustrated by the following reaction scheme E (see the end of the description).

Getting pyrone derivatives of General formula (I) is illustrated by the following examples that use the following abbreviations:

DMSO = dimethylsulfoxide

THF = tetrahydrofuran

NMR = nuclear magnetic resonance

IM = impact ionization

IR = infrared spectrum

MS = mass spectrum

Example 1

6-(3-chlorophenyl)-4-hydroxy-3-[(phenylmethyl)thio]-2H - Piran-2-he

According to the method And the solution of 1.50 g (11.6 mmol) of 3'-chloroacetophenone in 10.0 ml of tetrahydrofuran cooled to 78oC in nitrogen atmosphere and treated with 1.0 M solution of 12.5 ml (12.5 mmol) HEXAMETHYL of 1.47 ml (11.6 mmol) of tributyltinchloride.

The reaction mixture is stirred for 30 minutes at room temperature, after which she served in a mixture of 50 ml simple diethyl ether and 20 ml of saturated aqueous sodium bicarbonate. The layers are separated and the organic layer is washed with a mixture of brine and 20 ml of saturated sodium bicarbonate in a 1:1 ratio. The ether solution is dried over sodium sulfate and the solvent is removed in vacuum. Get selenology ether is fed into the flask containing 1.63 g (5,80 mmol) diethyl ether complex of 2-(thiobenzoyl)propane - 1,3-dicarboxylic acid. The mixture is heated to 160oC for 16 hours, after which she is allowed to cool to room temperature. The mixture is then diluted with 20 ml simple diethyl ether and extracted three times with saturated sodium carbonate, taken in an amount of 20 ml of the Aqueous layer was acidified with concentrated hydrochloric acid to achieve a pH of 0 and three times extracted with ethyl acetate, taken in an amount of 100 ml Organic layers are combined, dried over sodium sulfate and the solvent is removed in vacuum. The residue is purified by chromatography on silica with a particle size of 230 - 400 mesh using as eluent 100% dichloromethane and a mixture of dichloromethane with 1% methanol. Get 0,436 g target UP>1
H-NMR (400 MHz, DMSO-d6): = 11,950 (Shir.s,1H), 7,814 (s,1H), 7,761 (d, 1H, J = 7.5 Hz), 7,616 - 7,534 (m,2H), 7,271 - 7,185 (m, 5H), 6,811 (s, 1H), 4,023 (s,2H).

Example 2

6-(2-chlorophenyl)-4-hydroxy-3-[(phenylmethyl)thio]-2H-Piran-2-he

0,210 g of target compound (So pl. 99 - 101oC ) receiving by the method And with the use of 1.50 ml (11.6 mmol) of 2'- chloroacetophenone, to 6.80 ml (12.7 mmol) of 1.87 M hexamethyldisilazide potassium, 1,47 ml (11.6 mmol) of tributyltinchloride, 10.0 ml of tetrahydrofuran and 1,3 r (4,63 mmol) diethyl ether complex of 2-(thiobenzoyl)propane-1,3-dicarboxylic acid.

1H-NMR (400 MHz, DMSO-d6): = 12,153 (Shir.s, 1H), 7,639 (t, 2H, J= 9 Hz), 7,572 - 7,477 (m, 2H), 7,276 - 7,206 (m, 5H), 6,558 (s, 1H), 4,029 (s, 2H).

Example 3

6-(3,4-dichlorophenyl)-4-hydroxy-3-[(phenylmethyl)thio]-2H - Piran-2-he

0,201 g of target compound (So pl. 185 - 186oC) get method But using 1.5 g (7.9 mmol) of 3',4'- dichloroacetophenone, and 8.7 ml (8.69 mmol) of 1.0 M hexamethyldisilazide lithium, 1.0 ml (7.9 mmol) of tributyltinchloride, 10.0 ml of tetrahydrofuran and 0,89 g (3.2 mmol) of a compound diethyl ether 2-(thiobenzoyl)propane-1,3-dicarboxylic acid.

1H-NMR (400 MHz, DMSO-d6): = 12,000 (Shir.s, 1H), 8,018(s, 1H), 7,784 (s, 2H), 7,265 - 7,179 (m, 5H), 6,839 (s, 1H), 4,017 (s, 2H).

Example 4

4-hydroxy-6-(3-methoxyphenyl)-3-[(penile the ml (10.9 mmol) of 3'- methoxyacetophenone, 6,41 ml (12,0 mmol) hexamethyldisilazide potassium, 1,38 ml (10.9 mmol) of tributyltinchloride, 10.0 ml of tetrahydrofuran and of 1.23 g (4,36 mmol) diethyl ether complex of 2-(thiobenzoyl)propane-1,3 - dicarboxylic acid.

1H-NMR (400 MHz, DMSO-d6): = 11,880 (Shir.s, 1 H) 7,445 (t, 1 H, J = 8 Hz), 7,370 (d, 1H, J = 8 Hz), 7,286 - 7,094 (m, 6 H) 7,109 (m, 1 H) 6,770 (s, 1 H) 4,020 (s, 2H), 3,831 (s, 3H).

Example 5

4-hydroxy-3-[(phenylmethyl)thio]-6-(3,4,5-trimethoxyphenyl)-2H - Piran-2-he

0,385 g of target compound (So pl. 156 - 157oC) get method But using 2.0 g (9.5 mmol) 3',4',5'-trimethoxyflavone, 5.6 ml (10,45 mmol) hexamethyldisilazide potassium, 1.2 ml (9.5 mmol) of tributyltinchloride, 15 ml of tetrahydrofuran and 1.07 g (of 3.80 mmol) in diethyl ether complex of 2-(thiobenzoyl)propane-1,3-dicarboxylic acid.

1H-NMR (400 MHz, DMSO-d6): = 11,778 (Shir.s, 1 H), 7,265 -7,181 (m, 5H), 7,054 (s, 2H), 6,792 (s, 1H), 3,997 (s, 2H), 3,861 (C, 6N), 3,727 (s, 3H).

Example 6

6-(3-chlorophenyl)-4-hydroxy-3-[(2-phenylethyl)thio]-2H - Piran-2-he

was 0.138 g of target compound (So pl. 125 - 127oC) get method B with the use of 0.250 g (1.10 mmol) of 6-(3-chlorophenyl)-4 - hydroxy-2H-Piran-2-it, of 0.43 g (of 1.46 mmol) of complex ventilago ether p-toluoldisocyanate, of 0.35 ml (2.5 mmol) of triethylamine and 5.0 ml of ethanol.

Example 7

6-(4-chlorophenyl)-4-hydroxy-3-[(2-phenylethyl)thio]-2H - Piran-2-he

0,242 g of target compound (So pl. 161 - 163oC) get method B with the use of 0.250 g (1.12 mmol) of 6-(4-chlorophenyl)-4 - hydroxy-2H-Piran-2-it, 0,390 g (1.35 mmol) of complex ventilago p-toluoldisocyanate, 0,31 ml (2,24 mmol) of triethylamine and 10.0 ml of ethanol.

1H-NMR (400 MHz, DMSO-d6): = 12,085 (Shir.s, 1H), 7,827 (d, 2H, J=9 Hz), 7,605 (d, 2H, J = 9 Hz), 7,259 - 7,142 (m, 5H), 6,830 (s, 1H), 3,017 (t, 2H, J = 7.5 Hz), 2,785 (t, 2H, J = 7.5 Hz).

Example 8

4-hydroxy-6-phenyl-3-[(phenylmethyl)]thio]-2H-Piran-2-he

The target connection get method And using of 1.00 g (5,19 mmol) 1-phenyl-1-(trimethylsilyloxy)ethylene and 0,977 g (3.46 mmol) diethyl ether complex [(phenylmethyl)thio] - proponderance acid. So pl. 155-160oC.

1H-NMR (250 MHz, DMSO-d6): = 4,00 (s, 2H), 6,74 (s, 1H), 7.23 percent (m, 5H), 7,53 (m, 3H), 7,78 (m, 2H).

Example 9

4-hydroxy-6-phenyl-3-[(phenylmethyl)amino]-2H-Piran-2-he

The target connection get method G using 0,500 g (of 2.08 mmol) of the hydrochloride of 3-amino-4-hydroxy-6-phenyl-2H-Piran-2-it, 1% acetic acid in 20 ml of dimethylformamide, 0,233 ml (to 2.29 mmol) of benzaldehyde and 0,144 g (to 2.29 mmol) of cyanoborohydride, 3H), to 7.67 (m, 2H).

Example 10

N-(1,1-dimethylethyl)-N'-(4-hydroxy-2-oxo-6-phenyl-2H - Piran-3-yl)-N"-(phenylmethyl)urea

To a suspension 0,153 mmol of monohydrochloride 4-hydroxy-6-phenyl-3- (phenylmethyl)-amino-2H-Piran-2-it in 10 ml of ethyl acetate added to 2.0 ml of N-methylmorpholine and 2.0 ml of tert.utilizationof. The reaction mixture is stirred for 2.5 hours and diluted with ethyl acetate. The organic layer was washed with 5% citric acid and saturated sodium chloride and dried over anhydrous magnesium sulfate. After evaporation of the solvent in vacuum the crude product is purified by column chromatography on silica gel with a particle size of 230 - 400 mesh using as eluent dichloromethane to 5% methanol.

1H-NMR (250 MHz, DMSO-d6): = 1,24 (s, N), 4,47 (DD, 2H), 5,45 (Shir.s, 1H), 7.23 percent (m, 5H), 7,51 (m, 3H), of 7.75 (m, 2H).

Example 11

4-hydroxy-3-[(2-naphthalenyloxy)thio]-6-phenyl-2H - Piran-2-he

The target connection get method And using value (0.475) r (2,46 mmol) 1-phenyl-1-(trimethylsilyloxy)ethylene 0,500 g (1,64 mmol) dimethyl ether complex [(2-naphthalenyloxy)thio]proponderance acid. So pl. > 250oC (decomp.).

1H-NMR (250 MHz, DMSO-d6): = 4,06 (s, 2H), 6,47 (s, 1H), 7,46 (m, 6N), 7,78 (m, 6N).

Example the eating of 1.33 g (6,90 mmol) 1-phenyl-1-(trimethylsilyloxy)ethylene and 2.00 r (6,29 mmol) diethyl ether complex [(2-naphthalenyl)thio]proponderance acid. So pl. 246oC (decomp.).

1H-NMR (250 MHz, DMSO-d6): = 6,95 (1), 7,38 (m, 3H), 7,56 (m, 4H), a 7.85 (m, 5H).

Example 13

4-hydroxy-3-[(phenylmethyl)thio]-6-(2,4,6-trimetilfenil)-2H-Piran-2-he

The target connection get method And with the use of 1.86 g (11.5 mmol) 2',4',6'- trimethylacetate, 2,11 r (12,65 mmol) of bis(trimethylsilyl)amide lithium, 1.60 ml (12,65 mmol) of chlorotrimethylsilane, 127 ml of tetrahydrofuran and 2.95 g (10.4 mmol) diethyl ether complex [(phenylmethyl)thio]proponderance acid. So pl. 134 - 136oC.

1H-NMR (250 MHz, DMSO-d6): = 2,11 (C, 6N), and 2.26 (s, 3H), 3,98 (s, 2H), 6,03 (s, 1H), of 6.96 (s, 2H), 7,25 (m, 5H), 11,85 (Shir.s,1H).

Example 14

4-hydroxy-6-[4-[2-(4-morpholinyl)ethoxy] phenyl]-3- [(phenylmethyl)thio]- 2H-Piran-2-he

The target connection get by method A using 1,31 r (from 5.29 mmol) 4'-[2-(4-morpholinyl) ethoxy]acetophenone, 0,972 r (of 5.81 mmol) of bis(trimethylsilyl)amide lithium 0,738 ml (of 5.81 mmol) of chlorotrimethylsilane, 58 ml of tetrahydrofuran and 1.35 g (4,80 mmol) diethyl ether complex [(phenylmethyl)thio] proponderance acid. So pl. 207oC (decomp.).

1H-NMR (250 MHz, DMSO-d6): = 2,54 (s, 2H), 6.89 in (m, 4H), and 2.83 (t, 2H), 3,55 (m, 4H), of 3.96 (s, 2H), 4,22 (t, 2H), return of 6.58 (s, 1H), was 7.08 (d, 2H), 7.23 percent (m, 5H), 7,73 (d, 2H).

Example 15

4-oxg (11.6 mmol) of 2-acetonaphthone, 2,13 g (of 12.76 mmol) of bis(trimethylsilyl)amide lithium, to 1.61 ml (of 12.76 mmol) of chlorotrimethylsilane, 127 ml of tetrahydrofuran and 2,90 g (10.5 mmol) diethyl ether complex [(phenylmethyl)- thio]proponderance acid. So pl. 203oC (decomp.).

1H-NMR (250 MHz, DMSO-d6): = Android 4.04 (s, 2H), 6.89 in (s, 1H), 7.23 percent (m, 5 H), to 7.61 (m, 2H), to 7.84 (d, 2H), with 8.05 (m, 3H), 8,43 (s, 1H), 11,95 (Shir.s, 1H).

Example 16

4-hydroxy-6-phenyl-3-[(phenylthio)methyl]-2H-Piran-2-he

The target connection get method with the use of 1.00 g (5,31 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 10 ml of ethanol, 0,175 g (5,80 mmol) of paraformaldehyde, 1,40 ml (to 13.8 mmol) thiophenol, 0.5 ml of piperidine and 0.5 ml of acetic acid. So pl. 211oC (decomp.).

1H-NMR (400 MHz, DMSO-d6): = 3,98 (s, 2 H), 6.73 x (s, 1H), 7,17 (m, 1H), 7,30 (m, 2H), 7,37 (m, 2H), 7,54 (m, 3H), to 7.77 (m, 2H), 12,05 (Shir.s, 1H).

Example 17

4-hydroxy-6-(4 oksifenil)-3-[(phenylmethyl)thio]-2H-Piran-2-he

The target connection get by method A using 0,722 g (5,31 mmol) 4'-oxazolidinone, 1,95 g (11.6 mmol) of bis(trimethylsilyl)-amide lithium, to 1.48 ml (11.6 mmol) of chlorotrimethylsilane, 116 ml of tetrahydrofuran and 1.00 g (3.54 mmol) in diethyl ether complex [(phenylmethyl)thio]proponderance acid. So pl. 204oC (decomp.).

1H-NMR (250 MHz, DMSO-d6)xifei)-3-[(phenylmethyl)thio]-2H-Piran-2-he

The target connection get method And using 0,797 g (5,31 mmol) 4'-methoxyacetophenone, 0,977 r (of 5.84 mmol) of bis(trimethylsilyl)amide lithium, of 0.741 ml (of 5.84 mmol) of chlorotrimethylsilane, 58 ml of tetrahydrofuran and 1.00 g (3.54 mmol) in diethyl ether complex [(phenyl-methyl)thio]proponderance acid. So pl. 187oC (decomp.).

1H-NMR (400 MHz, DMSO-d6): = a 3.83 (s, 3H), 3,98 (s, 2H), 6,62 (s, 1H), 7,06 (m, 2H), 7,22 (m, 5H), 7,73 (m, 2H), 11,76 (Shir.s, 1H).

Example 19

4-hydroxy-6-(4-were)-3-[(phenylmethyl)thio]-2H - Piran-2-he

The target connection get method And using 0,712 r (5,31 mmol) 4'-methylacetophenone, 0,977 r (of 5.84 mmol) of bis(trimethylsilyl)-amide lithium, of 0.741 ml (of 5.84 mmol) of chlorotrimethylsilane, 58 ml of tetrahydrofuran and 1.00 g (3.54 mmol) in diethyl ether complex [(phenylmethyl)thio]proponderance acid. So pl. 205oC (decomp.).

1H-NMR (400 MHz, DMSO-d6): = is 2.37 (s, 3H), 3,99 (s, 2H), 6,69 (s, 1H), 7,26 (m, 7H), to 7.68 (m, 2H), 11,83 (Shir.s,1H).

Example 20

3-[bis(phenylmethyl)amino]-4-hydroxy-6-phenyl-2H-Piran - 2-he

The target connection get method G using 0,150 g (0,626 mmol) of the hydrochloride of 3-amino-4-hydroxy-6-phenyl-2H-Piran-2-it, 1% acetic acid in 7 ml of dimethylformamide, of 0.133 ml of 1.33 mmol) of benzaldehyde and 0,083 ml (1,3 (, 1H), 7,24 (m, 6N), 7,44 (m, 7H), of 7.69 (m, 2H).

Example 21

4-hydroxy-6-phenyl-3-[(2-phenylethyl)thio]-2H-Piran-2-he

The target connection get by method B using 0,500 g (to 2.65 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 7 ml of ethanol, to 2.65 ml of 1 N. sodium hydroxide and 0,770 g (to 2.65 mmol) of complex 2-phenethyl ester p-toluoldisocyanate. So pl. 121 - 124oC.

1H-NMR (400 MHz, DMSO-d6): = 2,78 (t, 2H), 2,99 (t, 2H), 6,80 (s, 1H), from 7.24 (m, 5H), 7,54 (m, 3H), 7,80 (m, 2H).

Example 22

4-hydroxy-6-phenyl-3-[(3-phenylpropyl)thio]-2H-Piran-2-he

The target connection get method And using 0,922 g (a 4.83 mmol) 1-phenyl-1-(trimethylsilyloxy)ethylene and 1.00 g (3,22 mmol) diethyl ether complex [(3-phenylpropyl)thio] proponderance acid. So pl. 114-116oC.

1H-NMR (400 MHz, DMSO-d6): = 1,74 (m, 2H), 2,71 (m, 4H), PC 6.82 (m, 1H), 7,16 (m, 3H), 7,25 (m, 2H), 7,54 (m, 3H), 7,81 (m, 2H), 11,95 (Shir.s, 1H).

Example 23

4-hydroxy-3-[(2-phenoxyethyl)thio]-6-phenyl-2H-Piran-2-he

The target connection get by method B using 0,500 g (to 2.65 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 7 ml of ethanol, to 2.65 ml (approximately 2.65 mmol) 1-N. of sodium hydroxide, 0,816 r (2,65 mmol) of complex 2-Phenoxyethanol ether p-toluoldisocyanate. So pl. 146 - 149oC.

1H-NMR (400 MHz, BR> 4-hydroxy-6-(2-were)-3-[(phenylmethyl)thio]-2H - Piran-2-he

The target connection get method And using 0,712 r (5,31 mmol) 2'-methylacetophenone, 0,977 r (of 5.84 mmol) of bis(trimethylsilyl)-amide lithium, of 0.741 ml (of 5.84 mmol) of chlorotrimethylsilane, 58 ml of tetrahydrofuran and 1.00 g (3.54 mmol) in diethyl ether complex [(phenylmethyl)-thio]proponderance acid.

1H-NMR (400 MHz, DMSO-d6): = of 2.34 (s, 3H), 4,01 (s, 2H), 6,32 (s, 1H), 7,32 (m, N).

Example 25

4-hydroxy-6-(2-phenylethyl)-3-[(phenylmethyl)thio]-2H - Piran-2-he

The target connection get method And with the use of 0.786 g (5,31 mmol) of 4-ventilationa, 0,977 g (of 5.84 mmol) of bis(trimethylsilyl)amide lithium, of 0.741 ml (of 5.84 mmol) of chlorotrimethylsilane, 58 ml of tetrahydrofuran and 1.00 g (3.54 mmol) in diethyl ether complex [(phenylmethyl)-thio]proponderance acid. So pl. 164 - 166oC.

1H-NMR (400 MHz, DMSO-d6): = 2,75 (t, 3H), 2,85 (t, 2H), 3,92 (s, 2H), of 5.92 (s, 1H), 7.23 percent (m, N), of 11.69 (Shir.s, 1H).

Example 26

4-hydroxy-6-(3 oksifenil)-3-[(phenylmethyl)thio]-2H - Piran-2-he

The target connection get method And using 0,722 g (5,31 mmol) 3'-oxazolidinone, 1,95 g (11.6 mmol) of bis(trimethylsilyl)-amide lithium, to 1.48 ml (11.6 mmol) of chlorotrimethylsilane, 116 ml of tetrahydrofuran and 1.00 g (3,54 2">

1H-NMR (400 MHz, DMSO-d6): = 4,00 (s, 2H), 6,66 (s, 1H), 6,92 (m, 1H), 7,21 (m, 7H), 7,32 (m, 1H).

Example 27

4-hydroxy-6-(4 oksifenil)-3-[(phenylethyl)thio]-2H - Piran-2-he

The target connection get method And using 0,688 g (of 5.06 mmol) 4'-oxazolidinone, 1.84 g (11.1 mmol) of bis(trimethylsilyl)- amide lithium, of 1.41 ml (11.1 mmol) of chlorotrimethylsilane, 111 ml of tetrahydrofuran and 1.00 g (3,37 mmol) diethyl ether complex [(2-phenylethyl)thio]proponderance acid.

1H-NMR (400 MHz, DMSO-d6): = 2,78 (t, 2 H), 2.95 and (t, 2H), 6,62 (s, 1H), 6.89 in (DD, 2H), 7,21 (m, 5H), the 7.65 (d, 2H), 10,22 (s, 1H), 11,05 (Shir.s, 1H).

Example 28

(E)-4-hydroxy-6-phenyl-3-[3-(phenyl-2-propenyl)thio]-2H - Piran-2-he

The target connection get by method B using 0,500 g (to 2.65 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 7 ml of ethanol, to 2.65 ml of 1 N. sodium hydroxide and 0,808 g (to 2.65 mmol) of complex 3 - phenyl-2-propilovogo ether p-toluoldisocyanate. So pl. 133 - 136oC.

1H-NMR (400 MHz, DMSO-d6) = 3,57 (d, 2 H), 6,24 (dt, 2H), 6,76 (s, 1H), from 7.24 (m, 5H), 7,51 (m, 3H), 7,78 (m, 2H).

Example 29

4-hydroxy-3-[(2-phenylethyl)thio]-6-[4-(phenylmethoxy)phenyl]-2H - Piran-2-he

The target connection get method And with the use of 1.14 g (of 5.06 mmol) 4'- benzyloxyacetophenone, 0.930 g (5,56 mmol) of bis (is th diethyl ether [(2-phenyl-ethyl)thio] proponderance acid. So pl. 139 - 142oC.

1H-NMR (400 MHz, DMSO-d6) = 2,77 (t, 2H), 2,98 (t, 2H), 5,19 (s, 2H), of 6.68 (s, 1H), 7,26 (m, 7H), the 7.43 (m, 5H), 7,76 (d, 2H).

Example 30

4-hydroxy-6-[4-(2-phenylethane)phenyl]-3-[(2-phenylethyl)thio]- 2H-Piran-2-he

The target connection get method And with the use of 1.21 g (of 5.06 mmol) of 4'-(2-phenylethane)of acetophenone, 0.930 g (5,56 mmol) of bis(trimethylsilyl)amide lithium 0,705 ml (5,56 mmol) of chlorotrimethylsilane, 57 ml of tetrahydrofuran and 1.00 g (3,37 mmol) diethyl ether complex [(2-phenyl-ethyl)thio]proponderance acid. So pl. 103 - 106oC.

1H-NMR (400 MHz, DMSO-d6): = was 2.76 (t, 2H), 2,97 (t, 2H), 3,06 (t, 2H), 4,27 (t, 2H), to 6.67 (s, 1H), 7,21 (m, N), 7,73 (d, 2H).

Example 31

4-hydroxy-3-[(2-phenylethyl)thio]-6-[4-(3-phenylpropoxy)phenyl]-2H - Piran-2-he

The target connection get method And using 1.28 g (of 5.06 mmol) of 4'-(3-phenylpropoxy)of acetophenone, 0.930 g (5,56 mmol) of bis(trimethylsilyl)amide lithium 0,705 ml (5,56 mmol) of chlorotrimethylsilane, 57 ml of tetrahydrofuran and 1.00 g (3,37 mmol) diethyl ether complex [(2-phenylethyl)thio]proponderance acid. So pl. 139 - 142oC.

1H-NMR (400 MHz, DMSO-d6): = 2,04 (m, 2H), 2,84 (m, 4H), 2,98 (t, 2H), and 4.40 (t, 2H), of 6.68 (s, 1H), 7,18 (m, N), of 7.75 (d, 2H), up 11,86 (Shir.s, 1H).

Example 32

4-OK is 2 r (5,31 mmol) 2'-oxazolidinone, 1,95 g (11.6 mmol) of bis(trimethylsilyl)amide lithium, to 1.48 ml (11.6 mmol) of chlorotrimethylsilane, 116 ml of tetrahydrofuran and 1.00 g (3.54 mmol) in diethyl ether complex [(phenylmethyl)thio] proponderance acid. So pl. 189oC (decomp.).

1H-NMR (400 MHz, DMSO-d6): = 4,01 (s, 2H), 6,97 (s, 1H), 7,25 (m, 7H), 7,71 (d, 1H), 10,75 (s, 1H), 11,85 (Shir.s, 1H).

Example 33

4-hydroxy-6-[3-(2-phenylethane)phenyl]-3-[(2-phenylethyl)thio]-2H - Piran-2-he

The target connection get method And using 0,336 g (1,40 mmol) 3'-(2-phenylethane)of acetophenone, 0,257 g (1.54 mmol) of bis(trimethylsilyl)amide lithium, of € 0.195 ml (1.54 mmol) of chlorotrimethylsilane, 15 ml of tetrahydrofuran and 0,417 g (1,40 mmol) diethyl ether complex [(2-phenylethyl)thio] proponderance acid. So pl. 104 - 106oC.

1H-NMR (400 MHz, DMSO-d6): = a 2.75 (t, 2H), 2,97 (t, 2H), 3.04 from (t, 2H), 4,25 (t, 2H), 6,79 (s, 1H), 7,25 (m, 14N), 11,95 (Shir.s, 1H).

Example 34

(+/-)-4-hydroxy-6-phenyl-3-[phenyl(phenylthio)methyl]-2H-Piran-2-he

The target connection get method D using 1,00 g (5,31 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 10 ml of ethanol, 0,593 ml (of 5.84 mmol) of benzaldehyde, 1,40 ml (to 13.8 mmol) thiophenol, 0.5 ml of piperidine and 0.5 ml of acetic acid. So pl. > 220oC (decomp.).

1H-NMR (400 MHz, DMSO-d6phenyl-2H-Piran-2-he

The target connection get by method B using 0,500 g (to 2.65 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 7 ml of ethanol, to 2.65 ml of 1 N. sodium hydroxide, 0,856 g (to 2.65 mmol) complex of 2-(2-methoxyphenyl)ethyl ester of n-toluoldisocyanate. So pl. 114 - 115oC

1H-NMR (400 MHz, DMSO-d6): = is 2.74 (t, 2 H), to 2.94 (t, 2H), of 3.73 (s, 1H), 6,85 (m, 3H), 7,15 (m, 2H), 7,54 (m, 3H), 7,82 (m, 2H).

Example 36

4-hydroxy-6-phenyl-3-[(4-phenylbutyl)thio]-2H-Piran-2-he

The target connection get by method B using 0,500 g (to 2.65 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 7 ml of ethanol, to 2.65 ml of 1 N. sodium hydroxide, 0,851 g (to 2.65 mmol) of complex 4 - phenylbutyramide ether p-toluoldisocyanate. So pl. 103 - 105oC.

1H-NMR (400 MHz, DMSO-d6): = 1,47 (m, 2H), of 1.66 (m, 2H), 2,54 (t, 2H), 2,77 (t, 2H), 6,80 (s, 1H), 7,17 (m, 5H), 7,53 (m, 3H), 7,81 (m, 2H).

Example 37

4-hydroxy-3-[[2-(3-methoxyphenyl)ethyl]thio]-6-phenyl-2H - Piran-2-he

The target connection get by method B using 0,500 g (to 2.65 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 7 ml of ethanol, to 2.65 ml of 1 N. sodium hydroxide, 0,856 g (to 2.65 mmol) complex of 2- (3-methoxyphenyl)ethyl ester of n-toluoldisocyanate. So pl. 112 - 113oC.

1H-NMR (400 MHz, DMSO-d6): = a 2.75 (t, 2H), 3,01 (t, 2H), 3,34 (s, 3H), 6.75 in (s, 1H), 7,16 (t, 1H), 7,54 (m, 3H), 7,80 (m, 2 which are square method B using 0,500 g (to 2.65 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 7 ml of ethanol, to 2.65 ml of 1 N. sodium hydroxide, 0,856 g (to 2.65 mmol) complex of 2- (4-methoxyphenyl)ethyl ester of n-toluoldisocyanate. So pl. 144 - 145oC.

1H-NMR (400 MHz, DMSO-d6): = a 2.71 (t, 2H), 2,96 (t, 2H), 3,66 (s, 3H), 6,77 (s, 1H), 6,80 (d, 2H), 7,12 (d, 2H), 7,54 (m, 3H), 7,80 (m, 2H).

Example 39

3-[[2-(3-chlorophenyl)ethyl]thio]-4-hydroxy-6-phenyl-2H-Piran-2-he

The target connection get by method B using 0,500 g (to 2.65 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 7 ml of ethanol, to 2.65 ml of 1 N. sodium hydroxide, 0,868 g (to 2.65 mmol) complex of 2- (2-chlorophenyl)ethyl ester of n-toluoldisocyanate. So pl. 133 - 134oC.

1H-NMR (400 MHz, DMSO-d6): = and 2.79 (t, 2H), to 3.02 (t, 2H), 6,77 (s, 1H), 7,25 (m, 4H), at 7.55 (m, 3H), 7,81 (m, 2H).

Example 40

6-(2,6-dimetilfenil)-4-hydroxy-3-[(phenylmethyl)thio]- 2H-Piran-2-he

The target connection get method And using 0,785 g (5,31 mmol) 2', 6'-dimethylacetophenone, 0,977 g (of 5.84 mmol) of bis(trimethylsilyl)amide lithium, of 0.741 ml (of 5.84 mmol) of chlorotrimethylsilane, 58 ml of tetrahydrofuran and 1.00 g (3.54 mmol) in diethyl ether complex [(phenyl-methyl)thio]proponderance acid. So pl. 140 - 143oC.

1H-NMR (400 MHz, DMSO-d6): = 2,15 (C, 6N), to 3.99 (s, 2H), 6,12 (s, 1H), 7,22 (m, 8H).

Example 41

4-hydroxy-6-[2-hydroxy-3-METI is the group of 1.29 g (of 5.06 mmol) of 4'-(benzyloxy-2'- hydroxy-3'-methylacetophenone), 2,11 g (12.6 mmol) of bis(trimethylsilyl)amide lithium, 1.60 ml (12.6 mmol) of chlorotrimethylsilane, 127 ml of tetrahydrofuran and 1.00 g (3,37 mmol) diethyl ether complex [(2-phenylethyl)thio] proponderance acid. So pl. 147 - 148oC.

1H-NMR (400 MHz, DMSO-d6): = and 2.14 (s, 3H), 2,77 (t, 2H), 2,98 (t, 2H), 5,17 (s, 2H), from 5.29 (s, 1H), 6,79 (d, 1H), 7,30 (m, 13H), 9,36 (s, 1H), 11,85 (Shir.s, 1H).

Example 42

4-hydroxy-3-[(2-phenylethyl)thio]-6-[3-(phenylmethoxy)phenyl]-2H-Piran - 2-he

The target connection get method And with the use of 1.14 g (of 5.06 mmol) 3'-benzyloxyacetophenone, 0.930 g (5,56 mmol) of bis (trimethylsilyl)-amide lithium 0,705 ml (5,56 mmol) of chlorotrimethylsilane, 57 ml of tetrahydrofuran and 1.00 g (3,37 mmol) diethyl ether complex [(2-phenyl-ethyl)thio]proponderance acid. So pl. 126 - 127oC.

1H-NMR (400 MHz, DMSO-d6): = 2,78 (t, 2H), 3,01 (t, 2H), 5,20 (s, 2H), for 6.81 (s, 1H), 7,22 (m, 6N), 7,41 (m, 7H).

Example 43

4-hydroxy-6-[4-(2-naphthalenyloxy)phenyl] -3-[(2-phenylethyl)thio] -2H - Piran-2-he

The target connection get method And with the use of 1.39 g (of 5.06 mmol) of 4'-(2 - naphthalenyloxy)of acetophenone, 0.930 g (5,56 mmol) of bis(trimethylsilyl)amide lithium 0,705 ml (5,56 mmol) of chlorotrimethylsilane, 57 ml of tetrahydrofuran and 1.00 g (3,37 mmol) diethyl ether complex [(2-Fe (t, 2 H), 2,98 (t, 2H), 5,38 (s, 2H), of 6.68 (s, 1H), 7,21 (m, 7H), 7,54 (m, 2H), 7,60 (d, 1H), of 7.96 (m, 4H).

Example 44

6-(3-chloro-4-methoxyphenyl)-4-hydroxy-3- [(phenylmethyl)thio]-2H-Piran-2-he

The target connection get method And using 0,979 g (5,31 mmol) 3'-chloro-4'-methoxyacetophenone, 0,977 g (of 5.84 mmol) of bis(trimethylsilyl)amide lithium, of 0.741 ml (of 5.84 mmol) of chlorotrimethylsilane, 58 ml of tetrahydrofuran and 1.00 g (3.54 mmol) in diethyl ether complex [(phenyl-methyl)thio]proponderance acid. So pl. 171oC (decomp.).

1H-NMR (400 MHz, DMSO-d6): = 3,93 (s, 3H), 3,99 (s, 2H), of 6.68 (s, 1H), 7,32 (m, 6N), to 7.77 (d, 1H), 7,83 (d, 1H).

Example 45

4-hydroxy-6-phenyl-3-[(phenylmethyl)sulfonyl]-2H-Piran - 2-he

This compound is produced by oxidation of 310 mg (1 mmol) 4-hydroxy-6-phenyl-3-[(phenylmethyl)thio] -2H-Piran-2-it 1,99 g (3 mmol) oxone at room temperature in 10 ml of methanol and 10 ml of water. After stirring at room temperature for 4 hours, the reaction mixture was diluted with water and extracted with 50 ml dichloromethane. The organic layer is dried over anhydrous magnesium sulfate. The solvents are evaporated and the residue purified by thin-layer chromatography to obtain a solid product.

Yield: 90 %. So pl. 152 - 153oC.

1H-NMR (40 3059, 1726, 1698, 1628, 1559, 1497, 1230, 957, 770, 689 cm-1; MC (AP) m/e 343 (6,8), 327 (15,54), 278 (15,99), 219 (40,99), 91 (100).

Example 46

4-hydroxy-6-(3-were)-3-[(phenylmethyl)thio]-2H - Piran-2-he

This compound is obtained condensing 1 g (3.54 mmol) in diethyl ether complex [(phenylmethyl)thio]- proponderance acid of 1.46 g (to 7.09 mmol) of the corresponding trimethylsilyl-analoog ether 3'-methylacetophenone described in the General method As follows.

Yield: 65 %. So pl. 137 - 138oC.

1H-NMR (400 MHz, DMSO-d6): = 11,9 (Shir.s, 1H), 7,6 (m, 2H), 7,39 (t, 1H), 7,35 (d, 1H), 7,25 (d, 4H), 7,2 (m, 1H), 6,7 (s, 1H), 4,0 (s, 2H), of 2.38 (s, 3H); IR (KBr) 3030, 2585, 1617, 1536, 1402, 1100, 787, 696 cm-1; MS (AP) m/e 325 (65), 291 (2), 233 (4), 119 (9), 91 (100).

Example 47

Ester 2-oxo-6-phenyl-3-[(phenylmethyl)thio]- 2H-Piran-4-yl - propionic acid

This connection is produced by means of processing 310 mg (1 mmol) of sodium salt of 4-hydroxy-6-phenyl-3-[(phenylmethyl)thio]-2H-Piran-2-it 222 mg (2.4 mmol) of Propionaldehyde described in method E way. Yield: 72%.

1H-NMR (400 MHz, DMSO-d6): = to 7.77 (m, 2H), 7,51 (m, 3H), 7,22 (m, 4H), 7,17 (m, 1H), 6,7 (s, 1H), 3,98 (s, 2H), 2,19 (kV, 2N), is 0.96 (t, 3H); IR (KBr) 3438, 3027, 2923, 1772, 1731, 1617, 1528, 1494, 1453, 1323, 1153, 1087, 1045, 979, 873, 767, 702 cm-1; MS (AP) m/e 366 (4), 311 (79), 189 (26), 105 (20), 91 (100).

oC.

1H-NMR (400 MHz, DMSO-d6): = 7,63 (m, 2H), 7,11 - 7,53 (m, 11N), of 6.68 (s, 1H), 5,22 (s, 1H), 2,98 (t, 2H), 2,77 (t, 2H), and 2.27 (s, 3H): IR (KBr) 3432, 3030, 2922, 1717, 1626, 1503, 1408, 1262, 1140, 1024, 696 cm-1; MS (AP) m/e 445 (2,12), 3553,34, 309 (3,81), 189 (8,33), 156 (14,78), 137 (16,19), 105 (94,34), 91 (100);

calculated: 72,95; N 5,44:

found: 72,25; N 5,43.

Example 49

4-hydroxy-6-(4-hydroxy-2-were)-3-[2 - phenylethyl)thio]-2H-Piran-2-he

This compound is obtained condensing 1 g (3,38 mmol) diethyl ether complex [(phenylethyl)thio]proponderance acid 2,94 r (10 mmol) of the corresponding simple trimethylsilyl - analoog ether 4'-hydroxy-2'-methylacetophenone described in the method And manner. Yield: 52%. So pl. 85 - 87oC.

1H-NMR (400 MHz, DMSO-d6): = 11,89 (Shir.s, 1H), becomes 9.97 (s, 1H), 7,35 (d, 1H), 7.23 percent (m, 5H), 6,72 (s, 2H), 6,33 (s, 1H), 3,0 (t, 2H), 2,78 (t, 2H), 2,34 (C, ZN); IR (KBR) 3300, 2926, 1672, 1604, 1541, 1244, 1194, 1120, 698 cm-1; MS (AP) m/e 355 (36), 250 (27),105 (93), 91 (30), 85 (100);

calculated: 67,78; N 5,12;

found: 67,53; N. of 5.40.

Example 50

4-hydroxy-6-(4-methoxy-3-were)-3-[(phenylmethyl)thio]-2H - Piran-2-he

This compound is obtained condensing 1 g diethyl ether complex [(phenylmethyl)thio] proponderance acid with the corresponding simple SUP>oC.

1H-NMR (400 MHz, CDCl3): = to 7.67 (DD, 1H), to 7.61 (s, 1H), 7,2 (m, 5H), 6,8 (d, 1H), 6,38 (s, 1H), 3.96 points (s, 2H), with 3.89 (s, 3H), of 2.25 (s, 3H): IR (KBR) 3432, 2945, 1613, 1507, 1402, 1262, 1142, 1030, 812, 704 cm-1; MS (AP) m/e 355 (78,3), 263 (19,6), 235 (11,8), 149 (12,7), 91 (100):

calculated: 67,78; N 5,12:

found: 67,35; N 5,17.

Example 51

Ester 2-oxo-6-phenyl-3-[(phenylmethyl)thio]- 2H-Piran-4-yl-acetic acid

This connection is produced by means of processing 310 mg (1.00 mmol) of sodium salt of 4-hydroxy-6 - phenyl-3-[(phenylmethyl)thio]-2H-Piran-2-it 188 mg (2.4 mmol) of acetylchloride described in method E.

Yield: 72%.

1H-NMR (400 MHz, DMSO-d6): = 7,81 (m, 2H), 7,53 (m, 3H), 7,22 (m, 4H), 7,16 (m, 1H), 3,99 (s, 2H), 1,92 (s, 3H).

Example 52

Ester 2-oxo-6-phenyl-2H-Piran-4-yl-1 - naphthaleneboronic acid

Connection get by method E using 0,250 g (1,32 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 15ml of tetrahydrofuran, 0,585 g (of 1.46 mmol) of 60% sodium hydride and 0,278 g (of 1.46 mmol) 1-naphtol-chloride. So pl. to 123.5-125oC.

1H-NMR (250 MHz, DMSO-d6): equals 6.54 (s, 1H), 7,49 (s, 1H), 7,65 (m, 6N), to 7.95 (m, 2H), 8,13 (d, 1H), 8.34 per (d, 1H), and 8.50 (d, 1H).

Example 53

3,3'-THIOBIS[4-hydroxy-6-phenyl-2H-Piran-2-it]

This compound is synthesized according to the following methodol stirred at room temperature overnight. Unreacted thionyl chloride is removed in vacuo and the residue will recrystallized from boiling methanol. So pl. > 240oC.

1H-NMR (250 MHz, d-THF): = 7,03 (s, 2H), 7,56 (m, 6N), 7,89 (m, 4H).

Example 54

3,3'-dithiobis[4-hydroxy-6-phenyl-2H-Piran-2-it]

0,105 ml (1,32 mmol) polularity sulfur dissolved in 1 ml of benzene. The solution was added dropwise to a suspension 0,500 g (to 2.65 mmol) 4-hydroxy-6 - phenyl-2H-Piran-2-7 ml of benzene while heating under reflux for 1.5 hours. The reaction mixture is mixed with a few drops of water and light the dark product is collected by filtration. Solid material is recrystallized from boiling acetic acid. So pl. > 280oC (decomp.).

1H-NMR (250 MHz, DMSO-d6): = 6,77 (s, 2H), 7,52 (m, 6N), 7,81 (m, 4 H).

Example 55

3-benzoyl-4-hydroxy-6-phenyl-2H-Piran-2-he

To a solution of 150 g (0.88 mmol) of ethylbenzylamine in 150 ml of 1,2-dichlorobenzene is added a small amount of sodium bicarbonate. The reaction mixture is heated under reflux. Collect approximately 20 ml of ethanol distillate. The reaction mixture was cooled to 0oC, then add 100 ml of diethyl ether to induce crystallization. The reaction mixture was stored in was built. 71 - 173oC .

1H-NMR (250 MHz, DMSO-d6): = 6,91 (s, 1H), to 7.59 (m, 6N), 7,87 (m, 4H).

Example 56

N -(4-hydroxy-2-oxo-6-phenyl-2H-Piran-3-yl)benzoylacetate

The target connection get method D using 0,150 g (0,626 mmol) of the hydrochloride of 3-amino-4-hydroxy-6 - phenyl-2H-Piran-2-it, 6 ml of methylene chloride, 0,348 ml (2,50 mmol) of triethylamine, and a catalytic amount of 4-dimethylaminopyridine and 0,106 g (0,626 mmol) fence-tallarida. So pl. 213oC (decomp.).

1H-NMR (250 MHz, DMSO-d60): = of 3.69 (s, 2H), 6,85 (s, 1H), 7,29 (m, 4H), 7,53 (m, 3 H), 7,83 (m, 2H), 9,40 (Shir.s, 1H).

Example 57

Ester 2-oxo-6-phenyl-2H-Piran-4-yl-2-naphthaleneboronic acid

The target connection get by method E using 0,200 g (0,835 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 8 ml of methylene chloride, 0,348 ml (2,50 mmol) of triethylamine, and a catalytic amount of 4-dimethylaminopyridine and 0,175 g (0,918 mmol) of 2-nafolklore. So pl. 143,5 - 144oC (decomp.).

1H-NMR (250 MHz, DMSO-d6): = 6,51 (s, 1H), 7,51 (m, 3H), 7,72 (m, 3H), 8,80 (m, 7H), 8,89 (Shir.s, 1H).

Example 58

3-[bis(2-naphthalenyloxy)amino]-4-hydroxy-6-phenyl-2H - Piran-2-he

The target connection get method G using 0,250 g (1.04 mmol) of the hydrochloride of 3-amino-4-OK mmol) cyanoborohydride sodium. So pl. 209oC (decomp.).

1H-NMR (250 MHz, DMSO-d6): = 4,46 (s, 4H), 6,38 (s, 1H), 7,44 (m, 8H), to 7.77 (m, 13H).

Example 59

N-(4-hydroxy-2-oxo-6-phenyl-2H-Piran-3-yl)-2 - naphthaleneacetic

The target connection get method D using 0,200 g (0,835 mmol) of the hydrochloride of 3-amino-4-hydroxy-6 - phenyl-2H-Piran-2-it, 9 ml of tetrahydrofuran, 0.037 ml (0,918 mmol) of 60% sodium hydride, 0,080 ml (0,918 mmol) oxalicacid and 0,170 g (0,918 mmol) 2-naftiluksusnoi acid. So pl. 227oC (decomp.).

1H-NMR (250 MHz, DMSO-d6): = 4,17 (s, 2H), at 6.84 (s, 1H), 7,50 (m, 6N), 7,83 (m, 4H), to 7.93 (d, 1H), 8,17 (d, 1H), 9,58 (s, 1H).

Example 60

N-(4-hydroxy-2-oxo-6-phenyl-2H-Piran-3-yl)-2-naphthaleneboronic

The target connection get method D using 0,150 g (0,626 mmol) of the hydrochloride of 3-amino-4-hydroxy-6 - phenyl-2H-Piran-2-it, 6 ml of tetrahydrofuran, 0,028 ml (0,688 mmol) of 60% sodium hydride and 0,131 g (0,688 mmol) 2-naphtol-chloride. So pl. 219oC (decomp.).

1H-NMR (250 MHz, DMSO-d6): = 6,92 (s, 1H), to 7.61 (m, 5H), of 7.97 (m, 6N), to 8.62 (s, 1H), being 9.61 (s, 1H).

Example 61

N-(4-hydroxy-2-oxo-6-phenyl-2H-Piran-3-yl)-benzene - propanamide

The target connection get method D using 0,150 r (0,626 mmol) of the hydrochloride of 3-amino-4-hydroxy-6-phenyl-2H - Piran-2-it, 6 moC.

1H-NMR (250 MHz, DMSO-d6): = to 2.65 (t, 2H), 2,89 (t, 2H), 6,86 (s, 1H), 7,26 (m, 5H), 7,53 (m, 3H), to 7.84 (m, 2H), 9.28 are (s, 1H).

Example 62

6-(1,3-benzodioxol-5-yl)-4-hydroxy-3- [(phenylmethyl)thio]-2H-Piran-2-he

The target connection get method And using 0,871 g (5,31 mmol) of 3',4'- (methylenedioxy)of acetophenone, 0,977 g (of 5.84 mmol) of bis(trimethylsilyl)amide lithium, of 0.741 ml (of 5.84 mmol) of chlorotrimethylsilane, 58 ml of tetrahydrofuran and 1.00 g (3.54 mmol) in diethyl ether complex [(phenyl-methyl)thio]proponderance acid. So pl. 170oC (decomp.).

1H-NMR (400 MHz, DMSO-d6): = 3,98 (s, 2H), 6,13 (s, 2H), is 6.61 (s, 1H), 7,05 (d, 2H), 7,27 (m, 7H).

Example 63

6-[4-(benzoyloxy)phenyl]-4-hydroxy-3- [(phenylmethyl)thio]-2H-Piran-2-he

The target connection get method And using 1.27 g (5,31 mmol) 4'-benzyloxyacetophenone, 0,977 g (of 5.84 mmol) of bis(trimethylsilyl)amide lithium, of 0.741 ml (of 5.84 mmol) of chlorotrimethylsilane, 58 ml of tetrahydrofuran and 1.00 r (3.54 mmol) in diethyl ether complex [(phenylmethyl)thio]proponderance acid. So pl. 205oC (decomp.).

1H-NMR (400 MHz, DMSO-d6): = 4,01 (s, 2H), 6.75 in (s, 1H), 7,21 (m, 1H), 7,25 (d, 4H), 7,47 (d, 2H), 7,63 (t, 2H), to 7.77 (t, 1H), of 7.90 (d, 2H), 8,16 (d, 2H).

Example 64

3-[cyclohexyl(phenylthio)methyl who enyl-2H-Piran-2-it, 10 ml of ethanol, 0,707 ml (of 5.84 mmol) cyclohexane-carboxaldehyde, 1,40 ml (to 13.8 mmol) thiophenol, 0.5 ml of piperidine and 0.5 ml of acetic acid. So pl. 87 - 90oC.

1H-NMR (400 MHz, DMSO-d6): = a 1.46 (m, 5H), to 1.61 (m, 4H), of 2.15 (m, 1H), 2,31 (d, 1H), 4.26 deaths (d, 1H), 6,65 (s, 1H), 7,16 (t, 1H), 7,27 (t, 2H), 7,37 (d, 2H), 7,52 (m, 3H), 7,74 (m, 2H), 11,80 (Shir.s, 1H).

Example 65

4-hydroxy-3-[(2-phenylethyl)thio]-6-[4-(phenylthio)- phenyl]-2H-Piran-2-he

The target connection get method And with the use of 1.15 g (of 5.06 mmol) of 4'-(phenylthio)of acetophenone, 0.930 g (5,56 mmol) of bis(trimethylsilyl)- amide lithium 0,705 ml (5,56 mmol) of chlorotrimethylsilane, 56 ml of tetrahydrofuran and 1.00 g (3,37 mmol) diethyl ether complex [(phenylethyl)-thio]proponderance acid. So pl. 120-121oC.

1H-NMR (400 MHz, DMSO-d6): = was 2.76 (t, 2H), 2,98 (t, 2H), 6,72 (s, 1H), from 7.24 (m, 7H), was 7.45 (m, 5H), 7,74 (d, 2H).

Example 66

4-hydroxy-6-[4-[(2-methoxyphenyl)methoxy] phenyl]-3-[(2 - phenylethyl)thio]- 2H-Piran-2-he

The target connection get method And using 1.29 g (of 5.06 mmol) 4'-[(2-methoxyphenyl)methoxy] phenylacetophenone, 0.930 g (5,56 mmol) of bis(trimethylsilyl)amide lithium 0,705 ml (5,56 mmol) of chlorotrimethylsilane, 56 ml of tetrahydrofuran and 1.00 g (3,37 mmol) diethyl ether complex [(2-phenylethyl)thio]proponderance key is (s, 1H), 6,97 (t, 1H), was 7.08 (d, 1H), 7,20 (m, 7H), 7,53 (t, 1H), 7,40 (d, 1H), 7,76 (d, 2H), 11,85 (Shir.s, 1H).

Example 67

4-hydroxy-6-[4-[(2-methoxyphenyl)methoxy] -3-were] - 3- [(2-phenylethyl)thio]-2H-Piran-2-he

The target connection get method And with the use of 1.36 g (of 5.06 mmol) 4'-[(2-methoxyphenyl)methoxy] -3'-methylacetophenone, 0.930 g (5,56 mmol) of bis(trimethylsilyl)amide lithium 0,705 ml (5,56 mmol) of chlorotrimethylsilane, 56 ml of tetrahydrofuran and 1.00 g (3,37 mmol) diethyl ether complex [(2-phenylethyl)thio]proponderance acid. So pl. 170oC (decomp.).

1H-NMR (400 MHz, DMSO-d6): = of 2.25 (s, 3H), 2,77 (t, 2H), 2,97 (t, 2H), of 3.84 (s, 3H), of 5.17 (s, 2H), to 6.67 (s, 1H), 6,98 (t, 1H), of 7.70 (d, 1H), 7,27 (m, 6N), 7,41 (t, 1H), 7,43 (d, 1H), 7,65 (m, 2H), 11,81 (Shir.s, 1H).

Example 68

6-(3, 5dimethylphenyl]-4-hydroxy-3-[(phenylmethyl)thio]- 2H-Piran-2-he

The target connection get method And using 0,785 g (5,31 mmol) of 3', 5'-dimethylacetophenone, 0,977 g (of 5.84 mmol) of bis(trimethylsilyl)-amide lithium, of 0.741 ml (of 5.84 mmol) of chlorotrimethylsilane, 58 ml of tetrahydrofuran and 1.00 g (3.54 mmol) in diethyl ether complex [(phenyl - methyl)thio]proponderance acid. So pl. 170oC (decomp.).

1H-NMR (400 MHz, DMSO-d6): = 2,33 (C, 6N), to 3.99 (s, 2H), to 6.67 (s, 1H), 7,21 (m, 6N), 7,39 (s, 2H).

Example 69

4-hydroxy,07 g (of 5.06 mmol) 4 phenoxyacetophenone, 0.930 g (5,56 mmol) of bis(trimethylsilyl)-amide lithium 0,705 ml (5,56 mmol) of chlorotrimethylsilane, 56 ml of tetrahydrofuran and 1.00 g (3,37 mmol) diethyl ether complex [(2-phenyl-ethyl)thio]proponderance acid. So pl. 127 - 128oC.

1H-NMR (400 MHz, DMSO-d6): ' = 2,77 (t, 2H), 2,99 (t, 2H), 6,72 (s, 1H), 7,18 (m, 10H), 7,46 (t, 2H), 7,82 (d, 2H).

Example 70

4-hydroxy-6-phenyl-3-[[[4-(phenylmethoxy]phenyl]methyl]thio]-2H - Piran-2-he

The target connection get by method B using 0,500 g (to 2.65 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 7 ml of ethanol, to 2.65 ml of 1 N. sodium hydroxide and 1.01 g (to 2.65 mmol) of complex [4-(phenylmethoxy)phenyl]-methyl ester p-toluoldisocyanate. So pl. 185 - 186oC.

1H-NMR (400 MHz, DMSO-d6): = 3,94 (s, 2H), to 5.03 (s, 2H), 6,72 (s, 1H), 6.89 in (d, 2H), 7,18 (d, 2H), 7,34 (m, 5H), 7,46 (m, 3H), 7,80 (m, 3H).

Example 71

4-hydroxy-3-[(2-phenylethyl)thio] -6-[4-(2-pyridinylmethyl)phenyl]- 2H-Piran-2-he

The target connection get method And with the use of 1.14 g (of 5.06 mmol) of 4'-(2-pyridinylmethyl]acetophenone, 0.930 g (5,56 mmol) of bis(trimethylsilyl)amide lithium 0,705 ml (5,56 mmol) of chlorotrimethylsilane, 56 ml of tetrahydrofuran and 1.00 g (3,37 mmol) diethyl ether complex [(2-phenylethyl)thio]proponderance acid. So pl. 179oC (decomp.).

Example 72

Complex ethyl ester 4-[4-hydroxy-2-oxo-3-[(2 - phenylethyl)thio]- 2H-Piran-6-yl]phenoxyalkanoic acid

To 3 ml 0,500 g (1,47 mmol) 4-hydroxy-6-(4 oksifenil)-3- [(2-phenylethyl)thio] -2H-Piran-2-it in methanol add 0,955 g (2,94 mmol) of cesium carbonate. The reaction mixture is stirred for 3 hours and concentrated in vacuum. To the mixture is added 15 ml of dimethylformamide and the residue concentrated in vacuo to dryness. Then the solid product was diluted with 3 ml of dimethylformamide and 0,491 ml (2,94 mmol) Bromeliaceae. The suspension is stirred for 3 hours. The reaction mixture is diluted with 100 ml of ethyl acetate. The organic layer is successively washed with 1-N. hydrochloric acid, water and saturated sodium chloride, then dried over anhydrous magnesium sulfate. The solvents are evaporated in vacuum. The crude product is purified by column flash chromatography on silica with a particle size of 230 - 400 mesh using as eluent first 15% ethyl acetate in hexano, and 50% ethyl acetate in hexano, and then a mixture of ethyl acetate, hexanol and methylene chloride in the ratio 30: 30: 40. So pl. 169-171oC.

1H-NMR (400 MHz, DMSO-d6): = 1,20 (t, 3H), of 2.75 (t, 2H), 2,96 (t, 2H), 4.16 the (q, 2H), to 4.87 (s, 2H is l]-6-phenyl-2H - Piran-2-he

The target connection get method with the use of 1.00 g (5,31 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 10 ml of ethanol, 0,912 g (of 5.84 mmol) 2-naphthaldehyde, 1,40 ml (to 13.8 mmol) thiophenol, 0.5 ml of piperidine and 0.5 ml of acetic acid. So pl. 98 - 101oC.

1H-NMR (400 MHz, DMSO-d6): = 5,96 (s, 1H), 6.73 x (s, 1H), 7,18 (t, 1H), was 7.36 (m, 4H), 7,52 (m, 5H), 7,88 (m, 3H), 8,07 (s, 1H).

Example 74

4-hydroxy-3-[(2-naphthalenethiol)phenylmethyl]-6-phenyl-2H - Piran-2-he

The target connection get method with the use of 1.00 g (5,31 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 10 ml of ethanol, 0,593 ml (of 5.84 mmol) of benzaldehyde, of 2.21 ml (to 13.8 mmol) 2-naphthalenethiol, 0.5 ml of piperidine and 0.5 ml of acetic acid. So pl. 200oC (decomp.).

1H-NMR (400 MHz, DMS-d6): = 5,9 (s, 1H), of 6.71 (s, 1H), 7,20 (m, 5H), 7,44 (m, 7H), to 7.75 (m, 3H), 7,82 (m, 2H).

Example 75

4-[4-hydroxy-2-oxo-3-[(2-phenylethyl)thio] -2H-Piran-6-yl] - phenoxyalkanoic acid

To 10 ml of solution (0,939 mmol) of a compound ethyl ester 4-[4-hydroxy-2-oxo-3-[(2-phenylethyl)thio] -2H - Piran-6-yl]phenoxyalkanoic acid in tetrahydrofuran add 2.34 mmol 1-N. of sodium hydroxide. The reaction mixture is stirred for 5 hours, then mixed with 10 ml of water and acidified with conc. hydrochloric acid until reaching values tracts washed with saturated sodium chloride and dried over anhydrous magnesium sulfate. The solvents are evaporated in vacuum. The crude product is purified column chromatography on silica gel with a particle size of 230 - 400 mesh using as elution solvent a mixture of methylene chloride, methanol and acetic acid in the ratio of 94 : 5 : 1. So pl. 182 - 183oC.

1H-NMR (400 MHz, DMSO-d6): = was 2.76 (t, 2H), 2,97 (t, 2H), 4,78 (s, 2H), to 6.67 (s, 1H), 7,06 (d, 2H), 7,21 (m, 5H), of 7.75 (d, 2H).

Example 76

4-hydroxy-3-[(2-phenylethyl)thio] -6-[4-(3-pyridinylmethyl)phenyl] - 2H-Piran - 2-he

The target connection get method And with the use of 1.14 g (of 5.06 mmol) of 4'-(3-pyridinylmethyl)of acetophenone, 0.930 g (5,56 mmol) of bis(trimethylsilyl)amide lithium 0,705 ml (5,56 mmol) of chlorotrimethylsilane, 56 ml of tetrahydrofuran and 1.00 g (3,37 mmol) diethyl ether complex [(2-phenylethyl)thio]proponderance acid. So pl. 178 - 179oC.

1H-NMR (400 MHz, DMSO-d6): = was 2.76 (t, 2H), 2,98 (t, 2H), 5.25 in (s, 2H), 6,69 (s, 1H), 7,21 (m, 7H), 7,45 (kV, 1H), to 7.77 (d, 2H), to $ 7.91 (d, 1H), 8,57 (Shir.s, 1H), 8,70 (Shir.s, 1H).

Example 77

6-[4-(cyclohexylmethoxy)phenyl] -4-hydroxy-3-[(2 - phenylethyl)thio]-2H-Piran-2-he

The target connection get method And using 2.50 g (10,77 mmol) 4'-(cyclohexylmethoxy)of acetophenone, 2.70 g (16,16 mmol) of bis(trimethylsilyl)amide lithium 2,05 ml (16,16 mmol) chlortrimeton acid. So pl. 130 - 132oC.

1H-NMR (400 MHz, DMSO-d6): = 1,15 (m, 5H), is 1.81 (m, 6N), 2,77 (t, 2H), 2,97 (t, 2H), 3,85 (d, 2H), to 6.67 (s, 1H), 7,21 (m, 5H), 7,45 (kV, 1H), 7,74 (d, 2H).

Example 78

4-hydroxy-3-[(2-phenylethyl)thio]-6-[4-(phenylsulfonyl)phenyl]- 2H-Piran-2-he

The target connection get method And using 2.50 g (being 9.61 mmol) of 4'-(phenylsulfonyl)of acetophenone, 2,41 g (14,42 mmol) of bis(trimethylsilyl)amide lithium and 1.83 ml (14,42 mmol) of chlorotrimethylsilane, 96 ml of tetrahydrofuran and 1.00 g (3,37 mmol) diethyl ether complex [(2-phenylethyl)thio]proponderance acid. So pl. 194 - 195oC.

H-NMR (400 MHz, DMSO-d6): = was 2.76 (t, 2H), 3,01 (t, 2H), 6.87 in (s, 1H), 7,19 (m, 5H), to 7.68 (m, 3H), of 8.04 (m, 6N), 12,05 (Shir.s, 1H).

Example 79

4-hydroxy-3-[(2-phenylethyl)thio]-6-[4-benzoyloxy)phenyl]- 2H-Piran-2-he

The target connection get method And using 2.50 g (10,41 mmol) 4'- benzyloxyacetophenone, 2,61 g (15.62 wide mmol) of bis(trimethylsilyl)amide lithium, to 1.98 ml (15.62 wide mmol) of chlorotrimethylsilane, 100 ml of tetrahydrofuran and 1.00 g (3,37 mmol) diethyl ether complex [(2-phenyl-ethyl)thio]proponderance acid. So pl. 164 - 166oC.

1H-NMR (400 MHz, DMSO-d6): = 2,78 (t, 2H), 3,01 (t, 2H), for 6.81 (s, 1H), 7,21 (m, 5H), 7,49 (d, 2H), 7,63 (t, 2H), to 7.77 (t, 1H), 7,92 (d, 2H), 12,00 (Shir.s, 1H).

ucaut method And using 2.50 g (10,24 mmol) 4'-(phenylsulfinyl)of acetophenone, to 2.57 g (15,36 mmol) of bis(trimethylsilyl)amide lithium, 1.94-oz (15,36 mmol) of chlorotrimethylsilane, 100 ml of tetrahydrofuran and 1.00 g (3,37 mmol) diethyl ether complex [(2-phenylethyl)thio]proponderance acid. So pl. 171 - 173oC.

1H-NMR (400 MHz, DMSO-d6): = was 2.76 (t, 2H), 3,01 (t, 2H), 6,83 (s, 1H), 7,19 (m, 5H), 7,54 (m, 3H), of 7.75 (d, 2H), 7,86 (d, 2H), 7,95 (d, 2H), 12,05 (Shir.s, 1H).

Example 81

4-hydroxy-3-[(2-phenylethyl)thio]-6-(4-pyridinyl)-2H - Piran-2-he

The target connection get method And using 2.50 g (20,63 mmol) of 4-acetylpyridine, 5,17 r (30,94 mmol) of bis(trimethylsilyl)amide lithium, to 3.92 ml (30,94 mmol) of chlorotrimethylsilane, 200 ml of tetrahydrofuran and 1.00 g (3,37 mmol) diethyl ether complex [(2-phenylethyl)thio]-proponderance acid. So pl. 149 - 152oC (decomp.).

1H-NMR (400 MHz, DMSO-d6): = 2,78 (t, 2H), 3.04 from (t, 2H), 6,98 (s, 1H), 7,20 (m, 5H), 7,74 (d, 2H), total of 8.74 (d, 2H).

Example 82

(+/-)-3-[1,4-bis(phenylthio)butyl]-4-hydroxy-6-phenyl - 2H-Piran-2-he

The target connection get method with the use of 1.00 g (5,31 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 10 ml of ethanol, 0,436 ml (of 5.84 mmol) cyclopropanecarboxaldehyde, 1,40 ml (to 13.8 mmol) thiophenol, 0.5 ml of piperidine and 0.5 ml of acetic acid. So pl. 75 - 77oC.

1H-NMR (400 MHz, DMSO-d6
The target connection get method with the use of 1.00 g (5,31 mmol) 4-hydroxy-6 - phenyl-2H-Piran-2-it, 10 ml of ethanol, 0,593 ml (of 5.84 mmol) of benzaldehyde, of 1.62 ml (to 13.8 mmol) benzylmercaptan, 0.5 ml of piperidine and 0.5 ml of acetic acid. So pl. 189-191oC.

1H-NMR (400 MHz, DMSO-d6): = 3,70 (DD, 2H), from 5.29 (s, 1H), 6,65 (s, 1H), 7.23 percent (m, 8H), to 7.50 (m, 5H), 7,73 (m, 2H), 11,96 (Shir.s, 1H).

Example 84

(+/-)-4-hydroxy-3-[[(2-methoxyphenyl)thio]phenylmethyl]- 6-phenyl-2H-Piran-2-he

The target connection get method with the use of 1.00 g (5,31 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 10 ml of ethanol, 0,593 ml (of 5.84 mmol) of benzaldehyde, of 1.93 ml (to 13.8 mmol) of 2-methoxythiophene, 0.5 ml of piperidine and 0.5 ml of acetic acid. So pl. 165 - 170oC.

1H-NMR (400 MHz, DMSO-d6): = 3,870 (s, 3H), of 5.81 (s, 1H), 6,70 (s, 1H), at 6.84 (t, 1H), 7,19 (m, 3H), 7,28 (m, 2H), 7,53 (m, 3H), of 7.75 (m, 2H), 12,13 (Shir.s, 1H).

Example 85

(+/-)-4-hydroxy-3-[3-methyl-1-(phenylthio)butyl]-6 - phenyl-2H-Piran-2-he

The target connection get method with the use of 1.00 g (5,31 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 10 ml of ethanol, 0,626 ml (of 5.84 mmol) izofluranovogo aldehyde, 1,40 ml (to 13.8 mmol) thiophenol, 0.5 ml of piperidine and 0.5 ml of acetic acid. So pl. 154 - 156oC.

1H-NMR (400 MHz, acetone-d6): = 0,89 (d, 3H), 0,93+/-)-3-[2-cyclohexyl-1-(phenylthio)ethyl]-4-hydroxy - 6-phenyl-2H-Piran-2-he

The target connection get method with the use of 1.00 g (5,31 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 10 ml of ethanol, 0,735 ml (of 5.84 mmol) cyclohexanecarboxaldehyde, 1,40 ml (to 13.8 mmol) thiophenol, 0.5 ml of piperidine and 0.5 ml of acetic acid. So pl. 205oC (decomp.).

1H-NMR (400 MHz, acetone-d6): = of 0.91 (d, 3H), 1,25 (m, 5H), at 1.73 (m, 5H), 2,58 (m, 1H), a 4.83 (DD, 1H), 6,69 (s, 1H), 7,22 (m, 3H), of 7.48 (m, 5H), 7,82 (m, 2 H).

Example 87

4-hydroxy-6-(3-phenoxyphenyl)-3-[(2-phenylethyl)thio]-2H - Piran-2-he

The target connection get method And using 2.00 g (9.43 mmol) of 3'-phenoxyacetophenone, a 2.36 g (14,15 mmol) of bis(trimethylsilyl)-amide lithium 1,79 ml (14,15 mmol) of chlorotrimethylsilane, 100 ml of tetrahydrofuran and 1.00 g (3,37 mmol) diethyl ether complex [(2-phenyl-ethyl)thio]proponderance acid. So pl. 114 - 115oC (decomp.).

1H-NMR (400 MHz, DMSO-d6): = was 2.76 (t, 2H), 2,99 (t, 2H), 6,76 (s, 1H), to 7.09 (m, 7H), 7,34 (s, 1H), 7,44 (t, 2H), 7,56 (m, 2H).

Example 88

4-hydroxy-6-[3-methoxy-4-(phenylmethoxy)phenyl]-3-[(2-phenylethyl)thio]- 2H-Piran-2-he

The target connection get method And using 2.00 g (7,81 mmol) of 4'-benzyloxy-3'- methoxyacetophenone, 1,96 g (11,71 mmol) of bis(trimethylsilyl)amide lithium, to 1.48 ml (11,71 mmol) of chlorotrimethylsilane, 80 ml tetrahydrofuran>.

1H-NMR (400 MHz, DMSO-d6): = 2,77 (t, 2H), 2,98 (t, 2H), 3,86 (s, 1H), 6.75 in (s, 1H), 7,21 (m, 7H), 7,40 (m, 6N).

Example 89

6-(3, 5dimethylphenyl)-4-hydroxy-3-[(2-phenylethyl)thio]- 2H-Piran-2-he

The target connection get method And with the use of 1.75 g (11,82 mmol) of 3', 5'-dimethylacetophenone, 1.89 g (17,73 mmol) diisopropylamide lithium, 2.25 ml (17,73 mmol) of chlorotrimethylsilane, 120 ml of tetrahydrofuran and 1.00 g (3,37 mmol) diethyl ether complex [(2-phenylethyl)thio]proponderance acid. So pl. 155 - 157oC.

1H-NMR (400 MHz, DMSO-d6): = 2,34 (C, 6N), 2,77 (t, 2H), 2,99 (t, 2H), 6,72 (s, 1H), 7,21 (m, 6N), 7,41 (s, 2H), total of 8.74 (d, 2H).

Example 90

4-hydroxy-3-[[(3-methoxyphenyl)methyl)thio]-6-phenyl-2H - Piran-2-he

The target connection get by method B using 1,00 g (5,31 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 15 ml of ethanol, 5,31 ml of 1 N. sodium hydroxide and 2.12 g (6,90 mmol) of a compound [3-(methoxy)phenyl]methyl ester of n-toluoldisocyanate. So pl. 134 - 136oC.

1H-NMR (400 MHz, DMSO-d6): = of 3.69 (s, 3H), 3,99 (s, 2H), 6.75 in (m, 2H), 6,83 (m, 2H), 7,16 (t, 1H), 7,53 (m, 3H), 7,79 (m, 2H).

Example 91

(+/-)-4-hydroxy-3-[4-methyl-1-(phenylthio)pentyl]-6 - phenyl-2H-Piran-2-he

The target connection get method with the use of 1.00 g (5,31 mmol) 4-hydroxy-6-phenyl acetic acid. So pl. 144 - 145oC (decomp.).

1H-NMR (400 MHz, DMSO-d6): = 0,80 (d, 3H), 0,81 (d, 3H), of 1.07 (m, 1H), 1,18 (m, 1H), 1,49 (m, 1H), 1,89 (m, 1H), 2,19 (m, 1H), 4,51 (DD, 1H), of 6.68 (s, 1H), 7,19 (t, 1H), 7,29 (m, 2H), 7,35 (d, 2H), 7,53 (m, 3H), 7,76 (m, 2H).

Example 92

4-hydroxy-6-phenyl-3-[[[(3-(phenylmethoxy)phenyl]methyl]thio]-2H - Piran-2-he

The target connection get by method B using 1,00 g (5,31 mmol) 4-hydroxy-6 - phenyl-2H-Piran-2-it, 15 ml of ethanol, 5,31 ml of 1 N. sodium hydroxide and 2.65 g (6,90 mmol) of a compound [3-(benzhexol)phenyl]methyl ester of n-toluoldisocyanate. So pl. 140 - 141oC.

1H-NMR (400 MHz, DMSO-d6): = 3,98 (s, 2H), free 5.01 (s, 2H), 6.75 in (s, 1H), 6,83 (m, 2H), 6,91 (m, 1H), 7,28 (m, 1H), 7,34 (m, 4H), 7,52 (m, 3H), 7,80 (m, 2H).

Example 93

3-[(1,3-benzodioxol-5-ylmethyl)thio]-4-hydroxy-6 - phenyl-2H-Piran-2-he

The target connection get by method B using 1,00 g (5,31 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 15ml of ethanol, 5,31 ml of 1 N. sodium hydroxide and 2,22 g (6,90 mmol) complex of 1,3-benzodioxol-5-yl - methyl ester p-toluoldisocyanate. So pl. 162 - 164oC.

1H-NMR (400 MHz, DMSO-d6): = to 3.92 (s, 2H), 5,95 (s, 2H), 6.75 in (m, 4H), 7,53 (m, 3H), 7,79 (m, 2H).

Example 94

4-hydroxy-3-[[(2-methoxyphenyl)methyl)thio]-6-phenyl-2H - Piran-2-he

The target connection get the 0,816 g (to 2.65 mmol) of a compound (2-methoxyphenyl)methyl ester of n-toluoldisocyanate. So pl. 152 - 153oC.

1H-NMR (400 MHz, DMSO-d6): = of 3.73 (s, 3H), of 3.95 (s, 2H), of 6.71 (s, 1H), for 6.81 (t, 1H), 6,91 (d, 1H), 7,13 (d, 1H), 7,17 (t, 1H), 7,53 (m, 3H), 7,79 (m, 2H).

Example 95

4-hydroxy-3-[[(2-were)methyl)thio]-6-phenyl-2H - Piran-2-he

The target connection get by method B using 1,00 g (5,31 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 15 ml of ethanol, 5,31 ml of 1 N. sodium hydroxide and 1.55 g (5,31 mmol) of a compound (2-were)methyl ester of n-toluoldisocyanate. So pl. 176 - 178oC.

1H-NMR (400 MHz, DMSO-d6): = 2,42 (s, 3H), 3,99 (s, 2H), 6,74 (s, 1H), to 7.09 (m, 4H), 7,53 (m, 3H), 7,79 (m, 2H).

Example 96

4-hydroxy-3-[[(3-were)methyl)thio]-6-phenyl-2H - Piran-2-he

The target connection get by method B using 1,00 g (5,31 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 15 ml of ethanol, 5,31 ml of 1 N. sodium hydroxide and 1.55 g (5,31 mmol) of a compound (3-were)methyl ester of n-toluoldisocyanate. So pl. 139 - 140oC.

1H-NMR (400 MHz, DMSO-d6): = of 2.23 (s, 3H), of 3.96 (s, 2H), 6,74 (s, 1H), 7,07 (m, 4H), 7,54 (m, 3H), 7,79 (m, 2H).

Example 97

4-hydroxy-3-[[(4-were)methyl]thio]-6-phenyl-2H - Piran-2-he

The target connection get by method B using 1,00 g (5,31 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 15 ml of ethanol, 5,31 ml of 1-ad hydraotes.

1H-NMR (400 MHz, DMSO-d6): = of 2.23 (s, 3H), of 3.96 (s, 2H), 6,74 (s, 1H), 7,06 (d, 2H), 7,14 (d, 2H), 7,53 (m, 3H), 7,79 (m, 2H).

Example 98

6-[1,1'-biphenyl]-3-yl-4-hydroxy-3-[(2-phenylethyl)thio]- 2H-Piran-2-he

The target connection get method And using 2.00 g (of 10.21 mmol) 3'-phenylacetophenone, a 2.36 ml (12,24 mmol) trimethylsilyltrifluoroacetamide, 2,84 ml (20,40 mmol) of triethylamine, 26 ml of methylene chloride and 1.00 g (3,37 mmol) diethyl ether complex [(2-phenyl-ethyl)thio]proponderance acid. So pl. 93 - 94oC.

1H-NMR (400 MHz, DMSO-d6): = and 2.79 (t, 2H), 3,01 (t, 2H), 6,92 (s, 1H), 7,21 (m, 5H), 7,42 (t, 1H), 7,52 (t, 2H), to 7.64 (t, 1H), of 7.75 (d, 2H), 7,82 (t, 2H), 8,02 (s, 1H).

Example 99

4-hydroxy-3-[[(4-methoxyphenyl)methyl]thio]-6-phenyl-2H - Piran-2-he

The target connection get by method B using 1,00 g (5,31 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 15 ml of ethanol, 5,31 ml of 1-AD. of sodium hydroxide and of 2.21 g (6,90 mmol) of a compound (4-methoxyphenyl)methyl ester of n-toluoldisocyanate. So pl. 168 - 170oC.

1H-NMR (400 MHz, DMSO-d6): = of 3.96 (s, 3H), of 3.95 (s, 2H), 6.73 x (s, 1H), for 6.81 (d, 2H), 7,17 (d, 2H), 7,53 (m, 3H), 7,79 (m, 2H).

Example 100

(+/-)-3-[2-cyclohexyl-1-(cyclohexylthio)ethyl] - 4-hydroxy-6-phenyl-2H-Piran-2-he

The target connection get method with applications to the, 1,60 g (to 13.8 mmol) cyclohexylethane, 0.5 ml of piperidine and 0.5 ml of acetic acid. So pl. 220oC (decomp.).

1H-NMR (400 MHz, DMSO-d6): = 0,86 (m, 2H), 1,18 (m, N), of 1.66 (m, 10H), 2,03 (m, 2H), 5,58 (m, 2H), 4,25 (m, 1H), of 6.68 (s, 1H), 7,53 (m, 3H), of 7.75 (m, 2H).

Example 101

(+/-)-3-[1-[(2,6-dimetilfenil)thio] -3-methylbutyl] -4-hydroxy - 6-phenyl-2H-Piran-2-he

The target connection get method with the use of 1.00 g (5,31 mmol) 4-hydroxy-6 - phenyl-2H-Piran-2-it, 10 ml of ethanol, 0.63 ml (of 5.84 mmol) izofluranovogo aldehyde, 1,90 g (to 13.8 mmol) of 2,6-dimethylthiophenol, 0.5 ml of piperidine and 0.5 ml of acetic acid. So pl. 166 - 167oC.oH-NMR (400 MHz, DMSO-d6): = 0,78(d, 3H), or 0.83 (d, 3H), of 1.42 (m, 1H), 1,47 (m, 1H), 2,46 (m, 1H), of 2.51 (s, 6N), 4,37 (m, 1H), 6,51 (s, 1H), of 7.70 (m, 3H), 7,52 (m, 3H), 7,74 (m, 2H).

Example 102

(+/-)-3-[1-(cyclohexylthio)-2-cyclopropylethyl] - 4-hydroxy-6-phenyl-2H-Piran-2-he

The target connection get method with the use of 1.00 g (5,31 mmol) 4-hydroxy-6-phenyl-2H - Piran-2-it, 10 ml of ethanol, to 0.67 g (of 5.84 mmol) cyclopropanecarboxaldehyde, 1,68 ml (to 13.8 mmol) cyclohexylethane, 0.5 ml of piperidine and 0.5 ml of acetic acid. So pl. 69 - 71oC.

oH-NMR (400 MHz, DMSO-d6): = 0,02 (m, 1H), 0,05 (m, 1H), 0,34 (m, 2H), 0.64 in (m, 2H), 1,22 (m, 5H), of 1.52 (m, 1H), 6,67 (m, 3H), of 1.84 (m, 1H), of 1.97 (m, 2H), 2,64 (m, 1H) the-6-phenyl-2H-Piran-2-he

The target connection get method with the use of 1.00 g (5,31 mmol) 4-hydroxy-6-phenyl-2H-Piran - 2-it, 10 ml of ethanol, and 0.62 g (of 5.84 mmol) izofluranovogo aldehyde, 2,74 g (to 13.8 mmol) of 2,6-Dichlorotoluene, 0.5 ml of piperidine and 0.5 ml of acetic acid. So pl. 158 - 162oC.

1H-NMR (400 MHz, DMSO-d6): = 0,83 (d, 3H), of 0.87 (d, 3H), 1,49 (m, 1H), 1,74 (m, 1H), 2,39 (m, 1H), and 4.68 (m, 1H), 6,769 (s, 1H), 7,49 (m, 5H), 7,74 (m, 3H).

Example 104

(+/-)-3-[1-(cyclohexylthio)-3,3-dimethylbutyl] -4 - hydroxy-6-phenyl-2H-Piran-2-he

The target connection get method with the use of 1.00 g (5,31 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 10 ml of ethanol, to 0.73 ml (of 5.84 mmol) 3,3-dimethylbutanol, of 1.86 ml (to 13.8 mmol) cyclohexylethane, 0.5 ml of piperidine and 0.5 ml of acetic acid. So pl. > 225oC.

1H-NMR (400 MHz, DMSO-d6): = 0,85 (s, N), 1,25 (m, 5H), of 1.65 (m, 7H), 4,30 (m, 1H), 6,69 (s, 1H), 7,54 (m, 3H), of 7.75 (m, 2H).

Example 105

Complex ethyl ester 4-[4-hydroxy-2-oxo-3-[(2 - phenylethyl)thio]-2H-Piran-6-yl]-2-methylphenoxyacetic acid

The target connection get method And using 2.00 g (of 8.47 mmol) of a compound ethyl ester of 4-acetyl-2-methylphenoxyacetic acid, to 3.92 ml (20,33 mmol) trimethylsilyltrifluoroacetamide, 4,72 ml (33,88 mmol) of triethylamine, 22 ml of methylene chloride and 1.00 g (3,>/P>1H-NMR (400 MHz, DMSO-d6): = 1,22 (t, 3H), and 2.26 (s, 3H), 2,77 (t, 2H), 2,97 (t, 2H), 4,17 (t, 2H), 4,91 (s, 2H), 6,66 (s, 1H), 6,99 (d, 1H), 7,21 (m, 5H), to 7.61 (m, 2H)

Example 106

6-[3,5-dimethyl-4-[dimethyl(1,1-dimethylethyl)silyl] oxy]phenyl]- 4-hydroxy-3- [(phenylmethyl)thio]-2H-Piran-2-he

The target connection get method And using 1.50 g (5,39 mmol) of 3',5'-dimethyl-4'-[[dimethyl(1,1 - dimethylethyl)silyl]oxy]acetophenone, 1,24 ml (6,47 mmol) trimethylsilyltrifluoroacetamide, 1.50 ml (10,78 mmol) of triethylamine, 13 ml of methylene chloride and 1.00 g (3.54 mmol) in diethyl ether complex [(phenylmethyl)thio]proponderance acid. So pl. 137-139oC.

1H-NMR (400 MHz, DMSO-d6): = 0,21 (C, 6N), 0,99 (s, N), 2,22 (C, 6N), of 3.96 (s, 2H), is 6.54 (s, 1H), 6,99 (d, 1H), 7,21 (m, 5H), 7,44 (m, 2H).

Example 107

4-hydroxy-3-[(2-phenylethyl)thio] -6-[4-(4-pyridinylmethyl)phenyl]- 2H-Piran-2-he

The target connection get method And using 2.00 g (8,81 mmol) 4'-(4-pyridinylmethyl)of acetophenone, 2,04 ml (10,57 mmol) trimethylsilyltrifluoroacetamide, of 2.45 ml (17,62 mmol) of triethylamine, 22 ml of methylene chloride and 1.00 g (3,37 mmol) diethyl ether complex [(2-phenylethyl)thio] proponderance acid. So pl. 212oC (decomp.).

1H-NMR (400 MHz, DMSO-d6): = 2,73 (t, 2H), 2,88 (t, 2H), from 5.29 (s, 2H), 6.48 in (s, 1H), 7,l-2H-Piran-2-he

The target connection get method with the use of 1.00 g (5,31 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 10 ml of ethanol, and 0.62 ml (of 5.84 mmol) izofluranovogo aldehyde, 1,43 ml (to 13.8 mmol) cyclopentylamine, 0.5 ml of piperidine and 0.5 ml of acetic acid. So pl. 146 - 149oC.

1H-NMR (400 MHz, DMSO-d6): = 0,85 (d, 2H), 0,87 (d, 2H), 1,32 (m, 1H), and 1.54 (m, 7H), of 1.85 (m, 1H), 2,00 (m, 2H), 3.04 from (m, 1H), 4,20 (DD, 1H), 6,69 (s, 1H), 7,53 (m, 3H), 7,76 (m, 2H), of 11.69 (Shir.s, 1H).

Example 109

[4-[4-hydroxy-2-oxo-3[(2-phenylethyl)thio] -2H-Piran-6 - yl]-2-methylphenoxy]-acetic acid

To a solution of 0.20 g (0.45 mmol) of a compound ethyl ester [4-[4-hydroxy-2-oxo-3[(2-phenylethyl)thio] -2H-Piran-6-yl] -2-methylphenoxy] acetic acid in 10 ml of tetrahydrofuran added 1.13 ml (1.13 mmol) of 1-AD. of sodium hydroxide. The reaction mixture is stirred for 5 hours, then mixed with 10 ml of water. Acidified with conc. hydrochloric acid to reach pH 2. The aqueous layer was extracted twice with ethyl acetate, taken in an amount of 100 ml the combined organic extracts washed with saturated sodium chloride solution and dried over anhydrous magnesium sulfate. The solvents are evaporated in vacuum. The crude product is purified by column chromatography on silica gel with dimensions of otnoshenii 94 : 5 : 1.

So pl. 210oC(decomp.).

1H-NMR (400 MHz, DMSO-d6): = and 2.26 (s, 3H), 2,78 (t, 2H), 2,98 (t, 2H), to 4.81 (s, 2H), to 6.67 (s, 1H), 6,97 (d, 2H), 7,21 (m, 12H), to 7.61 (d, 2H).

Example 110

(+/-)-3-[1-(cyclohexylthio)-2-cyclopentylmethyl] - 4-hydroxy-6-phenyl-2H-Piran-2-he

The target connection get method with the use of 1.00 g (5,31 mmol) 4-hydroxy-6-phenyl-2H-Piran - 2-it, 10 ml of ethanol, 0.65 g (of 5.84 mmol) cyclopentanecarboxaldehyde, 1,68 ml (to 13.8 mmol) cyclohexylethane, 0.5 ml of piperidine and 0.5 ml of acetic acid. So pl. 157 - 160oC.

1H-NMR (400 MHz, DMSO-d6): = the 1.44 (m, N), a 2.01 (m, 1H), 2,19 (m, 1H), 2,60 (m, 1H), 4,16 (m, 1H), of 6.68 (s, 1H), 7,53 (m, 3H), of 7.75 (m, 2H), 11,66 (Shir.s, 1H).

Example 111

4-hydroxy-6-(4-hydroxy-3, 5dimethylphenyl)-3-[(phenylmethyl)thio]- 2H-Piran-2-he

To a solution of 6-[3,5-dimethyl-4-[[dimethyl(1,1-dimethylethyl) silyl]-oxy]-phenyl]-4-hydroxy-3-[(phenylmethyl)thio]-2H-Piran-2-it in 10 ml of tetrahydrofuran added to 9.0 ml of 3 N. hydrochloric acid at a temperature of 0oC. the Reaction mixture is stirred for 48 hours at room temperature, after which the mixture is poured into ethyl acetate and sequentially washed with water and saturated sodium chloride solution. Dried over anhydrous magnesium sulfate. The solvents are evaporated in vacuum. The crude product is purified way of the enta mixture of ethyl acetate and hexanol in the ratio of 50 : 50. So pl. 174 - 176oC.

1H-NMR (400 MHz, DMSO-d6): = of 2.21 (s, 6N), 2,60 (m, 1H), 3.96 points (s, 2H), of 6.52 (s, 1H), 7.23 percent (s, 5H), 7,38 (s, 2H), 9,06 (s, 1H).

Example 112

4-hydroxy-6-phenyl-3-[[[3-(2-phenylethane)phenyl]methyl]thio]- 2H-Piran-2-he

The target connection get by method B using 1,00 g (5,31 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 15 ml of ethanol, 5,31 ml of 1 N. sodium hydroxide and 2,11 g (5,31 mmol) of a compound [3-(2-(phenylethane)-phenyl]methyl ester of n-toluoldisocyanate. So pl. 85 - 90oC.

1H-NMR (400 MHz, DMSO-d6): = 2,96 (t, 2H), 3.96 points (s, 2H), 4.09 to (t, 2H), 6,77 (m, 4H), 7,19 (m, 5H), 7,53 (m, 3H), to 7.77 (m, 2H).

Example 113

4-hydroxy-6-[4-(2-phenylethynyl)phenyl]-3-[(2 - phenylethyl)thio]-2H-Piran-2-he

The target connection get method And using 1.50 g (for 6.81 mmol) of 4'-(2-fentanyl)of acetophenone, of 1.57 ml (8.17 mmol) of trimethylsilyltrifluoroacetamide, 1.89 ml (13,62 mmol) of triethylamine, 17 ml of methylene chloride and 1.00 g (3,37 mmol) diethyl ether complex [(2-phenylethyl)thio]proponderance acid. So pl. 181 - 182oC.

1H-NMR (400 MHz, DMSO-d6): = 2,78 (t, 2H), to 3.02 (t, 2H), 6,85 (s, 1H), 7,21 (m, 5H), was 7.45 (m, 3H), to 7.59 (d, 2H), 7,86 (d, 2H).

Example 114

4-hydroxy-6-[4-(2-phenylethyl)phenyl]-3-[(2 - phenylethyl)thio]-2H-Piran-2-he

The target connection get the a, of 1.86 ml (made 13.36 mmol) of triethylamine, 17 ml of methylene chloride and 1.00 g (3,37 mmol) diethyl ether complex [(2-phenylethyl)thio]proponderance acid.

So pl. 122 - 123oC.

1H-NMR (400 MHz, DMSO-d6): = 2,77 (t, 2H), 2,93 (m, 4H), to 2.99 (t, 2H), 6.75 in (s, 1H), 7,26 (m, 5H), 7,38 (d, 2H), 7,71 (d, 2H).

Example 115

(+/-)-3-[(cyclohexylthio)phenylmethyl]-4-hydroxy-6 - phenyl-2H-Piran-2-he

The target connection get method with the use of 1.00 g (5,31 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 10 ml of ethanol, 0,593 ml (of 5.84 mmol) of benzaldehyde, 1,68 ml (to 13.8 mmol) cyclohexylethane, 0.5 ml of piperidine and 0.5 ml of acetic acid. So pl. 189-191oC.

1H-NMR (400 MHz, DMSO-d6): = 1,21 (m, 5H), of 1.52 (m, 1H), 1.91 a (m, 2H), 2,58 (m, 2H), lower than the 5.37 (s, 1H), 6,70 (s, 1H), 7,17 (t, 1H), 7,53 (m, 5H), 7,74 (m, 2H), 11,96 (Shir.s, 1H).

Example 116

4-hydroxy-3-[(phenylmethyl)thio]-6-[3-(triptoreline)phenyl]- 2H-Piran-2-he

The target connection get method But using 3 g (14.7 mmol) of 3'-triftormetilfullerenov, of 2.45 g (14.7 mmol) of bis(trimethylsilyl)amide lithium, 2,47 g (14.7 mmol) of chlorotrimethylsilane and 1.00 g (3.54 mmol) in diethyl ether complex [(phenylmethyl)thio]proponderance acid. So pl. 128-132oC.

1H-NMR (400 MHz, DMSO-d6): = a 4.03 (s, 2H), for 6.81 (s, 1H), 7,2 (m, 2+H, 37), 309 (8), 273 (7), 205 (3), 119 (10):

C19H13O4S1F3= 0,92 (m, 2H), 1.14 in (m, 3H), 1,19 (m, 1H), 1,61 (m, 3H) and 1.83 (m, 2H), 2,64 (d, 2H), 6,78 (s, 1H), 7,53 (m, 3H), 7,81 (m, 2H); IR (KBr) 3106, 2922, 1651, 1547, 1396, 1099, 766 cm-1; MS (AP) m/e 317 (M+H, 16), 279 (83), 242 (77), 201 (27), 177 (19), 134 (54), 105 (65), 97 (100);

Example 118

4-hydroxy-3-[(2-phenylethyl)thio] -6-[3-methyl-4-(3-pyridinylmethyl) phenyl]-2H-Piran-2-he

The target connection get method But using 2.0 g (8,29 mmol) 3'-methyl-4'-(3-pyridinylmethyl)of acetophenone, 1,53 g (9,13 mmol) of bis(trimethylsilyl)amide lithium, 1.54 g (9,137 mmol) of chlorotrimethylsilane and 1.00 g

(3.54 mmol) in diethyl ether complex [2-(phenylethyl)thio] proponderance acid. So pl. 149 151 polyurthaneoC.

1H-NMR (400 MHz, DMSO-d6): = of 2.25 (s, 3 H), 2,78 (t, 2H), 2,97 (t, 2H), 5,28 (s, 2H), 6,69 (s, 1H), 7,22 (m, 6N), 7,44 (DD, 1H), to 7.67(s + d, 2H), 7,92 (d, 1H) 8,58 (Shir.s, 1H), 8,72 (Shir.s, 1H), IR (KBR) 3430, 2926, 1713, 1626, 1505, 1263, 1136, 1028, 808, 705 cm-1: MS (AP) m/e 395 (M+H), 341 (15), 200 (6), 105 (100);

C26H33O4S1N1:

calculated: 70,09; N 5,20; N 3,14;

found: 70,31; N 5,27; N 2,95.

Example 119

6-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-hydroxy-3- [(phenylmethyl)thio] -2H - Piran-2-he

The target connection get method But using 2.5 g (of 14.25 mmol) of 1,4-benzodioxin-6-yl-methylketobemidone ether [(phenylmethyl)thio]proponderance acid. So pl. 192 - 193oC.

1H-NMR (400 MHz, DMSO-d6): = 3,99 (s, 2H), 4,17 (m, 4H), 6,8 (s, 1H), 7,0 (d, 1H), 7,2 (m, 1H), 2,28 (m, 7H); IR (KBR) 3435, 2924, 1649, 1624, 1508, 1288, 1066, 698 cm-1; MS (AP) m/e 369 (M+H), 277 (12), 233 (12), 163 (9), 107 (10), 91 (76)

C20H16O5S1:

calculated: 65,21; H to 4.38;

found: 64,80; H 4,17.

Example 120

4-hydroxy-3-[(2-phenylethyl)thio]-6-[3-(trifluoromethyl)phenyl]-2H - Piran-2-he

The target connection get method And using appropriate simple trimethylsilylacetamide ether (4.5 mmol) and of 1.33 g (4,55 mmol) diethyl ether complex [(2-phenylethyl)thio]proponderance acid. So pl. 117 - 118oC.

1H-NMR (400 MHz, DMSO-d6): = 2,8 (t, 2H), 3,03 (t, 2H), 6,94 (s, 1H), 7,2 (m, 5H), 7,8 (t, 1 H), 7,94 (t, 1 H), 8,08 (s, 1H), 8,14 (d, 1H); IR (KBr) 3435, 3026, 2924, 1720, 1635, 1543, 1327, 1171, 1130, 696 cm-1; MS (AP) m/e 393 (M+H, 100), 373 (9), 288 (38), 256 (20), 224 (11), 105 (62);

C20H15S1O3F3= of 3.97 (s, 2H), 6,53 (s, 1H), 7,25 (m, 5H), to 7.61 (t, 1H), of 7.75 (d, 1H), 8,03 (d, 1H), 8,08 (s, 1H); IR (KBr) 3434, 3244, 1678, 1628, 1535, 1522, 1435, 1341, 1316, 1192, 1132, 936, 706 cm-1MS (AP) m/e 379 (M+H), 257 (1), 91 (100):

C19H13O3S1F3:

calculated: 60,31; N. OF 3.46;

found: 60,53; N 3,57.

Example 122

4-hydroxy-3-[(phenylmethyl)thio]-6-[2,3,4-(trimethoxyphenyl]-2H - PNA, 1,43 g (8,56 mmol) of bis(trimethylsilyl)amide lithium, 1.8 ml (10,67 mmol) of chlorotrimethylsilane and 1.00 g (3.54 mmol) in diethyl ether complex [(phenylmethyl)thio]proponderance acid.

Example 123

N-[4-[4-hydroxy-2-oxo-3-[(2-phenylethyl)thio] -2H-Piran-6-yl] phenyl]- benzosulfimide

The target connection get method But using 3.0 g (10,91 mmol) of the corresponding benzosulfimide, of 3.65 g (21,82 mmol) of bis(trimethylsilyl)amide lithium, 3,68 ml (21,82 mmol) of chlorotrimethylsilane and 1.00 g (3,37 mmol) diethyl ether complex [(phenylethyl)thio]propane - dicarboxylic acid. So pl. 89 - 91oC.

1H-NMR (400 MHz, DMSO-d6): = 2,78 (t, 2H), 3,03 (t, 2H), 6,86 (s, 1H), 7,25 (m, 6H), 7,72 (t, 3H), 7,86 (m, 5H); IR (KBr) 3443, 3335, 1725, 1632, 1543, 1383, 1171, 912, 729, 581, 552 cm-1;

C25H21N1S2O5H2O:

calculated: 60,35: N 4,66, N 2,81;

found: 60,13; N To 4.47%; N 3,23.

Example 124

6-[4-[(3,5-dimethyl-4-isoxazolyl)methoxy] phenyl] - 4-hydroxy-3- [(2-phenylethyl)thio]-2H-Piran-2-he

The target connection get method And with the use of 1.65 g (6,74 mmol) 4'-(3,5-dimethyl-4-isoxazolyl)of acetophenone, 1.13 g (6,74 mmol) of bis(trimethylsilyl)amide lithium, to 1.14 ml (6,74 mmol) of chlorotrimethylsilane and 1.00 g (3,37 mmol) diethyl ether complex [(2-phenylethyl)t is s, 3H), 2,78 (t, 2H), 2,99 (t, 2H), to 5.03 (s, 2H), 6,69 (s, 1H), 7,17 (d, 3H), 7,25 (m, 4H), 7,78 (d, 2H); IR (KBr) 2936, 2979, 1640, 1510, 1406, 1182, 988, 820, 764 cm-1: MS (AP) m/e 450 (M+H), 341 (10), 236 (9), 112 (76), 105 (100);

C25H23N1O5S1:

calculated: 66,80: H 5,16; N 3,12;

found: 66,42; N 5,20: N 2,74.

Example 125

(+/-)-3-[(cyclohexylthio)phenylmethyl] -4-hydroxy-6- [3-methyl-4-(3-pyridinylmethyl)phenyl]-2H-Piran-2-he

The target connection receive according To the method using 0.5 g (of 1.62 mmol) 4-hydroxy-6-[3-methyl-4-(3-pyridinylmethyl)phenyl] -2H - Piran-2-it, 0,189 g (1.78 mmol) of benzaldehyde, 0,489 g (4,212 mmol) cyclohexylethane, 0.5 ml of piperidine and 0.5 ml of acetic acid. So pl. 84 - 87oC (decomp.). IR(KBR) 3059, 2930, 2853, 1676, 1601, 1449, 1260, 1134, 700 cm-1; MS (AP) m/e 446 (2), 331 (9), 226 (61), 205 (24), 135 (44);

Example 126

Methyl ester 2-[[(4-hydroxy-2-oxo-6 - phenyl-2H-Piran-3-yl)thio] methyl]-benzoic acid

The target connection get by method B using 2.0 g (10,63 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 3.57 g (10,63 mmol) of complex [2-(carbomethoxy)phenyl]methyl ester of n-toluoldisocyanate, 10,63 ml of 1-AD. of sodium hydroxide and 20 ml of ethanol. So pl. 122 - 123oC.

1H-NMR (400 MHz, DMSO-d6): = 3,81 (s, 3H), or 4.31 (s, 2H), to 6.67 (s, 1H), 7,25 (d, 1H), 7,31 (m, 1H), 7,44 (t, 1H), 7,44 (m, 3H), 7,53 (d, 1H),5 (14).

Example 127

(+/-)-3-[1 -(cyclohexylthio)-3-methylbutyl] -6-(2,3-dihydro - 1,4-benzodioxin-6-yl)-4-hydroxy-2H-Piran-2-he

The target connection receive according To the method using 1.0 g (4,06 mmol) 4-hydroxy-6-[1,4-benzodioxin-6-yl] -2H-Piran-2-it, 0.35 g (4,06 mmol) izofluranovogo aldehyde, 0,944 g (8,12 mmol) cyclohexylethane, 0.5 ml of piperidine and 0.5 ml of acetic acid. So pl. 161 - 162oC.

1H-NMR (400 MHz, DMSO-d6): = 0,85 (d, 3H), from 0.88 (d, 3H), 1,2 (m, 5H), of 1.39 (m, 1H), 1,53 (m, 2H), 1,65 (m, 2H), 1,81 (Shir.m, 1H), 2,04 (m, 2H), 4.2V (kV, 1H), 4,32 (Shir.kV, 4H), 6,53 (s, 1H), 6,99 (d, 1H), 7,2 (d, 1H), 7,25 (DD, 1H): IR (KBR) 1099, 2930, 2853, 1649, 1564, 1510, 1397, 1314, 1289, 1260, 1140, 1069, 891, 771, 608 cm-1< / BR>
Example 128

Methyl ester 2-[[4-(4-hydroxy-2-oxo-3- [(2-phenylethyl)thio]-2H - Piran-6-yl]phenoxy]methyl]-benzoic acid

The target connection get method But using 2.0 g (? 7.04 baby mortality mmol) of a compound methyl ester 2-[[(4-acetyl)phenoxy]methyl] benzoic acid, of 1.57 g (? 7.04 baby mortality mmol) trimethylsilyltrifluoromethane, 1.42 g (14,08 mmol) of triethylamine and 1.04 g (3,52 mmol) diethyl ether complex [(2-phenylethyl)thio]proponderance acid. So pl. 161 - 162oC.

1H-NMR (400 MHz, DMSO-d6): = 2,78 (t, 2H), 2,97 (t, 2H), 3,81 (s, 3H), and 5.5 (s, 2H), 6,69 (s, 1H), 7,14 (m, 3H), 7,25 (m, 4H), 7.5 (m, 2H), 7,78 (m, 2H), 7,78 (d, 247), 105(33).

Example 129

4-hydroxy-3-[(2-phenylethyl)thio] -6-[4-(1H-tetrazol-5 - ylethoxy)phenyl]- 2H-Piran-2-he

The target connection is received with the application of 0.5 g (1,32 mmol) of the compound of example 143 and 0,543 g (of 2.64 mmol) of the azide trimacinolone, 10 ml of toluene and 10 ml of ethanol at a temperature of phlegmy within 24 hours. The solvents evaporated. The residue is treated with 1-N. hydrochloric acid, then stirred at room temperature for 2 hours. The remainder served in methanol, the solvent evaporated and the resulting solid is washed with ethyl acetate to obtain pure compounds. So pl. 195 - 196oC (decomp.).

1H-NMR (400 MHz, DMSO-d6): = 2,78 (t, 2H), 2,99 (t, 3H), 5,6 (s, 2H), 6,72 (s, 1H), 7,22 (m, 7H), 7,81 (d, 2H); IR (KBR) 3121, 3028, 1657, 1549, 1512, 1410, 1256, 1186, 1059, 831, 696 cm-1; MS (AP) m/e 423 (M+H, 8), 341 (3), 137 (11), 105(100).

Example 130

4-hydroxy-6-[3-methyl-4-[(2-pyridinyl)methoxy] phenyl] - 3-[(2-phenylethyl)thio] -2H-Piran-2-he

The target connection get method But using 2.0 g (8,29 mmol) of 4-(2-pyridinylmethyl)-3-methylacetophenone, 1.84 g (8,29 mmol) trimethylsilyltrifluoromethane, 1.68 g (16,58 mmol) of triethylamine and 1.22 g (4,15 mmol) diethyl ether complex [(2-phenylethyl)thio]proponderance acid. So pl. 75 - 77oC.

(m, 2H), 7,86 (t, 2H), 8,61 (d, 1H): IR (KBR) 3063, 2924, 1719, 1603, 1505, 1267, 1138, 1039, 760 cm-1; MS (AP) m/e 446 (M+H, 90), 341 (16), 279 (17), 242 (21), 151 (25), 105 (100).

C26H23O4N1S1< / BR>
calculated: 70,09; H 5,2; N 3,4;

found: 70,68; N 5,28 N 3,14.

Example 131

(+/-)-3-[2-cyclopropyl-1-[(phenylmethyl)thio] ethyl] -4-hydroxy-6-phenyl - 2H-Piran-2-he

The target connection receive according To the method using 1.5 g (7,98 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, of 0.67 g (7,98 mmol) of 2-cyclopropanecarboxaldehyde, 1.98 g (15,96 mmol) benzylmercaptan, 0.5 ml of piperidine and 0.5 ml of acetic acid. So pl. 59 - 61oC.

1H-NMR (400 MHz, DMSO-d6): = 0,97 (m, 2H), and 0.28 (m, 2H), 0,58 (m, 1H), 1,61 (m, 1H), 2,01 (m, 1H), 3.72 points (AVG kV, 2H), 4,22 (kV, 1H), to 6.67 (s, 1H), 7,18 (t, 1H), 7,25 (d, 2H), 7,31 (m, 2H), 7,53 (m, 3H), of 7.75 (m, 2H); IR (KBR) 3061, 2919, 2631, 1649, 1564, 1404, 1267, 766, 691 cm-1; MS (AP) m/e 255 (M-Szl), (19), 201 (5), 147 (2);

C23H22O3S1:

calculated: 72,99: N 5,86;

found: 72,31; N between 6.08.

Example 132

(+/-)-4-hydroxy-3-[1-[(2-methoxyphenyl)thio] -3-methylbutyl]-6 - phenyl-2H-Piran-2-he

The target connection receive according To the method using 1.5 g (7,98 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 0,69 g (7,98 mmol) izofluranovogo aldehyde, 2.24 g (15,96 mmol) of 2-methoxythiophene, 1.0 ml of piperidine is 3 (m, 1H), 1.69 in (m, 1H), 2,19 (m, 1H), to 3.64 (s, 3H), 4,69 (kV, 1H), only 6.64 (s, 1H), 6.89 in (t, 1H), 6,94 (d, 1H), 7,17 (t, 1H), 7,33 (d, 1H), 7,53 (m, 3H) 7,78 (m, 2H): IR (KBR) 3063, 2955, 2635, 1649, 1564, 1406, 1242, 1026, 768, 750, 691 cm-1; MS (AP) m/e 257 (M-SPh(OMe)), (11), 201 (3), 169 (5), 141 (88);

C23H24O4S1:

calculated: 69,67; N 6,10;

found: 69,63; N. of 5.92.

Example 133

(+/-)-4-hydroxy-3-[1-[(2-methoxyphenyl)thio] -3-methylbutyl] -6-phenyl - 2H-Piran-2-he

The target connection receive according To the method using 1.5 g (7,98 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 0,69 g (7,98 mmol) izofluranovogo aldehyde, 1.98 g (15,96 mmol) benzylmercaptan, 1.0 ml of piperidine and 1.0 ml of acetic acid. So pl. 153 - 155oC.

1H-NMR (400 MHz, DMSO-d6): = 0,64 (d, 3H), 0,81 (d, 3H), 1,25 (m, 1H), 1,53 (m, 1H), 2,04 (m, 1H), 3,69 (AVH kV, 2H), 4,22 (kV, 1H), IR (KBR) 3086, 2955, 1651, 1566, 1497, 1404, 1311, 1127, 912, 766, (8).

Example 134

Methyl ester 4-[[4-[4-hydroxy-2-oxo-3- [(2-phenylethyl)thio]-2H - Piran-6-yl]phenoxy]methyl]benzoic acid

The target connection get method But using 2.0 g (? 7.04 baby mortality mmol) of a compound methyl ester 4-[[(4-acetyl)phenoxy]methyl] benzoic acid, a 2.36 g (14,08 mmol) hexamethyldisilazane lithium, of 2.38 g (14,08 mmol) of chlorotrimethylsilane and 1.0 g (3,05 mmol) diethyl ether complex [(2-phenylethyl)thio]propanda, N), 5,31 (s, 2H), to 6.67 (s, 1H), 7,17 (kV, 4H), 7,25 (m, 3H), to 7.61 (d, 2H), 7,78 (d, 2H), and 8.0 (d, 2H); IR (KBR) 3023, 2936, 2581, 1632, 1510, 1404, 1258, 1184, 1098, 1009, 818, 718 cm-1: MS (AP) m/e 517 (M-29,7), 489 (M+H, 55), 384 (19), 149 (40), 105 (100).

Example 135

Methyl ester 3-[[4-[4-hydroxy-2-oxo-3- [(2-phenylethyl)thio]-2H-Piran-6-yl]phenoxy]methyl]benzoic acid

The target connection get method But using 2.0 g (? 7.04 baby mortality mmol) of a compound methyl ester 3-[[(4-acetyl)phenoxy] methyl]benzoic acid, a 2.36 g (14,08 mmol) hexamethyldisilazane lithium, of 2.38 g (14,08 mmol) of chlorotrimethylsilane and 1.0 g (3,05 mmol) diethyl ether complex [(2-phenylethyl)thio]proponderance acid. So pl. 147 - 149oC.

1H-NMR (400 MHz, DMSO-d6): = 2,78 (t, 2H), 2,97 (t, 2H), 3,86 (s, 2H), 5,31 (s, 1H), 6,69 (1H), 7,2 (m, 7H), 7,58 (t, 1H), to 7.75 (m, 3H), 7,78 (d, 1H), 7,94 (d, 1H), 8,08 (s, 1H): IR (KBr) 3081, 2950, 1726, 1632, 1609, 1512, 1406, 1345, 1306, 1290, 1209, 1098, 1004, 820, 748, 696 cm-1; MS (AP) m/e 489 (M-H, 48), 384 (16), 341 (7), 236 (6), 149 (39), 119 (11), 105 (100).

Example 136

6-[4-[3,4-dichlorphenoxy] phenyl] -4-hydroxy-3-[(2 - phenylethyl)thio]-2H-Piran-2-he

The target connection get method But using 2.0 g (6,80 mmol) 4-[(3,4-dichlorophenyl)methoxy] acetophenone, 2.28 g (13,61 mmol) hexamethyldisilazane lithium, 2.3 g (13,61 mmol) of chlorotrimethylsilane and 1.0 g (3,40 mmol) sloger (400 MHz, DMSO-d6): ' = 2,78 (t, 2H), 2,97 (t, 2H), 5,22 (s, 1H), 6,69 (s, 1H), 7,17 (m, 8H), 7,47 (DD, 1H), 7,69 (d, 1H) 7,78: IR (KBR) 3054, 2602, 1713, 1611, 1512, 1399, 1291, 1179, 1109, 1042, 818, 754 cm-1; MS (AP) m/e 501 (17), 499 (24), 394 (12), 353 (1), 161 (20), 159 (27), 105 (100).

Example 137

Methyl ester 3-[[4-hydroxy-2-oxo-6-phenyl - 2H-Piran-3-yl]thio]methyl]benzoic acid

The target connection get by method B using 2.0 g (10,63 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 3.57 g (10,63 mmol) of complex 3-(carbomethoxy)phenyl)methyl ester of n-toluoldisocyanate, 10,63 ml of 1-AD. of sodium hydroxide and 20 ml of ethanol. So pl. 170-171oC.

1H-NMR (400 MHz, DMSO-d6): = of 3.78 (s, 3H), 4,06 (s, 2H), 6,72 (s, 1H), 7,42 (t, 1H), 7,53 (m, 4H), 7,78 (m, 3H), 7,83 (s, 1H); IR (KBr) 3108, 2947, 1716, 1644, 1549, 1400, 1302, 1100, 770, 713, 523 cm-1; MS (AP) m/e 369 (M-H, 7), 337 (8), 235 (6), 189 (4), 149 (11) 85 (100).

Example 138

Methyl ester 4-[[(4-hydroxy-2-oxo-6 - phenyl-2H-Piran-3-yl)thio] methyl]benzoic acid

The target connection get by method B using 2.0 g (10,63 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 3.57 g (10,63 mmol) of complex 4-(carbomethoxy)phenyl)methyl ester of n-toluoldisocyanate, 10,63 ml of 1-AD. of sodium hydroxide and 20 ml of ethanol. So pl. 215 - 216oC.

1H-NMR (400 MHz, DMSO-d6): = 3,81 (s, 3H), 4,06 (s, 2H), 6,69 (s, 1H, J = Hz),07 (18), 189 (37), 151 (55), 119 (20), 105 (21), 85 (28).

Example 139

6-[3,5-bis(trifluoromethyl)phenyl]-4-hydroxy-3-[(phenylmethyl)thio]-2H - Piran-2-he

The target connection get method And using 2.16 g (7.1 mmol) trimethylsilyl ether 3',5'- triftoratsetofenona (resulting from the interaction of 15 g (58,55 mmol) of 3,5-dateformatpattern and 13,01 g (58,55 mmol) trimethylsilylmethylamine in the presence 11,84 g (117,10 mmol) of triethylamine, followed by distillation) and 1.0 g (3,55 mmol) diethyl ether complex [(phenylmethyl)thio] proponderance acid. So pl. 80 - 82oC.

1H-NMR (400 MHz, DMSO-d6): = 4,0 (s, 2 H), of 6.61 (s, 1H), 7,22 (m, 2H), 7,28 (m, 3H), of 7.97 (s, 1H), 8,25 (s, 2H): IR (KBR) 3090, 1726, 1682, 1638, 1549, 1530, 1385, 1281, 1182, 1138, 902, 700 cm-1; MS (AP) m/e 475 (M+29, 3), 447 (M+H, 21), 213 (1), 149 (2), 91 (100).

Example 140

(+/-)-3-[1-[cyclohexyl)thio]-3-methylbutyl]-4-hydroxy-6-phenyl-2H - Piran-2-he

The target connection get method with application of 1.5 g (7,98 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 0,76 g (8,78 mmol) izofluranovogo aldehyde, 2,04 g (17,56 mmol) cyclohexylethane, of 1.05 ml of piperidine, 1.0 ml of acetic acid and 20 ml of ethanol. So pl. 210 - 212oC.

1H-NMR (400 MHz, DMSO-d6): = 0,89 (t, 6N), of 1.36 (m, 6N), the 1.44 (m, 1H), and 1.56 (m, 2H), 1.69 in (m, 2H), is 1.81 (m, 1H)m/e 259 (50), 257 (49), 201 (46), 189 (16), 147 (8), 105 (28), 83 (100).

Example 141

[4-[4-hydroxy-2-oxo-3-[(2-phenylethyl)thio] -2H-Piran - 6-yl] phenoxy] acetonitrile

The target connection get method But using 3.0 g (17,12 mmol) of the appropriate acetophenone, 3.8 g (17,12 mmol) trimethylsilyltrifluoromethane, of 3.46 g (34,24 mmol) of triethylamine and of 2.53 g (8,56 mmol) diethyl ether complex [(2-phenylethyl)thio]proponderance acid. So pl. 157 - 159oC.

1H-NMR (400 MHz, DMSO-d6): = 2,92 (t, 2H), 3,11 (t, 2H), a 4.86 (s, 2H), 6,56 (s, 2H), was 7.08 (d, 2H), 7,19 (t, 3H), and 7.3 (m, 3H), 7,86 (d, 2H); IR (KBr) 2933, 2577, 1634, 1510, 1404, 1342, 1302, 1226, 1188, 1098, 1051, 833, 717, 505 cm-1; MS (AP) m/e 380 (100), 275 (60), 205 (8), 105 (94).

Example 142

4-hydroxy-3-[(2-isopropylphenyl)thio]-6-phenyl-2H - Piran-2-he

The target connection get method And with the use of 1.24 g (6,45 mmol) 1-phenyl-1-(trimethylsilyloxy)ethylene and 1.0 g (3,23 mmol) diethyl ether complex (2-isopropylphenyl)thio] proponderance acid.

1H-NMR (400 MHz, DMSO-d6): = a 1.25 (d, 6N), 3,42 (m, 1H), 6.89 in (s, 1H), 6,92 (DD, 1H), 7,06 (t, 1H), 7,13 (t, 1H), 7,28 (d, 1H), 7,56 (m, 3H), a 7.85 (m, 2H); IR (KBr) 3117, 2962, 1661, 1551, 1406, 1365, 1101, 760 cm-1; MS (AP) m/e 339 (100), 305 (4), 219 (25), 189 (11), 147 (9), 105 (9);

C20H18O3S1:

calculated: 70,98; N ARE 5.36;

nydrocodone (So pl. 136 - 137oC) get by method B using 0,250 g (1,33 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 0,585 r (2,261 mmol) cyclopropylmethyl-p-colortoalpha.c, 0,158 g (of 1.46 mmol) of triethylamine, 0,110 g (of 1.33 mmol) of sodium bicarbonate and 10.0 ml of ethanol.

1H-NMR (250 MHz, CDCl3): = 7,994 - 7,726 (m, 2H), 7,683 - 7,406, (m, 3H), 6,665 (s, 1H), 2,724 - 2,694 (d, 2H, J=7,3 Hz), 1,063 -0,903 (m,1H), 0,608 - of 0.533 (m,2H), 0,270 - 0, 280 (m, 2H).

Example 144

6-(3-chlorophenyl)-4-hydroxy-3-[(4-phenylbutyl)thio]-2H - Piran-2-he

0,024 g of target compound (So pl. 123 - 124oC) get by method B using 0,250 g (1.13 mmol) of 6-(3-chlorophenyl)- 4-hydroxy-2H-Piran-2-it, 0.45 g (1,93 mmol) 4-phenylbutyl-p-colortoalpha.c, 0,115 g (1.13 mmol) of triethylamine, 0,094 g (1.13 mmol) of sodium bicarbonate and 5.0 ml of ethanol.

1H-NMR (400 MHz, DMSO-d6): = 7,848 - 7,839 (m, 1H), 7,729 (m, 1H), 7,479 -7,392 (m, 2H), 7,276 - 7,239 (m, 2H), 7,174 - 7,137 (m, 3H), USD6, 631 (s, 1H), 2,831 - 2,794 (t, 2H), 2,633 - 2,596 (t, 2H), 1,747 - 1,686 (m, 2H), 1,649 - 1,591 (m, 2H).

Example 145

4-hydroxy-3-[(2-oxo-2-phenylethyl)thio]-6-phenyl - 2H-Piran-2-he

The solution 0,175 g (0,840 mmol) 4-hydroxy-3-mercapto-6 - phenyl-2-pyrone in 3.0 ml of dichloromethane in a nitrogen atmosphere is treated first of 0.12 ml (0.84 mmol) of triethylamine, and then 0.167 g (0,840 mmol) bromoacetophenone. The mixture is stirred for 30 minutes ptri times extracted with a saturated solution of sodium carbonate, taken in an amount of 500 ml of the combined aqueous layers are acidified with conc. hydrochloric acid and extracted three times with dichloromethane, taken in an amount of 100 ml of the Organic layer are combined and dried over sodium sulfate. The solvent is removed in vacuum. Receive of 0.066 g of target compound, which is dried in vacuum. So pl. 164 - 166oC.

1H-NMR (300 MHz, DMSO-d6): = 9,900 (Shir.s, 1H), 7,970 (d, 2H, J = 7,1 Hz), 7,810 (d, 2H, J = 8 Hz), 7,615 (t, 1H, J = 4 Hz), 7,505 - 7,443 (m, 5H), 6,619 (s, 1H), 4,334 (s, 2H).

Example 146

4-hydroxy-3-[(2-Penilaian-2-ol)thio-6-phenyl-2H-Piran-2-he

To mix the solution 0,021 g (to 0.060 mmol) 4-hydroxy-3-[(2-oxo-2-phenylethyl)thio] -6-phenyl-2H-Piran-2-it in 1.0 ml of tetrahydrofuran, cooled to 0oC, in an atmosphere of nitrogen syringe add 0.05 ml (0.05 mmol) of 1.0 M solution BH3DMC in tetrahydrofuran. The mixture is stirred for hours, then served in a mixture of 4-N. hydrochloric acid and methanol in the ratio of 1:1. Then the mixture is extracted with diethyl ether. Layers are combined and dried over sodium sulfate. The solvent is removed in vacuum to obtain 0.015 g of target compound in the form of butter.

1H-NMR (200 MHz, CDCl3): = 7,873 - 7,777 (m, 4H), 7,516 - 7,153 (m, 6N), 6,667 (s, 1H), 4,820 - 4,755 (DD, 1H, J = 9.8 Hz, 3.2 Hz), 3,212 - 3,127 (DD,-he

A solution of 1.50 ml (11.3 mmol) of propiophenone in 40.0 ml of dichloromethane is cooled to 0oC in nitrogen atmosphere and treated first 3,14 ml (22,6 mmol) of triethylamine, then 2,60 ml (13.5 mmol) trimethylsilyltriflate. The solution is heated to room temperature and stirred for 15 minutes. Then the solution serves in a mixture of 50 ml of diethyl ether and 20 ml of saline solution and saturated aqueous sodium bicarbonate solution. The layers are separated and the organic layer washed with 20 ml of a mixture of a saturated solution of sodium bicarbonate in a 1:1 ratio.

The ether solution is dried over sodium sulfate and the solvent is removed in vacuum. Get selenology ether served in a flask containing of 1.00 g (3,76 mmol) diethyl ether complex of 2-(thiophenyl)propane-1,3-dicarboxylic acid. The mixture is heated to 140oC for 16 hours. The mixture is allowed to cool to room temperature, after which the mixture was diluted with diethyl ether and extracted three times with a saturated solution of sodium carbonate, taken in an amount of 20 ml Aqueous layers are combined to three times washed with diethyl ether, taken in an amount of 75 ml, and carefully acidified with conc. the hydrochloric acid. Then the mixture is extracted three times with dichloromethane, taken in colclusion 0,350 g of target compound. So pl. 166-167oC.

1H-NMR (400 MHz, DMSO-d6): = 6,309 - 6,285 (m, 2H), 6,227 - 6,211 (m, 3H), 5,983 (t, 2H, J = 8 Hz), 5,862 (d, 3H, J = 8 Hz), 0,705 (s, 3H).

Example 148

[4-[4-hydroxy-2-oxo-3-(phenylthio)-2H-Piran-6 - yl]phenoxy]-acetic acid

A solution of 2.50 g (10,86 mmol) of a compound methyl ester 4-(1-oxoethyl)phenoxyalkanoic acid 25,0 ml of dichloromethane is cooled to 0oC in nitrogen atmosphere and treated first 3,03 ml (by 21.7 mmol) of triethylamine, then 2,52 ml (13,0 mmol) trimethylsilyltrifluoroacetamide. The solution is heated to room temperature and stirred for 15 minutes. Then the solution serves in a mixture of 20 ml of diethyl ether and 20 ml of a saturated solution of aqueous sodium bicarbonate. The layers are separated and the organic layer washed with 20 ml of a mixture of salt solution and a saturated solution of sodium bicarbonate in a 1:1 ratio. The ether solution is dried over sodium sulfate and the solvent is removed in vacuum. Get selenology ether is fed into the flask containing 0.97 g (3.6 mmol) diethyl ether complex of 2-(thiophenyl)propane-1,3-dicarboxylic acid. The mixture is heated to 140oC for 16 hours. The mixture is allowed to cool to room temperature, after which the mixture is subjected to chromatography on silica with a size of the current 2% of methanol. Get the solid product was diluted with 20 ml diethyl ether and extracted three times with a saturated solution of sodium carbonate, taken in an amount of 20 ml Aqueous layers are combined to three times washed with diethyl ether, taken in an amount of 100 ml, and carefully acidified with conc. hydrochloric acid to achieve a pH of 0. Then the mixture is extracted three times with ethyl acetate, taken in an amount of 100 ml, the organic layers combined and dried over sodium sulfate. The solvent is removed in vacuum to obtain 0,695 g of target compound. So pl. 186 - 188oC.

1H-NMR (300 MHz, DMSO-d6): a = 13, 175 (lat.s, 1H), 12,425 (width, 1H), 7,809 (d, 2H, J = 9 Hz), 7,298 - 7,247 (m, 2H), 7,149 - 7,004 (m, 5H) 6,785 (s, 1H), 4,804 (s, 2H).

Example 149

[4-[4-hydroxy-5-methyl-2-oxo-3-(phenylthio)-2H-Piran - 6-yl]phenoxy]-acetic acid

0,691 g (So pl. 194 - 197oC) target connection get a similar way to that of [4-[4-hydroxy-2-oxo-3-(phenylthio)-2H-Piran - 6-yl]phenoxy]-acetic acid (example 50. In this case, applying a 2.00 g (8,81 mmol) of a compound methyl ester 4-(1-oxoethyl)phenoxyalkanoic acid, 3,68 ml (26,4 mmol) of triethylamine, 2.38 ml (12.3 mmol) of trimethylsilyltrifluoroacetamide, 20,0 ml dichloromethane and 1.34 g (5.00 mmol) diethyl ether complex of 2-(thiophenyl)propane-1,3 - dicarboxylic N, J = 9 Hz), 4,784 (s, 2H), 2,042 (s, 3H).

Example 150

4-hydroxy-3-phenoxy-6-phenyl-2H-Piran-2-he

In the autoclave serves 8,11 g (to 0.032 mmol) in diethyl ether complex 2-phenoxypropionic acid and 12,35 g (0,064 mmol) 1-phenyl-1-(trimethylsilyloxy)ethylene. The pressure in the reactor is brought to 42,19 kg/cm2in nitrogen atmosphere. The mixture is boiled at 100oC for 8 hours, then within 63,5 hours at a temperature of 147 - 154oC. the Reactor is cooled to room temperature and washed with ethyl acetate. The crude product subjected to flash chromatography using as eluent a mixture of hexane and ethyl acetate in the ratio of 1: 1 to obtain a partially purified product, which is then subjected to flash chromatography on silica gel using as eluent mixtures of hexane and ethyl acetate in the ratio 95:5-40:60. The resulting solid material is recrystallized from diethyl ether and ethyl acetate to obtain 1.64 g (18%) of target compound. So pl. 215 - 219oC.

1H-NMR (400 MHz, DMSO-d6): = 6,90 (s, 1H), 6,95 (DD, 2H), 7,02 (t, 1H), 7,28 - 7,33 (m, 2H), 7,52 - 7,56 (m, 3H), 7,80 - 7,856 (m, 2H), 12,0 (Shir.s, 1H).

Example 151

4-hydroxy-3-[(phenylmethyl)thio]-6-(3-pyridinyl)-2H - Piran-2-he

The target connection get method And resul]proponderance acid. So pl. 183 - 184oC.

NMR (DMSO-d6): = as 4.02 (s, 2H), 6,83 (s, 1H), 7,20 (m, 1H), 7,26 (d, 4H), 7,55 (m, 1H) 8,16 (m, 1H), 8,69 (m, 1H), 8,98 (d, 1H).

Example 152

6-(2,6-dimethyl-4-pyridinyl)-4-hydroxy-3-[(phenylmethyl)thio]-2H - Piran-2-he

The target connection get method And as a result of condensation trimethylsilylacetamide ether 4-acetyl-2,6-dimethylpyridine with diethyl ether complex [(phenylmethyl)thio]proponderance acid. So pl. 88 - 90oC.

NMR (DMSO-d6): = 2,55 (C, 6N), was 4.02 (s, 2H), 6,85 (s, 1H), 7,16 - 7,28 (m, 5H), 7,40 (s, 2H).

Example 153

4-hydroxy-3-[(phenylmethyl)thio]-6-(3-thienyl)-2H-Piran - 2-he

The target connection get method And as a result of condensation trimethylsilylacetamide ester 3-acetylthiophene with diethyl ether complex [(phenylmethyl)thio]proponderance acid. So pl. 150-151oC.

NMR (DMSO-d6): = 3,98 (s, 2H), return of 6.58 (s, 1H), from 7.24 (m, 5H), of 7.48 (m, 1H), 7,72 (m, 1H) 8,13 (d, 1H).

Example 154

3-[(2,6-dimetilfenil)methyl]thio]-4-hydroxy-6-phenyl - 2H-Piran-2-he

The target connection get by method B using 1,00 g (5,31 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 15 ml of ethanol, 5,31 ml of 1-AD. of sodium hydroxide and of 1.62 g (5,31 mmol) (2,6-dimetilfenil)methyl-p-colortoalpha.c. So pl. 231 - 233oC.



4-hydroxy-6-phenyl-3-[[(3-phenoxyphenyl)methyl)thio]-2H - Piran-2-he

The target connection get by method B using 1,00 g (5,31 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 15 ml of ethanol, 5,31 ml of 1 N. sodium hydroxide and 1.96 g (5,31 mmol) (3-phenoxyphenyl)methyl-p-colortoalpha.c. So pl. 131 - 133oC.

1H-NMR (400 MHz, DMSO-d6): = of 3.97 (s, 2H), 6.73 x (s, 1H), 6.87 in (m, 4H), 7,03 (m, 2H), 7,27 (m, 3H) 7,53 (m, 3H), 7,78 (m, 2H).

Example 156

(+/-)-3-[1-[cyclohexylmethyl)thio] -3-methylbutyl] - 4-hydroxy-6-phenyl-2H-Piran-2-he

The target connection get method with the use of 1.00 g (5,31 mmol) 4-hydroxy-6-phenyl-2H - Piran-2-it, 10 ml of ethanol, 0,462 ml (of 5.84 mmol) izofluranovogo aldehyde, 1,79 g (to 13.8 mmol) cyclohexylmethyl, 0.5 ml of piperidine and 0.5 ml of acetic acid. So pl. 146 - 148oC.

1H-NMR (400 MHz, DMSO-d6): = 0,58 (d, 6N), 1,11 (m, 5H), of 1.57 (m, 8H), 2,07 (m, 1H), 2,28 (DD, 1H) 2,38 (DD, 1H), 4,17 (DD, 1H), 6,69 (s, 1H), 7,54 (m, 3H), of 7.75 (m, 2H), 11,71 (Shir.s, 1H).

Example 157

(+/-)-3-[1-[cyclohexylmethyl)thio] phenylmethyl]-4 - hydroxy-6-phenyl-2H-Piran-2-he

The target connection get method with the use of 1.00 g (5,31 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 10 ml of ethanol, 0,593 ml (of 5.84 mmol) of benzaldehyde, 1,79 g (to 13.8 mmol) cyclohexylmethyl, 0.5 ml of piperidine and 0.5 m is 1H), to 1.61 (m, 3H), of 1.75 (m, 2H) 2,39 (m, 2H), and 5.30 (s, 1H), of 6.71 (s, 1H), 7,26 (t, 1H), 7,28 (m, 2H), 7,53 (m, 5H), 7,74 (m, 2H).

Example 158

4-hydroxy-6-[4-(2-acetoxy)phenyl]-3-[(2-phenylethyl)thio]-2H - Piran-2-he

To a solution of 0.30 r (0.70 mmol) of a compound ethyl ester [4-[4-hydroxy-2-oxo-3-[(2-phenylethyl)thio] -2H-Piran-6-yl] -phenoxy] acetic acid in 7 ml of tetrahydrofuran, add 0.5 ml (1.00 mmol) in 2.0 ml of lithium borohydride. The reaction mixture was stirred over night. Then added to the mixture of 2.0 ml of 1 N. hydrochloric acid and diluted with 50 ml ethyl acetate. The organic layer was separated, washed with a saturated solution of sodium chloride and dried over anhydrous magnesium sulfate. The solvents are evaporated in vacuum and the crude product purified by column chromatography on silica gel with a particle size of 230 - 400 mesh to use as a first eluent mixture of ethyl acetate and hexanol in the ratio of 50 : 50, and then 100% ethyl acetate. So pl. 123 - 125oC.

1H-NMR (400 MHz, DMSO-d6): = 2,77 (t, 2H), 2,97 (t, 2H), 3,37 (m, 2H), 4,07 (t, 2H), 4.92 in (lat. s, 1H) of 6.68 (s, 1H), to 7.09 (d, 2H), 7,19 (m, 5H), of 7.75 (d, 2H).

Example 159

Complex ethyl ester 3-[4-hydroxy-2-oxo-3-[(2 - phenylethyl]thio]- 2H-Piran-6-yl]phenoxy]acetic acid

The target connection get method While using the ritilin, 23 ml of methylene chloride and 1.00 g (3,37 mmol) diethyl ether complex [(2-phenylethyl)thio]-proponderance acid. So pl. 116 - 119oC.

1H-NMR (400 MHz, DMSO-d6): = 1,22 (t, 3H), 2,77 (t, 2H), 3,05 (t, 2H), a 4.86 (d, 2H), 6,80 (s, 1H) 7,20 (m, 7H), 7,44 (m, 2H).

Example 160

4-hydroxy-6-[4-[(5-methyl-3-phenyl-4-isoxazolyl)methoxy] phenyl] -3- [(2-phenylethyl)thio]-2H-Piran-2-he

The target connection get method And using 2.00 g (6,51 mmol) 4'-[(5-methyl-3-phenyl-4-isoxazolyl)methoxy]acetophenone and 1.51 ml (7,81 mmol) trimethylsilyltrifluoroacetamide, is 1.81 ml (13,02 mmol) of triethylamine, 16 ml of methylene chloride and 1.00 g (3,37 mmol) diethyl ether complex [(2-phenylethyl)thio]proponderance acid. So pl. 126 -128oC.

1H-NMR (400 MHz, DMSO-d6): = 2,54 (s, 3H), 2,77 (t, 2H), 2,98 (t, 2H), to 5.08 (s, 2H), 6,69 (s, 1H) 7,21 (m, 7H), 7,49 (m, 3H), 7,71 (m, 2H), to 7.77 (d, 2H).

Example 161

6-(3, 5dimethylphenyl)-4-hydroxy-3-(phenylthio)-2H-Piran-2-he

The target connection get method And with the use of 1.43 g (9,70 mmol) of 3', 5'-dimethylacetophenone, of 2.24 ml (11,64 mmol) trimethylsilyltrifluoroacetamide, 2,70 ml (19,40 mmol) of triethylamine, 24 ml of methylene chloride and 1.00 g (7,46 mmol) diethyl ether complex (phenylthio)-proponderance acid. So pl. 210-211oC.


(+/-)-3-[1-[cyclopentyl] -2-cyclopropylethyl] - 4-hydroxy-6-phenyl-2H-Piran-2-he

The target connection get method with the use of 1.00 g (5,31 mmol) 4-hydroxy-6-phenyl-2H - Piran-2-it, 10 ml of ethanol, 0,892 g (to 10.62 mmol) cyclopropanecarboxaldehyde, 1,43 ml (to 13.8 mmol) cyclopentenyl, 0.5 ml of piperidine and 0.5 ml of acetic acid. So pl. 75 - 80oC.

1H-NMR (400 MHz, DMSO-d6): = 0,04 (m, 2H), 0,07 (m, 2H), 0,66 (m, 1H), 1,53 (m, 7H), was 1.94 (m, 3H) 3,19 (m, 1H), 4,21 (DD, 1H), of 6.71 (s, 1H), 7,54 (m, 3H), 7,76 (m, 2H).

Example 163

N-[3-[4-hydroxy-2-oxo-3-[(2-phenylethyl)thio] -2H-Piran-6-yl] phenyl] - 4-methyl-benzosulfimide

The target connection get method And with the use of 1.38 g (of 5.06 mmol) 3'-(p-toluensulfonate)of acetophenone, of 2.34 ml (12,41 mmol) trimethylsilyltrifluoroacetamide, 2,82 ml (20,24 mmol) of triethylamine, 18 ml of methylene chloride and 1.00 g (3,37 mmol) diethyl ether complex [(2-phenylethyl)thio] proponderance acid. So pl. 133 - 135oC.

1H-NMR (400 MHz, DMSO-d6): = 2,32 (s, 3H), 2,77 (t, 2H), to 3.09 (t, 2H), of 6.68 (s, 1H), 7,19 (m, 6N) 7,40 (m, 4H), 7,53 (s, 1H), to 7.67 (d, 2H), 10,50 (s, 1H), a 12.03 (Shir.s, 1H).

Example 164

3-[cyclopentyl(cyclopentyl)methyl]-4-hydroxy-6 - phenyl-2H-Piran-2-he

The target connection get method with the use of 1.00 g (cyclopentenyl, 0.5 ml of piperidine and 0.5 ml of acetic acid. So pl. 139 - 142oC.

1H-NMR (400 MHz, DMSO-d6) = 1,03 (m, 1H), 1,64 (m, 15 NM), of 2.64 (m, 1H), 3,00 (m, 1H), 3,84 (d, 1H), 6,69 (s, 1H), 7,52 (m, 3H), 7,76 (m, 2H), 11,55 (Shir.s, 1H).

Example 165

6-(1,1'-Biden-3-yl)-4-hydroxy-3-[(2-isopropylphenyl)thio]-2H - Piran-2-he

The target connection get method And using 0,946 g (a 4.83 mmol) 3'-phenylacetophenone, 1,12 ml (5,79 mmol) trimethylsilyltrifluoroacetamide, of 1.34 ml (to 9.66 mmol) of triethylamine, 17 ml of methylene chloride and 1.00 g (3,22 mmol) diethyl ether complex [(2-isopropyl-phenyl)thio]-proponderance acid. So pl. 193 - 195oC.

1H-NMR (400 MHz, DMSO-d6): = a 1.25 (d, 6N), of 3.43 (m, 1H), 6,95 (d, 1H), 7,02 (s, 1H), 7,06 (t, 1H) 7,13 (t, 1H), 7,28 (d, 1H), 7,42 (t, 1H), 7,51 (t, 2H), 7,66 (t, 1H), of 7.75 (d, 2H), 7,85 (t, 2H), 8,07 (s, 1H).

Example 166

4-hydroxy-6-phenyl-3-[(2-propylphenyl)thio]-2H-Piran-2-he

The target connection get method And using 0,990 ml (a 4.83 mmol) 1-phenyl-1-(trimethylsilyloxy)ethylene and 1.00 g (3,22 mmol) diethyl ether complex [(2-propylphenyl)thio]- proponderance acid. So pl. 158-160oC.

1H-NMR (400 MHz, DMSO-d6): = 0,972 (t, 3H), of 1.64 (m, 2H), 2,71 (t, 2H), 6.87 in (s, 1H), 6,92 (m, 1H) 7,06 (m, 2H), 7,16 (m, 1H), 7,55 (m, 3H), a 7.85 (m, 2H).

Example 167

the use of 0,714 g (a 4.83 mmol) of 3', 5'-dimethylacetophenone, 1,12 ml (5,79 mmol) trimethylsilyltrifluoroacetamide, of 1.34 ml (to 9.66 mmol) of triethylamine, 17 ml of methylene chloride and 1.00 g (3,22 mmol) diethyl ether complex [(2-isopropylphenyl)thio]-proponderance acid.

So pl. 154 - 155oC.

1H-NMR (400 MHz, DMSO-d6): = 1,24 (d, 6N), 2,35 (C, 6N), 3,40 (m, 1H), 6.90 to (d, 1H), (t, 1H), 7,05 (t, 1H), 7,11 (dt, 2H), 7,20 (s, 1H), 7,27 (d, 1H), 7,45 (s, 2H).

Example 168

4-hydroxy-6-(4 oksifenil)-3-[(2-isopropylphenyl)thio]- 2H-Piran-2-he

The target connection get method And using 0,657 g (a 4.83 mmol) 4'-oxazolidinone, of 2.05 ml (to 10.62 mmol) trimethylsilyltrifluoroacetamide, 2,69 ml (19,32 mmol) of triethylamine, 20 ml of methylene chloride and 1.00 g (3,22 mmol) diethyl ether complex [(2-isopropylphenyl)thio]-proponderance acid. So pl. 250oC (decomp.).

1H-NMR (400 MHz, DMSO-d6): = 1,24 (d, 6N), 3,40 (m, 1H), 6,70 (s, 1H), 6.90 to (t, 3H), 7,05 (t, 1H) 7,10 (t, 1H), 7,26 (d, 1H), of 7.70 (d, 2H).

Example 169

3-[[2-(cyclopropylmethyl)phenyl]thio]-4-hydroxy-6-phenyl-2H-Piran-2-he

The target connection get method And using 0,990 ml (a 4.83 mmol) 1-phenyl-1-(trimethylsilyloxy)ethylene and 1.00 g (3.10 mmol) in diethyl ether complex [[(2-(cyclopropylmethyl)phenyl]thio]- proponderance sour is (s, 1H), 6,92 (m, 1H), 7,05 (m, 2H), 7,32 (m, 1H), 7,56 (m, 3H), 7,86 (m, 2H).

Example 170

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[4-(pyridine-3 - ylethoxy)phenyl]-2H-Piran-2-he

The target connection get method And with the use of 1.09 g (a 4.83 mmol) 4'-(pyridine-3-ylethoxy)of acetophenone, 1,12 ml (5,79 mmol) trimethylsilyltrifluoroacetamide, of 1.34 ml (to 9.66 mmol) of triethylamine, 17 ml of methylene chloride and 1.00 g (3,22 mmol) diethyl ether complex [(2-isopropylphenyl)thio]-proponderance acid. So pl. 255oC.

1H-NMR (400 MHz, DMSO-d6): = 1,23 (d, 6N), to 3.41 (m, 1H), 5,26 (s, 2H), 6,78 (s, 1H), 6.90 to (d, 1H), was 7.08 (dt, 2H), 7,21 (d, 2H), 7,29 (d, 1H), 7,45 (DD, 1H), 7,82 (d, 2H), to $ 7.91 (d, 1H), 8,56 (d, 1H), 8,71 (s, 1H).

Example 171

Complex ethyl ester 4-[4-hydroxy-5-[(2-isopropylphenyl)thio]- 6-oxo-6N-Piran-2-yl]phenoxyalkanoic acid

The target connection get method And with the use of 2.14 g (9,67 mmol) of a compound ethyl ester (4-acetyl-phenoxy)acetic acid, 4,48 ml (23,20 mmol) trimethylsilyltrifluoroacetamide, 12,93 ml (38,6 mmol) of triethylamine, 20 ml of methylene chloride and 2.00 g (6,45 mmol) diethyl ether complex [(2-isopropylphenyl)thio]-proponderance acid. So pl. 194-196oC.

1H-NMR (400 MHz, DMSO-d6): = of 1.57 (m, N), to 3.41 (m, 1H), 4,81 (kV, 2H), 4,89 (s, 2H), 6.75 in (with the EN-2-yl]- phenoxyalkanoic acid

To 0,319 g (0.75 mmol) of a compound ethyl ester 4-[4-hydroxy-5-[(2-isopropylphenyl)thio]-6-oxo-6N-Piran-2-yl] phenoxyalkanoic acid in 10 ml of tetrahydrofuran, add 1.80m (1,81 mmol) 1-N. of sodium hydroxide. The reaction mixture was stirred for 1.5 hours, after which the mixture add 10 ml of water, followed by acidification with conc.hydrochloric

acid to achieve a pH of 2. The aqueous layer was twice extracted with ethyl acetate, taken in an amount of 100 ml the combined organic extracts washed with saturated sodium chloride solution and dried over anhydrous magnesium sulfate. After removal of the solvent in vacuum the crude product is purified by column chromatography on silica gel with a particle size of 230 - 400 mesh using as elution solvent a mixture of methylene chloride, methanol and acetic acid in the ratio of 94 : 5 : 1. So pl. 217oC (decomp.).

1H-NMR (400 MHz, DMSO-d6): = a 1.25 (d, 6N), 3,42 (m, 1H), 4,79 (s, 2H), 6.75 in (s, 1H), 6.90 to (d, 1H), 7,06 (m, 4H), 7,26 (d, 1H), 7,79 (d, 2H).

Example 173

4-hydroxy-3-[(2-isopropylphenyl)thio]-6-(4-methoxyphenyl)-2H - Piran-2-he

The target connection get method And with the use of 2.26 g (15.1 mmol) of 4'-methoxyacetophenone, 3.5 ml (18,1 mmol) trimethylsilyltrifluoroacetamide, 4.26 deaths ml (30,6 what about]- proponderance acid. So pl. 221 - 223oC.

1H-NMR (400 MHz, DMSO-d6): = a 1.25 (d, 6N), 3,40 (m, 1H), 3,85 (s, 3H), 6,78 (s, 1H), 6,92 (m, 1H), 7,10 (m, 4H), 7,27 (m, 1H), 7,81 (d, 2H), 12,38 (Shir.s, 1H).

Example 174

4-hydroxy-3-[(2-isopropylphenyl)thio]-6-(4-were)- 2H-Piran-2-he

The target connection get method And using 2,02 g (15.1 mmol) of 4'-methylacetophenone, 3.5 ml (18,1 mmol) trimethylsilyltrifluoroacetamide, 4.26 deaths ml (30,6 mmol) of triethylamine, 30 ml of methylene chloride and 3.11 g (10.0 mmol) diethyl ether complex [(2-isopropylphenyl)thio]- proponderance acid. So pl. 191 - 193oC.

1H-NMR (400 MHz, DMSO-d6): = a 1.25 (d, 6N), 2,39 (s, 3H), 3,41 (m, 1H), 6,84 (s, 1H), 6,92 (m, 1H), 7,10 (m, 2H), 7,27 (m, 1H), 7,37 (m, 2H), of 7.75 (d, 2H).

Example 175

6-(3,4-dichlorophenyl)-4-hydroxy-3-[(2-isopropylphenyl)thio]-2H - Piran-2-he

The target connection get method And with the use of 2.46 g (12.8 mmol) of 3', 4'-dichloroacetophenone, 3.0 ml (to 15.4 mmol) trimethylsilyltrifluoroacetamide, 3.6 ml (26.0 mmol) of triethylamine, 30 ml of methylene chloride and 4.0 g (12.8 mmol) of the diethyl ether complex [(2-isopropylphenyl)thio]-proponderance acid. So pl. 204 - 207oC.

1H-NMR (400 MHz, CDCl3): = 1,33 (d, 6N), 3,55 (m, 1H), of 6.71 (s, 1H), 7,00 (m, 1H), was 7.08 (m, 1H), 7,20 (m, 1H), 7,30 (m, 1H), 7,56 (d, 1H), 7,69 (m, 1H), 7,74 (the first connection receiving method And with the use of 2.33 g (15.1 mmol) of 4'-chloroacetophenone, 3.5 ml (18,1 mmol) trimethylsilyltrifluoroacetamide, 4.26 deaths ml (30,6 mmol) of triethylamine, 30 ml of methylene chloride and 3.11 g (10.0 mmol) diethyl ether complex [(2-isopropylphenyl)thio]proponderance acid. So pl. 148 - 151oC.

1H-NMR (400 MHz, DMSO-d6): = a 1.25 (d, 6N), to 3.41 (m, 1H), 6,86 (s, 1H), 6,92 (m, 1H), was 7.08 (m, 2H), 7,27 (m, 1H), 7.62mm (m, 2H), 7,86 (m, 2H).

Example 177

Complex ethyl ester 4-[4-hydroxy-5-[(2-isopropylphenyl)thio]-6 - oxo-6N-Piran-2-yl]benzoic acid

The target connection get method And with the use of 2.93 g (15.1 mmol) of a compound ethyl ester 4-acetylbenzoic acid, 3.5 ml (18,1 mmol) trimethylsilyltrifluoroacetamide, 4.26 deaths ml (30,6 mmol) of triethylamine, 30 ml of methylene chloride and 3.11 g (10.0 mmol) diethyl ether complex [(2-isopropylphenyl)thio]proponderance acid. So pl. 201 -203oC.

1H-NMR (400 MHz, DMSO-d6): = a 1.25 (d, 6N), of 1.35 (t, 3H), 3,42 (m, 1H), 4,35 (kV, 2H), 6,94 (m, 1H), 7,00 (s, 1H), 7,10 (m, 2H), 7,28 (m, 1H), 7,99 (m, 2H), 8,11 (m, 2H).

Example 179

4-hydroxy-6-(3 oksifenil)-3-[(2-isopropylphenyl)thio]- 2H-Piran-2-he

The target connection get method And with the use of 2.06 g (15.1 mmol) of 3'-oxazolidinone, 7,0 ml (36,2 mmol) trimethylsilyltrifluoroacetamide, charged 8.52 ml (61,1 mmol) of triethylamine, 30 ml chloride M1 - 204oC.

1H-NMR (250 MHz, DMSO-d6): = a 1.25 (d, 6N), to 3.41 (m, 1H), PC 6.82 (s, 1H), 6,93 (m, 2H), to 7.09 (m, 2H), 7,30 (m, 4H), to 9.91 (width, 1H).

Example 180

4-hydroxy-3-[(2-isopropylphenyl)thio]-2H-6-(2-phenylethyl-1-ene)- Piran-2-he

The target connection get method And with the use of 2.23 g (15.1 mmol) of TRANS-4-phenyl-3-uten-2-it, 3.5 ml (18,1 mmol) trimethylsilyltrifluoroacetamide, 4.26 deaths ml (30,6 mmol) of triethylamine, 30 ml of methylene chloride and 3.11 g (10.0 mmol) diethyl ether complex [(2-isopropylphenyl)thio]proponderance acid. So pl. 190 - 192oC.

1H-NMR (400 MHz, DMSO-d6): = a 1.25 (d, 6N), 3,40 (m, 1H), 6,44 (s, 1H), 6.89 in (m, 1H), 7,10 (m, 3H), 7,27 (m, 1H), 7,40 (m, 4 H), 7,71 (d, 2H).

Example 181

6-(1,1'-Biden-4-yl)-4-hydroxy-3-[(2-isopropylphenyl)thio]-2H - Piran-2-he

The target connection get method And with the use of 3.06 g (15.1 mmol) of 4-acetylbiphenyl, 3.5 ml (18,1 mmol) trimethylsilyltrifluoroacetamide, 4.26 deaths ml (30,6 mmol) of triethylamine, 30 ml of methylene chloride and 3.11 g ( 10.1 mmol) diethyl ether complex [(2-isopropylphenyl)thio]-proponderance acid. So pl. 203 - 206oC.

1H-NMR (250 MHz, DMSO-d6): = 1,26 (d, 6N), 3,40 (m, 1H), 6,94 (m, 2H), 7,10 (m, 2H), 7,28 (m, 1H), 7,51 (m, 3H), to 7.77 (m, 2H), to $ 7.91 (kV, 4H).

Example 181

6-(1,1'-biphenyl-3-yl)mmol) 3'-phenylacetophenone, of 2.27 g (10,20 mmol) trimethylsilyltrifluoroacetamide, of 2.06 g (20,40 mmol) of triethylamine, 20 ml of methylene chloride and of 1.62 g (5.1 mmol) diethyl ether complex [(2-naphthalen-2-yl)thio]-proponderance acid. So pl. 183 - 185oC.

1H-NMR (400 MHz, DMSO-d6): = 7,07 (s, 1H), 7,33 (DD, 1H), 7,39 - 7,58 (m, 5H), 7,66 (s, 1H), 7,69 (d, 1H), 7,78 (d, 1H), 7,81 - a 7.92 (m, 6N), 8,11 (s, 1H).

Example 182

4-hydroxy-3-[(naphthalen-1-yl)thio]-6-phenyl-2H-Piran-2-he

The target connection get method And with the use of 1.95 g (10,14 mmol) 1-phenyl-1-(trimethylsilyloxy)ethylene and 1.61 g (5,07 mmol) diethyl ether complex [(1-naphthyl)thio] proponderance acid. So pl. 242 - 243oC.

1H-NMR (400 MHz, DMSO-d6): = 6,83 (s, 1H), 7,19 (d, 1H), 7,39 (t, 1H), of 7.64 - 7,42 (m, 5H), of 7.69 (d, 1H), 7,83 (m, 2H), 7,94 (d, 1H), 8,28 (d, 1H).

Example 183

6-(1,1'-biphenyl-3-yl)-3-[(2-cyclopropylethyl)phenylthio] -4 - hydroxy-2H-Piran-2-he

The target connection get method But using 2 g (10,20 mmol) 3'-phenylacetophenone, and 2.27 g (10,20 mmol) trimethylsilyltrifluoroacetamide, of 2.06 g (20,40 mmol) of triethylamine, 20 ml of methylene chloride and 1.14 g (5.1 mmol) diethyl ether complex [(2-cyclopropylethyl)phenyl)thio]proponderance acid. So pl. 88oC.

1H-NMR (400 MHz, DMSO-d6

Example 184

3-[(2-(cyclopropylmethyl)phenyl)thio] -6-(3,5-dimethyl-phenyl)- 4-hydroxy-2H-Piran-2-he

The target connection get method But using 2 g (13,51 mmol) of 3,3'-dimethylacetophenone, 3 g (of 13.1 mmol) trimethylsilyltrifluoroacetamide, 2,73 g (27,02 mmol) of triethylamine, 20 ml of methylene chloride and 2.18 g (6,76 mmol) diethyl ether complex [[2-(cyclopropylmethyl)-phenyl]thio] proponderance acid.

So pl. 168oC.

1H-NMR (400 MHz, DMSO-d6): = 0,28 (d, 2H), 0,39 (DD, 2H), 1,13 (m, 1H), 2,36 (C, 6N), to 2.67 (d, 2H), 6,85 (s, 1H), 6,92 (m, 1H), 7,11 (m, 2H), 7,22 (s, 1H), 7,33 (m, 1H), 7,47 (s, 2 H).

Example 185

6-(1,1'-biphenyl-3-yl)-4-hydroxy-3-[(2-isoutility)thio]- 2H-Piran-2-he

The target connection get method But using 2 g (10,20 mmol) 3'-phenylacetophenone, and 2.27 g (10.2 mmol) of trimethylsilyltrifluoroacetamide, of 2.06 g (20,40 mmol) of triethylamine, 20 ml of methylene chloride and 1.14 g (5.1 mmol) diethyl ether complex [(2-isobutylphenyl)thio]-proponderance acid. So pl. 187 - 188oC.

1H-NMR (400 MHz, DMSO-d6): = 0,83 (d, 6 H), of 1.78 (m, 1H), 2,4 (d, 2H), 7,03 (s, 1H), was 7.08 (s, 4H), 7,44 (t, 1H), 7,53 (t, 2H), to 7.67 (t, 1H), of 7.75 (s, 1H), 7,78 (s, 1H), 7,86 (m, 2H), 8,08 (s, 1H).

Example 186

4-hydroxy-3-[(2-isobutylphenyl)thio]-6-phenyl-2H-yloxy)ethylene and 1.64 g (5.1 mmol) diethyl ether complex [(2-isobutylphenyl)thio] proponderance acid.

So pl. 195oC.

1H-NMR (400 MHz, DMSO-d6): = 0,83 (d, 6N), of 1.64 (m, 1H), 2,39 (d, 2H), 6.89 in (s, 1H), 7,06 (s, 4H), 7,56 (m, 3H), 7,86 (m, 2H).

Example 187

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[4-(pyridin-3-yl)phenyl] - 2H-Piran-2-he

The target connection get method But using 1-g (3,22 mmol) diethyl ether complex [(2-isopropylphenyl)thio] proponderance acid, 1.18 g (5,31 mmol) trimethylsilyltrifluoroacetamide, and 0.98 g (to 9.66 mmol) of triethylamine and 0.95 g (a 4.83 mmol) 3-(pyridin-3-yl)-acetophenone. So pl. 145 - 147oC.

1H-NMR (400 MHz, DMSO-d6): = a 1.25 (d, 6N), 3,4 (m, 1H), 6.89 in (s, 1H), 6,92 (d, 1H), 7,06 (m, 2H), 7,25 (d, 1H), 7,53 (m, 1H), 7,69 (t, 1H), 7,89 (d, 2H), 8,14 (s, 1H), they were 8.22 (d, 1H), 8,61 (Shir.s, 1H), 8,97 (Shir.s, 1H).

Example 188

4-hydroxy-3-[(2-isopropylphenyl)thio]-6-(3-were))-2H-Piran-2-he

The target connection get method And with the use of 0.87 g (6,46 mmol) 3'-methylacetophenone, 1.44 g (6,46 mmol) trimethylsilyltrifluoroacetamide, 0,653 g (6,46 mmol) of triethylamine, 20 ml of methylene chloride and 1.0 g (3,23 mmol) diethyl ether complex [(2-isopropylphenyl)thio]-proponderance acid. So pl. 161 - 162oC.

1H-NMR (400 MHz, DMSO-d6): ' = 1,25 (d, 6N), 2,39 (s, 3H), 3,42 (m, 1H), 6,86 (s, 1H), 6,92 (d, 1H), 7,07 (t, 1H), 7,13 (t, 1H), 7,28 (d, 1H), 7,39 (d, 1H) who Evoe connection get method And using 2,62 g (to 13.6 mmol) 1-phenyl-1-trimethylsilyloxy)ethylene and 2.0 g (6.8 mmol) complex diethyl ether 2-(isopropyl) PEROXYDICARBONATE acid.

1H-NMR (250 MHz, DMSO-d6): = a 1.25 (d, 6N), 3,44 (m, 1H), to 6.67 (d, 1H), 6.89 in (s, 1H), 7,0 (t, 1H), to 7.09 (t, 1H), 7,29 (d, 1H), 7,53 (m, 3H), 7,83 (m, 2H).

Example 190

6-(3-chlorophenyl)-4-hydroxy-3-[(2-isopropylphenyl)thio]-2H - Piran-2-he

The target connection get method But using 3 g (19,41 mmol) 3'-chloroacetophenone, or 4.31 g (19,41 mmol) trimethylsilyltrifluoroacetamide, to 3.92 g (38,82 mmol) of triethylamine, 20 ml of methylene chloride and 3.0 g (9,71 mmol) diethyl ether complex [(2-isopropylphenyl)thio] proponderance acid. Yield: 70 %. So pl. 177 - 178oC.

1H-NMR (400 MHz, DMSO-d6): = 0,28 (d, 6N), 3,42 (m, 1H), 6,92 (d, 1H), 6,94 (s, 1H), 7,06 (t, 1H), 7,13 (t, 1H), 7,28 (d, 1H), 7,58 (t, 1H), 7,63 (t, 1H), 7,83 (d, 1H), 7,89 (s, 1H).

Example 191

6-(3,5-dichlorophenyl)-4-hydroxy-3-[(2-isopropylphenyl)thio]-2H - Piran-2-he

The target connection get method But using 2 g of 10.58 mmol) of 3,5-dichloroacetophenone, 2.35 g (of 10.58 mmol) trimethylsilyltrifluoroacetamide, 2.14 g (21,16 mmol) of triethylamine, 20 ml of methylene chloride and 1.64 g (from 5.29 mmol) in diethyl ether complex [(2-isopropylphenyl)thio]-proponderance acid. Yield: 70%. So pl. 168 - 169oC,

1H-NMR (400 MHz, DMSO-d6): = a 1.25 (d, 6N), 3,42 (m, 1H), 6,92 (d, 1H), 7,01 (s, 1H), 7,06 (t, 1H), 7,13 (t, 1H), 7,28 (d, 1H), 7,83 (m, 1H), 7,88 (m, 2H).

the using of 1.95 g (10,14 mmol) 1-phenyl-1-(trimethylsilyloxy)ethylene and 2.0 g (6.8 mmol) diethyl ether complex [(2,6-dimetilfenil)thio] proponderance acid. So pl. 248 - 249oC.

1H-NMR (400 MHz, DMSO-d6): = 2,47 (C, 6N), to 6.75 (s, 1H), was 7.08 (m, 3H), 7,39 (m, 3H), 7,78 (m, 2H).

Example 193

4-hydroxy-3-[(2-were)thio]-6-phenyl-2H-Piran-2-he

The target connection get method And with the use of 1.95 g (10,14 mmol) 1-phenyl-1-(trimethylsilyloxy)ethylene and 1.43 g (5,07 mmol) diethyl ether complex [(2-were)thio] proponderance acid. So pl. 210-211oC.

1H-NMR (400 MHz, DMSO-d6): = 2,47 (s, 3H), PC 6.82 (s, 1H), 6,86 (d, 1H),? 7.04 baby mortality (m, 2H), 7,17 (d, 1H), 7,56 (m, 3H), 7,86 (m, 2H).

Example 194

3-(2,6-dichlorophenyl)thio]-4-hydroxy-6-phenyl-2H-Piran - 2-he

The target connection get method And using 1,72 g (8,93 mmol) 1-phenyl-1-(trimethylsilyloxy)ethylene and 1,5 r (4,46 mmol) diethyl ether complex [(2,6-dichlorophenyl)thio]proponderance acid. So pl. 264 - 265oC.

1H-NMR (400 MHz, DMSO-d6): = 6.75 in (s, 1H), 7,31 (m, 1H), 7,49 (d, 2H), 7,56 (m, 3H), 7,78 (m, 2H).

Example 195

Complex ethyl ester(+/-)-4-[5-(1-cyclopentyl-3-methylbutyl)- 4 - hydroxy-6-oxo-6N-Piran-2-yl]benzoic acid

The target connection receive according To the method using 1.50 g (5,77 mmol) 4-hydroxy-6-(4'-carbamaxepine)- 2H-Piran-2-it, 15 ml of ethanol, 0,497 g (5,77 mmol) izofluranovogo al the>

1H-NMR (400 MHz, DMSO-d6): = 1,05 - 0,72 (m, 10H), 1,81 - 1,14 (m, 7H), 2,13 - of 1.81 (m, 3H), 3.04 from (t, 1H), 4,22 (m, 1H) 4,36 (kV, 2H), 6,8 (s, 1H), of 7.90 (d, 1H), 7,97 (kV, 1H), 8,15 (m, 2H).

Example 196

(+/-)-3-[[(benzylthio)pyridine-3-yl]methyl]-4-hydroxy - 6-phenyl-2H-Piran-2-he

The target connection receive according To the method using 1.50 g (7,98 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 10 ml of ethanol, 0,86 g (7,98 mmol) pyridine-3-carboxaldehyde, 1.98 g (15,96 mmol) benzylmercaptan, 0.5 ml of piperidine and 0.5 ml of acetic acid. So pl. 103 - 106oC.

1H-NMR (400 MHz, DMSO-d6): = a 3.75 (q, 2H), 5,31 (s, 1H), 6,33 (s, 1H), 7,2 (m, 1H), 7,28 (m, 5H), was 7.36 (m, 3H), 7,72 (m, 2H), 7,89 (d, 1H), scored 8.38 (DD, 1H), to 8.57 (s, 1H).

Example 197

3-(1-cyclopentyl-2-cyclopropylethyl)-6-(2,3 - dihydrobenzo[1,4] dioxin-6-yl)-4-hydroxy-2H-Piran-2-he

The target connection get method with the use of 1.00 g (4,06 mmol) 4-hydroxy-6-(2,3-dihydrobenzo[1,4] dioxin-6-yl)-2H-Piran-2 - it, 15 ml of ethanol, 0.34 g (4,06 mmol) cyclopropanecarboxaldehyde, or 0.83 g (8,12 mmol) cyclopentenyl, 1.0 ml of piperidine and 1.0 ml of acetic acid. So pl. 80 - 82oC.

1H-NMR (400 MHz, DMSO-d6): = 0,03 (m, 2H), 0,33 (m, 2H), 0.64 in (m, 1H), 1,28 -1,74 (m, 7H), 1,83 - to 2.06 (m, 3H), 3,06 (m, 1H), 4,2 (m, 1H), or 4.31 (m, 4H), 6,53 (s, 1H), 7,0 (d, 1H), 7,24 (d, 1H), 7,24 (DD, 2H).

Example 198

4-[[(4-the Ira 4-[[4-hydroxy-2-oxo-3- [(2-phenylethyl)thio] -2H-Piran-6-yl] ] phenoxy] methyl]benzoic acid in 20 ml of dioxane is added 2-N. sodium hydroxide, and then methanol to ensure homogeneity of the reaction mixture. The mixture is stirred at room temperature for 24 hours. The solvents are evaporated and the residue acidified with 3-N. hydrochloric acid. The precipitated product is filtered, washed with diethyl ether and dried in vacuum. So pl. 227oC.

1H-NMR (400 MHz, DMSO-d6): = 2,78 (t, 2H), 2,97 (t, 2H), from 5.29 (s, 2H), 6,72 (s, 1H), 7,14 - to 7.32 (m, 7H), 7,58 (d, 2H), 7,78 (d, 2H), of 7.97 (d, 2H).

Example 199

Complex ethyl ester of 4-(4-hydroxy-6-oxo-5-[(2-phenylethyl)thio]- 6N-Piran-2-yl)-benzoic acid

The target connection get method But using 3 g (15,61 mmol) of 4-carbomethoxyamino, 3,47 g (15,61 mmol) trimethylsilyltrifluoroacetamide, and 3.16 g (31,22 mmol) of triethylamine, 20 ml of methylene chloride and 2,31 g (7,81 mmol) diethyl ether complex [(2-phenylethyl)thio]proponderance acid. So pl. 156 - 158oC .

1H-NMR (400 MHz, DMSO-d6): = 1,36 (t, 3H), 2,78 (t, 2H), 3,01 (t, 2H), 4,35 (kV, 2H), 6,86 (s, 1H), 7,11 - 7,28 (m, 5H), 7,92 (d, 2H), 8,08 (d, 2H).

Example 200

4-(4-hydroxy-6-oxo-5-[(2-phenylethyl)thio]-6N-Piran-2 - yl)-benzoic acid

0.2 g of complex ethyl ester of 4-(4-hydroxy-6 - oxo-5-(2-phenylethyl)thio-6N-Piran-2-yl)benzoic acid omelet described in priorem, 5H), 7,92 (d, 1H), to 7.99 (d, 1H), with 8.05 (d, 1H), 8,08 (d, 1H).

Example 201

6-(2,3-dihydrobenzo[1,4] dioxin-6-yl)-4-hydroxy-3- [(2-isopropylphenyl)thio] -2H-Piran-2-he

The target connection get method But using 2 g (11,22 mmol) of 1,4-benzodioxin-6-yl-ketone, 2.5 g (11,22 mmol) trimethylsilyltrifluoroacetamide, and 2.27 g (of 22.44 mmol) of triethylamine, 20 ml of methylene chloride and 1.73 g (5,61 mmol) diethyl ether complex [(2-isopropylphenyl)thio]proponderance acid. So pl. 246 - 248oC.

1H-NMR (400 MHz, DMSO-d6): = a 1.25 (d, 6N), 3,4 (m, 1H), 4,32 (m, 4H), 6,72 (s, 1H), 6.89 in (d, 1H), 7,01 (t, 1H), 7,06 (t, 1H), 7,11 (t, 1H), 7,26 (d, 1H), 7,31 (d, 1H), 7,35 (DD, 1H).

Example 202

3-(1-benzylthio-3-methylbutyl)-6-(2,3-dihydrobenzo[1,4] dioxin-6-yl) -4-hydroxy-2H-Piran-2-he

The target connection get method with the use of 1.00 g (4,06 mmol) 4-hydroxy-6-(2,3-dihydrobenzo[1,4] dioxin-6-yl)-2H-Piran-2 - it, 15 ml of ethanol, 0.35 g (4,06 mmol) izofluranovogo aldehyde, 1.0 g (8,12 mmol) of benzyl mercaptan, 0.5 ml of piperidine and 0.5 ml of acetic acid.

1H-NMR (400 MHz, DMSO-d6): = 0,78 (t, 6N), of 1.36 (m, 1H), 1,5 (m, 1H), 2.06 to (m, 1H), 4,2 (m, 1H), or 4.31 (Shir.m, 6N), 6,56 (s, 1H), 7,03 (d, 2H), was 7.36 - 7,25 (m, 6N).

Example 203

(+/-)-3-[[(cyclohexylthio)pyridine-4-yl] methyl] -4 - hydroxy-6-phenyl)-2H-Piran-2-he

1H-NMR (400 MHz, DMSO-d6): = 1,25 (m, 5H), of 1.53 (m, 1H), 1,67 (m, 2H), 1,92 (m, 2H), 2,71 (m, 1H), 5,33 (s, 1H), 6,69 (s, 1H), 7.5 (m, 5H), to 7.75 (m, 2H), of 8.47 (d, 2H).

Example 204

(+/-)-3-[[(cyclohexylthio)pyridine-3-yl] methyl] -4 - hydroxy-6-phenyl)-2H-Piran-2-he

The target connection receive according To the method using 1.5 g (7,98 mmol) 4-hydroxy-6-phenyl-2H-Piran-2-it, 10 ml of ethanol, 0,86 g (7,98 mmol) pyridine-3-carboxaldehyde, 1.86 g (7,98 mmol) cyclohexylethyl, 0.5 ml of piperidine and 0.5 ml of acetic acid.

1H-NMR (400 MHz, DMSO-d6): = 1,25 (m, 5H), of 1.53 (m, 1H), 1,67 (m, 2H), 1,92 (m, 2H), 2,69 (m, 1H), 5,39 (s, 1H), 6,72 (s, 1H), 7,33 (m, 1H), 7,53 (m, 3H), 7,73 (m, 2H), of 7.97 (d, 1H), 8,39 (d, 1H), 8,67 (d, 1H).

Example 205

4-[[(4-hydroxy-2-oxo-6-phenyl-2H-Piran-3-yl)thio]methyl] benzoic acid

The target compound is obtained saponification 0.1 g complex methyl ester 4-[[(4-hydroxy-2 - oxo-6-phenyl-2H-Piran-3-yl) thio]methyl]benzoic acid described in example 200.

1H-NMR (400 MHz, DMSO-d6): = 4,06 (s, 2H), 6,72 (s, 1H), was 7.36 (d, 2H), 7,58 (m, 3H), 7,86 (m, 4H).

Example 206

3-[[(4-hydroxy-2-oxo-6-phenyl-2H-Piran-3-yl)thio]methyl] benzoic acid

Whole-yl)thio] methyl]benzoic acid described in example 200.

1H-NMR (400 MHz, DMSO-d6): = 4,4 (d, 1H), 4.72 in (d, 1H), 6,72 (s, 1H), and 7.4 (t, 1H), 7,44 - to 7.61 (m, 5H), 7,74 - a 7.92 (m, 4H).

Example 207

2-[[(4-hydroxy-2-oxo-6-phenyl-2H-Piran-3-yl)thio]methyl]benzoic acid

The target compound is obtained saponification 0.2 g complex methyl ester 2-[[(4-hydroxy-2-oxo-6-phenyl-2H-Piran-3-yl)thio]methyl] benzoic acid described in example 200.

1H-NMR (400 MHz, DMSO-d6): = 4,36 (s, 2H), 6,69 (s, 1H), 7,18 (d, 1H), 7,29 (m, 1H), 7,39 (t, 1H), 7,53 (m, 3H), 7,79 (m, 3H).

Example 208

3-[(2-chlorophenylthio)-4-hydroxy-6-phenyl-2H-Piran-2-he

The target connection get method And with the use of 1.95 g (10,14 mmol) 1-phenyl-1-(trimethylsilyloxy)ethylene and 1.53 g (5,07 mmol) diethyl ether complex [(2-chlorophenyl)thio] proponderance acid. So pl. 275 - 280oC.

1H-NMR (400 MHz, DMSO-d6): = is 6.78 (s, 1H), 6.89 in (DC, 1H), 7,08 (TT, 1H), 7,19 (TT, 1H), 7,42 (DD, 1H), 7,56 (m, 3H), of 8.06 (m, 2H).

Example 209

4-hydroxy-3-[(2-methoxyphenyl)thio]-6-phenyl-2H-Piran-2-he

The target connection get method And with the use of 1.95 g (10,14 mmol) 1-phenyl-1-(trimethylsilyloxy)ethylene and 1.51 g (5,07 mmol) diethyl ether complex [(2-methoxyphenyl)thio] proponderance acid. So pl. 208 - 209oC.

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Example 210

6-(4-benzyloxyphenyl)-4-hydroxy-3-[(2-isopropylphenyl)thio]-2H - Piran-2-he

The target connection get method And using 0.3 g (0,675 mmol) of 4-benzyloxyacetophenone, 0.15 g (0,675 mmol) trimethylsilyltrifluoroacetamide, 0.14 g (1.35 mmol) of triethylamine, 20 ml of methylene chloride and 0,210 g (0,675 mmol) diethyl ether complex [(2-isopropylphenyl)thio]-proponderance acid. So pl. 163 - 165oC.

1H-NMR (400 MHz, DMSO-d6): = 1,28 (d, 6N), 3,4 (m, 1H), 5,22 (s, 2H), only 6.64 (s, 1H), 6,92 (d, 1H), 7,06 (t, 1H), 7,11 (t, 1H), 7,19 (d, 1H), 7,28 (d, 1H), was 7.36 (q, 2H), 7,42 (d, 2H), 7,49 (d, 2H), 7,83 (d, 2H).

Example 211

3-[(3-chlorophenyl)thio]-4-hydroxy-6-phenyl-2H-Piran-2-he

The target connection get method And with the use of 1.95 g (10,14 mmol) 1-phenyl-1-(trimethylsilyloxy)ethylene and 1.53 g (5,07 mmol) diethyl ether complex [(3-chlorophenyl)thio] proponderance acid. So pl. 181 -182oC.

1H-NMR (400 MHz, DMSO-d6): = 6,88 (s, 1H), 7,13 (dt, 2H), 7,19 (dt, 1H), 7,29 (m, 1H), 7,56 (m, 3H), 7,86 (m, 2H).

Example 212

4-hydroxy-3-[(3-methoxyphenyl)thio]-6-phenyl-2H-Piran-2-he

The target connection get method And with the use of 1.95 g (10,14 mmol) 1-phenyl-1-(trimethylsilyloxy)ethylene and 1.51 g (5,07 mmol) diethyl ether complex [(3-UB>): = of 3.69 (s, 3H), 6,69 (DD, 1H), 6,72 (DD, 1H), 6.89 in (s, 1H), 7,2 (dt, 2H), 7,58 (m, 3H), 7,88 (m, 2 H).

Example 213

4-hydroxy-3-[(3-were)thio]-6-phenyl-2H-Piran-2-he

The target connection get method And with the use of 1.95 g (10,14 mmol) 1-phenyl-1-(trimethylsilyloxy)ethylene and 1.43 g (5,07 mmol) diethyl ether complex [(3-were)thio] proponderance acid. So pl. 197-198oC.

1H-NMR (400 MHz, DMSO-d6): = 2,24 (s, 3H), 6.89 in (s, 1H), 6,93 (t, 1H), 6,97 (s, 1H), 7,14 (t, 2H), 7,56 (m, 3H), 7,86 (m, 2H).

Example 214

3-[(2-ethylphenyl)thio]-4-hydroxy-6-phenyl-2H-Piran-2-he

The target connection get method And with the use of 4.17 g (21,72 mmol) 1-phenyl-1-(trimethylsilyloxy)ethylene and 1.5 g (10,86 mmol) diethyl ether complex [(2-ethylphenyl)thio] proponderance acid. So pl. 190-192oC.

1H-NMR (400 MHz, DMSO-d6): = a 1.25 (t, 3H), 2,78 (kV, 2H), 6.89 in (s, 1H), 6,92 (m, 1H), was 7.08 (m, 2H), 7,2 (m, 1H), 7,58 (m, 3H), 7,86 (m, 2H).

Example 215

Complex 3-[(2-isopropylphenyl)thio]2-oxo-6-phenyl - 2H-Piran-4-silt ether acetic acid

Connection get method W in the processing of 0.2 g (0.59 mmol) of sodium salt of 4-hydroxy-3-[2-isopropylphenyl)thio]-6-phenyl-2H-Piran-2-it is the acid chloride of acetic acid, taken in the amount of 0.09 g (1.18 mmol). is), ? 7.04 baby mortality (dt, 1H), 7,13 (dt, 1H), 7,28 (DD, 1H), 7,58 (m, 3H), 7,86 (m, 2H).

Example 216

4-hydroxy-6-phenyl-3-[(3-triptoreline)thio]-2H-Piran-2-he

The target connection get method And using 1,72 g (of 8.92 mmol) 1-phenyl-1- (trimethylsilyloxy)ethylene and 1.5 g (4,46 mmol) diethyl ether complex [(3-trifluoromethyl)phenyl)thio]proponderance acid. So pl. 228 - 229oC.

1H-NMR (400 MHz, DMSO-d6): = 6,89 (s, 1H), 7,4 - to 7.61 (m, 7H), 7,89 (m, 2H).

Example 217

3-[3, 5dimethylphenyl)thio]-4-hydroxy-6-phenyl-2H-Piran-2-he

The target connection get method And using 1.3 g (6,76 mmol) 1-phenyl-1-(trimethylsilyloxy)ethylene and 1.0 g (3,38 mmol) diethyl ether complex [(3, 5dimethylphenyl)thio] proponderance acid. So pl. 214-216oC.

1H-NMR (400 MHz, DMSO-d6): = 2,2 (s, 6N), 6.75 in (lat.s, 3H), 6.89 in (s, 1H), 7,56 (m, 3H), 7,86 (m, 2H).

Example 218

6-[4-(cyclohexylmethoxy)phenyl] -4-hydroxy-3-[(2-isopropylphenyl)thio] - 2H-Piran-2-he

The target connection get method But using 2.0 g (8,61 mmol) of 4-cyclohexylacetophenone, 1,91 g (8,61 mmol) trimethylsilyltrifluoroacetamide, 1,74 g (17,22 mmol) of triethylamine, 20 ml of methylene chloride and 4.0 g (12,92 mmol) diethyl ether complex [(2-isopropyl-phenyl)-, 11N), 1,61-to 1.87 (m, 6N), 3,4 (m, 1H), 3,86 (d, 2H), 6,76 (s, 1H), 6,92 (DD, 1H), 7,11 (m, 4H), 7,29 (DD, 1H), 7,81 (d, 2H).

Example 219

6-(3-benzyloxyphenyl)-4-hydroxy-3-(2-isopropylphenyl)thio]-2H - Piran-2-he

The target connection get method But using 2.0 g (8,84 mmol) 3-benzyloxyacetophenone, 1,96 g (8,84 mmol) trimethylsilyltrifluoroacetamide, 1,79 g (17,68 mmol) of triethylamine and 0,210 g (0,675 mmol) diethyl ether complex [(2-isopropylphenyl)thio] proponderance acid. So pl. 162 - 164oC.

1H-NMR (400 MHz, DMSO-d6): = a 1.25 (d, 6N), 3,42 (m, 1H), to 5.35 (s, 2H), 6.89 in (s, 1H), 6,92 (d, 1H), 7,06 (dt, 1H), 7,11 (dt, 1H), 7,22 (DD, 1H), 7,28 (DD, 1H), 7,39-7,51 (m, 8H).

Example 220

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[4-(3-phenylpropoxy) phenyl]- 2H-Piran-2-he

The target connection get method But using 2.0 g (7,86 mmol) of 4-phenylpropylamine, 1,75 g (7,86 mmol) trimethylsilyltrifluoroacetamide, 1,59 g (15,72 mmol) of triethylamine and 3,66 g (to 11.79 mmol) in diethyl ether complex [(2-isopropylphenyl)thio] proponderance acid. So pl. 132 - 133oC.

1H-NMR (400 MHz, DMSO-d6): = a 1.25 (d, 6N), e 2.06 (m, 2H), 2,75 (t, 2H), 3,39 (m, 1H), 4,08 (t, 2H), 6,78 (s, 1H), 6.90 to (d, 1H), 7,05 (dt, 2H), 7,08 (kV, 2H), 7,11 -7,31 (m, 6N), 7,81 (d, 2H).

Example 221

(+/-)-3-[(2-Deut.butylphenyl)thio]-4-hydroxy-what methylcellulose)ethylene and 1.0 g (3,09 mmol) diethyl ether complex [(2-Deut.butylphenyl)thio]proponderance acid. So pl. 170-171oC.

1H-NMR (400 MHz, DMSO-d6): = 0,86 (t, 3H), 1,22 (d, 3H), 1.57 in (m, 1H), 1,67 (m, 1H), up 3.22 (m, 1H), 6.89 in (s, 1H), 6,97 (d, 1H), 7,06 (t, 1H), 7,13 (t, 1H), 7,22 (d, 1H), 7,56 (m, 3H), 7,86 (m, 2H).

The following examples explain the possible drugs offer pharmaceutical compositions.

Example 222

5 mg of active substance of the formula (I), such as example 1, dissolved in 1 l of distilled water for the preparation of ready-to-use solution.

Example 223

5 MK of the active substance of the formula (I), for example, example 167, dissolved in 10% DMA stored in the buffer 50 mmol of lactic acid, pH of 4.0. Get ready-to-use solution.

Example 224

250 mg of active substance of the formula (1) is mixed with magnesium stearate, calcium silicate and polyvinylpyrrolidone, taken in an amount up to 1 g, and the resulting mixture is processed into tablets.

Example 225

In a solution of 700 ml of propylene glycol and 200 ml of distilled water for injection is diluted to 20.0 g of the active substance of the formula (1), for example of example 170. The pH of a solution of hydrochloric acid was adjusted to 5.5 and the volume adjusted to 1000 ml by adding distilled water. Composition sterilizer, poured into ampoules clearly desirous in nitrogen atmosphere.

Biological experiments

1. Determination of the inhibition of HIV protease

1.1. Training experience

Dithiothreitol buffer: each day prepare a solution of 1.0 mmol of dithiothreitol 0.1% polyethylene glycol (molecular weight 8000), 80 mmol sodium salt of acetic acid, 160 mmol of sodium chloride, 1.0 mmol ethylenediaminetetraacetic acid, which is brought to a pH of 4.7 with the use of hydrochloric acid.

HIV protease 1: Enzyme receive from the company Bachem Bioscience Inc. Frozen at -80oC undiluted enzyme was thawed and diluted 50-fold amount dithiothreitol buffer. The solution is stored at 0oC in an ice water and used in the test for 20 minutes after thawing. The substrate of the enzyme: Substrate III, received from the company Bachem Bioscience Inc., is undecapeptide H-His-Lys-Ala-Arg-Val-Leu-p-nitrovanillin-Glu - Ala-norleucine-Ser-NH2(purity more than 97%). Prepare 200 µmol main solution in dithiothreitol buffer and store on ice. The substrate solution is prepared every day.

The analyzed connection: 10 mmol inhibitor of the above formula (1) in dimethyl sulfoxide was diluted dithiothreitol buffer to a concentration of 200 µmol. This basic solution was diluted with 2% solution Dingley 2% solution of dimethyl sulfoxide in dithiothreitol buffer to a concentration of 100, 50, 20, 10, 5, 2, 1, 0,5 and 0 µmol. The total amount of inhibitor is 50 ál.

1.2 experiment

In each Cup serving 20 μl of substrate final concentration of 40 μmol, 50 μl of inhibitor such concentration that the final dilution to obtain the working concentration, and 20 μl dithiothreitol buffer. Title plate with 96 cups placed in the incubator at a temperature of 37oC for at least 5 minutes.

In each Cup add 10 µl of the diluted protease with simultaneous shaking of title records. After 10 seconds of shaking title plate put back in the incubator at a temperature of 37oC. the Final reaction volume is 100 μl.

Title plate incubated at 37oC for 5 minutes. The reaction is stopped by the filing of a title plate on the shaker and the addition of 20 µl of 10% triperoxonane acid, followed by shaking for 10 seconds. The degree of proteolysis is determined by the separation of undigested substrate and two split products using obetovannoi liquid chromatography under pressure with simultaneous measurement of the absorbance at 220 nm. Thus opredelyayushchii inhibitor. Data is put on the graph as a percentage of control (the percent conversion in the presence and absence of inhibitor, multiplied by 100) with respect to the concentration of inhibitor. The resulting data is used for the equation Y=100/1+(X/KT50)Awhere KT50represents the concentration of inhibitor at 50% inhibition, and a - line curve deceleration. The results are summarized in table 1.

1.3. Activity against HIV-1

With regard to the General data methods Polsa and others (see "Journal of Virological Methods", 16, pp. 171-185, 1987) and Mann and others (see "AIDS Research and Human Retroviruses", pages 254-255, 1989) carried out antivirus tests on the active infection with HIV-1 in cell line H9. Cultures were infected with 1 ml solution of 10% fetal calf serum in buffered RPMI 1640 containing 107cells and 105infectious doses of HIV-1iiiborder effective multiplication of infection of 0.01. After 2 hours of virus absorption, the cells were washed once and filed in microtiter plates with 96 cups (104cells per Cup). The compounds were applied in a Cup in order to obtain the desired concentration of the active principle and of 0.2% dimethylsulfoxide. The final volume of the medium was 200 ál. Uninfected cultures were kept to determine lscripts after 4 and 7 days after infection. The results are summarized in table 2.

Combination of protease inhibitors with other antiviral drugs, such as inhibitors of HIV reverse transcriptase AZT and ddC, can exhibit a synergistic effect. See J. C. Craig and others in the literature, "Antiviral Chem. Chemother", 4/3, pages 161-166, 1993; E. V. Connell and others in the literature, "Antimicrob. Agents Chemother.", 38, pages 348-352, 1994; D. M. Lambert, and others in the literature "Antiviral Res.", 21, pp. 327-342, 1993; A. M. Caliendo, and others in the literature Clin. Infect. Dis.", 18/4: pages 516-524, 1994

The proposed compounds exhibit antibacterial activity, as evidenced by the results microtiter dilution described Hypercom and others in the literature Antimicr. Agents & Chemoth.", 6, page 124, 1974

This method determined the minimum concentration of inhibition in μg/ml of the proposed compounds used in the fight against clinically significant gram-positive pathogens, which in recent years have become resistant to standard tools (see tab.3).

1. Derivatives Piron General formula I

< / BR>
where X is a group of the formula OR1or CO2R1where R1has the following value;

A and A1independent from each other represent a chemical bond, unsubstituted or sameday it substituents are one or a few residues, selected from the group comprising fluorine, chlorine, bromine, OR1, CO2R1, CON(R1)2, COR1, R1, OCH2O, OCH2CH2O, C=H, where R1independently means hydrogen, substituted or unsubstituted alkyl with 1 to 12 carbon atoms, or phenyl, substituted by one or more residues selected from the group comprising CO2R2, OR2, phenyl, naphthyl, morpholinyl, tetrazolyl, thienyl, isoxazolyl, pyridinyl or TRIFLUORIDE carbon, where R2independently mean alkyl with 1 to 12 carbon atoms or hydrogen;

R4is hydrogen or alkyl with 1 to 12 carbon atoms;

R3independently means hydrogen, (CH2)pR1or (CH2)pA, where p = 0 to 2, R1and A have the above meanings;

W, W1and W3independent and mean chemical bond, oxygen, NR3C(R3)2, CO, CO2, CR3=CR3, S(O)por SO2NR3where R3and p have the above meanings;

W2means oxygen, NR3, S(O)p, SO2NR3where R3and p have the above meanings;

m and n are independent and indicate an integer of 0 to 4;

if the remains of W and W1both mean heteroatoms, or if the OST(CH2)nA means methyl or ethyl,

and their pharmaceutically acceptable salts.

2. Derivatives Piron under item 1, where W2means SO2NR3or S(O)pwhile p = 0 - 2.

3. Derivatives Piron on p. 2, where A1does not mean the connection.

4. Derivatives Piron on p. 3, selected from the group including

4-hydroxy-3-[(2-isopropylphenyl)thio]-6-phenyl-2H-Piran-2-it,

4-hydroxy-3-[[(2-methylpropyl " phenyl]thio]-6-phenyl-2H-Piran-2-it,

3-[((2-cyclopropylethyl)phenyl]thio]-4-hydroxy-6-phenyl-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-(2,3-dihydro-1,4-benzodioxin-6-yl)-2H-Piran-2-it,

3-[(2,5-diisopropylphenyl)thio]-4-hydroxy-6-[(3-phenyl)phenyl]-2H-Piran-2-it,

6-phenyl-4-hydroxy-5-methyl-3-(phenylthio)-2H-Piran-2-it,

[4-[4-hydroxy-2-oxo-3-(phenylthio)-2H-Piran-6-yl]phenoxy]acetic acid,

[4-[4-hydroxy-5-methyl-2-oxo-3-(phenylthio)-2H-Piran-6-yl] phenoxy] acetic acid,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[1-(2-methylpropyl " cyclopentyl] -2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[1-(3-methylbutyl)cyclopentyl] -2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[1-(4-methylpentyl)cyclopentyl] -2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[1-(phenylmethyl)cyclopentyl]-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio]-RAS-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio]-6-[1-(2-methylpropyl " cyclopropyl]-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[1-(3-methylbutyl)cyclopropyl]-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio]-6-[1-(4-methylpentyl)cyclopropyl]-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[1-(phenylmethyl)cyclopropyl]-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio]-6-[1-(2-phenylethyl)cyclopropyl]-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio]-6-[1-(3-phenylpropyl)cyclopropyl]-2H-Piran-2-it,

4-hydroxy-6-(3 oksifenil)-3-[(2-isopropylphenyl)thio]-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio]-6-(pyridin-4-yl)-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio]-6-(pyridin-2-yl)-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio]-6-(4-nitrophenyl)-2H-Piran-2-it,

6-(4-forfinal)-4-hydroxy-3-[(2-isopropylphenyl)thio]-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio]-6-(2-were)-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio]-6-(2-methoxyphenyl)-2H-Piran-2-it,

6-(2-chlorophenyl)-4-hydroxy-3-[(2-isopropylphenyl)thio]-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[4-(N,N-dimethylamino)phenyl]-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio]-6-(3-triptoreline)-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[4-(1-naphthalenyloxy)phenyl] -2H-Piran-2-it,

4-hydroxy-3-[(2-isopropyl)ethoxy]phenyl]-2H-Piran-2-it,

6-(4-benzyloxy-3-methoxyphenyl)-4-hydroxy-3-[(2-isopropylphenyl)thio] -2H-Piran-2-it,

6-(4-benzyloxy-3-chlorophenyl)-4-hydroxy-3-[(2-isopropylphenyl)thio] -2H-Piran-2-it,

4-[4-hydroxy-2-oxo-3-[(2-isopropylphenyl)thio] -2H-Piran-6-yl]-2-methylphenoxy-acetic acid,

4-hydroxy-6-[4-(2-acetoxy)phenyl] -3-[(2-isopropylphenyl)thio]-2H-Piran-2-it,

2-[3-[4-hydroxy-5-[(2-isopropylphenyl)thio] -6-oxo-6H-Piran-2-yl] phenoxy] ndimethylacetamide,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[4-(2,3-pyrazinamidase)phenyl]-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio]-6-[4-(pyridine-3-ylethoxy)phenyl]-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[4-(pyridine-2-ylethoxy)-3-were]-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[4-(pyridine-4-ylethoxy)phenyl] -2H-Piran-2-it,

3-[(2-cyclopropylmethyl)thio] -4-hydroxy-6-[4-(pyridine-3-ylethoxy)phenyl] -2H-Piran-2-it,

4-hydroxy-3-[(2,5-diisopropylphenyl)thio] -6-[4-(pyridine-3-ylethoxy)phenyl]-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio]-6-[4-[2-(thiomorpholine-4-yl)ethoxy]phenyl] -2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[4-[2-(piperazine-1-yl)ethoxy] phenyl] -2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[4-[2-(methylpiperazin-1-yl)ethoxy] phenyl]-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[4-[2-(1,1-diocletianopolis-4-yl)ethoxy]phenyl]-2H-Piran-2--(4-phenyl-piperidine-4-yl)-2H-Piran-2-it,

complex 2-oxo-6-phenyl-3-[(2-isopropylphenyl)thio]-2H-Piran-2-he-4-silt ether of isopentanol acid,

complex 2-oxo-6-phenyl-3-[(2-isopropylphenyl)thio]-2H-Piran-2-he-4-silt ester propanoic acid,

complex 2-oxo-6-phenyl-3-[(2-isopropylphenyl)thio]-2H-Piran-2-he-4-silt ester of phenylacetic acid,

4-hydroxy-3-[(2-isopropyl-5-were)thio]-6-phenyl-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropyl-4-were)thio]-6-phenyl-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropyl-6-were)thio]-6-phenyl-2H-Piran-2-it,

3-[(4-chloro-2-isopropylphenyl)thio]-4-hydroxy-6-phenyl-2H-Piran-2-it,

4-hydroxy-3-[(4-hydroxy-2-isopropylphenyl)thio]-6-phenyl-2H-Piran-2-it,

3-[(2-cyclopropylmethyl)thio]-4-hydroxy-6-phenyl-2H-Piran-2-it,

3-[(2,5-diisopropylphenyl)thio]-4-hydroxy-6-phenyl-2H-Piran-2-it,

4-hydroxy-6-phenyl-3-[(2-tert.butylphenyl)thio]-2H-Piran-2-it,

3-[(2-cyclopropyl-5-isopropylphenyl)thio]-4-hydroxy-6-phenyl-2H-Piran-2-it,

3-[(2-cyclopentyl-5-isopropylphenyl)thio]-4-hydroxy-6-phenyl-2H-Piran-2-it,

3-[(2-cyclohexyl-5-isopropylphenyl)thio]-4-hydroxy-6-phenyl-2H-Piran-2-it,

4-hydroxy-6-phenyl-3-[(2-tert.butyl-5-isopropylphenyl)thio]-2H-Piran-2-it,

3-[(2,5-di-tert.butylphenyl)thio]-4-hydroxy-6-phenyl-2H-Piran-2-it,

3-[(2-cyclopentylphenol)thio]-4-hydroxy-6-phenyl-2H-Piran-2-it,

3-[(2-cyclohexylphenol)thio]-4-hydroxy-6-phenyl-2H-yl)phenyl]thio]-6-phenyl-2H-Piran-2-it,

4-hydroxy-3-[(6-isopropyl-indan-5-yl)thio]-6-phenyl-2H-Piran-2-it,

4-hydroxy-3-[(4-isopropyl-benzo[1,3] dioxol-5-yl)thio]-6-phenyl-2H-Piran-2-it,

3-[(2-tert. butyl-4-thiomorpholine-4-ylmethylene)thio] -4-hydroxy-6-phenyl-2H-Piran-2-it,

4-hydroxy-6-[4-(pyridine-3-ylethoxy)phenyl] -3-[(2-tert.butylphenyl)thio]-2H-Piran-2-it,

3-[[(2-cyclopropyl-5-isopropyl)phenyl] thio] -4-hydroxy-6-[4-(pyridine-3-ylethoxy)phenyl]-2H-Piran-2-it,

3-[[(2-cyclopentyl-5-isopropyl)phenyl] thio] -4-hydroxy-6-[4-(pyridine-3-ylethoxy)phenyl]-2H-Piran-2-it,

3-[[(2-cyclohexyl-5-isopropyl)phenyl] thio] -4-hydroxy-6-[4-(pyridine-3-ylethoxy)phenyl]-2H-Piran-2-it,

4-hydroxy-6-[4-(pyridine-3-ylethoxy)phenyl] -3-[(2-tert. butyl-5-isopropylphenyl)thio]-2H-Piran-2-it,

3-[(2,5-di-tert. butylphenyl)thio]-4-hydroxy-6-[4-(pyridine-3-ylethoxy)phenyl] -2H-Piran-2-it,

3-[(2-cyclopentylphenol] thio] -4-hydroxy-6-[4-(pyridine-3-ylethoxy)phenyl] -2H-Piran-2-it,

3-[(2-cyclohexylphenol] thio] -4-hydroxy-6-[4-(pyridine-3-ylethoxy)phenyl] -2H-Piran-2-it,

4-hydroxy-6-[4-(pyridine-3-ylethoxy)phenyl] -3-[(6-tert.Batiliman-5-yl)thio] -2H-Piran-2-it,

4-hydroxy-3-[(2-isopropyl-4-morpholine-4-ylmethyl-phenyl)thio] -6-[4-(pyridine-3-ylethoxy)phenyl]-2H-Piran-2-it,

complex 3-[(2-isopropylphenyl)thio] -2-oxo-6-[4-(pyridine-3-ylethoxy)phenyl]-2H-Piran-4-silt ether acetic acid,

the complex the complex 3-[(2-isopropylphenyl)thio] -2-oxo-6-[4-(pyridine-3-ylethoxy)phenyl]-2H-Piran-4-silt ether of 2,2-dimethylpropionic acid,

4-hydroxy-3-[(2-isopropylphenyl)sulfonyl] -6-[4-(pyridine-3-ylethoxy)phenyl] -2H-Piran-2-it,

3-[(2-tert.butylphenyl)sulfonyl]-4-hydroxy-6-phenyl]-2H-Piran-2-it,

6-(1-benzylbutyl)-4-hydroxy-3-[(2-isopropylphenyl)sulfonyl]-2H-Piran-2-it,

6-(1-benzylbutyl)-4-hydroxy-3-[(2-isopropylphenyl)thio]-2H-Piran-2-it,

6-(1-benzylbutyl)-3-[(2-tert.butylphenyl)thio]-4-hydroxy-2H-Piran-2-it,

N-[3-[[6-(1-benzylbutyl)-4-hydroxy-2-oxo-2H-Piran-3-yl] thio] -2-isopropylphenyl]benzosulfimide,

6-[1-cyclopropylmethyl-2-(tetrahydro-Piran-3-yl)ethyl] -4-hydroxy-3-[(2-isopropylphenyl)thio]-2H-Piran-2-it,

6-(1,1-dimethyl-3-phenylpropyl)-4-hydroxy-3-[(2-isopropylphenyl)thio] -2H-Piran-2-it,

6-(benzo[1,3] -dioxol-5-yl)-4-hydroxy-3-[(2-isopropylphenyl)thio]-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[1-(phenylmethyl)cyclobutyl] -2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[1-(2-phenylethyl)cyclobutyl] -2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio] -6-[1-(3-phenylpropyl)cyclobutyl]-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropyl-5-were)thio] -6-(1-benzylcarbamoyl)-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropyl-5-were)thio] -6-[1-(2-phenylethyl)cyclopropyl] -2H-Piran-2-it,

4-hydroxy-3-[(2-isopropyl-5-were)thio]-6-[1-(3-phenylpropyl)cyclopropyl]-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropyl-5-were)thio] -6-(1-BAA is,

4-hydroxy-3-[(2-isopropyl-5-were)thio]-6-[1-(3-phenylpropyl)cyclobutyl] -2H-Piran-2-it,

4-hydroxy-3-[(2-isopropyl-5-were)thio] -6-(1-benzyltoluenes)-2H-Piran-2-it,

4-hydroxy-3-[(2-isopropyl-5-were)thio] -6-[1-(2-phenylethyl)cyclopentyl] -2H-Piran-2-it,

4-hydroxy-3-[(2-isopropyl-5-were)thio]-6-[1-(3-phenylpropyl)cyclopentyl]-2H-Piran-2-it,

6-(1,1-dimethyl-3-phenylpropyl)-4-hydroxy-3-[(2-isopropylphenyl)thio]-2H-Piran-2-it,

6-(1,1-dimethyl-2-phenylethyl)-4-hydroxy-3-[(2-isopropylphenyl)thio] -2H-Piran-2-it,

4-hydroxy-3-[(2-isopropylphenyl)thio]-6-(1-methyl-1-phenylethyl)-2H-Piran-2-it,

6-(1,1-diethyl-3-phenylpropyl)-4-hydroxy-3-[(2-isopropylphenyl)thio] -2H-Piran-2-it,

6-(1-benzyl-1-ethylpropyl)-4-hydroxy-3-[(2-isopropylphenyl)thio] -2H-Piran-2-it,

6-(1-ethyl-1-phenylpropyl)-4-hydroxy-3-[(2-isopropylphenyl)thio]-2H-Piran-2-it.

5. Derivatives Piron on p. 2, where A1means relationship and the group (CH2)mW3does not mean the connection.

6. Derivatives Piron on p. 5, selected from the group including

6-[4-[(3,5-dimethyl-4-isoxazolyl)methoxy] phenyl] -4-hydroxy-3-[(2-phenylethyl)thio]-2H-Piran-2-it,

4-hydroxy-3-[(2-phenylethyl)thio]-6-[4-(phenylsulfinyl)phenyl]-2H-Piran-2-it,

6-(3, 5dimethylphenyl)-4-hydroxy-3-[(2-phenylethyl)thio]-2H-Piran-2-it,

4-hydroxy-6-(3-phenoxyphenyl)-3-[(2-femilet-oxo-2-phenylethyl)thio]-6-phenyl-2H-Piran-2-it,

4-hydroxy-6-phenyl-3-[(phenylmethyl)thio]-2H-Piran-2-it,

4-hydroxy-3-[(2-phenoxyethyl)thio]-6-phenyl-2H-Piran-2-it,

(E)-4-hydroxy-6-phenyl-3-[(3-phenyl-2-propenyl)thio]-2H-Piran-2-it,

ester 2-hydroxy-6-phenyl-3-[(phenylmethyl)thio]-2H-Piran-4-yl-3-methylbutanoic acid,

6-(3,4-dichlorophenyl)-4-hydroxy-3-[(phenylmethyl)thio]-2H-Piran-2-it,

6-(3-chlorophenyl)-4-hydroxy-3-[(phenylmethyl)thio]-2H-Piran-2-it,

ester 2-oxo-6-phenyl-3-[(phenylmethyl)thio]-2H-Piran-4-yl-propanoic acid,

4-hydroxy-6-(3-were)-3-[(phenylmethyl)thio]-2H-Piran-2-it,

4-hydroxy-6-(3 oksifenil)-3-[(phenylmethyl)thio]-2H-Piran-2-it,

4-hydroxy-6-(2-phenylethyl)-3-[(phenylmethyl)thio]-2H-Piran-2-it,

4-hydroxy-6-(4 oksifenil)-3-[(2-phenylethyl)thio]-2H-Piran-2-it,

4-hydroxy-3-[(2-phenylethyl)thio]-6-[4-(phenylmethoxy)phenyl]-2H-Piran-2-it,

4-hydroxy-6-[4-(2-phenylethane)phenyl]-3-[(2-phenylethyl)thio]-2H-Piran-2-it,

4-hydroxy-6-[3-(2-phenylethane)phenyl]-3-[(2-phenylethyl)thio]-2H-Piran-2-it,

4-hydroxy-6-(2 oksifenil)-3-[(phenylmethyl)thio]-2H-Piran-2-it,

4-hydroxy-6-(3-methoxyphenyl)-3-[(phenylmethyl)thio]-2H-Piran-2-it,

6-(3-chlorophenyl)-4-hydroxy-3-[(2-phenylethyl)thio]-2H-Piran-2-it,

4-hydroxy-6-(4-methoxy-3-were)-3-[(phenylmethyl)thio]-2H-Piran-2-it,

6-(3-chloro-4-methoxyphenyl)-4-hydroxy-3-[(phenylmethyl)thio]-2H-Piran-2-it,

4-hydroxy-3-[(2-phenylethyl)thio]-6-[3-(Fennell)thio]-4-hydroxy-6-phenyl-2H-Piran-2-it,

4-hydroxy-3-[(phenylmethyl)thio]-6-[3-(trifluoromethyl)phenyl]-2H-Piran-2-it,

4-hydroxy-3-[(phenylethyl)thio]-6-[3-(trifluoromethyl)phenyl]-2H-Piran-2-it,

6-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-hydroxy-3-[(phenylmethyl)thio] -2H-Piran-2-it,

4-hydroxy-3-[(2-phenylethyl)thio] -6-[3-methyl-4-(3-pyridinylmethyl)phenyl] -2H-Piran-2-it,

[4-[4-hydroxy-2-oxo-3-[(2-phenylethyl)thio] -2H-Piran-6-yl] phenoxy] acetic acid,

complex ethyl ester [4-[4-hydroxy-2-oxo-3-[(2-phenylethyl)thio]-2H-Piran-6-yl]phenoxy]acetic acid,

4-hydroxy-6-(4-phenoxyphenyl)-3-[(2-phenylethyl)thio]-2H-Piran-2-it,

4-hydroxy-3-[(2-phenylethyl)thio] -6-[4-(2-pyridinylmethyl)phenyl] -2H-Piran-2-it,

4-hydroxy-3-[(2-phenylethyl)thio] -6-[4-(3-pyridinylmethyl)phenyl] -2H-Piran-2-it,

4-hydroxy-6-[4-(2-methoxyphenyl)methoxy] phenyl] -3-[(2-phenylethyl)thio]-2H-Piran-2-it,

4-hydroxy-3-[(2-phenylethyl)thio]-6-[4-(phenylthio)phenyl]-2H-Piran-2-it,

6-(1,3-benzodioxol-5-yl)-4-hydroxy-3-[(phenylmethyl)thio]-2H-Piran-2-it,

6-(3, 5dimethylphenyl)-4-hydroxy-3-[(phenylmethyl)thio]-2H-Piran-2-it,

4-hydroxy-6-(2-naphthalenyl)-3-[(phenylmethyl)thio]-2H-Piran-2-it,

4-hydroxy-6-(4 oksifenil)-3-[(phenylmethyl)thio]-2H-Piran-2-it,

6-(2-chlorophenyl)-4-hydroxy-3-[(phenylmethyl)thio]-2H-Piran-2-it,

4-hydroxy-6-[2-(3-methylbutyl)phenyl]-3-[(phenylmethyl)thio]-2H-Piran-2-it,

6-(3, 5dimethylphenyl)-4-(oxymethyl)-3-[(penile the>/BR>4-hydroxy-6-[(4-methoxyphenyl)methyl] -3-[[1-(phenylmethyl)butyl] thio] -2H-Piran-2-it,

[[5-[2-oxo-4-hydroxy-3-[(3-methyl-1-phenylbutyl)thio] -2H-Piran-6-yl] -2-pyridinyl]oxy]acetic acid,

[[4-[4-hydroxy-2-oxo-3-[(phenylmethyl)thio] -2H-Piran-6-yl]-cyclohexyl]oxy] acetic acid,

6-[4-(cyclohexylmethoxy)phenyl] -4-hydroxy-3-[(2-phenylethyl)thio] -2H-Piran-2-it,

4-hydroxy-3-[(2-phenylethyl)thio]-6-[4-(phenylsulfonyl)phenyl]-2H-Piran-2-it,

4-hydroxy-3-[(2-phenylethyl)thio]-6-[4-(benzoyloxy)phenyl]-2H-Piran-2-it,

4-hydroxy-3-[(2-phenylethyl)thio]-6-[4-(phenylsulfinyl)phenyl]-2H-Piran-2-it,

4-hydroxy-3-[(2-phenylethyl)thio]-6-(4-pyridinyl]-2H-Piran-2-it,

4-hydroxy-6-(3-phenoxyphenyl)-3-[(2-phenylethyl)thio]-2H-Piran-2-it,

4-hydroxy-6-[3-methoxy-4-(phenylmethoxy)phenyl] -3-[(2-phenylethyl)thio] -2H-Piran-2-it,

6-(3, 5dimethylphenyl)-4-hydroxy-3-[(2-phenylethyl)thio]-2H-Piran-2-it,

4-hydroxy-3-[[(3-methoxyphenyl)methyl]thio]-6-phenyl-2H-Piran-2-it,

4-hydroxy-6-phenyl-3-[[[3-phenylmethoxy)phenyl]methyl]thio]-2H-Piran-2-it,

3-[(1,3-benzodioxol-5-ylmethyl)thio]-4-hydroxy-6-phenyl-2H-Piran-2-it,

4-hydroxy-3-[[(2-methoxyphenyl)methyl]thio]-6-phenyl-2H-Piran-2-it,

4-hydroxy-3-[[(2-were)methyl]thio]-6-phenyl-2H-Piran-2-it,

4-hydroxy-3-[[(3-were)methyl]thio]-6-phenyl-2H-Piran-2-it,

4-hydroxy-3-[[(4-were)methyl]thio]-6-phenyl-2H-Piran-2-it,

6-[,

complex ethyl ester [4-[4-hydroxy-2-oxo-3-[(2-phenylethyl)thio]-2H-Piran-6-yl]-2-methylphenoxy]acetic acid,

4-hydroxy-3-[(2-phenylethyl)thio] -6-[4-(4-pyridinylmethyl)phenyl] -2H-Piran-2-it,

[4-[4-hydroxy-2-oxo-3-[(2-phenylethyl)thio] -2H-Piran-6-yl] -2-methylphenoxy] acetic acid,

4-hydroxy-6-(4-hydroxy-3, 5dimethylphenyl)-3-[(2-phenylethyl)thio]-2H-Piran-2-it,

4-hydroxy-6-phenyl-3-[[[3-(2-phenylethane)phenyl]methyl]thio]-2H-Piran-2-it,

4-hydroxy-6-[4-(2-phenylethynyl)phenyl]-3-[(2-phenylethyl)thio]-2H-Piran-2-it,

4-hydroxy-6-[4-(2-phenylethyl)phenyl]-3-[(2-phenylethyl)thio]-2H-Piran-2-it,

4-hydroxy-3-[(phenylmethyl)thio]-6-[3-(triptoreline)phenyl]-2H-Piran-2-it,

3-[(cyclohexylmethyl)thio]-4-hydroxy-6-phenyl-2H-Piran-2-it,

4-hydroxy-3-[(2-phenylethyl)thio] -6-[3-methyl-4-(3-pyridinylmethyl)phenyl] -2H-Piran-2-it,

6-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-hydroxy-3-[(phenylmethyl)thio] -2H-Piran-2-it,

4-hydroxy-3-[(2-phenylethyl)thio]-6-[3-(trifluoromethyl)phenyl]-2H-Piran-2-it,

4-hydroxy-3-[(phenylmethyl)thio]-6-[3-(trifluoromethyl)phenyl]-2H-Piran-2-it,

4-hydroxy-3-[(phenylmethyl)thio]-6-(2,3,4-(trimethoxyphenyl]-2H-Piran-2-it,

N-[4-[4-hydroxy-2-oxo-3-[(2-phenylethyl)thio] -2H-Piran-6-yl] phenyl] benzosulfimide,

6-[4-[(3,5-dimethyl-4-isoxazolyl)methoxy] phenyl] -4-hydroxy-3-[(2-phenylethyl)thio]-2H-Piran-2-it,

methyl ester 2-[[(4-hydroxy-2-oxo is about]-2H-Piran-6-yl]phenoxy]methyl-benzoic acid,

4-hydroxy-3-[(2-phenylethyl)thio] -6-[4-(1H-tetrazol-5-ylethoxy)phenyl] -2H-Piran-2-it,

4-hydroxy-6-[3-methyl-4-(2-pyridinylmethyl)phenyl] -3-[(2-phenylethyl)thio] -2H-Piran-2-it,

methyl ester 4-[[4-hydroxy-2-oxo-3-[(2-phenylethyl)thio] -2H-Piran-6-yl]phenoxy]methyl-benzoic acid,

methyl ester 3-[[4-[4-hydroxy-2-oxo-3-[(2-phenylethyl)thio]-2H-Piran-6-yl]phenoxy]methyl]-benzoic acid,

6-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-4-hydroxy-3-[(2-phenylethyl)thio]-2H-Piran-2-it,

methyl ester 3-[[(4-hydroxy-2-oxo-6-phenyl-2H-Piran-3-yl)thio] methyl]benzoic acid

methyl ester 4-[[(4-hydroxy-2-oxo-6-phenyl-2H-Piran-3-yl)thio] methyl]benzoic acid

6-[3,5-bis(trifluoromethyl)phenyl]-4-hydroxy-3-[(phenylmethyl)thio]-2H-Piran-2-it,

[4-[4-hydroxy-2-oxo-3-[(2-phenylethyl)thio] -2H-Piran-6-yl] phenoxy]acetonitrile,

6-phenyl-4-hydroxy-3-[(cyclopropylmethyl)thio]-2H-Piran-2-it,

6-(3-chlorophenyl)-4-hydroxy-3-[(4-phenylbutyl)thio]-2H-Piran-2-it,

4-hydroxy-3-[(2-hydroxy-2-phenylethyl)thio]-6-phenyl-2H-Piran-2-it,

4-hydroxy-3-[(phenylmethyl)thio]-6-(3-pyridinyl)-2H-Piran-2-it,

6-(2,6-dimethyl-4-pyridinyl)-4-hydroxy-3-[(phenylmethyl)thio]-2H-Piran-2-it,

4-hydroxy-3-[(phenylmethyl)thio]-6-(3-thienyl)-2H-Piran-2-it.

7. Derivatives of the pyrone of formula I on p. 1, where W2means oxygen.


4-hydroxy-3-phenoxy-6-phenyl-2H-Piran-2-it,

4-hydroxy-3-(2-isopropyl-phenoxy)-6-[4-(pyridine-3-ylethoxy)phenyl]-2H-Piran-2-it,

4-hydroxy-3-(2-isopropyl-phenoxy)-6-phenyl-2H-Piran-2-it,

3-(2-tert. butyl-phenoxy)-4-hydroxy-6-[4-(pyridine-3-ylethoxy)phenyl]-2H-Piran-2-it,

3-(2-tert.butyl-5-methyl-phenoxy)-4-hydroxy-6-[4-(pyridine-3-ylethoxy)phenyl] -2H-Piran-2-it,

6-(1-benzylbutyl)-4-hydroxy-3-(2-isopropylphenoxy)-2H-Piran-2-it,

6-(1-benzylbutyl)-3-(2-tert.butylphenoxy)-4-hydroxy-2H-Piran-2-it.

10. Derivatives Piron under item 7, where A1means relationship and the group (CH2)mW3does not mean the connection.

11. Derivatives Piron on p. 10, selected from the group including

3-benzyloxy-4-hydroxy-6-[4-(pyridine-3-ylethoxy)phenyl]-2H-Piran-2-it,

methyl ester 2-[4-hydroxy-2-oxo-6-[4-(pyridine-3-ylethoxy)-phenyl]-2H-Piran-3-intoximeter]benzoic acid

complex ethyl ester 2-[[[6-(1-benzylbutyl)-4-hydroxy-2-oxo-2H-Piran-3-yl]oxy]methyl]benzoic acid

6-(1-benzylbutyl)-4-hydroxy-3-(1-phenylmethoxy)-2H-Piran-2-it.

12. Derivatives Piron formula I on p. 1, where W2selected from the group comprising NR3, SO2NR3and each time the value of the remainder W2the nitrogen atom bound to the carbon in Polo is

14. Derivatives Piron under item 12, selected from the group including

3-[bis(2-naphthalenyloxy)amino]-4-hydroxy-6-phenyl-2H-Piran-2-it,

6-(1-benzylbutyl)-3-(cyclopropylamino)-4-hydroxy-2H-Piran-2-it,

N-[3-[[6-(1-benzylbutyl)-4-hydroxy-2-oxo-2H-Piran-3-yl] cyclopropylamino] phenyl]benzosulfimide,

3-[cyclopropylamino]-4-hydroxy-6-(pyridine-3-ylethoxy)-2H-Piran-2-it,

3-(bis-cyclopentylmethyl-amino)-4-hydroxy-6-(pyridine-3-ylethoxy)-2H-Piran-2-it,

3-[cyclopentylmethyl(cyclopropylmethyl)amino] -4-hydroxy-6-(pyridine-3-ylethoxy)-2H-Piran-2-it,

6-[1-cyclopropylmethyl-2-(tetrahydro-Piran-3-yl)ethyl]-3-(cyclopropylamino)-4-hydroxy-2H-Piran-2-it.

15. Derivatives Piron under item 12, where W2means SO2NR3, with the nitrogen atom bound to the carbon in position 3 of the pyrone ring.

16. Derivatives Piron on p. 15, selected from the group including

N-(1,1'-dimethylethyl)-N'-(4-hydroxy-2-oxo-6-phenyl-2H-Piran-3-yl)-N'-(phenylmethyl)urea,

cyclopentylmethyl-[4-hydroxy-2-oxo-6-[(pyridine-3-ylethoxy)phenyl] -2H-Piran-3-yl]amide cyclopropanecarboxylic acid,

cyclopentylmethyl-[4-hydroxy-2-oxo-6-[4-(pyridine-3-ylethoxy)phenyl] -2H-Piran-3-yl]amide cyclopentanecarbonyl acid,

N-cyclopentylmethyl-N-[4-hydroxy-2-oxo-6-[4-(pyridine-3 is Noah and antibacterial activity, contains the active substance on the basis of pyrone derivatives and at least one pharmaceutically acceptable carrier, characterized in that as a pyrone derivative it contains at least one connection on the PP.1 - 16 in an effective amount.

18. The method of treatment caused by rotavirus infection or disease involving the introduction of a pyrone derivative in therapeutically effective amount, wherein introducing at least one connection on the PP.1 - 16.

Priority points and features:

19.11.93 on PP.17 and 18 when X = OR1where R1has the specified value, CO2R1where R1means hydrogen; A and A1= specified values; R4= specified value; R3= specified value; W, W1and W3= independent and mean chemical bond, NR3C(R3)2, CO, CO2; CR3= CR3where R3has a specified value; W2= oxygen, S(O)pand SO2NR3where R3and p have the indicated value; m and n = the specified values; disclaimer; pharmaceutically acceptable salts.

12.10.94 - when X = CO2R1where R1has the specified values with the exception of hydrogen, W, W1and W3

 

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