Thiazolobenzoheterocycles, preparation and medicines...

Details Thiazolobenzoheterocycles, preparation and medicines... Thiazolobenzoheterocycles, preparation and medicines...

2000-01-18

2002-04-09

Coleman, Brenda (Department: 1624)

Organic compounds -- part of the class 532-570 series

Organic compounds

Unsubstituted hydrocarbyl chain between the ring and the -c-...

C540S504000, C540S512000, C540S548000, C540S552000, C540S560000, C540S567000, C540S573000, C540S586000, C540S593000, C514S211090, C514S211100, C514S213010, C514S214010, C514S220000, C514S221000

Reexamination Certificate

active

06369221

ABSTRACT:

The present invention relates to compounds of formula;
their isomers, racemates, enantiomers, their salts, processes for preparing them and the medicaments containing them.
In formula (I),
R
1
represents a sulphur or selenium atom,
R
2
represents a hydrogen atom or an alkyl radical,
—R
3
—R
4
—R
5
—R
6
— represents a chain of formula
—CH
2
—CH
2
—CH
2
—CH
2
—, —CH
2
—CH
2
—CH
2
—CO—,
—CH
2
—CH
2
—CH
2
—CH(R
8
)—, —CH
2
—CH
2
—CH
2
—Se—,
—CH
2
—CH
2
—Se—CH
2
—, —CH
2
—CH
2
—CH
2
—S—,
—CH
2
—CH
2
—CH
2
—SO—, —CH
2
—CH
2
—CH
2
—SO
2
—,
—CH
2
—CH
2
—CH
2
—O—, —CH
2
—CH
2
—CH
2
—N(R
9
)—,
—CH
2
—CH
2
—CO—CH
2
—, —CH
2
—CH
2
—CH(R
8
)—CH
2
—,
—CH
2
—CH
2
—S—CH
2
—, —CH
2
—CH
2
—SO—CH
2
—,
—CH
2
—CH
2
—SO
2
—CH
2
—, —CH
2
—C(alk)(alk′)—S—CH
2
—, —CH
2
—
 C(alk) (alk′)—SO—CH
2
—, —CH
2
—C(alk) (alk′)—SO
2
—CH
2
—,
—CR
2
—CH (R
10
)—S—CH
2
—, —CH
2
—CH (R
10
)—SO—CH
2
—,
—CH
2
—CH (R
10
)—SO
2
—CH
2
—, —CH
2
—CH
2
—O—CH
2
—,
—CH
2
—CH
2
—N(R
9
)—CH
2
—or —CH
2
—CO—N(R
9
)—CH
2
—,
R
7
represents a polyfluoroalkyl or polyfluoroalkoxy radical,
R
8
represents a hydroxyl radical,
R
9
represents a hydrogen atom or an alkyl or benzyl radical,
R
10
represents an alkyl, —CH
2
OH, —COOalk, —COOH or —CONH
2
radical,
alk represents an alkyl radical,
alk′ represents an alkyl radical.
In the preceding definitions and in those which will be given hereinafter, unless otherwise indicated, the alkyl radicals and portions contain 1 to 6 straight- or branched-chain carbon atoms.
Among the polyfluoroalkyl radicals, there may be mentioned the trifluoromethyl, 2,2,2-trifluoroethyl, 1,1,2,2-tetrafluoroethyl, perfluoroethyl, perfluoropropyl and perfluorobutyl radicals.
Among the polyfluoroalkoxy radicals, there may be mentioned the trifluoromethoxy, perfluoroethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 2,2,3,3,3-pentafluoropropoxy, perfluoropropoxy and perfluorobutoxy radicals.
The preferred polyfluoroalkyl and polyfluoroalkoxy radicals are trifluoromethyl, trifluoromethoxy and pentafluoroethoxy radicals.
The invention also relates to the addition salts of the compounds of formula (I) with inorganic or organic acids.
The compounds of formula (I) which contain one or more asymmetric centres have isomeric forms; these isomers and mixtures form part of the invention. The racemates and the enantiomers of these compounds also form part of the invention.
The compounds of formula (I) for which R
1
represents a sulphur or selenium atom, R
2
represents a hydrogen atom, —R
3
—R
4
—R
5
—R
6
— represents a chain of formula —CH
2
—CH
2
—CH
2
—CH
2
—, —CH
2
—CH
2
—CH
2
—CO—, —CH
2
—CH
2
—CH
2
—CH(R
8
)—, —CH
2
—CH
2
—CH
2
—Se—, —CH
2
—CH
2
—Se—CH
2
—, —CH
2
—CH
2
—CH
2
—S—, —CH
2
—CH
2
—CH
2
—O—, CH
2
—CH
2
—CH
2
—N(R
9
)—, —CH
2
—CH
2
—CO—CH
2
—, —CH
2
—CH
2
—CH(R
8
)—CH
2
—, —CH
2
—CH
2
—S—CH
2
—, —CH
2
—C(alk) (alk′)—S—CH
2
—, —CH
2
—CH(R
10
)—S—CH
2
—, —CH
2
—CH
2
—O—CH
2
—, —CH
2
—CH
2
—N(R
9
)—CH
2
— or —CH
2
—CO—N(R
9
)—CH
2
—, R
8
represents a hydroxyl radical, R
9
represents a hydrogen atom or an alkyl or benzyl radical and R
10
represents an alkyl, COOalk or CONH
2
radical may be prepared by reacting an alkali metal thiocyanate or an alkali metal selenocyanate with a derivative of formula:
in which R
7
has the same meanings as in formula (I) and —R
3
—R
4
—R
5
—R
6
— represents a chain of formula —CH
2
—CH
2
—CH
2
—CH
2
—, —CH
2
—CH
2
—CH
2
—CO—, —CH
2
—CH
2
—CH
2
—CH (R
8
)—, —CH
2
—CH
2
—CH
2
—Se—, —CH
2
—CH
2
—Se—CH
2
—, —CH
2
—CH
2
—CH
2
—S—, —CH
2
—CH
2
—CH 2—O—, CH
2
—CH
2
—CH
2
—N(R
9
) —, —CH
2
—CH
2
—CO—CH
2
—, —CH
2
—CH
2
—CH(R
8
)—CH
2
—, —CH
2
—CH
2
—S—CH
2
—, —CH
2
—C(alk) (alk′)—S—CH
2
—, —CH
2
—CH(R
10
)—S—CH
2
—, —CH
2
—CH
2
—O—CH
2
—, —CH
2
—CH
2
—N(R
9
)—CH
2
— or —CH
2
—CO—N(R
9
)—CH
2
—, R
8
represents a hydroxyl radical, R
9
represents a hydrogen atom or an alkyl or benzyl radical and R
10
represents an alkyl, COOalk or CONH
2
radical, alk and alk′ represent an alkyl radical.
This reaction is generally carried out in the presence of bromine, chlorine, chloramide or copper(II) chloride, in an organic solvent such as acetic acid, at a temperature between 15° C. and the boiling point of the reaction medium. As alkali metal thiocyanate or alkali metal selenocyanate, it is preferable to use potassium thiocyanate or potassium selenocyanate.
The derivatives of formula (II) are new and, as such, form part of the invention.
The compounds of formula (I) for which R
2
represents an alkyl radical may be prepared by alkylation of a corresponding compound of formula (I) for which R
2
represents a hydrogen atom.
This alkylation is carried out by any method which makes it possible to alkylate an imine functional group. Preferably, the procedure is carried out by means of a derivative Ra-X in which Ra represents an alkyl radical and X represents a reactive group such as a halogen atom (preferably chlorine, bromine or iodine) or a tosyloxy radical, in an inert organic solvent such as an aliphatic alcohol (1-6C) (ethanol, propanol or butanol for example), a ketone (acetone or methyl ethyl ketone for example) or dimethylformamide, in the presence of a base such as an alkali metal carbonate (potassium carbonate for example), at a temperature between 20° C. and the boiling point of the reaction medium.
The compounds of formula (I) for which R
2
represents a hydrogen atom or an alkyl radical, —R
3
—R
4
—R
5
—R
6
— represents a chain of formula —CH—
2
—CH
2
—CH(R
8
) —CH
2
— or —CH
2
—CH
2
—CH
2
—CH(R
8
)— and R
8
represents a hydroxyl radical may also be obtained by reducing a corresponding compound of formula (I), for which R
2
represents a hydrogen atom or an alkyl radical and —R
3
—R
4
—R
5
—R
6
— represents a chain of formula —CH
2
—CH
2
—CO—CH
2
— or —CH
2
—CH
2
—CH
2
—CO—.
This reaction is carried out by any method which makes it possible to pass from a ketone to an alcohol. The procedure is generally carried out by means of sodium borohydride, in an alcohol such as methanol or ethanol, at a temperature of between 0 and 25° C.
The compounds of formula (I) for which R
2
represents a hydrogen atom or an alkyl radical and —R
3
—R
4
—R
5
—R
6
— represents a chain of formula —CH
2
—CH
2
—CH
2
—SO—, —CH
2
—CH
2
—CH
2
—SO
2
—, —CH
2
—CH
2
—SO—CH
2
—, —CH
2
—CH
2
—SO
2
—CH
2
—, —CH
2
—C (alk) (alk′)—SO—CH
2
—, —CH
2
—C(alk) (alk′)—SO
2
—CH
2
—, —CH
2
—CH(R
10
)—SO—CH
2
— or —CH
2
—CH(R
10
)—SO
2
—CH
2
— may be prepared by oxidizing a corresponding compound of formula (I) for which the chain —R
3
—R
4
—R
5
—R
6
— represents a chain of formula —CH
2
—CH
2
—CH
2
—S—, —CH
2
—CH
2
—S—CH
2
—, —CH
2
—C(alk) (alk′)—S—CH
2
—or —CH
2
—CH(R
10
)—S—CH
2
—.
This oxidation is carried out according to known methods of oxidizing sulphur—containing derivatives as described by M. HUDLICKY, Oxidations in Organic Chemistry, ACS Monograph, 186, 252-263 (1990). For example, the procedure is carried out by the action of an organic peracid or a salt of such an acid (percarboxylic or persulphonic acid, in particular perbenzoic acid, 3-chloroperbenzoic acid, 4-nitroperbenzoic acid, peracetic acid, pertrifluoroacetic acid, performic acid or monoperphthalic acid) or inorganic peracids or a salt of such an acid (for example periodic or persulphuric acid), in an inert solvent such as a chlorinated solvent (chloroform or dichloromethane for example), at a temperature of between 0 and 25° C. It is also possible to use hydrogen peroxide or a periodate (sodium periodate for example), in an inert solvent such as a lower aliphatic alcohol, water or a mixture of these solvents, at a temperature of between 0 and 20° C. It is also possible to carry out the procedure by means of tert-butyl hydroperoxide in the presence of titanium tetraisopropoxide or oxone
R
(potassium peroxymonosulphate) in a lower aliphatic alcohol or a water-alcohol mixture, at a temperature close to 25° C.
The compounds of formula (I) for which R
2
represents a hydrogen atom or an alkyl radical, —R
3
—R
4
—R
5
—R
6
— represents a chain of formula —CH
2
—CH(R
10
)—S—CH
2
— in which

Affiliated with

Also associated with

Rating

Thiazolobenzoheterocycles, preparation and medicines... does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Thiazolobenzoheterocycles, preparation and medicines..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Thiazolobenzoheterocycles, preparation and medicines... will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2859234