Thiosulfonate compound as an inhibitor of matrix metalloprotease and methods of treatment

 

The invention relates to thiosulfonate compounds of General formula Ia, which can be used as inhibitors of the matrix metalloprotease-13 (MMP-13). In the formula Ia, R1is a substituted phenyl, R2and R3represent a radical selected from the group consisting of a hydrogen atom, a C1-C6of alkyl, aralkyl with one ring having 1-3 carbon atoms in the alkyl chain, or R2and R6together with the carbon atoms to which they are linked, form a 5 - or 6-membered ring; R6represents a radical selected from the group consisting of C1-C6of alkyl, carboxyl, C1-C6alkoxycarbonyl. The invention also relates to methods for treating pathological conditions associated with abnormal activity of the matrix metalloprotease related to MMP-13. 5 C. and 15 C.p. f-crystals, 51 PL.

Description text in facsimile form (see graphic part)

Claims

1. Thiosulfonate compounds of General formula (Ia)

where R1represents phenyl, substituted R11, R11the a-position C1-C4alkoxy;

R2and R3are radicals independently selected from the group consisting of hydrogen, C1-C6of alkyl, aralkyl with one ring having 1-3 carbon atoms in the alkyl chain, or

R2and R6together with the carbon atoms to which they are linked, form a 5 - or 6-membered ring;

R6represents a radical selected from the group consisting of C1-C6of alkyl, carboxyl, C1-C6alkoxycarbonyl,

as an inhibitor of matrix metalloprotease.

2. Connection on p. 1, where R1represents phenyl, substituted C1-C6alkoxy, phenoxy or thiophenoxy.

3. Connection on p. 1, where R1represents phenyl substituted in position 4 C1-C6alkoxy, phenoxy or thiophenoxy.

4. Connection on p. 1, where R1represents phenyl, substituted R11in position 4, a R11is phenoxy, which itself is substituted in the meta - or para-positions of the C1-C4alkoxy.

5. Thiosulfonate compounds of General formula (Ib):

where PhR11represents phenyl, substituted R11in position 4;

R11is C1-C6al alkoxygroup;

R2represents a radical selected from the group consisting of a hydrogen atom, a C1-C6of alkyl, aralkyl with one ring having 1-3 carbon atoms in the alkyl chain, or

R2and R6together with the carbon atoms to which they are linked, form a 5 - or 6-membered ring;

R6represents a radical selected from the group consisting of C1-C6alkoxycarbonyl;

R2and R6are hydrogen atoms, if R2and R6together with the carbon atoms to which they are linked, form a 5 - or 6-membered ring, as an inhibitor of matrix metalloprotease type MMP-13.

6. Connection on p. 5, in which R11selected from the group consisting of phenoxy, thiophenoxy, where phenoxy, thiophenoxy substituted in the meta - or para-positions of the C1-C4alkoxy.

7. Connection on p. 6, in which R11represents phenoxy, substituted in the para-position of the C1-C7alkoxy.

8. Thiosulfonate compounds of General formula (IVa) or (Va):

where R1represents phenyl, substituted R11, R11is C1-C6alkoxy, phenoxy or thiophenoxy, Cora matrix metalloprotease type MMP-13.

9. Connection on p. 8, in which R1represents phenyl, substituted R11in position 4, and where R11selected from the group consisting of C1-C6alkoxy, phenoxy, thiophenoxy.

10. Connection on p. 8, in which R1represents phenyl, substituted R11in position 4, and R11selected from the group consisting of C1-C6alkoxy, phenoxy, thiophenoxy, where phenoxy or thiophenoxy substituted in meta or paraprotex C1-C4alkoxy.

11. A method of treating a mammal having a condition associated with pathological activity of the matrix of metalloprotease type MMP-13 by introducing to a mammal the compound or its pharmaceutically acceptable salt in an effective amount and a specified compound corresponds to the formula

where R1represents phenyl, substituted R11,

R11is C1-C6alkoxy, phenoxy or thiophenoxy, which can be substituted in the meta - or para-position C1-C4alkoxy;

R2and R3are radicals independently selected from the group consisting of hydrogen, C1-C6of alkyl, aralkyl with one ring having 1-3 asresult 5 - or 6-membered ring;

R6represents a radical selected from the group consisting of C1-C6of alkyl, carboxyl, C1-C6alkoxycarbonyl.

12. The method according to p. 11, where the condition associated with pathological activity of the matrix of metalloprotease type MMP-13, selected from the group consisting of osteoarthritis and angiogenesis.

13. The method according to p. 11, where R1is phenyl, substituted in position 4 by a Deputy selected from the group consisting of C1-C6alkoxy, phenoxy, thiophenoxy.

14. The method according to p. 11, where R1represents phenyl, substituted R11in position 4, and R11represents phenoxy substituted in the meta - or para-positions of the C1-C6alkoxy.

15. A method of treating a mammal having a condition associated with pathological activity of the matrix of metalloprotease type MMP-13, by introducing to a mammal the compound or its pharmaceutically acceptable salt in an effective amount and a specified compound corresponds to the formula

where PhR11represents phenyl, substituted R11in position 4;

R11is C1-C6alkoxy, phenoxy or thiophenoxy, which may be samewe is isimo selected from the group consisting of a hydrogen atom, a C1-C6of alkyl, aralkyl with one ring having 1-3 carbon atoms in the alkyl chain, or

R2and R6together with the carbon atoms to which they are linked, form a 5 - or 6-membered ring;

R6represents a radical selected from the group consisting of C1-C6alkoxycarbonyl;

R2and R6are hydrogen atoms, if R2and R6together with the carbon atoms to which they are linked, form a 5 - or 6-membered ring.

16. The method according to p. 15, where the condition associated with pathological activity of the matrix of metalloprotease type MMP-13, selected from the group consisting of osteoarthritis and angiogenesis.

17. The method according to p. 16, where R11is C1-C6alkoxy, phenoxy or thiophenoxy substituted in the meta - or para-position C1-C4alkoxygroup.

18. The method according to p. 16, where R11represents phenoxy and substituted in the para-position of the C1-C4alkoxy.

19. The method according to p. 11, where the condition associated with pathological activity of the matrix of metalloprotease is angiogenesis.

20. The method according to p. 15, where the condition associated with pathological activity of the matrix of metalloprotease is angiogen

 

Same patents:

The invention relates to an inhibitor of the activity of esterified cholesterol transport protein (HETB), comprising as active ingredient a compound represented by the formula (I), where R is a straight or branched alkyl group; a lower halogenating group; substituted or unsubstituted cycloalkyl group; substituted or unsubstituted cycloalkylcarbonyl group; substituted or unsubstituted aryl group, or substituted or unsubstituted heterocyclic group, X1X2X3and X4may be the same or different and each represents a hydrogen atom, halogen atom, lower alkyl group, lower halogenating group; a lower alkoxygroup; a cyano; a nitro-group; Y represents-CO -, and Z represents a hydrogen atom or mercaptohexanol group, or its pharmaceutically acceptable salt, or hydrate, or MES

The invention relates to 4-mercapto-benzoylpyridine formula (I), where R1denotes A; R2means And, unsubstituted or substituted by F, Cl, Br, phenyl, pyridyl; And - alkyl with 1-6 C-atoms, and their physiologically acceptable salts, methods for their production and pharmaceutical compositions based on them

The invention relates to a method of asymmetric obtain florfenicol formula I, which consists of the following stages: 1) stage rehospitalised opening of chiral epoxide of formula II by sequential processing of a strong base, Lewis acid and dichloroacetonitrile getting oxazoline formula (III); (II) stage selective inversion/isomerization received oxazoline formula (III) by sequential processing of the tertiary amine and the lower alkylsulfonamides, water, acid and alkali metal hydroxide getting oxazoline formula (IV); (III) stage of processing oxazoline formula IV agent fluorination and subsequent acid hydrolysis

Multicore bisazide // 2067572
The invention relates to new compounds of General formula I

< / BR>
Z=-SO2-, -X--Y--X-

X=O,S

Y=0, S, SO2; CO.,

which can be used as light-sensitive components of photoresists

The invention relates to new derivatives of benzonitrile formula I

where n = 1-2

Y is a group -(CH2)m- where: m = 0-1, or SNAN,

Z is hydrogen or a saturated unbranched alkyl with 1-3 carbon atoms;

And group

-- (CH2)q-Rcor -(CH2)q-Rc< / BR>
where Ra, Ra' and Ra" are each independently from each other the unbranched oxyalkyl or alkyl with 1-5 carbon atoms

Rc - saturated unbranched alkyl with 1-4 carbon atoms which may be substituted by fluorine atoms;

P = 1-2

q = 2-5 of the racemate, or pharmaceutically acceptable salts, which possess antiarrhythmic activity, and compositions comprising the compounds I for the treatment of cardiac arrhythmia

The invention relates to medicine, in particular to medicines used to treat erosive-ulcerative lesions of the mucous membranes of the rectum and vagina, as well as hepatitis a different etymology,

You know the "zelibor" (tablets) with antioxidant, hepatoprotective, immunomodulatory properties and produce FF "Darnitsa", Ukraine

The invention relates to new niftystories compounds of formula I, where R1and R2- H, -OH, -O(C1-C4alkyl), -OCOC6H5, -OCO(C1-C6alkyl), -OSO2(C4-C6alkyl); R3- 1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidinyl, 4-morpholino, dimethylamino, diethylamino, 1 hexamethyleneimino; intermediate compounds, which are suitable for easing symptoms of postmenopausal syndrome, including osteoporosis, hyperlipemia and estrogenzawisimy cancer, and inhibition of uterine fibroids, endometriosis and proliferation of aortic smooth muscle cells

The invention relates to iododerma biologically active compositions containing iodine and halides of nitrogenous bases of the formula I, where the values of the radicals a, b, C, R, X and m are specified in the claims

The invention relates to the field of medicine and relates to a method of producing an oral pharmaceutical preparation comprising an inert core and the active layer, dissolving or disintegrating in water obtained from water or water-alcohol suspesions solution containing the active substance having anti-ulcer effect of formula I, II or III), and at least one filler, and gasterosteidae external coating obtained from a solution containing the polymer for Intercollege coating and at least one filler, by drawing on the inert core of the active layer by spraying an aqueous or aqueous-alcoholic suspension solution, drying of the active layer, obtained at the previous stage, and coating the core with an active layer of a solution containing the polymer for Intercollege coating and filler

The invention relates to sterylsulfonate compounds of formula I, where n represents zero or one; R1selected from the group comprising chlorine, fluorine or bromine; and R2selected from the group comprising chlorine, fluorine and bromine; R3selected from the group comprising hydrogen and fluorine; each radical R1and R2may not be chlorine when R3represents hydrogen; and R1may not be chlorine when R2represents fluorine, and R3is hydrogen in the same connection

The invention relates to the field of medicine and for new dosage forms of demoliton
The invention relates to medicine, Mycology and dermatology, to methods of treatment of onychomycosis
The invention relates to medicine, namely to ophthalmology, and for the treatment of retinal detachment

The invention relates to medicine, namely to urology, and can be used to improve reservoir bladder in chronic cystitis

The invention relates to medicine, namely to the treatment of bladder dysfunction caused by hyperactivity of the detrusor

The invention relates to the field of medicine
Up!