1. An implantable body for intersomatic fusion, characterized in that it is made from a bioabsorbable, metallic material.
2. The implantable body as claimed in claim 1, characterized in that the metallic material is magnesium or iron, or it contains magnesium or iron as its main component.
3. The implantable body as claimed in claim 1, characterized in that the material is a magnesium alloy.
4. The implantable body as claimed in claim 1, characterized in that the material is an iron alloy.
5. The implantable body as claimed in claim 1, characterized in that the body is porous, in particular microporous.
6. The implantable body as claimed in claim 1, characterized in that the body has an open structure andor a structure with holes, cavities andor slits.
7. The implantable body as claimed in claim 1, characterized in that the body is provided with at least one active substance, in particular a biologically active substance, preferably with at least one growth factor, a cytostatic agent, a radioactive material, an antibiotic andor an antibody.
8. The implantable body as claimed in claim 1, characterized in that the body is provided with an extract of demineralized bone material.
9. The implantable body as claimed in claim 1, characterized in that the body is packaged, in particular in a sterile state.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A process for the preparation of a 2-ethylaminopyridine derivative of general formula (I) or a salt thereof
in which:
p is an integer equal to 1, 2, 3 or 4;
X is the same or different and is a hydrogen atom, a halogen atom, a nitro group, a cyano group, a hydroxy group, an amino group, a sulfanyl group, a pentafluoro-\u03bb6-sulfanyl group, a formyl group, a formyloxy group, a formylamino group, a carboxy group, a carbamoyl group, a N-hydroxycarbamoyl group, a carbamate group, a (hydroxyimino)-C1-C6-alkyl group, a C1-C8-alkyl, a C1-C8-halogenoalkyl having 1 to 5 halogen atoms, a C2-C8-alkenyl, a C2-C8-alkynyl, a C1-C8-alkylamino, a di-C1-C8-alkylamino, a C1-C8-alkoxy, a C1-C8-halogenoalkoxy having 1 to 5 halogen atoms, a C1-C8-alkylsulfanyl, a C1-C8-halogenoalkylsulfanyl having 1 to 5 halogen atoms, a C2-C8-alkenyloxy, a C2-C8-halogenoalkenyloxy having 1 to 5 halogen atoms, a C3-C8-alkynyloxy, a C3-C8-halogenoalkynyloxy having 1 to 5 halogen atoms, a C3-C8-cycloalkyl, a C3-C8-halogenocycloalkyl having 1 to 5 halogen atoms, a C1-C8-alkylcarbonyl, a C1-C8-halogenoalkylcarbonyl having 1 to 5 halogen atoms, a C1-C8-alkylcarbamoyl, a di-C1-C8-alkylcarbamoyl, a (N\u2014C1-C8-alkyl)oxycarbamoyl, a C1-C8-alkoxycarbamoyl, a (N\u2014C1-C8-alkyl)-C1-C8-alkoxycarbamoyl, a C1-C8-alkoxycarbonyl, a C1-C8-halogenoalkoxycarbonyl having 1 to 5 halogen atoms, a C1-C8-alkylcarbonyloxy, a C1-C8-halogenoalkylcarbonyloxy having 1 to 5 halogen atoms, a C1-C8-alkylcarbonylamino, a C1-C8-halogenoalkylcarbonylamino having 1 to 5 halogen atoms, a C1-C8-alkylaminocarbonyloxy, a di-C1-C8-alkylaminocarbonyloxy, a C1-C8-alkyloxycarbonyloxy, a C1-C8-alkylsulphenyl, a C1-C8-halogenoalkylsulphenyl having 1 to 5 halogen atoms, a C1-C8-alkylsulphinyl, a C1-C8-halogenoalkylsulphinyl having 1 to 5 halogen atoms, a C1-C8-alkylsulphonyl, a C1-C8-halogenoalkylsulphonyl having 1 to 5 halogen atoms, a (C1-C6-alkoxyimino)-C1-C6-alkyl, a (C1-C6-alkenyloxyimino)-C1-C6-alkyl, a (C1-C6-alkynyloxyimino)-C1-C6-alkyl, a (benzyloxyimino)-C1-C6-alkyl, a benzyloxy, a benzylsulfanyl, a benzylamino, a phenoxy, a phenylsulfanyl or a phenylamino; and as to the N-oxides of 2-pyridine thereof;
said process comprising:
(A)\u2014a first step according to reaction scheme 1:
in which:
X and p are as defined above;
R is a C1-C8-alkyl; and
Hal represents a halogen atom;
comprising:
a) the reaction of a 2-halogenopyridine derivative with an alkyl cyanoacetate, in a 2-halogenopyridine derivativealkyl cyanoacetate molar ratio of from 1 to 10, in a polar solvent, in the presence of a base, the base2-halogenopyridine derivative molar ratio being of from 1 to 4;
b) followed by an addition of acid until a pH value of the reaction mixture of from 1 to 5;
to provide a 2-methylcyanopyridine derivative;
(B)\u2014a second step according to reaction scheme 2:
in which:
X, p are as defined above;
R1 represents a C1-C6-alkyl;
R2 represents a halogen atom or a \u2014OCOAlk group; and
Alk represents a C1-C6-alkyl;
comprising the catalytic reduction of reaction of a 2-methylcyanopyridine derivative obtained in step one in the presence of an acylating agent of formula R1COR2 and of a catalyst, in a solvent, under a hydrogen pressure of from 4 to 40 bar, to provide a 2-ethylaminopyridyl derivative;
(C)\u2014a third step according to reaction scheme 3:
in which:
X and p are as defined above; and
R1 represents a C1-C6-alkyl group;
comprising the hydrolysis in water of a 2-ethylaminopyridine derivative obtained in step two by adding to it from 1 to 20 molar equivalent of an acid, at a temperature of from 20\xb0 C. to reflux, to provide a compound of general formula (I).
2. A process according to claim 1, characterised in that p is 2.
3. A process according to claim 1, characterised in that X is chosen, independently of the others, as being chlorine or CF3;
4. A process according to claim 1, characterised in that the 2-pyridyl moiety is substituted by X in 3- andor in 5-position.
5. A process according to claim 1, characterised in that the compound of formula (I) is:
N-2-3-chloro-5-(trifluoromethyl)-2-pyridinylethylamine, or
N-2-3,5-dichloro-2-pyridinylethylamine.
6. A process according to claim 1, characterised in that step A is conducted at a temperature of from 0\xb0 C. to reflux.
7. A process according to claim 1, characterised in that step B is conducted at a temperature of from 16\xb0 C. to 70\xb0 C.
8. A process according to claim 1, characterised in that it comprises a further step (D) according to the reaction scheme 4:
in which:
X and p are as defined above;
A represents a phenyl group or a 5-, 6- or 7-membered non-fused heterocycle with one, two or three heteroatoms which may be the same or different, the heterocycle being linked by a carbon atom; each of this group being optionally substituted by one or more substituents chosen independently of each other as being a halogen atom, a nitro group, a cyano group, a hydroxy group, an amino group, a sulfanyl group, a pentafluoro-\u03bb6-sulfanyl group, a formyl group, a formyloxy group, a formylamino group, a carboxy group, a C1-C8-alkyl, a C1-C8-halogenoalkyl having 1 to 5 halogen atoms, a C2-C8-alkenyl, a C2-C8-alkynyl, a C1-C8-alkylamino, a di-C1-C8-alkylamino, a C1-C8-alkoxy, a C1-C8-halogenoalkoxy having 1 to 5 halogen atoms, a C1-C8-alkoxy-C2-C8-alkenyl, a C1-C8-alkylsulfanyl, a C1-C8-halogenoalkylsulfanyl having 1 to 5 halogen atoms, a C1-C8-alkoxycarbonyl, a C1-C8-halogenoalkoxycarbonyl having 1 to 5 halogen atoms, a C1-C8-alkylcarbonyloxy, a C1-C8-halogenoalkylcarbonyloxy having 1 to 5 halogen atoms, a C1-C8-alkylsulphenyl, a C1-C8-halogenoalkylsulphenyl having 1 to 5 halogen atoms, a C1-C8-alkylsulphinyl, a C1-C8-halogenoalkylsulphinyl having 1 to 5 halogen atoms, a C1-C8-alkylsulphonyl, a C1-C8-halogenoalkylsulphonyl having 1 to 5 halogen atoms or a C1-C8-alkylsulfonamide;
comprising the coupling reaction of the 2-ethylaminopyridine obtained in step three of the above described process with a halide carboxyl derivative contained in an organic solvent in the presence of a base to produce a N-2-(2-pyridinyl)ethylcarboxamide derivative of general formula (II).
9. A process according to claim 8, characterised in that A is a phenyl group.
10. A process according to claim 9, characterised in that A is substituted by one or two substituents.
11. A process according to claim 9, characterised in that each substituent of A is chosen, independently of each other, as being chlorine or CF3.
12. A process according to claim 9, characterised in that the A is substituted in ortho position.
13. A process according to claim 8, characterised in that the compound of formula (II) is:
N-{2-3-chloro-5-trifluoromethyl)-2-pyridinylethyl}-2-trifluoromethylbenzamide;
N-{2-3-chloro-5-trifluoromethyl)-2-pyridinylethyl}-2-iodobenzamide; or
N-{2-3,5-dichloro-2-pyridinylethyl}-2-trifluoromethylbenzamide.
14. A compound of general formula (III)
in which:
p is an integer equal to 1, 2, 3 or 4;
X is the same or different and is a hydrogen atom, a halogen atom, a nitro group, a cyano group, a hydroxy group, an amino group, a sulfanyl group, a pentafluoro-\u03bb6-sulfanyl group, a formyl group, a formyloxy group, a formylamino group, a carboxy group, a carbamoyl group, a N-hydroxycarbamoyl group, a carbamate group, a (hydroxyimino)-C1-C6-alkyl group a C1-C8-alkyl, a C1-C8-halogenoalkyl having 1 to 5 halogen atoms, a C2-C8-alkenyl, a C2-C8-alkynyl, a C1-C8-alkylamino, a di-C1-C8-alkylamino, a C1-C8-alkoxy, a C1-C8-halogenoalkoxy having 1 to 5 halogen atoms, a C2-C8-alkylsulfanyl, a C1-C8-halogenoalkylsulfanyl having 1 to 5 halogen atoms, a C2-C8-alkenyloxy, a C2-C8-halogenoalkenyloxy having 1 to 5 halogen atoms, a C3-C8-alkynyloxy, a C3-C8-halogenoalkynyloxy having 1 to 5 halogen atoms, a C3-C8-cycloalkyl, a C3-C8-halogenocycloalkyl having 1 to 5 halogen atoms, a C1-C8-alkylcarbonyl, a C1-8-halogenoalkylcarbonyl having 1 to 5 halogen atoms, a C1-C8-alkylcarbamoyl, a di-C1-C8-alkylcarbamoyl, a (N\u2014C1-C8-alkyl)oxycarbamoyl, a C1-C8-alkoxycarbamoyl, a (N\u2014C1-C8-alkyl)-C1-C8-alkoxycarbamoyl, a C1-C8-alkoxycarbonyl, a C1-C8-halogenoalkoxycarbonyl having 1 to 5 halogen atoms, a C1-C8-alkylcarbonyloxy, a C1-C8-halogenoalkylcarbonyloxy having 1 to 5 halogen atoms, a C1-C8-alkylcarbonylamino, a C1-C8-halogenoalkylcarbonylamino having 1 to 5 halogen atoms, a C1-C8-alkylaminocarbonyloxy, a di-C1-C8-alkylaminocarbonyloxy, a C1-C8-alkyloxycarbonyloxy, a C1-C8-alkylsulphenyl, a C1-C8-halogenoalkylsulphenyl having 1 to 5 halogen atoms, a C1-C8-alkylsulphinyl, a C1-C8-halogenoalkylsulphinyl having 1 to 5 halogen atoms, a C1-C6-alkylsulphonyl, a C1-C6-halogenoalkylsulphonyl having 1 to 5 halogen atoms, a (C1-C6-alkoxyimino)-C1-C6alkyl, a (C1-C6-alkenyloxyimino)-C1-C6-alkyl, a (C1-C6-alkynyloxyimino)-C1-C6-alkyl, a (benzyloxyimino)-C1-C6-alkyl, a benzyloxy, a benzylsulfanyl, a benzylamino, a phenoxy, a phenylsulfanyl or a phenylamino; and as to the N-oxides of 2-pyridine thereof; and
R1 represents a C1-C6-alkyl group.