US 2003/0166620 A1 · Novel oxazolidinone derivatives and a process for the preparation thereof

Abstract

The present invention relates to novel oxazolidinone derivatives, their pharmaceutically acceptable salts and a process for the preparation thereof. More particularly, the present invention relates to oxazolidinone derivatives having pyridine or pyrimidine moeity substituted by heterocycle and heteroaromaticcycle at 4-position of phenyl ring. The compounds of the present invention have wide antibacterial spectrum, superior antibacterial activity and low toxicity, such that the compound of this invention can be used as an antibacterial agent.

(amended) derivatives of oxazolidinone of formula 1, and pharmaceutically acceptable salt thereof:

15
wherein,
R1 is H, F, Cl or CF3;
R2 is
16
where R3 is piperazinyl optionally substituted with R5,
where R5 is:
(a) H;
(b) triphenylmethyl;
(c) substituted or unsubstituted acetyl, provided that the substituted acetyl is selected from the group consisting of benzyloxyacetyl, acetoxyacetyl, hydroxy acetyl, C1-C3 alkylaminoacetoxyacetyl, acetyl substituted with halogen, morpholi-4-nylacetyl, imidazol-1-ylcarbonyloxy acetyl, C1-C3 alkoxycarbonylmethylaminoacetyl, C1-C3 alkoxyacetyl, t-butyl acetyl, phenyl acetyl optionally substituted with C1-C3 alkoxy, and C1-C3 alkoxyoxoacetyl;
(d) substituted or unsubstituted benzoyl, provided that the substituted benzoyl is selected from the group consisting of C1-C4 alkoxybenzoyl, trihalomethylbenzoyl and nitrobenzoyl;
(e) substituted or unsubstituted carbonyl, provided that the substituted carbonyl is selected from the group consisting of C1-C4 haloalkylcarbonyl, phenoxycarbonyl and benzyloxycarbonyl;
(f) C1-C3 alkoxyphenyl;
(g) acryloyl optionally substituted with C1-C3 alkyl;
(h) nicotinoyl;
(i) pivaloyl;
(j) crotonyl, or
(k) n-valeryl,
R4 is:
azido;
—(C═O)1—R6;
—NR7R8;
—(CH2)m—R9;
or —OR10,
where R6 is:
C1-C3 alkoxy;
amino;
C1-C3 alkylamino;
or C1-C3 hydroxyalkylamino,
l is an integer of 1 to 2,
R7 and R8, which may be the same or different, represent,
(a) C1-C4 alkyl substituted with one or more phenyl groups, or C1-C4 alkenyl substituted with C1-C3 alkylamino;
(b) substituted or unsubstituted acetyl, provided that the substituted acetyl is selected from the group consisting of acetoxyacetyl, hydroxyacetyl, C1-C3 alkylaminoacetoxyacetyl, C1-C3 alkoxyacetyl, aminoacetyl, azidoacetyl, acetylaminoacetyl, C1-C3 alkylaminoacetyl, aminopropionyl, and hydroxylpropionyl;
or
(c) nicotinoyl,
R9 is:
azido;
hydroxy;
C1-C3 alkylaminoacetoxy;
acetylthio, mercapto, cyano, a halogen atom, or a 5- or 6-membered heterocycle,
m is an integer of 1 to 4,
R10 is:
acetyl;
alkoxyalkyl;
methanesulfonyl;
or heterocylic rings selected from the group consisting of:
a) 5- or 6-membered heteroring containing one or more N, or O as ring members, preferably represented by the following formula:
17
b) a 5-membered heterocyclic ring containing at least one nitrogen or oxygen atom or both of them, as ring members, in which any one carbon atom is saturated with two hydrogen atoms or forms a double bond with oxygen (ketone), nitrogen (imino) or sulfur (thioketone), preferably of the following formula:
18
wherein A, B, and D, which may be the same or different, each represents a carbon, an oxygen or a nitrogen atom, and E represents two hydrogen atoms, an oxygen, a sulfur, or a nitrogen atom, and more preferably of the following formula:
19
c) 5- or 6-membered hetero aromatic ring containing C, N, O or S as ring members and preferably one or two N or O, or at least one nitrogen and at least one oxygen atom together, as ring members of the following formula:
20
where R11 and R12, which are the same or different, each represents:
(i) H, F, Cl, Br or I;
(ii) C1-C4 alkyl substituted optionally with at least one substituent, provided that the substituted alkyl is selected from the group consisting of hydroxyalkyl, alkoxycarbonylalkyl, trihaloalkyl, acetoxyalkyl, alkylaminoalkyl, alkoxyalkyl, and methanesulfonyloxyalkyl;
(iii) substituted or unsubstituted acetyl, provided that the substituted acetyl is selected from the group consisting of acetoxyacetyl, hydroxyacetyl, C1-C3 alkylamino acetoxyacetyl, C1-C3 alkoxyacetyl, aminoacetyl, azidoacetyl, acetylaminoacetyl, C1-C3 alkylaminoacetyl, aminopropionyl, and hydroxypropionyl;
(iv) azido, hydroxy, mercapto, cyano, ketone, or amino;
(v) substituted or unsubstituted imino, provided that the substituted imino is selected from the group consisting of hydroxyimino, alkylimino, alkoxyimino or methanesulfonyloxyimino;
(vi) hydrozino optionally substituted with alkoxycarbonyl;
(vii) —OR13, where R13 is H, C1-C3 alkyl, acetyl, alkoxyalkyl, hydroxyacetyl or methanesulfonyl;
(viii) —NR14R15, wherein R14 and R15 represent independently H, C1-C3 alkyl, acetyl, alkoxylalkyl, hydroxyacetyl or methansulfonyl;
(ix) —(C═O)—(R16)n—,
where R16 is:
1) C1-C6 alkyl, or alkenyl optionally substituted with C1-C3 alkyl;
2) alkoxycarbonyl;
3) acetoxymethyl, benzyloxymethyl, hydroxymethyl, C1-C3 alkylacetoxymethyl, halomethyl, C1-C3 alkoxymethyl, morpholinylmethyl, C1-C3 alkoxycarbonylmethyl aminomethyl, C1-C3 methanesulfonyloxymethyl, alkoxyoxomethyl, C1-C3 nicotinoyloxymethyl, alkoxyphenylmethyl, benzyl, or trihalomethyl;
4) C1-C3 alkoxy, phenyloxy, allyloxy, C1-C3 haloalkyloxy, benzyloxy optionally substituted with nitoro, or 9-fluorenylmethyloxy;
5) nicotinoylmethyl;
or
6) a 5- or 6-membered heterocyclic ring.

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Novel oxazolidinone derivatives and a process for the preparation thereof

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Novel oxazolidinone derivatives and a process for the preparation thereof

Life of this patent

Abstract

Claims7