Heterocyclic compounds having antibacterial activity: process for their preparation and pharmaceutical compositions containing them Number:7,160,912 from the United States Patent and Trademark Office (PTO) owispatent The present invention relates to novel oxazolidinone compounds of formula (I), their stereoisomers, their salts and pharmaceutical compositions containing them. ##STR00001## The present invention also relates to a process for the preparation of the above said novel compounds, their stereoisomers, their salts and pharmaceutical compositions.<H pharmaceutical, antibacterial, Heterocyclic, co, 7160912.html, Patent, pto, 7160912

Title: Heterocyclic compounds having antibacterial activity: process for their preparation and pharmaceutical compositions containing them

Abstract: The present invention relates to novel oxazolidinone compounds of formula (I), their stereoisomers, their salts and pharmaceutical compositions containing them. ##STR00001## The present invention also relates to a process for the preparation of the above said novel compounds, their stereoisomers, their salts and pharmaceutical compositions.

Patent Number: 7,160,912 Issued on 01/09/2007 to Selvakumar, et al.

Inventors: Selvakumar; Natesan (Hyderabad, IN), Das; Jagattaran (Hyderabad, IN), Trehan; Sanjay (Hyderabad, IN), Iqbal; Javed (Hyderabad, IN), Kumar; Magadi Sitaram (Hyderabad, IN), Rajagopalan; Ramanujam (Hyderabad, IN), Rao; Mamidi Naga Venkata Srinivasa (Hyderabad, IN)
Assignee: Dr.Reddy's Laboratories Ltd. (Hyderabad, IN)
Dr. Reddy's Laboratories, Inc. (Bridgewater, NJ)

Appl. No.: 10/613,414

Filed: July 3, 2003

Foreign Application Priority Data


Dec 26, 2000 [IN]			1124/MAS/2000
Jan 04, 2001 [IN]			15/MAS/2001

Current U.S. Class: 514/376 ; 544/106; 544/132; 544/139; 544/358; 544/370; 546/268.1; 546/272.7; 548/225; 548/229

Current International Class: A61K 31/421 (20060101); C07D 263/04 (20060101); C07D 413/12 (20060101)

Field of Search: 548/229 544/139,132,370 514/376 546/272.7

References Cited [Referenced By]

U.S. Patent Documents


2987505	June 1961	Werner et al.
3651079	March 1972	Skorez et al.
3963706	June 1976	Pfirrmann
4174958	November 1979	Pilgram
4910341	March 1990	Lang et al.
5883093	March 1999	Hutchinson et al.
6124334	September 2000	Hutchinson
6277985	August 2001	Gadwood et al.
6512112	January 2003	Gadwood et al.
6515135	February 2003	Gadwood et al.
6525193	February 2003	Gadwood et al.

Foreign Patent Documents


2357591	May., 1974	DE
3536066	Apr., 1986	DE
11-322729	Nov., 1999	JP
95/07271	Mar., 1995	WO
96/13502	May., 1996	WO
97/27188	Jul., 1997	WO
01/09107	Feb., 2001	WO
03/011859	Feb., 2003	WO

Other References

US. Patent 4,910,341 corresponding to German Publication DE 3536066, dated Apr. 17, 1986. cited by other .
U.S. Patent 3,963,706 corresponding to German Publication DE 2357591, dated May 22, 1974. cited by other .
Melissaris, A. P. and J. A. Mikroyannidis. "Thermally Stable Polymers Based on Bismaleimides Containing Amide, Imide and Ester Linkages", J. Polymer Science: Polymer Chemistry Part A (1989), 27: 245-262. cited by other .
Artico, M. et al. "Research on Compounds with Antiblastic Activity", Il Farmaco--Ed. Sci., (1969), 24(2): 179-190. cited by other .
Ueda, Minoru et al. "Syntheses and Novel Bioactivites of Artificial Leaf-Opening Substances of Lespedeza cuneata G. Don, Designed for the Bioorganic Studies of Nyctinasty", Tetrahedron (1999), 55: 10925-10936. cited by other .
Ricca, Jean-Marc and David H.G. Crout. "Selectivity and Specificity in Substrate Binding to Proteases: Novel Hydrolytic Reactions Catalysed by .alpha.-Chymotrypsin . . . " J. Chem. Soc. Perkin Trans. I (1993), 1225-1233. cited by other .
Braun, et al 1979, Liebigs, Annalen der Chemie, 2, 200-9. cited by other .
Sorokin, et al, 1987, Khimicheskaya Tekhnologiya, 24(5), 561-5. cited by other.

Primary Examiner: Shameem; Golam M. M.
Attorney, Agent or Firm: Cepeda; Milagros A. Pergament; Edward D.

Parent Case Text

This application is a continuation-in-part of copending application Ser. No. 10/032,392 filed on Dec. 21, 2001.

Claims

What is claimed is:

1. A compound that is an oxazolidinone derivative of the formula (I) ##STR00385## or a salt thereof, or a stereoisomer thereof, where R.sup.1 represents --NHR.sup.4 wherein R.sup.4 represents thio(C.sub.1 C.sub.10)acyl, --C(.dbd.S)-cyclo(C.sub.3 C.sub.8)alkoxy, --C(.dbd.S)--(C.sub.1 C.sub.10)alkoxy, --C(.dbd.S)--(C.sub.2 C.sub.10)alkenyloxy, --C(.dbd.S)-aryloxy, --(C.dbd.S)--S--(C.sub.1 C.sub.10)alkyl, --(C.dbd.S)--NH.sub.2, --(C.dbd.S)--NH--(C.sub.1 C.sub.10)alkyl, --C(.dbd.S)--N--((C.sub.1--C,o)alkyl).sub.2, --C(.dbd.S)--NH--(C.sub.2 C.sub.10)alkenyl, (C.dbd.S)--(C.dbd.O)--(C.sub.1 C.sub.10)alkoxy, --(C.dbd.S)--(C.dbd.O)-aryloxy, --C(.dbd.S)--O--(C.dbd.O)--(C.sub.1 C.sub.10)alkyl, C(.dbd.S)--C(.dbd.S)--(C.sub.1 C.sub.10)alkyl, --C(.dbd.S)--C(.dbd.S)-aryl, --C(.dbd.S)-thiomorpholinyl or --C(.dbd.S)-pyrrolidinyl; R.sup.2 and R.sup.3, which may be the same or different, are each independently hydrogen, halogen, (C.sub.1 C.sub.10)alkyl, halogenated (C.sub.1 C.sub.10)alkyl, cyano, nitro, SR.sup.a, NR.sup.a or OR.sup.a, in which R.sup.a is hydrogen, (C.sub.1 C.sub.10)alkyl or halogenated (C.sub.1 C.sub.10)alkyl; ##STR00386## is a heterocyclic moiety in which ##STR00387## is a 5-membered heterocyclic skeleton, Z represents .dbd.CH, --CH.sub.2 or NR.sup.b, where R.sup.b is hydrogen or a moiety, which may be substituted or unsubstituted, straight chain or branched, selected from the group consisting of (C.sub.1 C.sub.10)alkyl, (C.sub.2 C.sub.10)alkenyl, (C.sub.3 C.sub.8)cycloalkyl, hydroxy(C.sub.1 C.sub.10)alkyl, (C.sub.1 C.sub.10)alkylhydroxy, (C.sub.1 C.sub.10)alkylamino, amino(C.sub.1 C.sub.10)alkyl, (C.sub.1 C.sub.10)alkoxy, aryl, aralkyl, aryloxy, (C.sub.1 C.sub.10)alkylcarbonyl, arylcarbonyl, (C.sub.1 C.sub.10) alkoxycarbonyl and aryloxycarbonyl; Y.sup.1 represents .dbd.O or .dbd.S group and Y.sup.2 and Y.sup.3 independently represent hydrogen, halogen, cyano, nitro, formyl, hydroxy, amino, .dbd.O, .dbd.S group or substituted or unsubstituted groups selected from (C.sub.1 C.sub.10)alkyl, hydroxy(C.sub.1 C.sub.10)alkyl, (C.sub.1 C.sub.10)alkylhydroxy, (C.sub.1 C.sub.10)alkoxy(C.sub.1 C.sub.10)alkyl, (C.sub.1 C.sub.10)alkylcarbonyl, (C.sub.1 C.sub.10)alkoxycarbonyl, arylcarbonyl, carboxy(C.sub.1 C.sub.10)alkyl, (C.sub.1 C.sub.10)alkylsulfonyl, C.sub.1 C.sub.10)alkylcarbony(C.sub.1 C.sub.10)alkyl, arylcarbonylamino(C.sub.1 C.sub.10)alkyl, (C.sub.1 C.sub.10)alkylcarbonyloxy(C.sub.1 C.sub.10)alkyl, amino(C.sub.1 C.sub.10)alkyl, mono(C.sub.1 C.sub.10)alkylamino, di(C.sub.1 C.sub.10)alkylamino, arylamino, (C.sub.1 C.sub.10)alkoxy, aryl, aryloxy, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl or heterocycloalkyl; Y.sup.2 and Y.sup.3 when present on adjacent carbon atoms together may also form a substituted or unsubstituted 5 or 6 membered aromatic or non-aromatic cyclic structure, optionally containing one or two hetero atoms selected from oxygen, sulfur and nitrogen.

2. The compound of claim 1 having the structure ##STR00388## wherein X.sup.1 is oxygen or sulfur.

3. The compound of claim 1 having the structure ##STR00389## wherein X.sup.1 is oxygen or sulfur.

4. The compound of claim 1 having the structure ##STR00390## wherein X.sup.1 is oxygen or sulfur, and ##STR00391## is a substituted or unsubstituted 5- or 6-membered aromatic or non-aromatic cyclic structure optionally having one or two hetero atoms, formed by Y.sup.2 and Y.sup.3.

5. The compound of claim 4, wherein said cyclic structure formed by Y.sup.2 and Y.sup.3 is benzene, pyridine, pyrrolidine, furan thiophene, morpholine, piperazine or pyrrole.

6. The compound of formula (I) as defined according to claim 1 which is selected from: ##STR00392## ##STR00393## ##STR00394## ##STR00395## ##STR00396## ##STR00397## ##STR00398## ##STR00399##

7. A pharmaceutical composition comprising a) an antibacterially effective amount of the compound of claim 1; and b) a pharmaceutically acceptable carrier.

8. The compound of claim 1, having the structure ##STR00400##

9. The compound of claim 1, having the structure ##STR00401##

10. The compound of claim 1, having the structure ##STR00402##

11. The compound of claim 1, having the structure ##STR00403##

12. The compound of claim 1, having the structure ##STR00404##

13. The compound of claim 1, having the structure ##STR00405##

14. The compound of claim 1, having the structure ##STR00406##

15. The compound of claim 1, having the structure ##STR00407##

16. The compound of claim 1, having the structure ##STR00408##

17. The compound of claim 1, having the structure ##STR00409##

18. The compound of claim 1, having the structure ##STR00410##

19. The compound of claim 1, having the structure ##STR00411##

20. The compound of claim 1, having the structure ##STR00412##

21. The compound of claim 1, having the structure ##STR00413##

22. The compound of claim 1, having the structure ##STR00414##

23. The compound of claim 1, having the structure ##STR00415##

24. The compound of claim 1, having the structure ##STR00416##

25. The compound of claim 1, having the structure ##STR00417##

26. The compound of claim 1, having the structure ##STR00418##

27. The compound of claim 1, having the structure ##STR00419##

28. The compound of claim 1, having the structure ##STR00420##

29. The compound of claim 1, having the structure ##STR00421##

30. The compound of claim 1, having the structure ##STR00422##

31. The compound of claim 1, having the structure ##STR00423##

32. The compound of claim 1, having the structure ##STR00424##

Description

FIELD OF THE INVENTION

The present invention relates to novel oxazolidinone compounds of formula (I), their stereoisomers, their salts and pharmaceutical compositions containing them.

##STR00002##

The present invention also relates to a process for the preparation of the above said novel compounds, their stereoisomers, their salts and pharmaceutical compositions.

BACKGROUND OF THE INVENTION

Since the discovery of penicillin, pharmaceutical companies have produced more than one hundred antibacterial agents to combat a wide variety of bacterial infections. In the past several years, there has been rapid emergence of bacterial resistance to several of these antibiotics. The multi-drug resistance among these bacterial pathogens may also be due to mutation leading to more virulent clinical isolations. The most disturbing milestone has been the acquisition of resistance to vancomycin, an antibiotic generally regarded as the agent of last resort for serious Gram-positive infections. It is believed that the proliferation of multidrug resistant bacteria is brought on by a wide spread use, or rather misuse, of existing antibacterials, further exacerbated by the use of antibacterials as feed supplements in farm animals and poultry.

Bacterial infection is a long-term problem that requires innovative new therapeutics. Moreover, in view of the increasing reports of vancomycin-resistant bacterial isolates and growing problem of bacterial resistance, there is an urgent need for new molecular entities effective against the emerging bacterial organisms. The growing problem of multidrug resistance has intensified the search for new antibiotics. Yet new drugs are difficult to develop and bacterial strains resistant to new drugs may quickly emerge. For example, soon after introduction of Linezolid (Zyovx.TM., Pharmacia Upjohn), a representative of a first entirely new class of antibacterials released into the market over the past 30 years, clinics reported cases of resistance (Lancet 2001, 358(9277): 207 8). Resistant strains have been selected in the lab where a target site alteration was found to reduce drug binding (Antimicrob. Agents Chemother. 2001, 3(3): 288 294).

Oxazolidinones, a class of compounds that includes Linezolid, contain an oxazolidinone moiety

##STR00003##

For example, compounds of the generalized structure

##STR00004## are known in the prior art. In these compounds, a heterocyclic moiety (Het) is connected to the oxazolidinone moiety through an aromatic nucleus (Ar). Specific examples of oxazolidinone compounds are disclosed in International publication nos. WO 01/09107, WO 97/27188, WO 96/13502 and WO 96/13502. Certain oxazolidinones are believed to be useful as antibacterials (J. Med. Chem., 1996, 39, 673), antihistamines and anti allergic agents (EP 291,244), anticonvulsants (DE 3,915,184), as well as for treating cognition disorders, anti psychotics, anti platelet aggregators, antidepressants, sedatives, hypnotics, and as monoamine oxidase inhibitors (WO 97/13768).

SUMMARY OF THE INVENTION

In accordance with one aspect, the invention provides compounds that are new oxazolidinone derivatives, or salts thereof, or stereoisomers thereof, the molecules of which include a) a heterocyclic moiety containing a 5-membered heterocyclic skeleton that is at least partially saturated; b) a benzene ring, which may be substituted or unsubstituted; and c) an oxazolidinone moiety, wherein the heterocycliclic moiety is connected to the oxazolidinone moiety through the benzene ring. Specific embodiments are described in detail.

In accordance with others aspects, the invention also provide a method of using various oxazolidinone compounds, processes for their preparation, and pharmaceutical compositions containing such compounds.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides a novel oxazolidinone compounds having the general formula (I),

##STR00005## or a salt thereof or a stereoisomer thereof,

where R.sup.1 is halo, azido, isothiocyano, thioalcohol, --OR.sup.4, --NHR.sup.4 or --N(R.sup.4).sub.2, where R.sup.4 represents hydrogen atom, or substituted or unsubstituted groups selected from (C.sub.1 C.sub.10)alkyl, (C.sub.1 C.sub.10)acyl, thio(C.sub.1 C.sub.10)acyl, --C(.dbd.O)--(C.sub.1 C.sub.10)alkoxy, --C(.dbd.S)--(C.sub.3 C.sub.8)cycloalkoxy, --C(.dbd.O)--(C.sub.2 C.sub.10)alkenyloxy, --C(.dbd.O)--(C.sub.2 C.sub.10)alkenyl, --C(.dbd.O)-aryloxy, --C(.dbd.S)--C.sub.1 C.sub.10)alkoxy, --C(.dbd.S)--(C.sub.2 C.sub.10)alkenyloxy, --C(.dbd.S)-aryloxy, --C(.dbd.O)--C(.dbd.O)--(C.sub.1 C.sub.10)alkyl, --C(.dbd.O)--C(.dbd.O)-aryl, --C(.dbd.O)--C(.dbd.O)--(C.sub.1 C.sub.10)alkoxy, --C(.dbd.O)--C(.dbd.O)-aryloxy, --(C.dbd.S)--S--(C.sub.1 C.sub.10)alkyl, --(C.dbd.S)--NH.sub.2, --(C.dbd.S)--NH--(C.sub.1 C.sub.10)alkyl, --C(.dbd.S)--N--((C.sub.1 C.sub.10)alkyl).sub.2, --C(.dbd.S)--NH--(C.sub.2 C.sub.10)alkenyl, (C.dbd.S)--(C.dbd.O)--(C.sub.1 C.sub.10)alkoxy, --(C.dbd.S)--(C.dbd.O)-aryloxy, --C(.dbd.S)--O--(C.dbd.O)--(C.sub.1 C.sub.10)alkyl, C(.dbd.S)--C(.dbd.S)--(C.sub.1 C.sub.10)alkyl, --C(.dbd.S)--C(.dbd.S)-aryl, thiomorpholinyl-C(.dbd.S)-- or pyrrolidinyl-C(.dbd.S)--;

R.sup.2 and R.sup.3, which may be the same or different, are each independently hydrogen, halogen, (C.sub.1 C.sub.10)alkyl, halogenated (C.sub.1 C.sub.10)alkyl, cyano, nitro, SR.sup.a, NR.sup.a, or OR.sup.a, in which R.sup.a is hydrogen, (C.sub.1 C.sub.10)alkyl or halogenated (C.sub.1 C.sub.10)alkyl;

##STR00006## is a heterocyclic moiety in which

##STR00007## is a 5-membered heterocyclic skeleton, Z represents O, S, .dbd.CH, --CH.sub.2 or NR.sup.6, where R.sup.b is hydrogen or a moiety, which may be substituted or unsubstituted, straight chain or branched, selected from the group consisting of (C.sub.1 C.sub.10)alkyl, (C.sub.2 C.sub.10)alkenyl, (C.sub.3 C.sub.8)cycloalkyl, hydroxy(C.sub.1 C.sub.10)alkyl, (C.sub.1 C.sub.10)alkylhydroxy, (C.sub.1 C.sub.10)alkylamino, amino(C.sub.1 C.sub.10)alkyl, (C.sub.1 C.sub.10)alkoxy, aryl, aralkyl, aryloxy, (C.sub.1 C.sub.10)alkylcarbonyl, arylcarbonyl, (C.sub.1 C.sub.10)alkoxycarbonyl and aryloxycarbonyl;

Y.sup.1 represents .dbd.O or .dbd.S group and Y.sup.2 and Y.sup.3 independently represent hydrogen, halogen, cyano, nitro, formyl, hydroxy, amino, .dbd.O, .dbd.S group or substituted or unsubstituted groups selected from (C.sub.1 C.sub.10)alkyl, hydroxy(C.sub.1 C.sub.10)alkyl, (C.sub.1 C.sub.10)alkylhydroxy, (C.sub.1 C.sub.10)alkoxy C.sub.1 C.sub.10alkyl, (C.sub.1 C.sub.10)alkylcarbonyl, (C.sub.1 C.sub.10)alkoxycarbonyl, arylcarbonyl, carboxy(C.sub.1 C.sub.10)alkyl, (C.sub.1 C.sub.10)alkylsulfonyl, (C.sub.1 C.sub.10)alkylcarbonyl (C.sub.1 C.sub.10)alkyl, arylcarbonylamino(C.sub.1 C.sub.10)alkyl, (C.sub.1 C.sub.10)alkylcarbonyloxy (C.sub.1 C.sub.10)alkyl, amino(C.sub.1 C.sub.10)alkyl, mono(C.sub.1 C.sub.10)alkylamino, di(C.sub.1 C.sub.10)alkylamino, arylamino, (C.sub.1 C.sub.10)alkoxy, aryl, aryloxy, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl or heterocycloalkyl; Y.sup.2 and Y.sup.3 when present on adjacent carbon atoms together may also form a substituted or unsubstituted 5 or 6 membered aromatic or non-aromatic cyclic structure, optionally containing one or two hetero atoms selected from oxygen, sulfur or nitrogen.

Suitable groups represented by R.sup.4 may be selected from hydrogen atom, (C.sub.1 C.sub.10)alkyl group such as methyl, ethyl, propyl, butyl and the like, which may be substituted; (C.sub.1 C.sub.10)acyl group of the formula --C(.dbd.O)R.sup.z where R.sup.z is hydrogen, (C.sub.1 C.sub.10)alkyl, aryl or heteroaryl wherein aryl is a group such as phenyl, naphthyl and the like; and heteroaryl is a group such as pyridyl, pyrrolidinyl, piperidinyl, indolyl, furyl and the like; wherein the acyl group is a group such as --C(.dbd.O)H, --C(.dbd.O)CH.sub.3, --C(.dbd.O)CH.sub.2CH.sub.3, --C(.dbd.O)(CH.sub.2).sub.2CH.sub.3, --C(.dbd.O)(CH.sub.2).sub.3CH.sub.3, --C(.dbd.O)(CH.sub.2).sub.4CH.sub.3, --C(.dbd.O)(CH.sub.2).sub.5CH.sub.3, --C(.dbd.O)Ph and the like, the acyl group may be substituted; thio(C.sub.1 C.sub.10)acyl group of the formula --C(.dbd.S)R.sup.z where R.sup.z is hydrogen, (C.sub.1 C.sub.10)alkyl, aryl or heteroaryl wherein aryl is a group such as phenyl, naphthyl and the like; and heteroaryl is a group such as pyridyl, pyrrolidinyl, piperidinyl, indolyl, furyl and the like wherein the thioacyl group is a group such as --C(.dbd.S)H, --C(.dbd.S)CH.sub.3, --C(.dbd.S)CH.sub.2CH.sub.3, --C(.dbd.S)Ph and the like, the thioacyl group may be substituted; --C(.dbd.O)--(C.sub.1 C.sub.10)alkoxy group, containing (C.sub.1 C.sub.10)alkyl group which may be linear or branched, such as --C(.dbd.O)-methoxy, --C(.dbd.O)-ethoxy, --C(.dbd.O)-propoxy, --C(.dbd.O)-isopropoxy and the like, the --C(.dbd.O)--(C.sub.1 C.sub.10)alkoxy group may be substituted; --C(.dbd.S)-cyclo(C.sub.3 C.sub.8)alkoxy group such as --C(.dbd.S)-cyclopropoxy, --C(.dbd.S)-cyclobutoxy, --C(.dbd.S)-cyclopentoxy, --C(.dbd.S)-cyclohexoxy and the like, the --C(.dbd.S)-cyclo(C.sub.3 C.sub.6)alkoxy may be substituted; --C(.dbd.O)--(C.sub.2 C.sub.6)alkenyl such as --C(.dbd.O)-ethenyl, --C(.dbd.O)-propenyl, --C(.dbd.O)-butenyl and the like, the --C(.dbd.O)--(C.sub.2 C.sub.10)alkenyl may be substituted; --C(.dbd.O)--(C.sub.2 C.sub.10)alkenyloxy group such as --C(.dbd.O)-ethenyloxy, --C(.dbd.O)-propenyloxy, --C(.dbd.O)-butenyloxy and the like, the --C(.dbd.O)--(C.sub.2 C.sub.6)alkenyloxy may be substituted; --C(.dbd.O)-aryloxy group such as --C(.dbd.O)-phenoxy, --C(.dbd.O)-benzyloxy group and the like, the --C(.dbd.O)-aryloxy group may be substituted; --C(.dbd.S)--(C.sub.1 C.sub.10)alkoxy group such as CH.sub.3O--C(.dbd.S)--, C.sub.2H.sub.5O--C(.dbd.S)--C.sub.3H.sub.7O--C(.dbd.S)--, isopropoxy-C(.dbd.S)-- and the like, which may be substituted; --C(.dbd.S)--(C2 C10)alkenyloxy group such as --C(.dbd.S)-ethenyloxy, --C(.dbd.S)-propenyloxy, --C(.dbd.S)-butenyloxy and the like, the --C(.dbd.S)--(C.sub.2 C.sub.10)alkenyloxy group may be substituted; --C(.dbd.S)-aryloxy group such as phenyl-O--C(.dbd.S)--, benzyl-O--C(.dbd.S)-- and the like, which may be substituted; --C(.dbd.O)--C(.dbd.O)--(C.sub.1 C.sub.10)alkyl group such as --C(.dbd.O)--C(.dbd.O)methyl, --C(.dbd.O)--C(.dbd.O)ethyl, --C(.dbd.O)--C(.dbd.O)propyl, --C(.dbd.O)--C(.dbd.O)butyl and the like, which may be substituted; --C(.dbd.O)--C(.dbd.O)-aryl group such as --C(.dbd.O)--C(.dbd.O)phenyl, --C(.dbd.O)--C(.dbd.O)naphthyl and the like, which may be substituted; --C(.dbd.O)--C(.dbd.O)--(C.sub.1 C.sub.10)alkoxy group such as --C(.dbd.O)--C(.dbd.O)methoxy, --C(.dbd.O)--C(.dbd.O)ethoxy, --C(.dbd.O)--C(.dbd.O)propyloxy and the like, which may be substituted; --C(.dbd.O)--C(.dbd.O)-aryloxy group such as --C(.dbd.O)--C(.dbd.O)phenoxy, --C(.dbd.O)--C(.dbd.O)benzyloxy, which may be substituted; --(C.dbd.S)--S--(C.sub.1 C.sub.10)alkyl such as --(C.dbd.S)--S-methyl, --(C.dbd.S)--S-ethyl, --(C.dbd.S)--S-propyl and the like, which may be substituted; --(C.dbd.S)--NH.sub.2; --(C.dbd.S)--NH--(C.sub.1 C.sub.10)alkyl such as --(C.dbd.S)--NH-methyl, --(C.dbd.S)--NH-ethyl, --(C.dbd.S)--NH-propyl and the like, which may be substituted; --C(.dbd.S)--N--((C.sub.1 C.sub.10)alkyl).sub.2 such as --C(.dbd.S)--N-(methyl).sub.2, --C(.dbd.S)--N-(ethyl).sub.2, --C(.dbd.S)--N-(propyl).sub.2 and the like, which may be substituted; --C(.dbd.S)--NH--(C.sub.2 C.sub.10)alkenyl such as --C(.dbd.S)--NH-ethenyl, --C(.dbd.S)--NH-propenyl, --C(.dbd.S)--NH-butenyl and the like, which may be substituted; --(C.dbd.S)--(C.dbd.O)--(C.sub.1 C.sub.10)alkoxy such as --(C.dbd.S)--(C.dbd.O)-methoxy, --(C.dbd.S)--(C.dbd.O)-ethoxy, --(C.dbd.S)--(C.dbd.O)-propoxy and the like, which may be substituted; --(C.dbd.S)--(C.dbd.O)-aryloxy such as --(C.dbd.S)--(C.dbd.O)-phenoxy, --(C.dbd.S)--(C.dbd.O)-naphthyloxy and the like, which may be substituted; --C(.dbd.S)--O--(C.dbd.O)--(C.sub.1 C.sub.10)alkyl such as --C(.dbd.S)--O--(C.dbd.O)-methyl, --C(.dbd.S)--O--(C.dbd.O)-ethyl, --C(.dbd.S)--O--(C.dbd.O)-propyl and the like, which may be substituted; --C(.dbd.S)--C(.dbd.S)--(C.sub.1 C.sub.10)alkyl group such as --C(.dbd.S)--C(.dbd.S)methyl, --C(.dbd.S)--C(.dbd.S )ethyl, --C(.dbd.S)--C(.dbd.S)propyl and the like, which may be substituted; --C(.dbd.S--)--C(.dbd.S)aryl group such as --C(.dbd.S)--C(.dbd.S)phenyl, --C(.dbd.S)--C(.dbd.S)naphthyl and the like, which may be substituted; thiomorpholinyl-C(.dbd.S)-- which may be substituted; or pyrrolidinyl-C(.dbd.S)-- which may be substituted.

When the groups represented by R.sup.4 are substituted, the substituents may be selected from halogen atom such as chlorine, fluorine, bromine and iodine; hydroxy, amino, mono(C.sub.1 C.sub.10)alkylamino such as methylamino, ethylamino, propylamino and the like, di(C.sub.1 C.sub.10)alkylamino such as dimethylamino, diethylamino, methylethylamino, dipropylamino, ethylpropylamino and the like, cyano, nitro, (C.sub.1 C.sub.10)alkoxy, aryl such as phenyl, naphthyl and the like; hydroxyaryl, pyridyl, hydroxy(C.sub.1 C.sub.10)alkyl, (C.sub.1 C.sub.10)alkylhydroxy, (C.sub.1 C.sub.10)alkoxyaryl or carboxyl and its derivatives such as amides like CONH.sub.2, CONHMe, CONMe.sub.2, CONHEt, CONEt.sub.2, CONHPh and the like, and esters such as COOMe, COOEt and the like.

Suitable groups represented by R.sup.2 and R.sup.3 may be selected from hydrogen, halogen atom such as fluorine, chlorine or bromine; (C.sub.1 C.sub.10)alkyl group such as methyl, ethyl, n-propyl, isopropyl, n-butyl, iso-butyl, t-butyl, n-pentyl, iso-pentyl, n-hexyl and the like; halo(C.sub.1 C.sub.10)alkyl group such as halomethyl, haloethyl, halopropyl, trihalomethyl and the like, wherein the halo group is selected from fluorine, chlorine, bromine or iodine; cyano, nitro; SR.sup.a, NR.sup.a, OR.sup.a where R.sup.a represents hydrogen or substituted or unsubstituted (C.sub.1 C.sub.10)alkyl group such as methyl, ethyl, propyl, isopropyl and the like; halo(C.sub.1 C.sub.10)alkyl such as halomethyl, haloethyl, halopropyl, haloisopropyl and the like, where the halo group is selected from fluro, chloro, bromo or iodo.

The substituents on R.sup.a are selected from hydroxy, halogen, nitro, amino, (C.sub.1 C.sub.10)alkoxy, carboxyl or cyano.

Suitable groups represented by Z may be selected from S, O, .dbd.CH or NR.sup.b where R.sup.b represents hydrogen or substituted or unsubstituted (C.sub.1 C.sub.10)alkyl such as methyl, ethyl, propyl, butyl, pentyl and the like, which may be substituted; (C.sub.2 C.sub.10)alkenyl such as ethenyl, propenyl, butenyl and the like, which may be substituted; (C.sub.3 C.sub.8)cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like, which may be substituted; hydroxy(C.sub.1 C.sub.10)alkyl such as hydroxymethyl, hydroxyethyl, hydroxypropyl, propyldihydroxy and the like, which may be substituted; (C.sub.1 C.sub.10)alkylhydroxy such as methylhydroxy, ethylhydroxy, propylhydroxy. propyldihydroxy and the like, which may be substituted; (C.sub.1 C.sub.10)alkylamino such as methylamino, ethylamino, propylamino, butylamino and the like, which may be substituted, amino(C.sub.1 C.sub.10)alkyl such as aminomethyl, aminoethyl, aminopropyl, aminobutyl and the like, which may be substituted; (C.sub.1 C.sub.10)alkoxy such as methoxy, propoxy, isopropoxy and the like, which may be substituted; aryl group such as phenyl, naphthyl and the like, which may be substituted; aralkyl such as benzyl, phenethyl and the like, which may be substituted; aryloxy such as phenyloxy, naphthyloxy and the like, which may be substituted; (C.sub.1 C.sub.10)alkylcarbonyl such as methylcarbonyl, ethylcarbonyl, propylcarbonyl and the like, which may be substituted; arylcarbonyl such as phenylcarbonyl, naphthylcarbonyl and the like, which may be substituted; (C.sub.1 C.sub.10)alkoxycarbonyl such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl and the like, which may be substituted; or aryloxycarbonyl such as phenyloxycarbonyl, naphthyloxycarbonyl and the like, which may be substituted.

The substituents on R.sup.b are selected from hydroxy, halogen, pyrrolidinyl-C(.dbd.S)--, nitro, amino, (C.sub.1 C.sub.10)alkyl, (C.sub.1 C.sub.10)alkoxy, carboxyl, oxo, thiooxo or cyano.

Y.sup.1 represents .dbd.O or .dbd.S group, Y.sup.2 and Y.sup.3 are selected from hydrogen, halogen such as fluorine, chlorine, bromine or iodine; cyano, nitro, formyl, hydroxy, amino, .dbd.O, .dbd.S group, substituted or unsubstituted (C.sub.1 C.sub.10)alkyl such as methyl, ethyl, n-propyl, isopropyl, n-butyl, iso-butyl, t-butyl and the like; hydroxy(C.sub.1 C.sub.10)alkyl such as hydroxymethyl, hydroxyethyl, hydroxypropyl, propyldihydroxy and the like, which may be substituted; (C.sub.1 C.sub.10)alkylhydroxy such as methyl hydroxy, ethylhydroxy, propylhydroxy. propyldihydroxy and the like, which may be substituted; (C.sub.1 C.sub.10)alkoxy(C.sub.1 C.sub.10)alkyl group such as methoxymethyl, methoxyethyl, ethoxyethyl, ethoxymethyl, methoxypropyl, propoxymethyl, propoxyethyl and the like, which may be substituted; (C.sub.1 C.sub.10)alkylcarbonyl group such as methylcarbonyl, ethylcarbonyl and the like, which may be substituted; arylcarbonyl group such as phenylcarbonyl, naphtylcarbonyl and the like, which may be substituted; (C.sub.1 C.sub.10)alkoxycarbonyl group such as methoxycarbonyl, ethoxycarbonyl and the like, which may be substituted; carboxy(C.sub.1 C.sub.10)alkyl such as CH.sub.3--COO, CH.sub.3--CH.sub.2--COO and the like, which may be substituted; (C.sub.1 C.sub.10)alkylsulfonyl group such as methylsulfonyl, ethylsulfonyl and the like, which may be substituted; (C.sub.1 C.sub.10)alkylcarbonylamino(C.sub.1 C.sub.10)alkyl groups such as methylcarbonylaminomethyl, ethylcarbonylaminomethyl, methylcarbonylaminoethyl, ethylcarbonylaminoethyl and the like, which may be substituted; arylcarbonylamino(C.sub.1 C.sub.10)alkyl such as phenylcarbonylaminomethyl, phenylcarbonylaminoethyl, naphtylcarbonylaminomethyl, naphthylcarbonylaminoethyl and the like, which may be substituted; (C.sub.1 C.sub.10)alkylcarbonyloxy(C.sub.1 C.sub.10)alkyl group such as methylcarbonyloxymethyl, ethylcarbonylxoymethyl, methylcarbonyloxyethyl, propylcarbonyloxymethyl, propylcarbonyloxyethyl, propylcarbonyloxypropyl and the like, which may be substituted; amino(C.sub.1 C.sub.10)alkyl such as aminomethyl, aminoethyl, aminopropyl and the like, which may be substituted; mono(C.sub.1 C.sub.10)alkylamino such as methylamino, ethylamino, propylamino and the like, which may be substituted; di(C.sub.1 C.sub.10)alkylamino sich as dimethylamino, diethylamino, methylethylamino, dipropylamino, ethylpropylamino and the like, which may be substituted; arylamino such as phenylamino, benzylamino and the like, which may be substituted; (C.sub.1 C.sub.10)alkoxy group such as methoxy, ethoxy, propoxy, isopropoxy and the like, which may be substituted; aryl group such as phenyl, naphthyl and the like, which may be substituted; aryloxy group such as phenoxy, naphthyloxy and the like, the aryloxy group may be substituted; aralkyl such as benzyl, phenethyl, C.sub.6H.sub.5CH.sub.2CH.sub.2CH.sub.2, naphthylmethyl and the like, the aralkyl group may be substituted; heteroaryl groups such as pyridyl, thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, pyrazolyl, imidazolyl, oxadiazolyl, tetrazolyl, benzopyranyl, benzofuranyl and the like, which may be substituted; heteroaralkyl such as imidazolemethyl, imidazoleethyl, pyridylmethyl, furyl methyl, oxazolemethyl, imidazolyl and the like, which may be substituted; heterocyclyl group such as pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl and the like; heterocycloalkyl groups such as pyrrolidinemethyl, piperidinemethyl, morpholinemethyl, piperazinemethyl and the like, which may be substituted.

When the groups represented by Y.sup.2 and Y.sup.3 are substituted, the substituents may be selected from hydroxy, nitro, cyano, amino, (tert-butyldimethylsilyloxy) TBSO, halogen atom, (C.sub.1 C.sub.10)alkyl, (C.sub.1 C.sub.10)alkoxy, (C.sub.3 C.sub.8)cycloalkyl, aryl group such as phenyl, naphthyl and the like, benzyloxy, acyl group such as formyl, acetyl, and the like, carboxyl or acyloxy group such as formyloxy, acetyloxy and the like.

Suitable cyclic structure formed by Y.sup.2 and Y.sup.3 when present on adjacent carbon atoms which they are attached may be selected from substituted or unsubstituted benzene, pyridine, pyrrolidine, furan, thiophene, morpholine, piperazine, pyrrole and the like. The substituents on the cyclic structure formed by Y.sup.2 and Y.sup.3 are selected from halogen, hydroxyl, amino, cyano, nitro, oxo, thioxo, (C.sub.1 C.sub.10)alkyl or (C.sub.1 C.sub.10)alkoxy, where (C.sub.1 C.sub.10)alkyl and (C.sub.1 C.sub.10)alkoxy groups are as defined earlier.

When the groups R.sup.1, R.sup.4, R.sup.b, Y.sup.2 and Y.sup.3 are substituted, they may be mono- or di- or tri substituted.

The invention provides separate embodiments of the compounds of the invention, which are however not necessarily exclusive of one another. In one embodiment, there are provided oxazolidinone derivatives of the structure in accordance with the formula (I).

Oxazolidinone derivatives of one group of this embodiment have the structure

##STR00008## wherein X.sup.1 is oxygen or sulfur.

Oxazolidinone derivatives of another group of this embodiment have the structure

##STR00009## wherein X.sup.1 is oxygen or sulfur.

Oxazolidinone derivatives of yet another group of this embodiment have the structure

##STR00010## wherein X.sup.1 is oxygen or sulfur, and

##STR00011## is a substituted or unsubstituted 5- or 6-membered aromatic or non-aromatic cyclic structure optionally having one or two hetero atoms, formed by Y.sup.2 and Y.sup.3.

Oxazolidinone derivatives of another group of this embodiment have the structure

##STR00012## wherein X.sup.1 is oxygen or sulfur.

Oxazolidinone derivatives of another group of this embodiment have the structure

##STR00013## wherein X.sup.1 is oxygen or sulfur.

In another embodiment, the invention also provides oxazolidinone derivatives that have the structure, in accordance with the compound of formula (I)

##STR00014## or a salt thereof or a stereoisomer thereof,

where R.sup.N is

##STR00015##

wherein R.sup.b is hydrogen or a moiety, which may be substituted or unsubstituted, straight chain or branched, selected from the group consisting of (C.sub.1 C.sub.10)alkyl, (C.sub.2 C.sub.10)alkenyl, (C.sub.3 C.sub.8)cycloalkyl, (C.sub.1 C.sub.10)alkoxy, aryl, aralkyl, aryloxy, (C.sub.1 C.sub.10)alkylhydroxy, hydroxy(C.sub.1 C.sub.10)alkyl, (C.sub.1 C.sub.10)alkylcarbonyl, (C.sub.1 C.sub.10)alkylamino, amino (C.sub.1 C.sub.10)alkyl, arylcarbonyl, (C.sub.1 C.sub.10)alkoxycarbonyl or aryloxycarbonyl; R.sup.7 represents hydrogen, (C.sub.1 C.sub.10)alkyl or (C.sub.1 C.sub.10)alkoxy;

R.sup.2 and R.sup.3, which may be same or different, are each independently hydrogen, halo, (C.sub.1 C.sub.10)alkyl, halogenated(C.sub.1 C.sub.10)alkyl, hydroxyl or (C.sub.1 C.sub.10)alkoxy; and

R.sup.4 represents hydrogen atom, or substituted or unsubstituted groups selected from (C.sub.1 C.sub.10)acyl, thio(C.sub.1 C.sub.10)acyl, --C(.dbd.O)--(C.sub.1 C.sub.10)alkoxy, --C(.dbd.S)-cyclo(C.sub.3 C.sub.8)alkoxy, --C(.dbd.O)--(C.sub.2 C.sub.10)alkenyloxy, --C(.dbd.O)--(C.sub.2 C.sub.10)alkenyl, --C(.dbd.O)-aryloxy, --C(.dbd.S)--(C.sub.1 C.sub.10)alkoxy, --C(.dbd.S)--(C.sub.2 C.sub.10)alkenyloxy, --C(.dbd.S)-aryloxy, --C(.dbd.O)--C(.dbd.O)--(C.sub.1 C.sub.10)alkyl, --C(.dbd.O)--C(.dbd.O)-aryl, --C(.dbd.O)--C(.dbd.O)--(C.sub.1 C.sub.10)alkoxy, --C(.dbd.O)--C(.dbd.O)-aryloxy, --(C.dbd.S)--S--(C.sub.1 C.sub.10)alkyl, --(C.dbd.S)--NH.sub.2, --(C.dbd.S)--NH--(C.sub.1 C.sub.10)alkyl, --C(.dbd.S)--N--((C.sub.1 C.sub.10)alkyl).sub.2, --C(.dbd.S)--NH--(C.sub.2 C.sub.10)alkenyl, (C.dbd.S)--(C.dbd.O)--(C.sub.1 C.sub.10)alkoxy, --(C.dbd.S)--(C.dbd.O)-aryloxy, --C(.dbd.S)--O--(C.dbd.O)--(C.sub.1 C.sub.10)alkyl, C(.dbd.S)--C(.dbd.S)--(C.sub.1 C.sub.10)alkyl, --C(.dbd.S)--C(.dbd.S)-aryl, thiomorpholinyl-C(.dbd.S)-- or pyrrolidinyl-C(.dbd.S)--. In one embodiment R.sup.2 and R.sup.3 are each independently hydrogen, fluoro or trifluoromethyl. Oxazolidinone derivatives of another group of this embodiment have the above structure, wherein R.sup.N is

##STR00016##

In another embodiment R.sup.n is

##STR00017## and R.sup.7 is hydrogen, (C.sub.1 C.sub.10)alkyl or (C.sub.1 C.sub.10)alkoxy.

Oxazolidinone derivatives of one group of this embodiment have the above structure (Ia), wherein R.sup.N is

##STR00018## in which R.sup.b is hydrogen, substituted or unstubstituted (C.sub.1 C.sub.10)alkyl, halogenated (C.sub.1 C.sub.10)alkyl, (C.sub.2 C.sub.10)alkenyl, (C.sub.1 C.sub.10)alkylhydroxy, hydroxy(C.sub.1 C.sub.10)alkyl, halogenated (C.sub.1 C.sub.10)alkylhydroxy, halogenated hydroxy(C.sub.1 C.sub.10)alkyl, (C.sub.1 C.sub.10)alkylamino or amino (C.sub.1 C.sub.10)alkyl, the group of the structure

##STR00019## the group of the structure the group of the structure the group of the structure the group of the structure in which R' is hydrogen, (C.sub.1 C.sub.10)alkyl or carboxy (C.sub.1 C.sub.10)alkyl; R.sup.6 is hydrogen, halogen or (C.sub.1 C.sub.10)alkoxy and m is ranging from 1 to 4. Specific non-limiting examples of the group R.sup.b are

##STR00020## or R.sup.b has the structure

##STR00021## in which R.sup.6 is hydrogen, fluoro or methoxy group, or R.sup.b has the structure

##STR00022## where R.sup.6 is hydrogen, fluoro or methoxy group. Oxazolidinone derivatives of another group of this embodiment have the above structure, wherein R.sup.N is

##STR00023## In another embodiment R.sup.N is

##STR00024## and R.sup.b is hydrogen or methyl. Oxazolidinone derivatives of another group of this embodiment have the above structure, wherein R.sup.N is

##STR00025## In another embodiment R.sup.N is

##STR00026## and R.sup.b is hydrogen, methyl, benzyl, p-methoxybenzyl, n-butyl, propenyl or methylhydroxy or Rb has the structure

##STR00027## Oxazolidinone derivatives of another group of this embodiment have the above structure, wherein R.sup.N is

##STR00028## In another embodiment R.sup.N is

##STR00029## and Rb is methyl. Oxazolidinone derivatives of another group of this embodiment have the above structure, wherein R.sup.N is

##STR00030## In another embodiment R.sup.N is

##STR00031## and Rb is methyl, benzyl, p-fluorobenzyl, p-fluorophenyl or phenyl. Oxazolidinone derivatives of another group of this embodiment have the above structure, wherein R.sup.N is

##STR00032## and R.sup.7 is hydrogen, (C.sub.1 C.sub.10)alkyl or (C.sub.1 C.sub.10)alkoxy.

The moiety R.sup.N also has the structure

##STR00033##

Oxazolidinone derivatives of another group of this embodiment have the above structure, wherein R.sup.N is

##STR00034## in which R.sup.b is hydrogen, substituted or unsubstituted (C.sub.1 C.sub.10)alkyl, halogenated (C C.sub.1 C.sub.10)alkyl, (C.sub.2 C.sub.10)alkenyl, aralkyl, (C.sub.1 C.sub.10)alkylcarbonyl, (C.sub.1 C.sub.10)alkoxy(C.sub.1 C.sub.10)alkyl, (C C.sub.1 C.sub.10)alkylhydroxy, hydroxy(C.sub.1 C.sub.10)alkyl, dihydroxy(C.sub.1 C.sub.10)alkyl halogenated (C.sub.1 C.sub.10)alkylhydroxy, halogenated hydroxy(C.sub.1 C.sub.10)alkyl; wherein R.sup.4 is --C(.dbd.O)--H, substituted or unsubstituted --C(.dbd.O)--(C.sub.1 C.sub.10)alkyl, --C(.dbd.O)--(C.sub.1 C.sub.10)alkylhydroxy, --C(.dbd.O)-halogenated(C.sub.1 C.sub.10)alkyl, --C(.dbd.O)--(C.sub.2 C.sub.10)alkenyl, --C(.dbd.S)--H, --C(.dbd.S)--(C.sub.1 C.sub.10)alkyl, --C(.dbd.S)--(C.sub.1 C.sub.10)alkoxy, --C(.dbd.S)--NH.sub.2, --C(.dbd.S)--(C C.sub.1 C.sub.10)alkylhydroxy, --C(.dbd.S)-halogenated(C.sub.1 C.sub.10)alkyl, --C(.dbd.S)-phenyl; and R.sup.2 and R.sup.3 are each independently hydrogen, fluoro or trifluoromethyl group.

Oxazolidinone derivatives of yet another group of this embodiment have the above structure, wherein R.sup.N is

##STR00035## in which R.sup.b is hydrogen, methyl, ethyl, propyl, n-butyl, benzyl, p-methoxybenzyl, hydroxy ethyl (ethylhydroxy), methoxyethyl, propenyl,

##STR00036## and R.sup.4 is --C(.dbd.O)--H, --C(.dbd.O)--CH.sub.3--C(.dbd.S)--CH.sub.3, --C(.dbd.S)--OCH.sub.3, --C(.dbd.S)--OCH.sub.2CH.sub.3. --C(.dbd.S)-(iso-propoxy) or --C(.dbd.S)--NH(pyridyl).

Oxazolidinone derivatives of yet another group of this embodiment have the above structure, wherein R.sup.N is

##STR00037##

R.sup.4 is --C(.dbd.O)--H, substituted or unsubstituted --C(.dbd.O)--(C.sub.1 C.sub.10)alkyl, --C(.dbd.O)-halogenated(C.sub.1 C.sub.10)alkyl, --C(.dbd.O)--(C.sub.2 C.sub.10)alkenyl, --C(.dbd.O)--C(.dbd.O)--(C.sub.1 C.sub.10)alkoxy, --C(.dbd.O)--(C.sub.1 C.sub.10)alkoxy, --C(.dbd.S)--(C.sub.1 C.sub.10)alkyl, --C(.dbd.S)-halogenated (C.sub.1 C.sub.10)alkyl, --C(.dbd.S)--S--(C.sub.1 C.sub.10)alkyl, --C(.dbd.S)--(C.sub.1 C.sub.10)alkoxy, --C(.dbd.S)--O--C(.dbd.O)--(C.sub.1 C.sub.10)alkyl, --C(.dbd.S)--(C.sub.3 C.sub.8)cycloalkoxy, --C(.dbd.S)--(C.sub.2 C.sub.10)alkenyloxy, --C(.dbd.S)-pyrrolidinyl, --C(.dbd.S)--NH.sub.2, --C(.dbd.S)--N((C.sub.1 C.sub.10)alkyl).sub.2, --C(.dbd.S)--NH--(C.sub.2 C.sub.10)alkenyl, --C(.dbd.S)-thiomorpholinyl; and R.sup.2 and R.sup.3 are each independently hydrogen, fluoro or trifluoromethyl group.

Oxazolidinone derivatives of another embodiment have the above structure, where R.sup.n has the structure

##STR00038## and

R.sup.2 and R.sup.3 are each independently hydrogen, fluoro or trifluoromethyl group and R.sup.4 is --C(.dbd.S)--CH.sub.3, --C(.dbd.S)--CH.sub.2--CH.sub.3, --C(.dbd.S)--CH.sub.2--CF.sub.3, --C(.dbd.S)--S--CH.sub.3, --C(.dbd.S)--O--CH.sub.3, --C(.dbd.S)--O--CH.sub.2--CH.sub.3, --C(.dbd.S)--O--CH.sub.2--CH.sub.2--CH.sub.3, --C(.dbd.S)--O-(iso-propyl), --C(.dbd.S)--O--CH.sub.2--CF.sub.3, --C(.dbd.S)--O-cyclohexyl, --C(.dbd.S)--O--CH.sub.2--CH.dbd.CH.sub.2, --C(.dbd.S)--CH.sub.2--CH.sub.2--N(CH.sub.3).sub.2, --C(.dbd.S)--O--CH.sub.2--CH.sub.2OH, --C(.dbd.S)--CH.sub.2--CH.sub.2--OCH.sub.3, --C(.dbd.S)--O--C(.dbd.O)--CF.sub.3, --C(.dbd.S)--NH.sup.2, --C(.dbd.S)--NH--CH.sub.2, C(.dbd.S)--NH--CH.sub.2--CH.sub.2--OH, --C(.dbd.S)--N(CH.sub.2CH.sub.3).sub.2, --C(.dbd.S)--NH--CH.sub.2--CH.dbd.CH.sub.2, --C(.dbd.S)--NH-benzyl, --C(.dbd.S)--NH-pyridyl, --C(.dbd.S)--NH-(p-methoxybenzyl), --C(.dbd.S)--NH--CH.sub.2-pyridyl, --C(.dbd.S)-thiomorpholinyl,

##STR00039##

##STR00040##

Pharmaceutically acceptable salts forming part of this invention include salts derived from inorganic bases such as Li, Na, K, Ca, Mg, Fe, Cu, Zn, Mn; salts of organic bases such as N,N'-diacetylethylenediamine, betaine, caffeine, 2-diethylaminoethanol, 2-dimethylaminoethanol, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, hydrabamine, isopropylamine, methylglucamine, morpholine, piperazine, piperidine, procaine, purines, theobromine, triethylamine, trimethylamine, tripropylamine, tromethamine, diethanolamine, meglumine, ethylenediamine, N,N'-diphenylethylenediamine, N,N'-dibenzylethylenediamine, N-benzyl phenylethylamine, choline, choline hydroxide, dicyclohexylamine, metformin, benzylamine, phenylethylamine, dialkylamine, trialkylamine, thiamine, aminopyrimidine, aminopyridine, purine, spermidine, and the like; chiral bases like alkylphenylamine, glycinol, phenyl glycinol and the like, salts of natural amino acids such as glycine, alanine, valine, leucine, isoleucine, norleucine, tyrosine, cystine, cysteine, methionine, proline, hydroxy proline, histidine, omithine, lysine, arginine, serine, threonine, phenylalanine; unnatural amino acids such as D-isomers or substituted amino acids; guanidine, substituted guanidine wherein the substituents are selected from nitro, amino, alkyl such as methyl, ethyl, propyl and the like; alkenyl such as ethenyl, propenyl, butenyl and the like; alkynyl such as ethynyl, propynyl and the like; ammonium or substituted ammonium salts and aluminum salts. Salts may include acid addition salts where appropriate which are, sulphates, nitrates, phosphates, perchlorates, borates, halides, acetates, tartrates, maleates, citrates, succinates, palmoates, methanesulphonates, benzoates, salicylates, hydroxynaphthoates, benzenesulfonates, ascorbates, glycerophosphates, ketoglutarates and the like. Pharmaceutically acceptable solvates may be hydrates or comprising other solvents of crystallization such as alcohols.

The compounds which are provided by way of illustration only and therefore should not be construed to limit the scope of the invention are:

##STR00041## ##STR00042## ##STR00043## ##STR00044## ##STR00045## ##STR00046## ##STR00047## ##STR00048## ##STR00049## ##STR00050## ##STR00051## ##STR00052## ##STR00053## ##STR00054## ##STR00055## ##STR00056## ##STR00057## or its steroisomers like (R) or mixture of (R) and (S) isomers; or pharmaceutically acceptable salts thereof.

Me represent methyl

Et represent ethyl

Pro represents propyl.

In the structures described herein whenever an open ended bond is present that represents a methyl group.

THP represent tetrahydropyranyl

The present invention also relates to a process for the preparation of the compound of formula (I) where R.sup.1 represents --NHR.sup.4, wherein R.sup.4 represents hydrogen atom and all other symbols are as defined earlier, which comprises:

(i) reacting a compound of formula (III)

##STR00058## where all the symbols are as defined earlier, with a compound of formula (IV)

##STR00059## where L represents a leaving group such as halogen atom, (C.sub.1 C.sub.10)alkoxy, such as methoxy, ethoxy, propoxy and the like; sulfonyl groups such as methylsulfonyl, ethylsulfonyl, p-toluenesulfonyl and the like; R.sup.2 and R.sup.3 are as defined earlier, to produce a compound of formula (V)

##STR00060## where Y.sup.1, Y.sup.2, Y.sup.3, R.sup.2, R.sup.3 and Z are as defined earlier,

(ii) reducing the compound of formula (V) to produce a compound of formula (VI)

##STR00061## where Y.sup.1, Y.sup.2, Y.sup.3, R.sup.2, R.sup.3 and Z are as defined earlier,

(iii) reacting the compound of formula (VI) with alkylchloroformate, to produce a compound of formula (VII)

##STR00062## where R.sub.c represents (C.sub.1 C.sub.10)alkyl group such as methyl, ethyl, propyl, and the like, or aralkyl group such as benzyl, allyl group and the like; Y.sup.1, Y.sup.2, Y.sup.3, R.sup.2, R.sup.3 and Z are as defined earlier,

(iv) reacting the compound of formula (VII) with a compound of formula (VIII)

##STR00063## where R.sup.12 represents (C.sub.1 C.sub.10)alkyl group such as methyl, ethyl, propyl and the like, in the presence of a base to produce a compound of formula (I)

##STR00064## where R.sup.1 represents hydroxy; Y.sub.1, Y.sup.2, Y.sup.3, R.sup.2, R.sup.3 and Z are as defined earlier, (v) reacting the compound of formula (I) with (C.sub.1 C.sub.10)alkylsulfonyl chloride or aryl sulfonyl chloride to produce a compound of formula (I), where R.sup.1 represents alkyl sulfonyl or aryl sulfonyl, which in turn was reacted with NaN.sub.3 to produce compound of formula (I)

##STR00065## where R.sup.1 represents azido; Y.sup.1, Y.sup.2, Y.sup.3, R.sup.2, R.sup.3 and Z are as defined earlier and

(vi) reducing the compound of formula (I) wherein R.sup.1 represents azido group, to produce compound of formula (I)

##STR00066## where R.sup.1 represents --NHR.sup.4 wherein R.sup.4 represents hydrogen atom; Y.sup.1, Y.sup.2, Y.sup.3, R.sup.2, R.sup.3 and Z are as defined earlier.

The reaction of a compound of formula (III) with a compound of formula (IV) to produce a compound of formula (V) may be carried out using a base such as potassium hydroxide (KOH), sodium hydroxide (NaOH), potassium carbonate (K.sub.2CO.sub.3), sodium carbonate (Na.sub.2CO.sub.3), sodium hydride (NaH), potassium hydride (KH), triethylamine, diisopropylethyl amine and the like. The reaction may be carried out using a solvent such as dimethylsulfoxide (DMSO), dimethylformamide (DMF), tetrahydrofuran (THF), acetonitrile, chloroform and the like or mixtures thereof. The reaction may be carried out in inert atmosphere, which may be maintained using inert gases such as nitrogen (N.sup.2) or argon (Ar). The reaction may be carried out at a temperature in the range of 20 to 100.degree. C., preferably at a temperature in the range of ambient to 80.degree. C. The reaction time may range from 1 to 15 h, preferably from 6 to 12 h.

The reduction of a compound of formula (V) to produce a compound of formula (VI) may be carried out in the presence of gaseous hydrogen and a catalyst such as Ru, Pd, Rh, Pt, Ni on solid beads such as charcoal, alumina, asbestos and the like. The reduction may be conducted in the presence of a solvent such as dioxane, acetic acid, ethyl acetate, THF, alcohol such as methanol, ethanol and the like or mixtures thereof. A pressure between atmospheric pressure to 60 psi may be used. The reaction may be carried out at a temperature in the range of 25 to 60.degree. C., preferably at room temperature. The reaction time ranges from 2 to 48 h. The reduction may also be carried out by employing metal in mineral acids such as Sn/HCl, Fe/HCl, Zn/HCl, Zn/CH.sub.3CO.sub.2H and the like.

The conversion of compound of formula (VI) to compound of formula (VII) may be carried out with alkylchloroformates such as methychloroformate, ethylchloroformate, propylchloroformate, benzylchloroformate and the like. The solvent of the reaction may be selected from water, acetone, THF, acetonitrile, dichloromethane (DCM) and the like or mixtures thereof. The reaction may be carried out in the presence of base such as K.sub.2CO.sub.3, Na.sub.2CO.sub.3, NaH, KOH, triethylamine (Et.sub.3N) and the like. The temperature of the reaction may be carried out in the presence of 0 to 60.degree. C., preferably at 0.degree. C. to room temperature. The time of the reaction is maintained in the range of 1 12 h, preferably in the range of 1 4 h.

The reaction of a compound of formula (VII) with a compound of formula (VIII) to produce a compound of formula (I), where R.sup.1 represents hydroxy group, defined above may be carried out in the presence of a base such as alkali metal hydrides like NaH or KH or organolithiums like methyllithium (CH.sub.3Li), butyllithium (BuLi), lithium diisopropylamide (LDA) and the like or alkoxides such as sodiummethoxide (NaOMe), sodiumethoxide (NaOEt), potassium tert-butoxide (t-BuOK). The reaction may be carried out in the presence of a solvent such as THF, dioxane, DMF, DMSO, ethylene glycol dimethylether (DME) and the like or mixtures thereof. Hexamethylphosphamide (HMPA) may be used as a cosolvent. The reaction temperature may range from -78 to 150.degree. C., preferably at a temperature in the range of -78 to 30.degree. C. The duration of the reaction may range from 3 to 12 h.

The compound of formula (I) where R.sup.1 represents OH is converted to compound of formula (I) where R.sup.1 represents alkylsulfonyl or arylsulfonyl by treating with alkylsulfonylchloride or arylsulfonylchloride such as methanesulfonyl chloride, p-toluenesulfonyl chloride and the like. The reaction may be carried out in the presence of chloroform, DCM, THF, dioxane and the like or mixtures thereof. The base used in the reaction may be selected from Et3N, diisopropyl ethylamine, Na.sub.2CO.sub.3, K.sub.2CO.sub.3 and the like. The temperature of the reaction is maintained in the range of 0 to 50.degree. C., preferably in the range of 0 to room temperature. The time of the reaction should be maintained in the range of 1 12 h, preferably in the range of 1 4 h. The compound of formula (I) where R.sup.1 represents alkylsulfonyl or arylsulfonyl is converted to compound of formula (I) where R.sup.1 represents azido group, by treating with sodium azide (NaN.sub.3) or lithium azide (LiN.sub.3). The solvent used in the reaction may be selected from DMF, DMSO, acetonitrile and the like. The temperature of the reaction is maintained in the range of room temperature to 120.degree. C., preferably room temperature to 80.degree. C. The time of the reaction is maintained in the range of 1 12 h, preferably 1 4 h.

The reduction of a compound of formula (I) where R.sup.1 represents azido group, to produce a compound of formula (I) where R.sup.1 represents --NHR.sup.4 wherein R.sup.4 represents hydrogen atom, may be carried out in the presence of gaseous hydrogen and a catalyst such as Ru, Pd, Rh, Pt, Ni on solid beads such as charcoal, alumina, asbestos and the like. The reduction may be conducted in the presence of a solvent such as dioxane, acetic acid, ethyl acetate, THF, alcohol such as methanol, ethanol and the like or mixtures thereof. A pressure between atmospheric pressure to 60 psi may be used. The reaction may be carried out at a temperature in the range of 25 to 60.degree. C., preferably at room temperature. The reaction time ranges from 2 to 48 h. The reduction may also be carried out by employing PPh.sub.3 in water.

In still another embodiment of the present invention there is provided another process for the preparation of compound of formula (I) where R.sup.1 represents hydroxy and all the symbols are as defined earlier, which comprises:

(i) reacting the compound of formula (VI)

##STR00067## where all the symbols are as defined earlier, with a compound of formula (IX)

##STR00068## where R.sup.1 represents hydroxy, to produce a compound of formula (X)

##STR00069## where R.sup.1 represents hydroxy; Y.sup.1, Y.sup.2, Y.sup.3, R.sup.2, R.sup.3 and Z are as defined earlier, and

(ii) carbonylating the compound of formula (X) with a suitable carbonylating agent to produce the compound of formula (I) where R.sup.1 represents hydroxy and all other symbols are as defined above.

The reaction of a compound of formula (VI) defined above with a compound of formula (IX) defined above to produce a compound of formula (X) may be carried out in the presence or absence of a base such as K.sub.2CO.sub.3, NaH, t-BuOK and the like or mixtures thereof. The reaction may be carried out in the presence of a solvent such as DMF, toluene, THF, acetonitrile and the like or mixtures thereof. The reaction may also be carried out in the presence of Lewis acids such as BF.sub.3.OEt.sub.2, ZnC.sub.12, Ti(OiPr).sub.4, lanthanide metal complexes and the like in the presence of dichloroethylene (DCE), DMF, THF and the like or mixtures thereof. The reaction temperature may be in the range of 0 to 120.degree. C., preferably at a temperature in the range of 0 to 100.degree. C. The reaction time may range from 3 to 24 h, preferably from 4 to 12 h.

The conversion of compound of formula (X) to a compound of formula (I) may be carried out using a carbonylating agent such as dialkyl carbonate, dihalo carbonyl, 1,1'-carbonyldiimidazole and the like in the presence or absence of a base. The base may be selected from triethylamine, tributylamine, diisopropylethylamine, 1,4-diazabicyclo[2.2.2]octane (DABCO), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,1,5-diazabicyclo[4.3.0]non-5-ene (DBN), alkoxides like NaOMe, NaOEt and the like or the inorganic base such as NaOH, KOH and the like. The reaction may be carried out in the presence of a solvent such as dichloromethane, THF, DMF, ethyl acetate and the like or mixtures thereof. The reaction temperature may be in the range of -20 to 135.degree. C., preferably at a temperature in the range of 15 to 80.degree. C. The reaction time may range from 2 to 72 h, preferably from 2 to 50 h.

In still another embodiment of the present invention there is provided yet another process for the preparation of compound of the formula (I) where R.sup.1 represents azido and all other symbols are as defined earlier, which comprises:

(i) reacting a compound of formula (VII)

##STR00070## where R.sup.c represents (C.sub.1 C.sub.10)alkyl group such as methyl, ethyl, propyl, and the like; or aralkyl group such as benzyl, allyl group and the like; and all other symbols are as defined earlier, with a compound of formula (XI)

##STR00071## where L represents a leaving group such as halogen atom, (C.sub.1 C.sub.10)alkoxy group such as methoxy, ethoxy, propoxy and the like, or sulphonyl group such as methylsulfonyl, ethylsulfonyl, p-toluenesulfonyl and the like; to produce a compound of formula (XII)

##STR00072## where R.sup.c, Y.sup.1, Y.sup.2, Y.sup.3, R.sup.2, R.sup.3 and Z are as defined earlier,

(ii) converting the compound of formula (XII) defined above to a compound of formula (XIII)

##STR00073## where Y.sup.1, Y.sup.2, Y.sup.3, R.sup.2, R.sup.3 and Z are as defined earlier, and

(iii) converting the compound of formula (XIII) defined above to a compound of formula (I) by reacting with organic or inorganic azide,

##STR00074## where R.sup.1 represents azido group; Y.sup.1, Y.sup.2, Y.sup.3, R.sup.2, R.sup.3 and Z are as defined earlier.

The reaction of a compound of formula (VII) with a compound of formula (XI) may be carried out in the presence of base such as NaH, KH, K.sub.2CO.sub.3, t-BuOK, LDA, NaOMe, with or without phase transfer catalyst such as tetrabutylammonium halide and the like. The reaction may be carried out in the presence of a suitable solvent such as THF, DMF, DMSO, benzene and the like or mixtures thereof. The reaction may be carried out at a temperature in the range of -78 to 120.degree. C., preferably at -78 to 60.degree. C. The reaction time may range from 2 to 20 h, preferably from 4 to 10 h.

The conversion of a compound of formula (XII) to a compound of formula (XIII) defined above may be carried in the presence of reagents such as I.sub.2, KI, or NaI. The reaction may be carried out in the presence of a solvent such as chloroform (CHCl.sub.3), dichloromethane (CH.sub.2Cl.sub.2), THF, DMF, DMSO, acetonitrile and the like or mixtures thereof. The reaction temperature may be in the range of 0 to 100.degree. C., preferably at ambient temperature. The reaction time may range from 2 to 24 h, preferably from 2 to 12 h.

The conversion of a compound of formula (XIII) to a compound of formula (I) where R.sup.1 represents azido group, may be carried out in the presence of one or more equivalents of metal azide such as LiN.sub.3, NaN.sub.3 or trialkyl silylazide. The reaction may be carried out in the presence of solvent such as THF, acetone, DMF, DMSO and the like or mixtures thereof. The reaction may be carried out in inert atmosphere, which may be maintained using N.sub.2 or Ar. The reaction may be carried out at a temperature in the range of ambient temperature to reflux temperature of the solvent, preferably at a temperature in the range of 50 to 80.degree. C. The reaction time may range from 0.5 to 18 h, preferably 1 to 4 h.

In yet another embodiment of the present invention, there is provided a process for the preparation of compound of formula (I), where R.sup.1 represents hydroxy group and all other symbols are as defined earlier, which comprises:

(i) reacting a compound of formula (VII)

##STR00075## where all the symbols are as defined earlier, with a compound of formula (XIV)

##STR00076## where L represents a leaving group such as halogen atom, (C.sub.1 C.sub.10)alkoxy group such as methoxy, ethoxy, propoxy and the like, sulphonyl group such as methylsulfonyl, ethylsulfonyl, p-toluenesulfonyl and the like; to produce a compound of formula (XV)

##STR00077## where R.sup.c, Y.sup.1, Y.sup.2, Y.sup.3, R.sup.2, R.sup.3 and Z are as defined earlier,

(ii) hydrolysing the acetonide moiety in the compound of formula (XV) using conventional methods to produce a compound of formula (XVI)

##STR00078## where R.sup.c, Y.sup.1, Y.sup.2, Y.sup.3, R.sup.2, R.sup.3 and Z are as defined earlier, and

(iii) cyclising the compound of formula (XVI) with or without a base to a compound of formula (I)

##STR00079## where R.sup.1 represents hydroxy group and all other symbols are as defined earlier.

The reaction of a compound of formula (VII) with a compound of formula (XIV) to produce a compound of formula (XV) may be carried out in the presence of a base. The base employed may be selected from K.sub.2CO.sub.3, NaH, t-BuOK, LDA and the like. The reaction may be carried out in the presence of a solvent such as DMF, THF, DMSO, methanol, ethanol, propanol, iso-propanol and the like. The reaction may be carried at a temperature in the range of -78 to 120.degree. C., preferably at a temperature in the range of -78 to 100.degree. C. The reac