US 2003/0125367 A1Published application

Bicyclo[3,1,0]hexane containing oxazolidinone antibioytics and derivatives thereof

AssigneeKyorin Pharmaceutical Co., Ltd.

InventorsYasumichi Fukuda, Milton L. Hammond

Life of this patent

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Abstract

Oxazolidinones having a bicyclic[3.1.0] hexane containing moiety, which are effective against aerobic and anerobic pathogens such as multi-resistant staphylococci, streptococci and enterococci, Bacteroides spp., Clostridia spp. species, as well as acid-fast organisms such as Mycobacterium tuberculosis and other mycobacterial species. The compounds are represented by structural formula I: 1 its enantiomer, diastereomer, or pharmaceutically acceptable salt or ester thereof, and wherein the variables R1, R2, R3, R4, R4a, A, Ar, HAr, n, r, and s are as defined herein.

Claims49

Dependent claims

A compound of the following formula I:

59
its enantiomer, diastereomer, or pharmaceutically acceptable salt, hydrate or prodrug it thereof wherein:
A represents C (when — is present), CH, or N (when — is not present);
— represents a bond;
R represents hydrogen, or C1-6 alkyl;
R1 and R2 independently represent
i) hydrogen,
ii) NR5R6,
iii) CR7R8R9, C(R)2OR14, CH2NHR14,
iv) C(═O)R13, C(═NOH)H, C(═NOR13)H, C(═NOR13)R13, C(═NOH)R13, C(═O)N(R13)2, C(═NOH)N(R13)2, NHC(═XI)N(R13)2, (C═NH)R7, N(R13)C(═X1)N(R13)2, COOR13, SO2R14, N(R13)SO2R14, N(R13)COR14, or (C1-6alkyl)CN, CN, CH═C(R)2, OH, C(═O)CHR13, C(═NR13)R13, NHC(═X1)R13;
60
vi) C5-10 heterocycle optionally substituted with 1-3 groups of R7, which may be attached through either a carbon or a heteroatom;
61
represents aryl or heteroaryl, heterocycle, heterocyclyl or heterocyclic,
Rx represents hydrogen or C1-6 alkyl;
R3 represent
i) NH(C═X2)R12,
ii) NHSO2R14,
iii) NH(CH2)0-4aryl,
iv) NH(CH2)0-4heteroaryl,
v) S(CH2)0-4aryl,
vi) S(CH2)04heteroaryl,
vii) O(CH2)0-4aryl, or
viii) O(CH2)0-4heteroaryl;
R4 and R4a independently represent
i) hydrogen,
ii) halogen,
iii) C1-6 alkoxy, or
iv) C1-6 alkyl
r and s independently are 1-3, with the provision that when (R4a)s and (R4)r are attached to an Ar or HAr ring the sum of r and s is less than or equal to 4;
R5 and R6 independently represent
i) hydrogen,
ii) C1-6 alkyl optionally substituted with 1-3 groups of halogen, CN, OH, C1-6 alkoxy, amino, imino, hydroxyamino, alkoxyamino, C1-6 acyloxy, C1-6 alkylsulfenyl, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, aminosulfonyl, C1-6 alkylaminosulfonyl, C1-6 dialkylaminosulfonyl, 4-morpholinylsulfonyl, phenyl, pyridine, 5-isoxazolyl, ethylenyloxy, or ethynyl, said phenyl and pyridine optionally substituted with 1-3 halogen, CN, OH, CF3, C1-6 alkyl or C1-6 alkoxy;
iii) C1-6 acyl optionally substituted with 1-3 groups of halogen, OH, SH, C1-6 alkoxy, naphthalenoxy, phenoxy, amino, C1-6 acylamino, hydroxylamino, alkoxylamino, C1-6 acyloxy, aralkyloxy, phenyl, pyridine, C1-6 alkylcarbonyl, C1-6 alkylamino, C1-6 dialkylamino, C1-6 hydroxyacyloxy, C1-6 alkylsulfenyl, phthalimido, maleimido, succinimido, said phenoxy, phenyl and pyridine optionally substituted with 1-3 groups of halo, OH, CN, C1-6 alkoxy, amino, C1-6 acylamino, CF3 or C1-6 alkyl;
iv) C1-6 alkylsulfonyl optionally substituted with 1-3 groups of halogen, OH, C1-6 alkoxy, amino, hydroxylamino, alkoxylamino, C1-6 acyloxy, or phenyl;
said phenyl optionally substituted with 1-3 groups of halo, OH, C1-6 alkoxy, amino, C1-6 acylamino, CF3 or C1-6 alkyl;
v) arylsulfonyl optionally substituted with 1-3 of halogen, C1-6 alkoxy, OH or C1-6 alkyl;
vi) C1-6 alkoxycarbonyl optionally substituted with 1-3 of halogen, OH, C1-6 alkoxy, C1-6 acyloxy, or phenyl, said phenyl optionally substituted with 1-3 groups of halo, OH, C1-6 alkoxy, amino, C1-6 acylamino, CF3 or C1-6 alkyl;
vii) aminocarbonyl, C1-6 alkylaminocarbonyl or C1-6 dialkylaminocarbonyl, said alkyl groups optionally substituted with 1-3 groups of halogen, OH, C1-6 alkoxy or phenyl
viii) five to six membered heterocycles optionally substituted with 1-3 groups of halogen, OH, CN, amino, C1-6 acylamino, C1-6 alkylsulfonylamino, C1-6 alkoxycarbonylamino, C1-6 alkoxy, C1-6 acyloxy or C1-6 alkyl, said alkyl optionally substituted with 1-3 groups of halogen, or C1-6 alkoxy;
ix) C3-6 cycloalkylcarbonyl optionally substituted with 1-3 groups of halogen, OH, C1-6 alkoxy or CN;
x) benzoyl optionally substituted with 1-3 groups of halogen, OH, C1-6 alkoxy, C1-6 alkyl, CF3, C1-6 alkanoyl, amino or C1-6 acylamino;
xi) pyrrolylcarbonyl optionally substituted with 1-3 of C1-6 alkyl;
xii) C1-2 acyloxyacetyl where the acyl is optionally substituted with amino, C1-6 alkylamino, C1-6 dialkylamino, 4-morpholino, 4-aminophenyl, 4-(dialkylamino)phenyl, 4-(glycylamino)phenyl;
or
R5 and R6 taken together with any intervening atoms can form a 3 to 7 membered heterocyclic ring containing 1-2 heteroatoms independently chosen from O, S, SO, SO2, N, or NR8;
R7 represent
i) hydrogen, halogen, OH, C1-6 alkoxy, C1-6 alkyl, alkenyl, ii) amino, C1-6 alkylamino, C1-6 dialkylamino, hydroxylamino or C1-2 alkoxyamino all of which can be optionally substituted on the nitrogen with C1-6 acyl, C1-6 alkylsulfonyl or C1-6 alkoxycarbonyl, said acyl and alkylsulfonyl optionally substituted with 1-2 of halogen or OH;
R8 and R9 independently represents
i) H, CN,
ii) C1-6 alkyl optionally substituted with 1-3 halogen, CN, OH, C1-6 alkoxy, C1-6 acyloxy, or amino,
iii) phenyl optionally substituted with 1-3 groups of halogen, OH, C1-6 alkoxy;
or
R7 and R8 taken together can form a 3-7 membered ring optionally interrupted with 1-2 heteroatoms chosen from O, S, SO, SO2, NH, and NR8;
X1 represents O, S or NR13, NCN, or NSO2R1 4×2 represents O, S, NH or NSO2R14;
R10 represents hydrogen, C1-6 alkyl or CO2R15;
R11 represents hydrogen, C1-6 alkyl, C1-6 alkanoyl, halogen, amino, C1-6 acylamino, C1-6 alkoxy, OH or CF3,;
NHC1-6 alkyl, or N(C1-6 alkyl)2, where said alkyl may be substituted with 1-3 groups of halo, OH or C1-6 alkoxy;
R12 represents hydrogen, C1-6 alkyl, NH2, C1-6 alkylamino, C1-6 alkoxy or C1-6 dialkylamino, where said alkyl may be substituted with 1-3 groups of halo, OH or C1-6 alkoxy;
Each R13 represents independently hydrogen, C1-6 alkyl, NR5R6, SR8, S(O)R8, S(O)2R, CN, C1-6 alkylS(O)R, C1-6 alkoxycarbonyl, hydroxycarbonyl, C1-6acyl, C3-7 membered carbon ring optionally interrupted with 1-4 heteroatoms chosen from O, S, SO, SO2, NH and NR8 where said C1-6 alkyl or C1-6 acyl groups may be independently substituted with 0-3 halogens, hydroxy, N(R)2, CO2R, C610aryl, C5l0heteroaryl, or C1-6alkoxy groups;
When two R13 groups are attached to the same atom or two adjacent atoms they may be taken together to form a 3-7 membered ring optionally interrupted with 1-2 heteroatoms chosen from O, S, SO, SO2, NH, and NR8;
R14 represents amino, C1-6 alkyl, C -6 haloalkyl, five to six membered heterocycles or phenyl, said phenyl and heterocycles optionally substituted with 1-3 group of halo, C1-6 alkoxy, C1-6 acylamino, or C1-6 alkyl, hydroxy and/or amino, said amino and hydroxy optionally protected with an amino or hydroxy protecting group;
R15 is C1-6 alkyl or benzyl said benzyl optionally substituted with 1-3 groups of halo, OH, C1-6 alkoxy, amino, C1-6 acylamino, or C1-6 alkyl;
and
m, n, and q represents 0-1.

62 more elements

A compound which is:

N-[5(S)-3-[4-[(1α,5α,6α)-6-(N-Benzyl)amino-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-(N-Benzyloxyacetyl)amino-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-(N-hydroxyacetyl)amino-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-(N-Benzyl-N-methyl)amino-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-(N-methyl)amino-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-(N-Benzyloxyacetyl-N-methyl)amino-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-(N-hydroxyacetyl-N-methyl)amino-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-Amino-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-(N-Benzyl-N-t-butoxycarbonyl)ainino-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-(N-Benzyl-N-t-butoxycarbonyl)amino-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]thioacetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-(N-Benzyl)amino-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]thioacetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-(N-Benzyl)amino-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]thiourea,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-hydroxymethyl-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-[(2-tetrahydropyranyl)oxy]methyl-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro4-[(1α,5α,6α)-6-methoxymethyl-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-(3-isoxazolyl)oxymethyl-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[()-6-Acetylamino-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-Benzoylamino-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-phenylsulfonylamino-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-methanesulfonylamino-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-carbamoylamino-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-fonmyl-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-Carboxyl-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-[(1-Iminoethyl)amino]-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-Bromomethyl-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-Cyanomethyl-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl] acetamide,
N-[4-[1-(5(S)-Acetylaminomethyl-2-oxooxazolidin-3-yl)-3-fluoro]phenyl-(1α,5α,6α)-3-azabicyclo[3.1.0]hexan-6-yl]methylpyridinium bromide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-succinimidoyloxycarbonyl-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-Carbamoyl-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-methoxycarbonyl-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-[N,N″-Bis(benzyloxycarbonyl)guanigino]-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-guanidino-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-methylcarbamoyl-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-Dimethylcarbamoyl-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-[(piperidin-1-yl)carbonyl]-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-[(morpholin-4-yl)carbonyl]-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-[N-(2-hydroxyethyl)carbamoyl]-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-(2-Aminoethyl)-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-(1-hydroxyethyl)-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-Acetyl-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
(E)-N-[5(S)-3-[3-Fluoro4-[(1α,5α,6α)-6-[(hydroxyimino)methyl]-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
(Z)-N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-[(hydroxyimino)methyl]-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-[(methoxyimino)methyl]-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-[(t-Butoxycarbonylmethyloxyimino)methyl]-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-[(Carboxy]methyloxyimino)methyl]-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-Cyano-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[((5S)-3-{4-[(1R,5R,6S)-6-cyanobicyclo[3.1.0]hex-2-en-3-yl]-3-fluorophenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-Aminobicyclo[3.1.0]hex-2-en-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide hydrochloride,
N-[((5S)-3-{4-[(1S,5S,6R)-6-cyanobicyclo[3.1.0.]hex-2-en-3-yl]-3-fluorophenyl}-2-oxo-1,3-oxazolidin-5-yl)methyl]acetamide,
N-[5(S)-3-[4-[(1R,5R,6S)-6-Cyanobicyclo[3.1.0]hex-2-en-3-yl]-3,5-difluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1S,5S,6R)-6-Cyanobicyclo[3.1.0]hex-2-en-3-yl]-3,5-difluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1R,5R,6S)-6-Aminobicyclo[3.1.0]hex-2-en-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1S,5S,6R)-6-Aminobicyclo [3.1.0]hex-2-en-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1R,5R,6S)-6-Aminobicyclo[3.1.0]hex-2-en-3-yl]-3,5-difluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1S,5S,6R)-6-Aminobicyclp[3.1.0]hex-2-en-3-yl]-3,5-difluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1R,5R,6S)-6-hydroxymethylbicyclo[3.1.0]hex-2-en-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1S,5S,6R)-6-hydroxymethylbicyclo[3.1.0]hex-2-en-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3,5-Difluoro-4-[(1R,5R,6S)-6-hydroxymethylbicyclo[3.1.0]hex-2-en-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3,5-Difluoro-4-[(1S,5S,6R)-6-hydroxymethylbicyclo[3.1.0]hex-2-en-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,4α,5α,6α)-6-Aminobicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,4β, 5α,6α)-6-Aminobicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,4α,5α,6α)-6-Aminobicyclo[3.1.0]hexan-3-yl]-3,5-difluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,4α,5α,6α)-6-Aminobicyclo[3.1.0]hexan-3-yl]-3,5-difluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,4α,5α,6α)-6-Cyanobicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,4β,5α,6α)-6-Cyanobicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,4α,5α,6α)-6-Cyanobicyclo[3.1.0]hexan-3-yl]-3,5-difluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,4β,5α,6α)-6-Cyanobicyclo[3.1.0]hexan-3-yl]-3,5-difluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,4α,5α,6α)-6-hydroxymethylbicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,4β,5α,6α)-6-hydroxymethylbicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3,5-Difluoro-4-[(1α,4α,5α,6α)-6-hydroxymethylbicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3,5-Difluoro-4-[(1α,4β,5β,6α)-6-hydroxymethylbicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
(E)-N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-[(hydroxyimino)aminomethyl]-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetaride,
(Z)-N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-[(hydroxyimino)aminomethyl]-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-[(2-(methoxy)ethoxyimino)methyl]-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-[(2-(Dimethylamino)ethoxyimino)methyl]-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-[(3-(Dimethylamino)propoxyimino)methyl]-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-[(N-(4-morpholinyl)imino)methyl]-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-[(1-(1-t-Butoxycarboxyl-1-methyl)ethoxy)iminomethyl]-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-[(1-(1-Carboxyl-1-methyl)ethoxy)iminomethyl]-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-[(2-hydroxyethoxy)iminomethyl]-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-[(5-tetrazolylmethoxy)iminomethyl]-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-yhmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-Cyano-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide N-Oxide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-Ethenyl-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-hydroxy-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-(t-Butyldimethylsilyl)oxy-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro4-[(1α,5α,6α)-6-(2-hydroxyethyl)-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-(1,2-Dihydroxyethyl)-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-(2-(t-Buthyldimethylsilyl)oxy-1-hydroxyethyl)-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-[(2-(t-Buthyldimethylsilyl)oxy)acetyl]-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-hydroxyacetyl-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-[(1-(2,3-Dihydroxy)propyloxy)iminomethyl]-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-[(2-(1,3-Dihydroxy)propyloxy)iminomethyl]-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-[(1-(2-(2-hydroxyethoxy))ethoxy)iminomethyl]-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-(Cyanomethyloxy)iminomethyl]-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-[(1-(2-methylthio)ethoxy)iminomethyl]-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-[(1-(2-methylsulfinyl)ethoxy)iminomethyl]-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-[(1-(2-methylsulfonyl)ethoxy)iminomethyl]-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-Aminomethyl-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-(hydroxyethyl)amino-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-(2-Aminoethyl)amino-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-(pyridin-2-yl)amino-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-(3-Cyanopyridin-2-yl)amino-3-azabicyclo[3.1.0]hexan-3-yl]-3fluorophienyl]-2-oxooxazolidin-5-yhmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-(5-Cyanopyridin-2-yl)amino-3-azabicyclo[3.1.0]hexan-3-yl]-3fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-(3-Cyanopyrazin-2-yl)amino-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6α)-6-(pyrimidin-2-yl)amino-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-(4-Aminopyrimidin-2-yl)amino-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-Amino-3-azabicyclo[3.1.0]hexan-3-yl]-3,5-difluorophenyl]-2-oxooxazolidin-5-yhethyl]acetamide,
N-[5(S)-3-[3,5-Difluoro-4-[(1α,5α,6α)-6-hydroxymethyl-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3,5-Difluoro-4-[(1α,5α,6α)-6-formyl-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-Cyanomethyl-3-azabicyclo[3.1.0]hexan-3-yl]-3,5-difluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3,5-Difluoro-4-[(1α,5α,6α)-6-[(hydroxyimino)methyl]-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-Cyano-3-azabicyclo[3.1.0]hexan-3-yl]-3,5-difluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3,5-Difluoro-4-[(1α,5α,6α)-6-[(1-(2,3-dihydroxy)propyloxy)ininomethyl]-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyllacetamide,
N-[5(S)-3-[3,5-Difluoro-4-[(1α,5α,6α)-6-[(2-(1,3-dihydroxy)propyloxy)iminomethyl]-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3,5-Difluoro-4-[(1α,5α,6α)-6-[(1-(2-(2-hydroxyethoxy))ethoxy)iminomethyl]-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3,5-Difluoro-4-[(1α,5α,6α)-6-[(2-hydroxyethoxy)iminomethyl]-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-Amino-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]difluoroacetamide,
5(S)-3-[4-[(1α,5α,6α)-6-Amino-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-5-(methoxythiocarbonyl)aminomethyloxazolidin-2-one,
5(R)-3-[4-[(1α,5α,6α)-6-Amino-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-5-(isoxazol-3-yl)oxymethyloxazolidin-2-one,
5(S)-3-[4-[(1α,5α,6α)-6-Amino-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-5-(isoxazol-3-yl)aminomethyloxazolidin-2-one,
5(S)-3-[4-[(1α,5α,6α)-6-Cyano-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-5-(isoxazol-3-yl) aminomethyloxazolidin-2-one,
5(S)-3-[4-[(1α,5α,6α)-6-Amino-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-5-(1,2,4-oxadiazol-3-yl)aminomethyloxazolidin-2-one,
5(S)-3-[4-[(1α,5α,6α)-6-Cyano-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-5-(1,2,4-oxadiazol-3-yl)aminomethyloxazolidin-2-one, or
5(S)-3-[4-[(1α,5α,6α)-6-Amino-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-5-(pyridin-2-yl)aminomethyloxazolidin-2-one.

121 more elements

A compound selected from the group consisting of:

5(S)-3-[4-[(1α,5α,6α)-6-Amino-3-azabicyclo[3.1.0]hexan-3-yl]-3,5-difluorophenyl]-5-[(1,2,4-oxadiazolyl-3-yl)amino]methyloxazolidin-2-one,
5(S)-3-[4-[(1α,5α,6α)-6-Amino-3-azabicyclo[3.1.0]hexan-3-yl]-3,5-difluorophenyl]-5-[(isoxazolyl-3-yl)amino]methyloxazolidin-2-one,
5(S)-3-[4-[(1α,5α,6α)-6-Amino-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-5-[(isoxazolyl-3-yl)amino]methyloxazolidin-2-one,
5(S)-3-[4-[(1α,5α,6α)-6-Cyanobicyclo[3.1.0]hex-2-en-3-yl]phenyl]-5-[N-(1,2,4-oxadiazolyl-3-yl)]aminomethyloxazolidin-2-one,
5(S)-3-[4-[(1α,5α,6α)-6-Cyanobicyclo[3.1.0]hex-2-en-3-yl]phenyl]-5-[(isoxazolyl-3-yl)amino]methyloxazolidin-2-one,
5(R)-3-[4-[(1α,5α,6α)-6-Cyanobicyclo[3.1.0]hex-2-en-3-yl]phenyl]-5-[(isoxazolyl-3-yl)oxy]methyloxazolidin-2-one,
N-[5(S)-3-[4-[(1α,5α,6α)-6-[(N-Cyano-1-iminoethyl)amino]-3-azabicyclo[3.1.0]hexan-3-yl]-3,5-difluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-(5-Amino-4-cyano-1,3-oxazol-2-yl)-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-(5-Amino-4-cyano-1,3-oxazol-2-yl)bicyclo[3.1.0]hex-2-en-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-Amino-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-Hydroxymethylbicyclo[3.1.0]hex-2-en-2-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-[(Hydroxyimino)methyl]bicyclo[3.1.0]hex-2-en-2-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-Cyanobicyclo[3.1.0]hex-2-en-2-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3-Fluoro-4-[(1α,5α,6β)-6-hydroxymethylbicyclo[3.1.0]hex-2-en-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6β)-6-Cyanobicyclo[3.1.0]hex-2-en-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6β)-6-Hydroxymethylbicyclo[3.1.0]hex-2-en-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6β)-6-Cyanobicyclo[3.1.0]hex-2-en-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[S(S)-3-[4-[(1α,5α,6α)-6-Hydroxymethylbicyclo[3.1.0]hex-2-en-3-yl]phenyl]-2oxoox azolidin-5-ylmethyl]acetamide (diastereomer A),
N-[5(S)-3-[4-[(1α,5α,6α)-6-Cyanobicyclo[3.1.0]hex-2-en-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetade (diastereomer A),
N-[5(S)-3-[4-[(1α,5α,6α)-6-Hydroxymethylbicyclo[3.1.0]hex-2-en -3-yl]phenyl]-2-oxooxa zolidin-5-ylnethyl]acetamide (diastereomer B),
N-[5(S)-3-[4-[(1α,5α,6α)-6-Cyanobicyclo[3.1.0]hex-2-en-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide (diastereomer B),
N-[5(S)-3-[4-[(1α,5α,6α)-6-[(Cyano-2-dimethylamino)ethen-1-y1]-3-azabieyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2oxooxazolidin5ylmethyl)acetamide, or
N-[5(S)-3-[4-[(1α,5α,6α)-6-(3-Amino-1H-pyrazol-4-yl)-3-azabicyclo[3-yl-]hexan-3-yl-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyllacetamide.

20 more elements

A compound selected from the group consisting of:

(E)-N-[5(S)-3-[4-[(1α,5α,6α)-6-[Amino (hydroxyimino)methyl]-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
(Z)-N-[5(S)-3-[4-[(1α,5α,6α)-6-[Amino (hydroxyimino)methyl]-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-[1-(2-t-Butyldiphenylsilyloxy-1-hydroxy)ethyl]-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-[(2-(t-Butyldiphenylsilyl)oxy)acetyl]-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[5-[(1α,5α,6α)-6-Hydroxymethylbicyclo[3.1.0]hex-2-en-3-yl]pyridin-2-yl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[5-[(1α,5α,6α)-6-[(t-Butyldiphenylsilyl)oxy]methylbicyclo[3.1.0]hex-2-en-3-yl]pyridin-2-yl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[5-[(1α,5α,6α)-6-Cyanobicyclo[3.1.0]hex-2-en-3-yl]pyridin-2-yl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3,5-Difluoro-4-[(1α,5α,6α)-6-[(hydroxyimino)methyl]bicyclo[3.1.0]hex-2-en-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[3,5-Difluoro-4-[(1α,5α,6α)-6-formylbicyclo[3.1.0]hex-2-en-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1R,5R,6S)-6-cyanobicyclo[3.1.0]hex-2-en-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1S,5S,6R)-6-cyanobicyclo[3.1.0]hex-2-en-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-(1-Cyanoethyl)-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-(1-Cyano-1-methylethyl)-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide,
5(S)-3-[4-[(1R,5R,6S)-6-Cyanobicyclo[3.1.0]hex-2-en-3-yl]-3-fluorophenyl]-5-[(1,2,4-oxadiazolyl-3-yl)amino]methyloxazolidin-2-one,
5(S)-3-[4-[(1S,5S,6R)-6-Cyanobicyclo[3.1.0]hex-2-en-3-yl]-3-fluorophenyl]-5-[(1,2,4-oxadiazolyl-3-yl)amino]methyloxazolidin-2-one,
N-[5(S)-3-[6-[(1α,5α,6α)-6-Hydroxymethylbicyclo[3.1.0]hex-2-en-3-yl]pyridin-3-yl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[6-[(1α,5α,6α)-6-(Hydroxyimino)methylbicyclo[3.1.0]hex-2-en-3-yl]pyridin-3-yl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[6-[(1α,5α,6α)-6-Cyanobicyclo[3.1.0]hex-2-en-3-yl]pyridin-3-yl]-2-oxooxazolidin-5-ylmethyl]acetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-Cyano-3-azabicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]thioacetamide,
N-[5(S)-3-[6-[(1α,5α,6α)-6-Cyanobicyclo[3.1.0]hex-2-en-3-yl]pyridin-3-yl]-2-oxooxazolidin-5-ylmethyl]thioacetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-Cyanobicyclo[3.1.0]hex-2-en-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]thioacetamide,
N-[5(S)-3-[4-[(1α,5α,6α)-6-(N-Benzyl-N-t-butoxycarbonyl)amino-3-azabicyclo[3.1.0]hexan-3-yl]-3,5-difluorophenyl]-2-oxooxazolidin-5-ylmethyl]acetamide, or
N-[5(S)-3-[4-[(1α,3α,5α,6α)-6-Cyanobicyclo[3.1.0]hexan-3-yl]-3-fluorophenyl]-2-oxooxazolidin-5-ylmethyl]thioacetamide.

20 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/123,285Filed 17 Apr 2002
Priority: 17 Apr 2001
Published: 3 Jul 2003
Term ends: Not estimatedThe source records don’t support an estimate.

Classification6 codes

C07D 263/10
Having one double bond between ring members or between a ring member and a non-ring member: with only hydrogen atoms, hydrocarbon or substituted…
A61P 31/04
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics: antibacterial agents
C07D 405/10
Containing two hetero rings: linked by a carbon chain containing aromatic rings
C07D 413/10
Containing two hetero rings: linked by a carbon chain containing aromatic rings

Family

Application60/283,956Us provisional application · filed 17 Apr 2001
US 6,897,230 B2Related patent
US 2003/0125367 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound of the following formula I:

59
its enantiomer, diastereomer, or pharmaceutically acceptable salt, hydrate or prodrug it thereof wherein:
A represents C (when — is present), CH, or N (when — is not present);
— represents a bond;
R represents hydrogen, or C1-6 alkyl;
R1 and R2 independently represent
i) hydrogen,
ii) NR5R6,
iii) CR7R8R9, C(R)2OR14, CH2NHR14,
iv) C(═O)R13, C(═NOH)H, C(═NOR13)H, C(═NOR13)R13, C(═NOH)R13, C(═O)N(R13)2, C(═NOH)N(R13)2, NHC(═XI)N(R13)2, (C═NH)R7, N(R13)C(═X1)N(R13)2, COOR13, SO2R14, N(R13)SO2R14, N(R13)COR14, or (C1-6alkyl)CN, CN, CH═C(R)2, OH, C(═O)CHR13, C(═NR13)R13, NHC(═X1)R13;
60
vi) C5-10 heterocycle optionally substituted with 1-3 groups of R7, which may be attached through either a carbon or a heteroatom;
61
represents aryl or heteroaryl, heterocycle, heterocyclyl or heterocyclic,
Rx represents hydrogen or C1-6 alkyl;
R3 represent
i) NH(C═X2)R12,
ii) NHSO2R14,
iii) NH(CH2)0-4aryl,
iv) NH(CH2)0-4heteroaryl,
v) S(CH2)0-4aryl,
vi) S(CH2)04heteroaryl,
vii) O(CH2)0-4aryl, or
viii) O(CH2)0-4heteroaryl;
R4 and R4a independently represent
i) hydrogen,
ii) halogen,
iii) C1-6 alkoxy, or
iv) C1-6 alkyl
r and s independently are 1-3, with the provision that when (R4a)s and (R4)r are attached to an Ar or HAr ring the sum of r and s is less than or equal to 4;
R5 and R6 independently represent
i) hydrogen,
ii) C1-6 alkyl optionally substituted with 1-3 groups of halogen, CN, OH, C1-6 alkoxy, amino, imino, hydroxyamino, alkoxyamino, C1-6 acyloxy, C1-6 alkylsulfenyl, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, aminosulfonyl, C1-6 alkylaminosulfonyl, C1-6 dialkylaminosulfonyl, 4-morpholinylsulfonyl, phenyl, pyridine, 5-isoxazolyl, ethylenyloxy, or ethynyl, said phenyl and pyridine optionally substituted with 1-3 halogen, CN, OH, CF3, C1-6 alkyl or C1-6 alkoxy;
iii) C1-6 acyl optionally substituted with 1-3 groups of halogen, OH, SH, C1-6 alkoxy, naphthalenoxy, phenoxy, amino, C1-6 acylamino, hydroxylamino, alkoxylamino, C1-6 acyloxy, aralkyloxy, phenyl, pyridine, C1-6 alkylcarbonyl, C1-6 alkylamino, C1-6 dialkylamino, C1-6 hydroxyacyloxy, C1-6 alkylsulfenyl, phthalimido, maleimido, succinimido, said phenoxy, phenyl and pyridine optionally substituted with 1-3 groups of halo, OH, CN, C1-6 alkoxy, amino, C1-6 acylamino, CF3 or C1-6 alkyl;
iv) C1-6 alkylsulfonyl optionally substituted with 1-3 groups of halogen, OH, C1-6 alkoxy, amino, hydroxylamino, alkoxylamino, C1-6 acyloxy, or phenyl;
said phenyl optionally substituted with 1-3 groups of halo, OH, C1-6 alkoxy, amino, C1-6 acylamino, CF3 or C1-6 alkyl;
v) arylsulfonyl optionally substituted with 1-3 of halogen, C1-6 alkoxy, OH or C1-6 alkyl;
vi) C1-6 alkoxycarbonyl optionally substituted with 1-3 of halogen, OH, C1-6 alkoxy, C1-6 acyloxy, or phenyl, said phenyl optionally substituted with 1-3 groups of halo, OH, C1-6 alkoxy, amino, C1-6 acylamino, CF3 or C1-6 alkyl;
vii) aminocarbonyl, C1-6 alkylaminocarbonyl or C1-6 dialkylaminocarbonyl, said alkyl groups optionally substituted with 1-3 groups of halogen, OH, C1-6 alkoxy or phenyl
viii) five to six membered heterocycles optionally substituted with 1-3 groups of halogen, OH, CN, amino, C1-6 acylamino, C1-6 alkylsulfonylamino, C1-6 alkoxycarbonylamino, C1-6 alkoxy, C1-6 acyloxy or C1-6 alkyl, said alkyl optionally substituted with 1-3 groups of halogen, or C1-6 alkoxy;
ix) C3-6 cycloalkylcarbonyl optionally substituted with 1-3 groups of halogen, OH, C1-6 alkoxy or CN;
x) benzoyl optionally substituted with 1-3 groups of halogen, OH, C1-6 alkoxy, C1-6 alkyl, CF3, C1-6 alkanoyl, amino or C1-6 acylamino;
xi) pyrrolylcarbonyl optionally substituted with 1-3 of C1-6 alkyl;
xii) C1-2 acyloxyacetyl where the acyl is optionally substituted with amino, C1-6 alkylamino, C1-6 dialkylamino, 4-morpholino, 4-aminophenyl, 4-(dialkylamino)phenyl, 4-(glycylamino)phenyl;
or
R5 and R6 taken together with any intervening atoms can form a 3 to 7 membered heterocyclic ring containing 1-2 heteroatoms independently chosen from O, S, SO, SO2, N, or NR8;
R7 represent
i) hydrogen, halogen, OH, C1-6 alkoxy, C1-6 alkyl, alkenyl, ii) amino, C1-6 alkylamino, C1-6 dialkylamino, hydroxylamino or C1-2 alkoxyamino all of which can be optionally substituted on the nitrogen with C1-6 acyl, C1-6 alkylsulfonyl or C1-6 alkoxycarbonyl, said acyl and alkylsulfonyl optionally substituted with 1-2 of halogen or OH;
R8 and R9 independently represents
i) H, CN,
ii) C1-6 alkyl optionally substituted with 1-3 halogen, CN, OH, C1-6 alkoxy, C1-6 acyloxy, or amino,
iii) phenyl optionally substituted with 1-3 groups of halogen, OH, C1-6 alkoxy;
or
R7 and R8 taken together can form a 3-7 membered ring optionally interrupted with 1-2 heteroatoms chosen from O, S, SO, SO2, NH, and NR8;
X1 represents O, S or NR13, NCN, or NSO2R1 4×2 represents O, S, NH or NSO2R14;
R10 represents hydrogen, C1-6 alkyl or CO2R15;
R11 represents hydrogen, C1-6 alkyl, C1-6 alkanoyl, halogen, amino, C1-6 acylamino, C1-6 alkoxy, OH or CF3,;
NHC1-6 alkyl, or N(C1-6 alkyl)2, where said alkyl may be substituted with 1-3 groups of halo, OH or C1-6 alkoxy;
R12 represents hydrogen, C1-6 alkyl, NH2, C1-6 alkylamino, C1-6 alkoxy or C1-6 dialkylamino, where said alkyl may be substituted with 1-3 groups of halo, OH or C1-6 alkoxy;
Each R13 represents independently hydrogen, C1-6 alkyl, NR5R6, SR8, S(O)R8, S(O)2R, CN, C1-6 alkylS(O)R, C1-6 alkoxycarbonyl, hydroxycarbonyl, C1-6acyl, C3-7 membered carbon ring optionally interrupted with 1-4 heteroatoms chosen from O, S, SO, SO2, NH and NR8 where said C1-6 alkyl or C1-6 acyl groups may be independently substituted with 0-3 halogens, hydroxy, N(R)2, CO2R, C610aryl, C5l0heteroaryl, or C1-6alkoxy groups;
When two R13 groups are attached to the same atom or two adjacent atoms they may be taken together to form a 3-7 membered ring optionally interrupted with 1-2 heteroatoms chosen from O, S, SO, SO2, NH, and NR8;
R14 represents amino, C1-6 alkyl, C -6 haloalkyl, five to six membered heterocycles or phenyl, said phenyl and heterocycles optionally substituted with 1-3 group of halo, C1-6 alkoxy, C1-6 acylamino, or C1-6 alkyl, hydroxy and/or amino, said amino and hydroxy optionally protected with an amino or hydroxy protecting group;
R15 is C1-6 alkyl or benzyl said benzyl optionally substituted with 1-3 groups of halo, OH, C1-6 alkoxy, amino, C1-6 acylamino, or C1-6 alkyl;
and
m, n, and q represents 0-1.

62 more elements

Facts

Application

10/123,285Filed 17 Apr 2002

Priority

17 Apr 2001

Published

3 Jul 2003

Term ends

Not estimatedThe source records don’t support an estimate.

Classification6 codes

C07D 263/10
Having one double bond between ring members or between a ring member and a non-ring member: with only hydrogen atoms, hydrocarbon or substituted…
A61P 31/04
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics: antibacterial agents
C07D 405/10
Containing two hetero rings: linked by a carbon chain containing aromatic rings
C07D 413/10
Containing two hetero rings: linked by a carbon chain containing aromatic rings