ZA200510192B

ZA200510192B - Novel lincomycin derivatives possessing antimicrobial activity

Info

Publication number: ZA200510192B
Application number: ZA200510192A
Authority: ZA
Inventors: Jason G Lewis; O'dowd Hardwin; Dinesh V Patel; Anandan Sampath-Kumar; Mikhail F Gordeev
Original assignee: Vicuron Pharm Inc
Priority date: 2003-06-17
Filing date: 2005-12-14
Publication date: 2006-12-27
Also published as: CN1823083B; CN1823083A

Description

NOVEL LINCOMYCIN DERIVATIVES

POSSESSING ANTIMICROBIAL ACTIVITY

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation-in-part of U.S Patent Application No. 10/777,455, filed February 11, 2004, which is a continuation-in-part of U.S. Patent Application No. 10/642,807, filed August 15, 2003, and further claims the benefit under 35 U.S.C. §1 19(e) of

U.S. Provisional Application No. 60/479,296 filed on June 17, 2003 and of U.S. Provisional

Application No. 60/479,502, filed on June 17, 2003, the disclosures of which are hereby incorporated by reference in their entirety.

BACKGROUND OF THE INVENTION FIELD OF THE INVENTION

[0002] This invention relates to lincomycin derivatives that exhibit antibacterial activity as’ “well as to methods for using such derivatives. ‘ STATE OF THE ART

[0003] Lincomycin is a biosynthetic product that adversely affects growth of various microorganisms, in particular gram positive bacteria. The characteristics and preparation of lincomycin are disclosed in U.S. Patent No. 3,086,912. A variety of derivatives of lincomycin, which also have antimicrobial activity, have been prepared. These derivatives include, for example, clindamycin, which is described in U.S. Patent No. 3,496,163.

[0004] Lincomycin derivatives remain attractive targets for antibacterial drug discovery.

Accordingly, lincomycin derivatives that possess antimicrobial activity are desired as potential antibacterial agents.

SUMMARY OF THE INVENTION

[0005] The present invention provides lincomycin derivatives that possess antibacterial activity. In some embodiments, said novel lincomycin derivatives exhibit antibacterial activity against gram positive and anaerobe pathogens. Surprisingly, selected novel lincomycin compounds described herein exhibit atypical potency against Enterocci species such as Enterocci faecium and Enterocci faecalis, and/or against fastidious gram-negative pathogens such as Haemophilus influenzae, when compared against known compounds such as clindamycin.

[0006] In one of its composition aspects, this invention is directed to a compound of

Formula (I): o w—/ rR

HN R2 lo!

HO coniliR?

He “om ® wherein: 9

W is a nitrogen-containing ring: R® , whereinm is 0, 1, 2, or 3; wherein when m is 2, the nitrogen-containing ring may optionally contain a double bond between the 4 and 5 nitrogen-containing ring positions; wherein when m is 3, the nitrogen- containing ring may optionally contain one double bond between either the 4 and 5 nitrogen- containing ring positions or between the 5 and 6 nitrogen-containing ring positions; wherein the nitrogen-containing ring positions are consecutively numbered counterclockwise beginning with “1” at the nitrogen;

R! is selected from the group consisting of hydrogen, alkyl, substituted alkyl, hydroxyalkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, cycloalkylalkyl, halo, alkylsulfanyl, and substituted alkylsulfanyl;

R? and R? are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted : . alkenyl, alkoxy, substituted alkoxy, cyano, alkylsulfanyl, substituted alkylsulfanyl, hydroxy,

halo, or one of R? and R? is =NOR’ and the other is absent, or one of R? and R? is =CH, and the other is absent;

R¢is selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, cycloalkyl, substituted alkyl, iminomethyl, -C(O)O-alkyl, -C(0)O-substituted alkyl, -

C(0)O-aryl, -C(0)O-substituted aryl, -C(O)O-heteroaryl, -C(O)O-substituted heteroaryl, - (carboxamido)alkyl, (carbamoyl)alkyl, 5-alkyl-[1,3]dioxol-2-one-4-yl-methyl, S-alkyl- [1,3]}dioxol-2-one-4-yl-methoxy-carbonyl, or N(R®- fragment is part of the amidine, N- cyanoamidine, N-hydroxyamidine, or N-alkoxyamidine structure;

R’ is H or alkyl;

R®, which can be singly or multiply substituted in the ring on the same or different carbons, is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, cycloalkylalkyl, substituted alkenyl, substituted oxygen, substituted nitrogen, halogen, phenyl, substituted phenyl, alkylsulfanyl, substituted alkylsulfanyl, substituted arylsulfanyl, heteroarylsulfanylalkyl, heterocyclicsulfanylaikyl, heteroarylsulfanyl, and heterocyclicsulfanyl, propylidene (FCHCH,CHj), azido, -(CH),-OH, -(CHy),-NR*R’, and branched chain isomers thereof wherein n is an integer of from 1 to 8 : inclusive and R* and R are H or alkyl, alkoxyalkoxy, aryl, substituted aryl, alkenyl, substituted alkenyl, and -S(O)R" where q is an integer equal to zero, one or two and RBis selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic and substituted heterocyclic, and wherein not more than one S(O)R"” group is present on the nitrogen-containing ring; or a prodrug and/or pharmaceutically acceptable salt thereof.

[0007] In another one of its composition aspects, this invention is directed to a compound of Formula (II): ~ R20

Rr

HN lo}

HO eR!

HO “on an wherein:

RO

RP

N

W is a nitrogen-containing ring: L , whereinm is 0, 1, 2, or 3; wherein when m is 2, the nitrogen-containing ring may optionally contain a double bond between the 4 and 5 nitrogen-containing ring positions; wherein when m is 3, the nitrogen- containing ring may optionally contain one double bond between either the 4 and 5 nitrogen- containing ring positions or between the 5 and 6 nitrogen-containing ring positions; wherein the nitrogen-containing ring positions are consecutively numbered counterclockwise beginning with “1” at the nitrogen;

R! is selected from the group consisting of hydrogen, alkyl, substituted alkyl, hydroxyalkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, cycloalkylalkyl, halo, alkylsulfanyl, and substituted alkylsulfanyl; .

[0001] R? and R? are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, cyano, alkylsulfanyl, substituted alkylsulfanyl, hydroxy, halo, or one of R? and R* is =NOR” and the other is absent, or one of R?® and R* is =CH, and the other is absent, or R?® and R* taken together are cycloalkyl, aryl, substituted aryl, heterocyclic, or heteroaryl;

RSis selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, cycloalkyl, substituted alkyl, iminomethyl, -C(O)O-alkyl, -C(O)O-substituted alkyl, - : C(0)O-aryl, -C(O)O-substituted aryl, ~C(O)O-heteroaryl, -C(O)O-substituted heteroaryl, - (carboxamido)alkyl, (carbamoyl)alkyl, 5-alkyl-{1,3]dioxol-2-one-4-yl-methyl, S-alkyl- [1,3]dioxol-2-one-4-yl-methoxy-carbonyl, or —-N(R®- fragment is part of the amidine, N- cyanoamidine, N-hydroxyamidine, or N-alkoxyamidine structure;

R’ is H or alkyl,

R®, which can be singly or multiply substituted in the ring on the same or different carbons, is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, cycloalkylalkyl, substituted alkenyl, substituted oxygen, substituted nitrogen, halogen, phenyl, substituted phenyl, alkylsulfanyl, substituted alkylsulfanyl, substituted arylsulfanyl, heteroarylsulfanylalkyl, heterocyclicsulfanylalkyl, heteroarylsulfanyl, and heterocyclicsulfanyl, propylidene (=CHCH,CHj), azido, (CH2),-OH, -(CH2).-NR*R’, and branched chain isomers thereof wherein n is an integer of from 1 to 8 inclusive and R* and R® are H or alkyl, alkoxyalkoxy, aryl, substituted aryl, alkenyl, substituted alkenyl, and -S(0);R" where q is an integer equal to zero, one or two and RBs selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic and substituted heterocyclic, and wherein not more than one -S(O)(R" group is present on the nitrogen-containing ring; or a prodrug and/or pharmaceutically acceptable salt thereof.

[0008] In another one of its composition aspects, this invention is directed to a compound of Formula (IA): : (o] mt! A

R® HN/yy,, R2 lo} ou

HO “Yo

Ia) wherein: the --——-- represents a bond that may be a double bond or a single bond;

R! is selected from the group consisting of -S-alkyl, -S-substituted alkyl, hydrogen, alkyl, substituted alky), alkenyl, substituted alkenyl, alkoxy, substituted alkoxy and halo;

R? and R? are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, cyano, alkylsulfanyl, substituted alkylsulfanyl, hydroxy, halo, or one of R? and R? is =NOR” and the other is absent, or one of R? and R?® is =CH, and the other is absent;

Réis selected from the group consisting of hydrogen, alkyl, substituted alkyl, -C(0)0-alkyl, -C(O)O-substituted alkyl, -C(0)O-aryl, -C(O)O-substituted aryl,

-C(0)O-heteroaryl, -C(0)O-substituted heteroaryl, -(carboxamido)alkyl, (carbamoyl)alkyl, [+] [o] or -N(R%)- fragment is part of the amidine, N-cyanoamidine, N-hydroxyamidine, or N- alkoxyamidine structure;

Ris selected from the group consisting of hydrogen and alkyl;

R®, which can be singly or multiply substituted in the ring on the same or different carbons, is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkoxyalkoxy, cycloalkyl, substituted cycloalkyl, substituted oxygen, substituted nitrogen, halo, aryl, substituted aryl, alkenyl, substituted alkenyl, and -S(O);R"” wheregisan integer equal to zero, one or two and RY is selected from the group consisting of alkyl, So : substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted -- aryl, heteroaryl, substituted heteroaryl, heterocyclic and substituted heterocyclic; and wherein m' = 0-2; and wherein t = 0-3; or pharmaceutically acceptable salts and/or prodrugs thereof; with the following provisos:

A. that in the compounds of formula (I) when --—- is a single bond, m’ is zero or one,

R? and R? are independently hydrogen, alkyl, hydroxy, fluoro, cyanoalkyl or one of

R? and R3 is =NOR” and the other is absent, or one of R? and R® is =CH, and the other is absent,

RS is hydrogen, alkyl, hydroxyalkyl, -C(0)O-alkylene-cycloalkyl, -C(0)O-alkylene- substituted alkyl, -C(0)O-alkyl, -C(O)O-substituted alkyl, -C(O)O-aryl, -C(0)O-substituted aryl, -C(O)O-heteroaryl, -C(O)O-substituted heteroaryl, -C(O)O- heterocyclic, -C(0)O-substituted hetercyclic, -[C(0)O],-alkylene-heterocycle, ~-[C(0)O],-alkylene-substituted heterocycle, where p is zero or one, and

Ris selected from the group consisting of hydrogen and alkyl;

R’ is hydrogen, alkyl, substituted alkyl, alkoxyalkoxy, cycloalkyl, substituted cycloalkyl, substituted oxygen, substituted nitrogen, halo, phenyl, substituted phenyl, - (CH»),-OH, -(CH2)NR'R’, -alkylene-R" where R® is selected from monofluorophenyl or monochlorophenyl, and branched isomers thereof wherein # is an integer from 1to 8 inclusive and R* and R® are hydrogen or alkyl; and then R! is not —S-alkyl

B. in the compounds of formula (I), when -—--- is a single bond, oo

R? and R® are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, cyano, alkylsulfanyl, substituted alkylsulfanyl, hydroxy, halo, or one of R? and R? is =NOR” and the other is absent, or one of R? and R® is =CH, and the other is absent, with the provisos that both R? and R? are not hydrogen; when one of R? and R? is halo, the other is not hydrogen or hydroxy; and when one of R? and R® is hydroxy, the other is not hydrogen or hydroxy;

Réis selected from the group consisting of hydrogen, alkyl, substituted alkyl, ~C(0)0-alkyl, -C(0)O-substituted alkyl, -C(0)O-aryl, -C(O)O-substituted aryl, -C(0)O-heteroaryl, -C(O)O-substituted heteroaryl, -(carboxamido)alkyl, (carbamoyl)alkyl, ~~. or -N(R®)- fragment is part of the amidine, N-cyanoamidine, N-hydroxyamidine, or N- E alkoxyamidine structure;

R'is selected from the group consisting of hydrogen and alkyl; and

R! is selected from the group consisting of -S-alkyl, -S-substituted alkyl, hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy and halo; then at least one of R® is other than hydrogen, alkyl, substituted alkyl, alkoxyalkoxy, cycloalkyl, substituted cycloalkyl, substituted oxygen, substituted nitrogen, halo, phenyl, substituted phenyl, -(CHz),-OH, -(CH,).NR'R’, -alkylene-R® where R* is selected from monofluorophenyl or monochlorophenyl, and branched isomers thereof wherein » is an integer from 1 to 8 inclusive and R* and R’ are hydrogen or alkyl,

C. in the compounds of formula (I), when —--- is a single bond,

R? and R? are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, cyano, alkylsulfanyl, substituted alkylsulfanyl, hydroxy, halo, or one of R? and R® is =NOR’ and the other is absent, or one of R? and R3 is =CH, and the other is absent, with the provisos that both R? and R? are not hydrogen; when one of R?

and R’ is halo, the other is not hydrogen or hydroxy; and when one of R? and R? is hydroxy, the other is not hydrogen or hydroxy;

R'is selected from the group consisting of hydrogen and alkyl; and

R!is selected from the group consisting of -S-alkyl, -S-substituted alkyl, (heteroaryl)alkyl, hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy and halo;

R’ is independently selected from other than hydrogen, alkyl, substituted alkyl, alkoxyalkoxy, cycloalkyl, substituted cycloalkyl, substituted oxygen, substituted nitrogen, halo, phenyl, substituted phenyl, -(CHz)»-OH, oC -(CH,):NR*R’, -alkylene-R* where R® is selected from monofluorophenyl or monochlorophenyl, and branched isomers thereof wherein 7 is an integer from 1t0 8 inclusive and R* and R® are hydrogen or alkyl, then R® is selected from the group consisting of substituted alkyl (other than monosubstituted heterocycle or substituted heterocycle), (carboxamido)alkyl, and an -N(R®)- fragment that is part of an amidine, N-cyanoamidine, N- hydroxyamidine, or N-alkoxyamidine structure; wherein, as used in these provisos only, the following specific terms have the following specific meanings: substituted alkyl refers to alkyl groups wherein one or more of the hydrogen atoms has been replaced by a halogen, oxygen, hydroxy, amine (primary), amine (secondary-alkyl : substituted by alkyl as above), amine (tertiary-alkyl substituted by alkyl as defined above), sulfur, -SH or phenyl), substituted cycloalkyl refers to cycloalkyl substituted with an alkyl group, wherein alky] is as defined above or a group wherein one or more of the hydrogen atoms has been replaced by a halogen, oxygen, hydroxy, amine (primary), amine (secondary-alkyl substituted by alkyl as above), amine (tertiary-alkyl substituted by alkyl as defined above), sulfur, -SH or phenyl,

Claims

CLAIMS WHAT IS CLAIMED IS:

1. A compound of Formula (IA): (Go) 4

[0] md A Rr? HN, R2 0 HO «nr! HO KK» 1A) wherein: the ---— represents a bond that may be a double bond or a single bond; . R! is selected from the group consisting of -S-alkyl, -S-substituted alkyl, SMe, S:"" * (2-hydroxyethyl), (heteroaryl)alkyl, hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, cycloalkylalkyl, halo, and substituted alkylsulfanyl; R2 and R® are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, cyano, alkylsulfanyl, substituted alkylsulfanyl, hydroxy, halo, or one of R? and R? is =NOR and the other is absent; RSs selected from the group consisting of hydrogen, alkyl, substituted alkyl, (carboxamido)alkyl, (carbamoyl)alkyl, alkoxycarbonyl, (alkoxycarbonyDalkyl, (alkoxycarbonylamino)alkyl, or ~N(RS)- fragment is part of the amidine, N-cyanoamidine, N-hydroxyamidine, or N-alkoxyamidine structure; : R'is selected from the group consisting of hydrogen and alkyl; R®, which can be singly or multiply substituted in the ring on the same or different carbons, is independently selected from the group consisting of hydrogen, substituted alkyl, halo, substitutedalkenyl, alkenyl, (heteroarylalkenyl, and -S(O),R" where g is an integer equal to zero, one or two and RY is selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic and substituted heterocyclic; 245 i and wherein m = 0-2; and wherein t = 0-3; or pharmaceutically acceptable salts and/or prodrugs thereof; with the proviso excluding the following compounds: the compounds when ----- is a single bond and each R® is hydrogen; and the compounds when — is a single bond, R’ is substituted alkyl having a single substituent said single substituent is other than halo, oxygen, hydroxy, primary amine, amine(secondary alkyl substituted by alkyl above), amine (tertiary alkyl substituted by alkyl as above), sulfur, -SH, phenyl, or -(CH2),NR’R” where n is an integer of from 1 to 8 and R’ and R” are hydrogen or alkyl; and the compounds when -——-- is a single bond, R” is halo.

2. A compound of Formula (1A): hy al A 3 : oo L HN/py,,, 2 [o} . HO Rr! HO “Yo da) the -—-- represents a bond that may be a double bond or a single bond; Ris selected from the group consisting of -S-alkyl, -S-substituted alkyl, SMe, S- (2-hydroxyethy}), (heteroarylalkyl, hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, cycloalkylalkyl, halo, and substituted alkylsulfanyl; R? and R® are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, cyano, alkylsulfanyl, substituted alkylsulfanyl, hydroxy, halo, or one of R2 and R® is =NOR’ and the other is absent; RSis selected from the group consisting of hydrogen, alkyl, substituted alkyl, (carboxamido)alkyl, (carbamoyl)alkyl, alkoxycarbonyl, (alkoxycarbonyl)alkyl,

(alkoxycarbonylamino)alkyl, or —N(R®)- fragment is part of the amidine, N-cyanoamidine, N-hydroxyamidine, or N-alkoxyamidine structure; R'is selected from the group consisting of hydrogen and alkyl; R®, which can be singly or multiply substituted in the ring on the same or different carbons, is independently selected from the group consisting of hydrogen, substituted alkyl, halo, substitutedalkenyl, alkenyl, (heteroaryl)alkenyl, and -S(O)R"” where q is an integer equal to zero, one or two and RY is selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic and substituted heterocyclic; and wherein m = 0-2; and wherein t = 0-3; or pharmaceutically acceptable salts and/or prodrugs thereof; with the proviso excluding the following compounds: the compounds when ---—- is a single bond and each R’ is hydrogen; and the compounds when -—-- is a single bond, R’ is substituted alkyl having a single substituent said single substituent is other than halo, oxygen, hydroxy, primary amine, " amine(secondary alkyl substittited by alkyl above), amine (tertiary alkyl substituted by alkyl ~~ + as above), sulfur, -SH, phenyl, or - fo «(CH).NR’R” where n is an integer of from 1 to 8 and R’ and R” are hydrogen or alkyl; and the compounds when —-—- is a single bond, R%is halo. -

3. The compound of either Claim 1 or 2 wherein wherein the nitrogen-containing ring in Formulas (T) and (II) is selected from:

rR R® Re N N N . lh ls l R® F rR® SN N N . l, le RR F 0s ls Co a A compound selected from the group consisting of: | | BS © 1-(28)-4-(S)-(ethylthio)pyrrolidin-2-yI)}-N-{1-(R)-[2-(S), 3-(8), 4-(5), 5-R)- trihydroxy-6-(R)-(methylsulfanyl)tetrahydropyran-2-yl]-2-hydroxy-prop-1-yl} acetamide; 1-(2-(S)-4-(R)-(ethylthio)pyrrolidin-2-y1)-N-{1-(R)-[2-(8), 38), 4-(5), 5-(R)- trihydroxy-6-(R)-(methylsulfanyl)tetrahydropyran-2-yl}-2-hydroxy-prop-1-yl }acetamide; 1-(2-(S)-4-(R)-(ethylthio)pyrrolidin-2-y1)-N-{1-(R)-[2-(8), 3S), 4-(S), 5-(R)- trihydroxy-6-(R)-(methylsulfanyl)tetrahydropyran-2-yl]-2-chloro-prop-1-yl}acetamide; 1-(2-(S)-4-(S)-(ethylthio)pyrrolidin-2-y1)-N-{1-(R)-[2-(S), 38), 4-(S), 5-R)- trihydroxy-6-(R)-(methylsulfanyl)tetrahydropyran-2-yl}-2-chloro-prop-1-yl}acetamide; 1-(2-(S)-4~(S)-(3-p-fluorophenyl)thiopyrrolidin-2-y1)-N-{1-(R)-[2-(S), 38), 4S), 5- (R)-trihydroxy-6-(R)-(methylsulfanyl)tetrahydropyran-2-yl]-2-hydroxy-prop-1-yl} acetamide; 1-(2-(S)~4-(S)-(n-butylthio)pyrrolidin-2-yI)-N-{1-(R)-[2-(S), 3-8), 4-(S), 5-(R)- trihydroxy-6-(R)-(methylsulfanyl)tetrahydropyran-2-yl]-2-hydroxy-prop-1-yl } acetamide; 1-(2-(S)-4~(S)~(3,3 3-triflucroprop-1-yl-thio)pyrrolidin-2-yl)-N-{1-(R)-[2-(8), 3-(S), 4-(S), 5-(R)-trihydroxy-6-(R)-(methylsulfanyl)tetrahydropyran-2-yl]-2-hydroxy-prop-1- yl}acetamide;

1-(2-(S)-4-(S)-(2-(2-chlorophenyl)-ethylthio)pyrrolidin-2-yD-N-{1-R)-{2-(S), 3-8), 4-(S), 5.(R)-trihydroxy-6-(R)-(methylsulfany)tetrahydropyran-2-yl]-2-hydroxy-prop-1- yl}acetamide; 1-(2-(S)-4-(S)-(3-methylbut-1-ylthio)pyrrolidin-2-y1}-N-{ 1-(R)-[2-(8), 3-(S), 4-(S), 5- (R)-tribydroxy-6-(R )-(methylsulfanyl)etrahydropyran-2-yi]-2-hycroxy-prop-1-yl} acetamide; 1-(2-(S)-4-(S)-(2-ethoxythiol)-ethylthio)pyrrolidin-2-y1)-N-{1-(R)-{2-(S), 3-(8), 4-(S), 5-(R)-trihydroxy-6-(R)-(methylsulfanyl)tetrahydropyran-2-yl]-2-hydroxy-prop-1- yl}acetamide; 1-(2(S)-4-(S)-(2,2,2-rifluoroethylthio)pyrrolidin-2-y1)-N-{ 1-(R)-[2-(S), 3-(8), 4-(S), 5-(R)-trihydroxy-6-(R)-(methylsulfanyl)tetrabydropyran-2-yl]-2-hydroxy-prop-1- yl}acetamide; 1-(2-(S)-4~(S)-(m-methylphenyl)methylsulfanylpyrrolidin-2-y)-N-{1-(R)-{2-(S), 3- (S), 4-(S), 5-(R)-trihydroxy-6-(R)-(methylsulfanyl)tetrahydropyran-2-yl]-2-hydroxy-prop-1- yl}acetamide; 1-(2-(S)-4-(S)-(p-pyridinylthio)pyrrolidin-2-yI)}-N-{1-(R)-[2-(8), 3-(S), 4-(8), 5-(R)- trihydroxy-6-(R)-(methylsulfanylytetrahydropyran-2-yl]-2-hydroxy-prop-1-yl acetamide; : 1-(24S)-4-(S)-(p-trifluoromethoxyphenyl)methylsulfanyl)-N-{1-(R)-[2-(S), 3-(S), : 4-8), 5-(R)-trihydroxy-6-(R)-(methylsulfanyl)tetrahydropyran-2-yl]-2-hydroxy-prop-1- yl}acetamide; 1-(2-(S)-4-(S)-(o, p-dichlorophenyl)methylsulfanyl)-N-{1-(R)-[2-(S), 3-(S), 4-(S), 5-(R)-trihydroxy-6-(R)-(methylsulfanyl)tetrahydropyran-2-yl]-2-hydroxy-prop-1- yl }acetamide; 1-(2~(S)-4~(S)-(p-pyridinylthio)pyrrolidin-2-y)-N-{1-(R)-[2-(8), 3-(S), 4-(5), 3-(R)- trihydroxy-6-(R)-(methylsulfanyl)tetrahydropyran-2-y1]-2-hydroxy-prop-1-yl} acetamide; 4-(Thiophen-2-ylmethylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1- (3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(4-Fluoro-benzylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(4-Methyl-benzylsulfany))-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3.4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; 4«(Pyridin-2-ylmethylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide;

4-(Pyrazin-2-ylmethylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-Fluoro-4-propyl-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3 ,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(2,4-Dichloro-benzylsulfanyl)-pyrrolidine-2-carboxylic acid [2- methyl -1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl] -amide; 4-Butylsulfanyl-pyrrolidine-2-carboxylic acid [2- methyl -1-(3 ,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(3,3-Difluoro-allyl)-pyrrolidine-2-carboxylic acid [2- methyl -1-(3,4,5-trihydroxy- ’ 6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl] -amide; 1-Carbamoylmethyl-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl] -amide; : 1-Cyanomethyl-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; .. 4-(3-Pyridin-4-yl-allyl)-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- : : trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl] -amide; : : . SE 4-(3-Pyridin-4-yl-propyl)-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- : . trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; - ~~ : 1-(2-Methoxy-ethyl)-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- . trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl] -amide; 1-(1H-Imidazol-2-ylmethyl)-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1- 3 4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 1-(2-Formylamino-ethyl)-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl] -amide; 1-(2-Amino-ethyl)-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1~(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; 4-(3-Cyclobexyloxy-propyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; {2-[2-Methyl-1-(3 4 5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)- propylcarbamoyl]-4-pentyl-pyrrolidin-1 -yl}-acetic acid methyl ester; 1-Methylcarbamoylmethyl-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1- (3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide;

4-(2-[1,3]Dithiolan-2-yl-ethyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 1-Iminomethyl-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; © 4-[3-(Furan-2-ylmethylsulfanyl)-propyl}-piperidine-2-carboxylic acid [2-methyl-1- 3 ,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; : 4-(3-Imidazol-1-yl-propyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; 4-[3-(Thiophen-2-ylsulfanyl)-propyl}-piperidine-2-carboxylic acid [2-methyl-1- (3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(3-Imidazol-1-yl-propyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-[3-(2-Oxo-pyrrolidin-1-yl)-propyl]-piperidine-2-carboxylic acid [2-methyl-1- . (3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide;

: . 4-[2-(4-Methyl-thiazol-2-y1)-ethyl]-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- . + -trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide;: ~~ . : Lo a 4-(3-Methoxyimino-propyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- = trihydroxy-6-iethylsulfany)-tetrahydro-pyran-2-yl)-propyl]-amide; vo 4-[2-(4-Ethyl-thiazol-2-yl)-ethyl]-piperidine-2-carboxylic acid [2-methyl-1-3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(3-Ethylsulfanyl-propyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(3-Ethoxyimino-propyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-Pyrrol-1-ylmethyl-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 2-[2-Methyl-1-(3 ,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yi)- propylcarbamoyl}-4-propyl-piperidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester; 2-[2-Methyl-1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)- propylcarbamoy!]-4-propyl-piperidine-1-carboxylic acid ethyl ester; 4-(3-Cyano-propyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide;

2-[2-Methyl-1-(3 4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)- propylcarbamoyl]-4-propyl-piperidine-1-carboxylic acid phenyl ester; 2-[2-Methyl-1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)- propylcarbamoyl]-4-propyl-piperidine-1-carboxylic acid phenyl ester; . 4-(2-[1,2,3]Triazol-1-yl-ethyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-Propylidene-piperidine-2-carboxylic acid [2-methyl-1-(3 ,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 1-(5-Methyl-2-oxo0-[1 ,3]dioxol-4-ylmethyl)-4-propyl-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propylj-amide; 4-Fluoro-4-propyl-piperidine-2-carboxylic acid [2-methyl-1-(3 ,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; : 4-Fluoro-4-propyl-piperidine-2-carboxylic acid [2-chloro-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide;

~~. 4-Fluoro~4-propyl-pyrrolidine-2-carboxylic acid [2-chloro-1-(3,4,5-trihydroxy-6-. methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; ne -

“+... 4-Fluoro-4-propyl-pyrrolidine-2-carboxylic acid [2-chloro-1-(3,4,5-trihydroxy-6- So ~ methylsulfanyl-tetrahydro-pyran-2-yl)-propyl])-amide; ~~ - RE 4-Fluoro-4-propyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-Fluoro-4-propyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; 4-(3-Difluoromethylsulfanyl-propyl)-piperidine-2-carboxylic acid [2-chloro-1- (3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-Propyl-1,2,3,6-tetrahydro-pyridine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-Propyl-1,2,3,6-tetrahydro-pyridine-2-carboxylic acid [2-chloro-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; and 4-(3-Difluoromethylsuifanyl-propyl)-piperidine-2-carboxylic acid [2-methyl-1- (3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide. 4-Fthylsulfanyl-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrah ydro-pyran-2-yl)-propyl]-amide;

4-Ethylsulfanyl-pyrrolidine-2-carboxylic acid [2-chloro-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(4-Fluoro-phenylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5- trihydroxy-6-methylsul fanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-Butylsulfanyl-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; . 4-(3,3,3-Trifluoro-propylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1- 3 ,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(2-Chloro-benzylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(3-Methyl-butylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-[2-(2-Mercapto-ethoxy)-ethylsulfanyl]-pyrrolidine-2-carboxylic acid [2-hydroxy- 1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; : oo oo . 4+(2,2,2-Trifluoro-ethylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5 Co : trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyi]-amide; EIR UL 4-(3-Methyl-benzylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(Pyridin-4-ylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5- : trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(4-Trifluoromethoxy-benzylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1- (3,4,5-trihydroxy-6-méthylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(2,4-Dichloro-benzylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(Thiophen-2-ylmethylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1- (3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; 4-(4-Fluoro-benzylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(4-Methyl-benzylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5- trihydroxy-6-methylsuifanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(Pyridin-2-ylmethylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide;

4-(Pyrazin-2-ylmethylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-~1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl] -amide; 4-Fluoro-4-propyl-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(2,4-Dichloro-benzylsulfanyl)-pyrrolidine-2-carboxylic acid [2- methyl -1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; 4-Butylsulfanyl-pyrrolidine-2-carboxylic acid [2- methyl -1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(3,3-Difluoro-allyl)-pyrrolidine-2-carboxylic acid [2- methyl -1-(3,4,5-trihydroxy- 6-methylsuifanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 1-Carbamoylmethyl-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 1-Cyanomethyl-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; ' 4«(3-Pyridin-4-yl-allyl)-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- . oo trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; - SE - REN “5... 4-(3-Pyridin-4-yl-propyl)-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- ~~. "+ trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; + ~ « © 1-(2-Methoxy-ethyl)-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 1-(1H-Imidazol-2-ylmethyl)-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1- (3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 1-(2-Formylamino-ethyl)-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 1-(2-Amino-ethyl)-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(3-Cyclohexyloxy-propyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-~pyran-2-yl)-propyl]-amide; {2-[2-Methyl-1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)- propylcarbamoyl]-4-pentyl-pyrrolidin-1-yl}-acetic acid methyl ester; 1-Methylcarbamoylmethyl-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1- (3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 254 i

4-(2-[1,3]Dithiolan-2-yl-ethyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 1-Iminomethyl-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yI)-propyl]-amide; 4-[3-(Furan-2-ylmethylsulfanyl)-propyl]-piperidine-2-carboxylic acid [2-methyl-1-

(3.,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4~(3-Imidazol-1-yl-propyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-[3-(Thiophen-2-ylsulfanyl)-propyl}-piperidine-2-carboxylic acid [2-methyl-1- (3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(3-Imidazol-1-yl-propyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-[3-(2-Oxo-pyrrolidin-1-yl)-propyl]-piperidine-2-carboxylic acid [2-methyl-1- (3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; : 4-[2-(4-Methyl-thiazol-2-yl)-ethylj-piperidine-2-carboxylic acid [2-methyl-1-(3 4,5 . : trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; - EA or

“7. 4-(3-Methoxyimino-propyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- . °° -~ + trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; co 4-[2-(4-Ethyl-thiazol-2-yl)-ethyl]-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; oo 4-(3-Ethylsulfanyl-propyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyi-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(3-Ethoxyimino-propyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-Pyrrol-1-ylmethyl-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 2-[2-Methyl-1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)- propylcarbamoyl]-4-propyl-piperidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester; 2-[2-Methyl-1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)- propylcarbamoyl]-4-propyl-piperidine-1-carboxylic acid ethyl ester; 4-(3-Cyano-propyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; 255 ha

2-[2-Methyl-1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)- propylcarbamoyl}-4-propyl-piperidine-1-carboxylic acid phenyl ester; 2-[2-Methyl-1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)- propylcarbamoyl]-4-propyl-piperidine-1-carboxylic acid phenyl ester; ¢ 4-(2-[1,2,3]Triazol-1-yl-ethyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; 4-Propylidene-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-y!)-propyl]-amide; 1-(5-Methyl-2-oxo-[1,3]dioxol-4-ylmethyl)-4-propyl-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-Fluoro-4-propyl-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-Fluoro-4-propyl-piperidine-2-carboxylic acid [2-chloro-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; . x * 4-Fluoro-4-propyl-pyrrolidine-2-carboxylic acid [2-chloro-1-(3,4,5-trihydroxy-6- ~~ Co - methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; -- ~~ : SE Caw 4-Fluoro-4-propyl-pyrrolidine-2-carboxylic acid [2-chloro-1-(3,4,5-trihydroxy-6- = « ~-. : methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; SE ek RTI 4-Fluoro-4-propyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-Fluoro-4-propyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(3-Difluoromethylsulfanyl-propyl)-piperidine-2-carboxylic acid [2-chloro-1- (3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-Propyl-1,2,3,6-tetrahydro-pyridine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; 4-Propyl-1,2,3,6-tetrahydro-pyridine-2-carboxylic acid [2-chloro-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; and 4~(3-Difluoromethylsulfanyl-propyl)-piperidine-2-carboxylic acid [2-methyl-1- (3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide.

5. A compound of Formula (IB):

AC In . AoC |. l, HN 2 Lo} HO “HRY HO “on (IB) wherein: : R! is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, cycloalkylalkyl, halo, and substituted alkylsulfanyl; SL © R%and ®’ are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, cyano, alkylsulfanyl, substituted alkylsulfanyl, hydroxy, Co "halo, or one of R? and R* is NOR and the other is absent; Ce I Ris H, alkyl, or hydroxyalkyl; | ’ | : R’ is H or alkyl; R®, which can be singly or multiply substituted in the ring on the same or different carbons, is selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, substituted oxygen, substituted nitrogen, halogen, phenyl, substituted phenyl, (CH,),-OH, -(CHz),-NR*R, and branched chain isomers thereof wherein n is an integer of from 1 to 8 inclusive and R* and R® are H or alkyl; and mis lor2; or a prodrug and/or a pharmaceutically acceptable salt thereof; with the proviso that the compound of formula I has a minimum inhibition concentration of 32 pg/ml or less against at least one of the organisms selected from the group consisting of Streptococcus pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Enterococcus faecium, Haemophilus influenzae, Moraxella catarrhalis, Escherichia coli, Bacteroides fragilis, Bacteroides thetaiotaomicron, and Clostridium difficile.

6. A compound selected from the group consisting of: 4-Pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-tetrahydro- pyran-2-yl)-propyl]-amide; 4-Pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6-propyl- tetrahydro-pyran-2-yl)-propyl}-amide; 4-Propyl-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6-propyl- tetrahydro-pyran-2-yl)-propyl}-amide; 1-(2-Hydroxy-ethy})-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-propyl-tetrahydro-pyran-2-yl)-propyl]}-amide; 4-Propyl-piperidine-2-carboxylic acid {2-methyl-1-[3,4,5-trihydroxy-6-(2,2,2- trifluoro-ethylsulfanyl)-tetrahydro-pyran-2-yl}-propyl}-amide; 4-Pentyl-pyrrolidine-2-carboxylic acid [1-(6-butoxy-3,4,5-trihydroxy-tetrahydro- pyran-2-yl)-2-methyl-propyl]-amide; 4-Butyl-1-methyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6- + propyl-tetrahydro-pyran-2-yl)-propyl]-amide; BEES Co : SAREE

~~. Phosphoric acid mono-(4,5-dihydroxy-6-{2-methyl-1-[(4-pentyl-pymolidine-2- © . * carbonyl)-amino]-propyl } 2-propyl-tetrahydro-pyran-3-yl) ester; : SE Hexadecanoic acid 4,5-dihydroxy-6-{2-methyl-1-[(4-pentyl-pyrrolidine-2- carbonyl)-amino]-propyl}-2-propyl-tetrahydro-pyran-3-yl ester; Phosphoric acid mono-(4,5-dihydroxy-6-{2-methyl-1-[(4-propyl-pyrrolidine-2- carbonyl)-amino]-propyl}2-propyl-tetrahydro-pyran-3-yl) ester; Hexadecanoic acid 4,5-dihydroxy-6-{2-methyl-1-[(4-propyl-pyrrolidine-2- carbonyl)-amino]-propyl}-2-propyl-tetrahydro-pyran-3-yl ester; 1-(5-Methyl-2-0xo~[1,3]dioxol-4-ylmethyl)-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6-propyl-tetrahydro-pyran-2-yl)-propyl]-amide; 2-[2-Methyl-1-(3,4,5-trihydroxy-6-propyl-tetrahydro-pyran-2-yl)-propylcarbamoyl]- 4-pentyl-pyrrolidine-1-carboxylic acid 5-methyl-2-oxo0-[1,3]dioxol-4-ylmethyl ester; 1-(5-Methyl-2-ox0-[1,3]dioxol-4-ylmethyl)- 4-propyl -pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6-propyl-tetrahydro-pyran-2-yl)-propyl]-amide; 2-[2-Methyl-1-(3,4,5-trihydroxy-6-propyl-tetrahydro-pyran-2-yl)-propylcarbamoyl]- 4-propyl -pyrrolidine-1-carboxylic acid 5-methyl-2-oxo-[1,3]dioxol-4-ylmethy] ester;

PCT/US2004/019689 4- Propyl-pyrrolidine-2-carboxylic acid {2-methyl-1-[3,4,5-trihydroxy-6-)2- hydroxy-ethyl)-tetrahydro-pyran-2-yl]-propyl}-amide; 4- Propyl-pyrrolidine-2-carboxylic acid {2-methyl-1-[3,4,5-tnhydroxy-6-)3- hydroxy-propyl)-tetrahydro-pyran-2-yl]-propyl}-amide; 4- Propyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6- hydroxymethyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4- Propyl-pyrrolidine-2-carboxylic acid {2-methyl-1-[3,4,5-trihydroxy-6-(2- methylsulfanyl-ethyl)-tetrahydro-pyran-2-yl]-propyl}-amide; 4- Propyl-pyrrolidine-2-carboxylic acid [1-(6-cyclopropylmethyl-3,4,5- trihydroxy-tetrahydro-pyran-2-yl)-2-methyl-propyl]-amide; or a prodrug and/or a pharmaceutically acceptable salt thereof.

7. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of any one of claims 1, 2 or S.

8. Use of a compound of any one of claims 1, 2 or S in the manufacture of a medicament for the treatment of a microbial infection in a mammal.

9. Use of a pharmaceutical composition of claim 7 in the manufacture of a medicament for the treatment of a microbial infection in a mammal.

10. Use according to claim 8 or claim 9, wherein the medicament is administerable to the mammal orally, parenterally, transdermally, topically, rectally, or intranasally.

11. Use according to claim 8 or claim 9, wherein an effective amount of the compound is from about 0.1 to about 100 mg/kg body weight/day.

12. A compound of Formula (I): 259 AMENDED SHEET ad R? HN _2 o) ' A HO “on @ wherein: ANC haW : CL W is a nitrogen-containing ring: + R® ,mis0, 1, 2 or 3; wherein . . . whenm is 2, the nitrogen-containing ring inay optionally contain a double bond between the . : 4 and 5 nitrogen-containing ring positions; wherein when m is 3, the nitrogen-containing ring may optionally contain one double bond between either the 4 and 5 nitrogen-containing ring positions or between the 5 and 6 nitrogen-containing ring positions; wherein the nitrogen- containing ring positions are consecutively numbered counterclockwise beginning with “1” at the nitrogen;

R! is selected from the group consisting of hydrogen, alkyl, substituted alkyl, hydroxyalkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, cycloalkylalkyl, halo, alkylsulfanyl, and substituted alkylsulfanyl;

R? and R? are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, cyano, alkylsulfanyl, substituted alkylsulfanyl, hydroxy, halo, or one of R? and R? is NOR’ and the other is absent, or one of R? and R® is =CH and the other is absent;

Réis selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, cycloalkyl, substituted alkyl, iminomethyl, -C(0)O-alkyl, -C(0)O-substituted alkyl, - C(0)O-aryl, -C(O)O-substituted aryl, -C(O)O-heteroaryl, -C(O)O-substituted heteroaryl, - (carboxamido)alkyl, (carbamoylalkyl, 5-alkyl-{1,3]dioxol-2-one-4-yl-methyl, 5-alkyl-

[1,3]dioxol-2-one-4-yl-methoxy-carbonyl, or -N(R®)- fragment is part of the amidine, N- cyanoamidine, N-hydroxyamidine, or N-alkoxyamidine structure; R’isHor alkyl; R®, which can be singly or multiply substituted in the ring on the same or different carbons, is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, cycloalkylalkyl, substituted alkenyl, substituted oxygen, substituted nitrogen, halogen, phenyl, substituted phenyl, alkylsulfanyl, substituted alkylsulfanyl, substituted arylsulfanyl, heteroarylsulfanylalkyl, heterocyclicsulfanylalkyl, heteroarylsulfanyl, and heterocyclicsulfanyl, propylidene (=<CHCH,CH3), azido, -(CH2),-OH, -(CH2)n-NR*R®, and branched chain isomers thereof wherein n is an integer of from 1 to 8 inclusive and R* and R® are H or alkyl, alkoxyalkoxy, aryl, substituted aryl, alkenyl, substituted alkenyl, and -S(0),R" where q is an integer equal to zero, one or two and RB is selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, : heterocyclic and substituted heterocyclic, and wherein not more than one -S(0)R" group is . EE present on the nitrogen-containing ring; Ce. SL : : :

Ja. - and wherein t.= 0-3; Co no TE Co EA

So . ora prodrug and/or pharmaceutically acceptable salt thereof; oe with the proviso excluding the following compounds: the compounds when -—-- is a single bond and each R’ is hydrogen; and the compounds when ----- is a single bond, R’ is substituted alkyl having a single substituent said single substituent is other than halo, oxygen, hydroxy, primary amine, amine(secondary alkyl substituted by alkyl above), amine (tertiary alkyl substituted by alkyl as above), sulfur, -SH, phenyl, or ~(CH)nNR’R” where n is an integer of from 1 to 8 and R’ and R” are hydrogen or alkyl; and the compounds when --—- is a single bond, R’ is halo.

13. A compound of Formula (1A):

(GN ml A . le HN/1y,,. 2 0) HO salir! HO Kn (1A) wherein: the —-- represents a bond that may be a double bond or a single bond; R!is selected from the group consisting of -S-alkyl, -S-substituted alkyl, SMe, S- (2-hydroxyethyl), (heteroaryl)alkyl, hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, cycloalkylalkyl, halo, and substituted alkylsulfanyl; R? and R? are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted . alkenyl, alkoxy, substituted alkoxy, cyano, alkylsulfanyl, substituted alkylsulfanyl, hydroxy, :@ = . halo, or one of R? and R® is =NOR” and the other is absent; ‘ Co I : R®is selected from the group consisting of hydrogen, alkyl, substituted alkyl, :

. (carboxamido)alkyl, (carbamoyl)alkyl, alkoxycarbonyl, (alkoxycarbonyl)alkyl, - (alkoxycarbonylamino)alkyl, or -N(R®)- fragment is part of the amidine, N-cyanoamidine, : N-hydroxyamidine, or N-alkoxyamidine structure; R’ is selected from the group consisting of hydrogen and alkyl; R®, which can be singly or multiply substituted in the ring on the same or different carbons, is independently selected from the group consisting of hydrogen, substituted alkyl, halo, substitutedalkenyl, alkenyl, (heteroaryl)alkenyl, and -S(0)R" where ¢ is an integer equal to zero, one or two and R'? is selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic and substituted heterocyclic; and wherein m = 0-2; and wherein t=0-3; or pharmaceutically acceptable salts and/or prodrugs thereof; with the proviso excluding the following compounds: the compounds when ---— is a single bond and each R’ is hydrogen;

and the compounds when ----- is a single bond, R’ is substituted alkyl having a single substituent said single substituent is other than halo, oxygen, hydroxy, primary amine, amine(secondary alkyl substituted by alkyl above), amine (tertiary alkyl substituted by alkyl as above), sulfur, -SH, phenyl, or -(CH,),NR’R” where n is an integer of from 1 to 8 and R’ and R” are hydrogen or alkyl; and the compounds when ~—--- is a single bond, R’ is halo.

14. A compound of Formula (IA): R% (© { 0) R® HJ, i” ’ . .. . | . | : - | Q - A ’ : . } h © HO nIR! : (IA) : wherein: the —--- represents a bond that may be a double bond or a single bond; R'is selected from the group consisting of -S-alkyl, -S-substituted alkyl, SMe, S- (2-hydroxyethyl), (heteroaryl)alkyl, hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, cycloalkylalkyl, halo, and substituted alkylsulfanyl; R? and R® are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, cyano, alkylsulfanyl, substituted alkylsulfanyl, hydroxy, halo, or one of R? and R® is =NOR and the other is absent; R®is selected from the group consisting of hydrogen, alkyl, substituted alkyl, (carboxamido)alkyl, (carbamoyl)alkyl, alkoxycarbonyl, (alkoxycarbonyl)alkyl, (alkoxycarbonylamino)alkyl, or <N(R%)- fragment is part of the amidine, N-cyanoamidine, N-hydroxyamidine, or N-alkoxyamidine structure;

R'is selected from the group consisting of hydrogen and alkyl; R®, which can be singly or multiply substituted in the ring on the same or different carbons, is independently selected from the group consisting of hydrogen, substituted alkyl, halo, substitutedalkenyl, alkenyl, (heteroaryl)alkenyl, and -S(O),R"* where g is an integer - equal to zero, one or two and R" is selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic and substituted heterocyclic; and wherein m = 0-2; and wherein t = 0-3; or pharmaceutically acceptable salts and/or prodrugs thereof; with the proviso excluding the following compounds: the compounds when ----- is a single bond and each R’ is hydrogen; and the compounds when -—- is a single bond, R? is substituted alkyl having a single substituent said single substituent is other than halo, oxygen, hydroxy, primary amine, amine(secondary alkyl substituted by alkyl above), amine (tertiary alkyl substituted by alkyl . as above), sulfur, -SH, phenyl, or RE Ce ~(CH,).NR’R” where n is an integer of from 1 to 8 and R’ and R” are hydrogen or - alkyl; ~ : ] - : and the compounds when ———- is a single bond, R’ is halo.

15. A compound of Formula (IA): (R% [ mi! . 0 © R® HN/py,, 2 [o] HO -nliR! : HO “low Ia) wherein: the —-- represents a bond that may be a double bond or a single bond;

R! is selected from the group consisting of -S-alkyl, -S-substituted alkyl, hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy and halo; R? and R? are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, cyano, alkylsulfanyl, substituted alkylsulfanyl, hydroxy, : halo, or one of R? and R? is =NOR’ and the other is absent, or one of R? and R? is =CH, and the other is absent; Ris selected from the group consisting of hydrogen, alkyl, substituted alkyl, -C(0)0-alkyl, -C(O)O-substituted alkyl, -C(0)O-aryl, -C(O)O-substituted aryl, -C(0)O-heteroaryl, -C(O)O-substituted heteroaryl, -(carboxamido)alkyl, (carbamoyl)alkyl, [o} fo] A [e} oo he or NRY- fragment is part of the amidine, N-cyanoamidine, N-hydroxyamidine, or N- alkoxyamidine structure; R'is selected from the group consisting of hydrogen and alkyl; R®, which can be singly or multiply substituted in the ring on the same or different carbons, is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkoxyalkoxy, cycloalkyl, substituted cycloalkyl, substituted oxygen, substituted nitrogen, halo, aryl, substituted aryl, alkenyl, substituted alkenyl, and -S(0)R" where ¢q is an integer equal to zero, one or two and R" is selected from the group consisting of alkyl,

. substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic and substituted heterocyclic; and wherein m' = 0-2; and wherein t= 0-3; or pharmaceutically acceptable salts and/or prodrugs thereof; with the following provisos:

A. that in the compounds of formula (T) when -—- is a single bond, m’ is zero or one,

R2 and R® are independently hydrogen, alkyl, hydroxy, fluoro, cyanoalky! or one of R2 and R? is =NOR’ and the other is absent, or one of R? and R? is =CH; and the other is absent, RS is hydrogen, alkyl, hydroxyalkyl, -C(0)O-alkylene-cycloalkyl, -C(0)O-alkylene- substituted alkyl, -C(O)O-alkyl, -C(O)O-substituted alkyl, -C(0)O-aryl, -C(0)O-substituted aryl, -C(0)O-heteroaryl, -C(O)O-substituted heteroaryl, -C(O)O- heterocyclic, -C(O)O-substituted hetercyclic, -[C(0)O],-alkylene-heterocycle, -[C(0)O},-alkylene-substituted heterocycle, where p is zero or one, and R’ is selected from the group consisting of hydrogen and alkyl; R’ is hydrogen, alkyl, substituted alkyl, alkoxyalkoxy, cycloalkyl, substituted cycloalkyl, substituted oxygen, substituted nitrogen, halo, phenyl, substituted phenyl, - (CHa),-OH, (CH,).NR*R’, -alkylene-R® where R® is selected from monofluorophenyl or monochlorophenyl, and branched isomers thereof wherein 7 is an integer from 1 to 8 inclusive and R* and R® are hydrogen or alkyl; and then R! is not —S-alkyl,

B. in the compounds of formula (I), when -—-- is a single bond, oe . Rand R® are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted "alkenyl, alkoxy, substituted alkoxy, cyano, alkylsulfanyl, substituted alkylsilfanyl, hydroxy, "- : halo, or one of R? and R? is =NOR” and the other is absent, or one of R? and R® is =CH, and the other is absent, with the provisos that both R? and R? are not hydrogen; when one of R? and R is halo, the other is not hydrogen or hydroxy; and when one of R? and R? is hydroxy, the other is not hydrogen or hydroxy, R®is selected from the group consisting of hydrogen, alkyl, substituted alkyl, -C(0)O-alkyl, -C(O)O-substituted alkyl, -C(0)O-aryl, -C(O)O-substituted aryl, -C(0)O-heteroaryl, -C(0)O-substituted heteroaryl, -(carboxamido)alkyl, (carbamoyl)alkyl, or -N(R®)- fragment is part of the amidine, N-cyanoamidine, N-hydroxyamidine, or N- alkoxyamidine structure; R'is selected from the group consisting of hydrogen and alkyl; and R'is selected from the group consisting of -S-alkyl, -S-substituted alkyl, hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy and halo; then at least one of R® is other than hydrogen, alkyl, substituted alkyl, alkoxyalkoxy, cycloalkyl, substituted cycloalkyl, substituted oxygen, substituted nitrogen, halo, phenyl, substituted phenyl, -(CHy)o-OH, -(CH).NR*R’, 266 i

-alkylene-R* where R® is selected from monofluorophenyl or monochlorophenyl, and branched isomers thereof wherein n is an integer from 1 to 8 inclusive and R* and R® are hydrogen or alkyl,

C. in the compounds of formula (I), when ---— is a single bond, R? and R? are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, cyano, alkylsulfanyl, substituted alkylsulfanyl, hydroxy, halo, or one of R? and R? is =NOR’ and the other is absent, or one of R? and R? is =CH; and the other is absent, with the provisos that both R? and R? are not hydrogen; when one of R? and R® is halo, the other is not hydrogen or hydroxy; and when one of RZand Ris hydroxy, the other is not hydrogen or hydroxy; R'is selected from the group consisting of hydrogen and alkyl; and R'is selected from the group consisting of -S-alkyl, -S-substituted alkyl, (heteroaryl)alkyl, hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy and halo; : R? is independently selected from other than hydrogen, alkyl, substituted alkyl, . alkoxyalkoxy, cycloalkyl, substituted cycloalkyl, substituted oxygen, substituted nitrogen, Le ... halo, phenyl, substituted phenyl, -(CH,),-OH, Co WL no + «(CHa)NRR’, -alkylene-R® where R? is selected from monofluorophenyl or. EN monochlorophenyl, and branched isomers thereof wherein # is an integer from 1 to 8 : inclusive and R* and R® are hydrogen or alkyl, then R®is selected from the group consisting of substituted alkyl (other than monosubstituted heterocycle or substituted heterocycle), A ~ | — (carboxamido)alkyl, and an ~N(R®)- fragment that is part of an amidine, N-cyanoamidine, N- hydroxyamidine, or N-alkoxyamidine structure; wherein, as used in these provisos only, the following specific terms have the following specific meanings:

, substituted alkyl refers to alkyl groups wherein one or more of the hydrogen atoms has been replaced by a halogen, oxygen, hydroxy, amine (primary), amine (secondary-alkyl substituted by alkyl as above), amine (tertiary-alkyl substituted by alkyl as defined above), sulfur, -SH or phenyl), substituted cycloalkyl refers to cycloalkyl substituted with an alky! group, wherein alkyl is as defined above or a group wherein one or more of the hydrogen atoms has been replaced by a halogen, oxygen, hydroxy, amine (primary), amine (secondary-alkyl substituted by alkyl as above), amine (tertiary-alkyl substituted by alkyl as defined above), sulfur, -SH or phenyl, substituted oxygen refers to the group —OR! where R! is alkyl, haloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, allkenyl, cycloalkyl, and substituted cycloalkyl, substituted nitrogen or amino refers to the group ~NR°R® wherein R® and R® are independently hydrogen, alkyl, haloalkyl, alkenyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl and substituted heteroaryl, SE

: . + substituted aryl refers to an aryl ring substituted with one or more substituents I , : selected from the group consisting of alkyl, alkenyl, alkynyl, halo, alkoxy, acyloxy, amino, = : hydroxy, carboxy, cyano, nitro, alkylthio and thioalkyl where alkyl thio refers to the group— =: : S-alkyl and thioalkyl refers to an alkyl group having one or more —SH groups, and substituted heteroaryl refers to a heteroaryl ring substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, alkynyl, halo, alkoxy, acyloxy, amino, hydroxy, carboxy, cyano, nitro, alkylthio and thioalkyl where alkyl thio refers to the group —S-alkyl and thioalkyl refers to an alkyl group having one or more ~SH groups.

16. The compound of any of the Claims 12-15 wherein the nitrogen-containing ring in Formulas (I) and (IA) is selected from:

RR rR R® ; R? of OL TL 0 R® L Re Re oe F ’ R? Jot . Re Re | ¥

17. A compound of Formula (IB): ; RY oo ~N hn o . E

-. EOL LE N° : — RR. at LL - . . eo Lo le HN R? . -

Q . HO -eattiRY (IB) wherein: R! is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, cycloalkylalkyl, halo, and substituted alkylsulfanyl; R? and R? are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, cyano, alkylsulfanyl, substituted alkylsulfanyl, hydroxy, halo, or one of R? and R? is =NOR’ and the other is absent; Réis H, alkyl, or hydroxyalkyl;

Ris H or alkyl; R®, which can be singly or multiply substituted in the ring on the same or different carbons, is independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, substituted oxygen, substituted nitrogen, halogen, phenyl, substituted phenyl, -(CHz)s-OH, -(CH2),-NR*R’, and branched chain isomers thereof wherein n is an integer of from 1 to 8 inclusive and R* and R’ are H or alkyl; and mis1or2; or prodrugs and/or pharmaceutically acceptable salts thereof.

18. A compound of Formula (II): [o) wW—_/ rR? R% HN } vo | ‘HOM Co yesR? : : : nd “on 1y wherein: Ng ml P= W is a nitrogen-containing ring: RE ,mis 0,1, 2, or 3; wherein when m is 2, the nitrogen-containing ring may optionally contain a double bond between the 4 and 5 nitrogen-containing ring positions; wherein when m is 3, the nitrogen-containing ring may optionally contain one double bond between either the 4 and 5 nitrogen-containing ring positions or between the 5 and 6 nitrogen-containing ring positions; wherein the nitrogen- containing ring positions are consecutively numbered counterclockwise beginning with “1” at the nitrogen;

R! is selected from the group consisting of hydrogen, alkyl, substituted alkyl, hydroxyalkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, cycloalkylalkyl, halo, alkylsulfanyl, and substituted alkylsulfanyl; R? and R? are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, cyano, alkylsulfanyl, substituted alkylsulfanyl, hydroxy, halo, or one of R% and R? is =NOR’ and the other is absent, or one of R”’ and R*! is =CH, and the other is absent; or R%’ and R?' taken together are cycloalkyl, aryl, or heterocyclic group; R®is selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, cycloalkyl, substituted alkyl, iminomethyl, -C(O)O-alkyl, -C(O)O-substituted alkyl, - C(0)O-aryl, -C(O)O-substituted aryl, -C(0)O-heteroaryl, -C(0)O-substituted heteroaryl, - (carboxamido)alkyl, (carbamoyl)alkyl, 5-alkyl-{1,3]dioxol-2-one-4-yl-methyl, S-alkyl- [1,3]dioxol-2-one-4-yl-methoxy-carbonyl, or N(R®)- fragment is part of the amidine, N- cyanoamidine, N-hydroxyamidine, or N-alkoxyamidine structure; R’ is H or alkyl; R®, which can be singly or multiply substituted in the ring on the same or different :

i . carbons, is independently selected from the group consisting of hydrogen, alkyl, substituted ~~ ~~ , alkyl, cycloalkyl, substituted cycloalkyl, cycloalkylalkyl, substituted alkenyl, substituted

. oxygen, substituted nitrogen, halogen, phenyl, substituted phenyl, alkylsulfanyl, substituted alkylsulfanyl, substituted arylsulfanyl, heteroarylsulfanylalkyl, heterocyclicsulfanylalkyl, heteroarylsulfanyl, and heterocyclicsulfanyl, propylidene (FCHCH,CHs), azido, -(CHz)»-OH, -(CH2),"NR'R’, and branched chain isomers thereof wherein n is an integer of from 1 to 8 inclusive and R* and R® are H or alkyl, alkoxyalkoxy, aryl, substituted aryl, alkenyl, substituted alkenyl, and -S(O)R"™ where g is an integer equal to zero, one or two and RBis selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic and substituted heterocyclic, and wherein not more than one -S(0)R® group is present on the nitrogen-containing ring; or a prodrug and/or pharmaceutically acceptable salt thereof.

19. A compound selected from the group consisting of:

4-(Thiophen-2-ylmethylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1- 3 4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(4-Fluoro-benzylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-y1)-propyl]-amide; . 4-(4-Methyl-benzylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5- trihydroxy-6-methylsulfany-tetrahydro-pyran-2-yl)-propyl}-amide; : 4-(Pyridin-2-ylmethylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(Pyrazin-2-ylmethylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-Fluoro-4-propyl-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(2,4-Dichloro-benzylsulfanyl)-pyrrolidine-2-carboxylic acid [2- methyl -1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; : 4-Butylsulfanyl-pyrrolidine-2-carboxylic acid [2- methyl -1-(3,4,5 -trihydroxy-6- : méthylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; TL NE Co Lo oo 4-(3,3-Difluoro-allyl)-pyrrolidine-2-carboxylic acid [2- methyl -1-(3,4,5-trihydroxy- a 6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; - - . 1-Carbamoylmethyl-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- : trihydroxy-6-methylsulfany-tetrahydro-pyran-2-yl)-propyl]-amide; 1-Cyanomethyl-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyi]-amide; 4-(3-Pyridin-4-yl-allyl)-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(3-Pyridin-4-yl-propyl)-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 1-(2-Methoxy-ethyl)-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 1-(1H-Imidazol-2-ylmethyl)-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1- (3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; 1-(2-Formylamino-ethyl)-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide;

1-(2-Amino-ethyl)-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(3-Cyclohexyloxy-propyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; {2-[2-Methyl-1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)- propylcarbamoyl]-4-pentyl-pyrrolidin-1-yl}-acetic acid methyl ester; 1-Methylcarbamoylmethyl-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1- (3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(2-[1,3]Dithiolan-2-yl-ethyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 1-Iminomethyl-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-[3-(Furan-2-ylmethylsulfanyl)-propyl]}-piperidine-2-carboxylic acid [2-methyl-1- (3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(3-Imidazol-1-yl-propyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- . + trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; IEEE vo '4-[3-(Thiophen-2-ylsulfanyl)-propyl]-pipetidine-2-carboxylic acid [2-methyl-1- - ++ (3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; : IE 4-(3-Imidazol-1-yl-propyl)-piperidine-2-carboxylic acid [2-methyl-1-3,4,5- - . = trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-[3-(2-Oxo-pyrrolidin-1-yl)-propyl]-piperidine-2-carboxylic acid [2-methyl-1- (3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; 4-[2-(4-Methyl-thiazol-2~yl)-ethyl]-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; 4-(3-Methoxyimino-propyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-[2-(4-Ethyl-thiazol-2-yl)-ethyl]-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(3-Ethylsulfanyl-propyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- tribydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(3-Ethoxyimino-propyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide;

4-Pyrrol-1-ylmethyl-piperidine-2-carboxylic acid [2-methyl-1-(3 ,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 2-[2-Methyl-1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)- propylcarbamoyl]-4-propyl-piperidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester; : 2-[2-Methyl-1-(3 4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)- propylcarbamoyl]-4-propyl-piperidine-1-carboxylic acid ethyl ester; 4-(3-Cyano-propyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; 2-[2-Methyl-1-(3 4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)- propylcarbamoyl]-4-propyl-piperidine- 1-carboxylic acid phenyl ester; 2-{2-Methyl-1-(3 4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)- propylcarbamoyl]-4-propyl-piperidine- 1-carboxylic acid phenyl ester; 4-(2-[1,2,3]Triazol-1-yl-ethyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyi-tetrahydro-pyran-2-yl)-propyl}-amide; 4-Propylidene-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6- . methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; Sem x .. 1«5-Methyl-2-oxo-[1,3]dioxol-4-ylmethyl)-4-propyl-piperidine-2-carboxylic.acid - a. [2-methyl-1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; : . 4-Fluoro-4-propyl-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6- - methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; : : 4-Fluoro-4-propyl-piperidine-2-carboxylic acid [2-chloro-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-Fluoro-4-propyl-pyrrolidine-2-carboxylic acid [2-chloro-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; 4-Fluoro-4-propyl-pyrrolidine-2-carboxylic acid [2-chloro-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; 4-Fluoro-4-propyl-pyrrolidine-2-carboxylic acid {2-methyl-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; 4-Fluoro-4-propyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; 4-(3-Difluoromethylsulfanyl-propyl)-piperidine-2-carboxylic acid [2-chloro-1- (3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide;

4-Propyl-1,2,3,6-tetrahydro-pyridine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; 4-Propyl-1,2,3,6-tetrahydro-pyridine-2-carboxylic acid [2-chloro-1-(3,4,5- . trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; and - 4-(3 -Difluoromethylsulfanyl-propyl)-piperidine-2-carboxylic acid [2-methyl-1- (3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide. 4-Ethylsulfanyl-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3 ,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-Ethylsulfanyl-pyrrolidine-2-carboxylic acid [2-chloro-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4~(4-Fluoro-phenylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3 ,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-Butylsulfanyl-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5 -trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide;

Lo . 4+(3,3,3-Trifluoro-propylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1- - + (3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; Coe wo. ov. 4-(2-Chloro-benzylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3 4,5-

¥ .* trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; : 4-(3-Methyl-butylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5- : trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-]2-(2-Mercapto-ethoxy)-ethylsulfanyl]-pyrrolidine-2-carboxylic acid [2-hydroxy- 1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(2,2,2-Trifluoro-ethylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(3-Methyl-benzylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(Pyridin-4-ylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5- trihydroxy-6-methylsulfanyi-tetrahydro-pyran-2-yl)-propyl}-amide; 4~(4-Trifluoromethoxy-benzylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1- (3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(2,4-Dichloro-benzylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; ’ 275 i

4-(Thiophen-2-ylmethylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1- (3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; 4-(4-Fluoro-benzylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; 4-(4-Methyl-benzylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; 4-(Pyridin-2-ylmethylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; 4-(Pyrazin-2-ylmethylsulfanyl)-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; 4-Fluoro-4-propyl-pyrrolidine-2-carboxylic acid [2-hydroxy-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yli)-propyl]-amide; 4-(2,4-Dichloro-benzylsulfanyl)-pyrrolidine-2-carboxylic acid [2- methyl -1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; : 4-Butylsulfanyl-pyrrolidine-2-carboxylic acid [2- methyl -1-(3,4,5-trihydroxy<6- + - methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; Pilon . cy

=. ..-4-3,3-Difluoro-allyl)-pyrrolidine-2-carboxylic acid [2- methyl -1-(3,4,5-trihydroxy- .<.. = 6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; : : ) wo 1-Carbamoylmethyl-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 1-Cyanomethyl-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]}-amide; 4-(3-Pyridin-4-yl-allyl)-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4~(3-Pyridin-4-yl-propyl)-pyrrolidine-2-carboxylic acid [2-methyl-1-(3.4,5- : trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 1-(2-Methoxy-ethyl)-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 1-(1H-Imidazol-2-ylmethyl)-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1- (3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 1-(2-Formylamino-ethyl)-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide;

1-(2-Amino-ethyl)-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; 4-(3-Cyclohexyloxy-propyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; {2-[2-Methyl-1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)- propylcarbamoyl]-4-pentyl-pyrrolidin-1-yl}-acetic acid methyl ester; : 1-Methylcarbamoylmethyl-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1- (3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(2-[1 3]Dithiolan-2-yl-ethyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 1-Iminomethyl-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfany)-tetrahydro-pyran-2-yl)-propyl]-amide; 4-[3-(Furan-2-ylmethylsulfanyl)-propyl]-piperidine-2-carboxylic acid [2-methyl-1- ) (3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; . 4-(3-Imidazol-1-yl-propyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- . trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; x Coo . CL 4-[3-(Thiophen-2-ylsulfanyl)-propyl]-piperidine-2-carboxylic acid [2-methyl-1- . : - . (3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; : . 4-(3-Imidazol-1-yl-propyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-[3~(2-Oxo-pyrrolidin-1-yl)-propyl]-piperidine-2-carboxylic acid [2-methyl-1- (3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-[2-(4-Methyl-thiazol-2-yl)-ethyl]-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(3-Methoxyimino-propyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylisulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-[2-(4-Ethyl-thiazol-2-yl)-ethyl]-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(3-Ethylsulfanyl-propyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(3-Ethoxyimino-propyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide;

4-Pyrrol-1-ylmethyl-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; 2-[2-Methyl-1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)- propylcarbamoy1]-4-propyl-piperidine-1-carboxylic acid SH-fluoren-9-ylmethyl ester; 2-[2-Methyl-1-(3 4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)- propylcarbamoyl]-4-propyl-piperidine-1-carboxylic acid ethyl ester; 4-(3-Cyano-propyl)-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; 2-[2-Methyl-1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-y1)- propylcarbamoyl}-4-propyl-piperidine-1-carboxylic acid phenyl ester; 2-[2-Methyl-1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)- propylcarbamoyl]-4-propyl-piperidine-1-carboxylic acid phenyl ester; 4-(2-[1,2,3]Triazol-1-yl-ethyl)-piperidine-2-carboxylic acid [2-methyl-1-3,4,5- trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; : : ~ 4-Propylidene-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6- Co . +. - methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; . ~~ ~~. + . Vr oe ~ + + + 1-(5-Methyl-2-0x0-[1,3]dioxol-4-ylmiethyl)-4-propyl-piperidine-2-carboxylic acid qe - [2-inethyl-1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; . ~~ =» - 4-Fluoro-4-propyl-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-Fluoro-4-propyl-piperidine-2-carboxylic acid [2-chloro-1-(3,4,5-trihydroxy-6- : methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-Fluoro-4-propyl-pyrrolidine-2-carboxylic acid [2-chloro-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-Fluoro-4-propyl-pyrrolidine-2-carboxylic acid [2-chloro-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-Fluoro-4-propyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-Fluoro-4-propyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6- methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-(3-Difluoromethylsulfanyl-propyl)-piperidine-2-carboxylic acid [2-chloro-1- (3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide;

4-Propyl-1,2,3 6-tetrahydro-pyridine-2-carboxylic acid [2-methyl-1-(3,4.5- trihydroxy-6-methylsulfany -tetrahydro-pyran-2-yl)-propyl]-amide; 4-Propyl-1,2,3 6-tetrahydro-pyridine-2-carboxylic acid [2-chloro-1-(3,4,3- tribydroxy-6-mefhylsulfanyl-tetrahydro-pyran-2-yl)-propyl -amide; 3-(3 _Cyclobutyl-propyl)-azetidine-2-carboxylic acid [2-chloro-1-(3 ,4,5-trihydroxy- 6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide 4-(3-Difluoromethylsulfanyl-propyl)-piperidine-2-carboxylic acid [2-methyl-1- ~

3 4.5-trihydroxy-6-methylsulfany}-tetrahydro-pyran-2:y1)-propyl-amide; and : 4-(2-Cyclopropyl-ethyl)-piperidine-2-carboxylic acid [2-chloro-1-(3 ,4,5-trihydroxy- 6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl]-amide

20. A compound selected from the group consisting of: Phosphoric acid mono-(6- (2-chloro-1-[(5-propyl-azepane-2-carbonyl)-aminol- propyl} 4 5-dihydroxy-2-methylsulfanyl-tetrahydro-pyran-3-y1) ester; - Phosphoric acid mono~(6- {2-chloro-1-[(5-fluoro-5-propyl-azepane-2-carbonyl)- g - . .-- amino] _propyl}-4,5-dihydroxy-2-methylsulfanyl-tetrahydro-pyran-3 -yD ester; ~ wo Co Phosphoric acid mono-(6- (2-chloro-1-[(5-cyclopropylmethyl-azepane-2-carbonyl)- : oo i. amino]-propyl}-4,5-dihydroxy-2-methylsulfanyl-tetrahtydro-pyran-3 ylester; + © Phosphoric acid mono-(6-{2-chloro-1 [(4-fluoro-4-propyl-piperidine-2-carbonyl)- amino)-propyl}-4,5 dihydroxy-2-methylsulfanyl-tetrahydro-pyran-3 -yl) ester; Hexadecanoic acid 6- {2-chloro-1-[(5-propyl-azepane-2-carbonyl)-amino]-propyl}- 4 5-dihydroxy-2-methylsulfany}-tetrahydro-pyran-3 -yl ester; Hexadecanoic acid 6-{2-chloro-1 _{(5-fluoro-5-propyl-azepane-2-carbonyl)-amino}- propyl}-4,5 dihydroxy-2-methylsulfanyl-tetrahydro-pyran-3-yl ester; Hexadecanoic acid 6-{2-chloro-1 [(5-cyclopropylmethyl-azepane-2-carbonyl)- amino]-propyl}4,5-dihydroxy-2-methylsulfanyl-tetrahydro-pyran-3 -yl ester; Hexadecanoic acid 6- (2-chioro-1-{(4-fluoro-4-propyl-piperidine-2-carbonyl)-amino]- propyl} 4, 5-dihydroxy-2-methylsulfanyl-tetrahydro-pyran-3 -yl ester.

21. A compound selected from the group consisting of: 2-[2-Chloro-1-(3 4 5-trihydroxy-6-methylsulfany)-tetrahydro-pyran-2-y)- propylcarbamoyl]-5-propyl-azepane-1-carboxylic acid 5-methyl-2-oxo-[1,3]dioxol-4- ylmethyl ester;

2-[2-Chloro-1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)- propylcarbamoyl]-5-fluoro-5-propyl-azepane-1-carboxylic acid 5-methyl-2-oxo-[1,3]dioxol- 4-ylmethyl ester; : 5-Fluoro-1-(5-methyl-2-oxo-[1,3]dioxol-4-ylmethyl)-5-propyl-azepane-2-carboxylic ~~ - acid [2-chloro-1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)-propyl}-amide; 5-Cyclopropylmethyl-1-(5-methyl-2-oxo-{1,3]dioxol-4-ylmethyl)-azepane-2- carboxylic acid [2-chloro-1-(3,4,5 -trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)- : propyl]-amide; 2-[2-Chloro-1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)- propylcarbamoyl]-5-cyclopropylmethyl-azepane-1-carboxylic acid 5-methyl-2-oxo-~ [1,3]dioxol-4-ylmethy] ester; 2-[2-Chloro-1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)- propylcarbamoyl}-4-fluoro-4-propyl-piperidine- 1-carboxylic acid 5-methyl-2-oxo- [1,3)dioxol-4-ylmethyl ester; : .4-Fluoro-1-(5-methyl-2-0x0-[1,3]dioxol-4-ylmethyl)-4-propyl-piperidine-2- : - carboxylic acid [2-chloro-1-(3,4,5-trihydroxy-6-methylsulfanyl-tetrahydro-pyran-2-yl)- ~~ . ie ©. propyl]-amide;: EE RAEI Le we x

22. A compound of Formula (IB): Rr? Ths N R® I, HN R2 0] HO TY HE “on B) wherein:

R! is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, cycloalkylalkyl, halo, and substituted alkylsulfanyl; R? and R? are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted : alkenyl, alkoxy, substituted alkoxy, cyano, alkylsulfanyl, substituted alkylsulfanyl, hydroxy, halo, or one of R? and R® is =NOR” and the other is absent; Réis H, alkyl, or hydroxyalkyl; ' R’ is H or alkyl; R?, which can be singly or multiply substituted in the ring on the same or different carbons, is selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, substituted oxygen, substituted nitrogen, halogen, phenyl, substituted phenyl, (CHa),-OH, -(CHy),-NR*R’, and branched chain isomers thereof wherein n is an integer of from 1 to 8 inclusive and R* and R® are H or alkyl; and mis lor2; } : : or a prodrug and/or a pharmaceutically acceptable salt thereof; Ce

Co .-+ with the proviso that the compound of formula I has a minimum inhibition Ea . concentration of 32 pg/ml. or less against at least one of the organisms selected fromthe ~~ ~~ : group consisting of Streptococcus pneumoniae, Staphylococcus aureus, Staphylococcus + epidermidis, Enterococcus faecalis, Enterococcus faecium, Haemophilus influenzae, Moraxella catarrhalis, Escherichia coli, Bacteroides fragilis, Bacteroides thetaiotaomicron, and Clostridium difficile.

23. A compound selected from the group consisting of: 4-Pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-tetrahydro- pyran-2-yl)-propyl]-amide; 4-Pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6-propyl- tetrahydro-pyran-2-yl)-propyl]-amide; 4-Propyl-piperidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6-propyl- tetrahydro-pyran-2-yl)-propyl]-amide; 1-(2-Hydroxy-ethyl)-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5- trihydroxy-6-propyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-Propyl-piperidine-2-carboxylic acid {2-methyl-1-[3,4,5-trihydroxy-6-(2,2,2- trifluoro-ethylsulfanyl)-tetrahydro-pyran-2-yl}-propyl} -amide;

4-Pentyl-pyrrolidine-2-carboxylic acid [1-(6-butoxy-3,4,5-trihydroxy-tetrahydro- pyran-2-yl)-2-methyl-propyl}-amide; 4-Butyl-1-methyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6- propyl-tetrahydro-pyran-2-yl)-propyl]-amide; Phosphoric acid mono-(4,5-dihydroxy-6-{2-methyl-1-[(4-pentyl-pyrrolidine-2- carbonyl)-amino}-propyl}2-propyl-tetrahydro-pyran-3-yl) ester; Hexadecanoic acid 4,5-dihydroxy-6-{2-methyl-1-[(4-pentyl-pyrrolidine-2- carbonyl)-amino]-propyl}-2-propyl-tetrahydro-pyran-3-yl ester; Phosphoric acid mono-(4,5-dihydroxy-6-{2-methyl-1-[(4-propyl-pyrrolidine-2- carbonyl)-amino]-propyl}2-propyl-tetrahydro-pyran-3-yl) ester; Hexadecanoic acid 4,5-dihydroxy-6-{2-methyl-1-[(4-propyl-pyrrolidine-2- carbonyl)-amino]-propyl }-2-propyl-tetrahydro-pyran-3-yl ester; 1-(5-Methyl-2-ox0-[1,3]dioxol-4-ylmethyl)-4-pentyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6-propyl-tetrahydro-pyran-2-yl)-propyl]-amide;

RE . 2-[2-Methyl-1-(3,4,5-trihydroxy-6-propyl-tetrahydro-pyran-2-yl)-propylcarbamoyl]- . + + 4-pentyl-pyrrolidine-1-carboxylic acid 5-methyl-2-oxo-[1,3]dioxol-4-ylmethyl ester; PEI 1(5-Methyl-2-oxo-[1,3]dioxol-4-ylmethyl)- 4-propyl -pyrrolidine-2-carboxylic acid

; .* [2-methyl-1-(3,4,5-trihydroxy-6-propyl-tetrahydro-pyran-2-yl)-propyl]-amide; 2-[2-Methyl-1-(3,4,5-trihydroxy-6-propyl-tetrahydro-pyran-2-yl)-propylcarbamoyl}- 4-propyl -pyrrolidine-1-carboxylic acid 5-methyl-2-oxo-[1,3]dioxol-4-ylmethy] ester; 4-Propyl-pyrrolidine-2-carboxylic acid {2-methyl-1-[3,4,5-trihydroxy-6-(2- hydroxy-ethyl)-tetrahydro-pyran-2-yl]-propyl } -amide; 4-Propyl-pyrrolidine-2-carboxylic acid {2-methyl-1-[3,4,5-trihydroxy-6-(3- hydroxy-propyl)-tetrahydro-pyran-2-yl]-propyl} -amide; 4-Propyl-pyrrolidine-2-carboxylic acid [2-methyl-1-(3,4,5-trihydroxy-6- hydroxymethyl-tetrahydro-pyran-2-yl)-propyl]-amide; 4-Propyl-pyrrolidine-2-carboxylic acid {2-methyl-1-[3,4,5-trihydroxy-6-(2- methylsulfanyl-ethyl)-tetrahydro-pyran-2-yl]-propyl } -amide; 4-Propyl-pyrrolidine-2-carboxylic acid [1-(6~cyclopropylmethyl-3,4,5-trihydroxy- tetrahydro-pyran-2-yl)-2-methyl-propyl]-amide, or a prodrug and/or a pharmaceutically acceptable salt thereof.

PCT/US2004/019689

24. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of any one of claims 12- 23,

25. Use of a compound of any one of claims 12-23 in the manufacture of a medicament for the treatment of a microbial infection in a mammal.

26. Use of a pharmaceutical composition of claim 24 in the manufacture of a medicament for the treatment of a microbial infection in a mammal.

27. Use according to claim 25 or claim 26 for the treatment of a microbial infection caused by any of the following bacterial pathogens: H. influenzae, E. faecalis, and E. faecium.

28. Use according to any one of claims 25 to 27, wherein the medicament is administerable to the mammal orally, parenterally, transdermally, topically, rectally, or intranasally.

29. Use according to any one of claims 25 to 27, wherein an effective amount of the compound is from about 0.1 to about 100 mg/kg body weight/day.

30. A substance or composition for use in a method for the treatment of a microbial infection in a mammal, said substance or composition comprising a compound of any one of claims I, 2, 5 or 12 - 23, and said method comprising administering to the mammal a therapeutically effective amount of said substance or composition.

31. A substance or composition for use in a method of treatment according to claim 30, wherein said substance or composition is administered to the mammal orally, parenterally, transdermally, topically, rectally, or intranasally.

32. A substance or composition for use in a method of treatment according to claim 30, wherein an effective amount of said compound is from about 0.1 to about 100 mg/kg body weight/day. 283 AMENDED SHEET :

PCT/US2004/019689

33. A compound of any one of claims 1 to 6 or 12 to 23, substantially as herein described and illustrated.

34. A composition of claim 7 or claim 24, substantially as herein described and illustrated.

35. Use of any one of claims 8 to 11 or 25 to 29, substantially as herein described and illustrated.

36. A substance or composition for use in a method of treatment of any one of claims 30 to 32, substantially as herein described and illustrated.

37. A new compound, a new composition, a new use of a compound of any one of claims 1, 2, 5 or 12 to 23, or a substance or composition for a new use in a method of treatment, substantially as herein described. 284 AMENDED SHEET