US 8,076,301 B2Granted

10-substituted macrolide antibiotics

AssigneeC10 Pharma AS

InventorsKjell Undheim, Solvi Gunnes

Life of this patent

Estimating the term…

Abstract

Disclosed herein are 10-desmethyl, 10 substituted-macrolides, their preparation, pharmaceutical compositions containing them, their use and methods of treatment using them. The 10-desmethyl macrolides are particularly useful as antibiotics.

Claims3

Dependent claims

A 10-substituted-10-desmethyl macrolide of formula II, IV or V

wherein R is selected from the group consisting of
(1) methyl substituted with one or more substituents selected from the group consisting of
(i) CN,
(ii) F,
(iii) CO2R3 wherein R3 is selected from hydrogen, C1-C3-alkyl or aryl substituted C1-C3-alkyl, or heteroaryl substituted C1-C3-alkyl,
(iv) OR4 wherein R4 is selected from hydrogen, C1-C4-alkyl or aryl substituted C1-C4-alkyl, or heteroaryl substituted C1-C4-alkyl, heterocycloalkyl and optionally substituted cycloalkyl, C1-C3-alkoxy-C1-C3-alkoxy, C2-C4-alkenyl or aryl substituted C2-C4-alkenyl, or heteroaryl substituted C2-C4-alkenyl, heterocycloalkyl and optionally substituted cycloalkyl, aryl or optionally substituted aryl, heteroaryl or optionally substituted heteroaryl,
(v) S(O)nR3 wherein n=0, 1 or 2 and R3 is as previously defined
(vi) NR4C(O)R3 wherein R3 and R4 are as previously defined
(vii) NR4C(O)NR5R6 wherein R4 is defined as defined previously, and R5 and R6 are independently selected from hydrogen, C1-C3-alkyl, C1-C3 alkyl substituted with aryl, substituted aryl, heteroaryl, substituted heteroaryl
(viii) NR7R8 wherein R7 and R8 are independently selected from the group consisting of
(a) hydrogen
(b) C1-C12-alkyl, and optionally substituted C1-C12-alkyl
(c) C2-C12-alkenyl, and optionally substituted C2-C12-alkenyl
(d) C2-C12-alkynyl, and optionally substituted C2-C12-alkynyl
(e) aryl, and optionally substituted aryl
(f) heteroaryl, and optionally substituted heteroaryl
(g) heterocycloalkyl, and optionally substituted heterocycloalkyl
(h) C1-C12 alkyl substituted with aryl, and optionally substituted with substituted aryl
(i) C1-C12 alkyl substituted with heteroaryl, and optionally substituted with substituted heteroaryl
(j) C1-C12 alkyl substituted with heterocycloalkyl, and with optionally substituted heterocycloalkyl, and
(k) R7 and R8 taken together with the atom to which they are attached form a 3-10-membered heterocycloalkyl ring which may contain one or more additional heteroatoms and may be substituted with one or more substituents independently selected from the group consisting of
(aa) halogen, hydroxy, C1-C3-alkoxy, alkoxy-C1-C3- alkoxy, oxo, C1-C3-alkyl, aryl and optionally substituted aryl, heteroaryl and optional substituted heteroaryl
(bb) CO2R3 wherein R3 is as previously defined, and
(cc) C(O)NR5R6 wherein R5 and R6 are as previously defined,
(ix) aryl, and optionally substituted aryl, and
(x) heteroaryl, and optionally substituted heteroaryl,
(2) C2-C10-alkyl,
(3) C2-C10-alkyl substituted with one or more substituents selected from the group consisting of
(i) halogen,
(ii) OR4 wherein R4 is as defined previously
(iii) —CHO,
(iv) oxo,
(v) NR7R8 wherein R7 and R8 are defined as previously
(vi) ═N—O—R4 is wherein R3 is as previously defined
(vii) —CN
(viii) —S(O)nR3 wherein n=0, 1 or 2 and R3 is as previously defined
(ix) aryl, and optionally substituted aryl
(x) heteroaryl, and optionally substituted heteroaryl
(xi) C3-C8-cycloalkyl, and optionally substituted C3-C8-cycloalkyl
(xii) heterocycloalkyl, and optionally substituted heterocycloalkyl
(xiii) NR4C(O)R3 where R3 and R4 are as previously defined
(xiv) NR4C(O)NR5R6 wherein R4, R5 and R6 are as previously defined
(xv) ═N—NR7R8 wherein R7 and R8 are as previously defined
(xvi) ═N—R4 wherein R4 is as previously defined
(xvii) ═N—NR4C(O)R3 wherein R3 and R4 are as previously defined, and
(xviii) ═N—NR4C(O)NR5R6 wherein R4, R5 and R6 are as previously defined,
(4) C2-C10-alkenyl,
(5) C2-C10-alkenyl substituted with one or more substituents selected from the group consisting of
(i) halogen,
(ii) OR4 wherein R4 is as previously defined
(iii) O—S(O)nR3 where n and R3 are as previously defined
(iv) —CHO,
(v) oxo,
(vi) —CO2R3 where R3 is as previously defined
(vii) —C(O)—R4 where R4 is as previously defined
(viii) —CN
(ix) aryl, and optionally substituted aryl
(x) heteroaryl, and optionally substituted heteroaryl
(xi) C3-C7-cycloalkyl
(xii) C1-C12-alkyl substituted with heteroaryl
(xiii) NR7R8 wherein R7 and R8 are as previously defined
(xiv) NR4C(O)R3 where R3 and R4 are as previously defined
(xv) NR4C(O)NR5R6 where R4, R5 and R6 are as previously defined
(xvi) ═N—O—R4 where R4 is as previously defined
(xvii) ═N—NR7R8 wherein R7 and R8 are as previously defined
(xviii) ═N—NR4 wherein R4 is as previously defined
(xix) ═N—NR4C(O)R3 wherein R3 and R4 are as previously defined, and
(xx) ═N—NR4C(O)NR5R6 wherein R4, R5 and R6 are as previously defined,
(6) C2-C10-alkynyl
(7) C2-C10-alkynyl substituted with one or more substituents selected from the group consisting of
(i) trialkylsilyl
(ii) halogen,
(iii) —CN
(iv) OR4 where R4 is defined as previously
(v) —CHO,
(vi) oxo,
(vii) —CO2R3 where R3 is as previously defined
(viii) —C(O)NR5R6 wherein R5 and R6 are as previously defined
(ix) NR7R8 wherein R7 and R8 are as previously defined
(x) O—S(O)nR3 where n and R3 are as previously defined
(xi) C3-C7-cycloalkyl
(xii) C1-C12-alkyl substituted with heteroaryl
(xiii) aryl, and optionally substituted aryl
(xiv) heteroaryl, and optionally substituted heteroaryl
(xv) NR4C(O)R3 where R3 and R4 are as previously defined
(xvi) NR4C(O)NR5R6 where R4, R5 and R6 are as previously defined
(xvii) ═N—O—R4 where R4 is as previously defined
(xviii) ═N—NR7R8 wherein R7 and R8 are as previously defined
(xix) ═N—NR4C(O)R3 wherein R3 and R4 are as previously defined, and
(xx) ═N—NR4C(O)NR5R6 wherein R4, R5 and R6 are as previously defined,
(8) cyclic substituents
(i) aryl, and optionally substituted aryl
(ii) heteroaryl, and optionally substituted heteroaryl
(iii) heterocycloalkyl, and optionally substituted heterocycloalkyl, and
(iv) C3-C7-cycloalkyl, and optionally substituted C3-C7-cycloalkyl, and
(9) C1 substituents with the exception of 10-methyl derivatives which are part of the above definitions under (1)
(i) —CHO
(ii) —CN
(iii) CO2R3 wherein R3 is as previously defined
(iv) C(O)NR5R6 wherein R5 and R6 are as previously defined
(v) C(S)NR5R6 wherein R5 and R6 are as previously defined
(vi) C(NR4)NR5R6 wherein R4, N5 and R6 are as previously defined
(vii) CH═N—O—R4 wherein R4 is as previously defined
(viii) CH═N—R4 is wherein R4 is as previously defined
(ix) CH═N—NR7R8 wherein R7 and R8 are as previously defined
(x) CH═N—NR4C(O)R3 wherein R3 and R4 are as previously defined, and
(xi) CH═N-NR4C(O)NR5R6 wherein R4, R5 and R6 are as previously defined;
R1 is selected from the group consisting of
(1) H
(2) methyl
(3) methyl substituted with one or more substituents selected from the group consisting of
(i) F
(ii) —CN
(iii) —CO2R11 where R11 is C1-C3-alkyl or aryl substituted C1-C3-alkyl, or heteroalkyl substituted C1-C3-alkyl
(iv) —C(O)NR5R6 wherein R5 and R6 are defined as previously
(v) aryl, and optionally substituted aryl, and
(vi) heteroaryl, and optionally substituted heteroaryl
(4) C2-C10-alkyl
(5) substituted C2-C10-alkyl with one or more substituents selected from the group consisting of
(i) halogen,
(ii) OR4 where R4 is defined as previously
(iii) C1-C3-alkoxy-C1-C3-alkoxy
(iv) —CHO
(v) oxo
(vi) NR7R8 wherein R7 and R8 are as previously defined
(vii) ═N—O—R4 where R4 is as previously defined
(viii) —CN
(ix) —S(O)nR3 where n=0, 1, or 2 and R3 is as previously defined
(x) aryl, and optionally substituted aryl
(xi) heteroaryl, and optionally substituted heteroaryl
(xii) C3-C8-cycloalkyl, and optionally substituted C3-C8-cycloalkyl
(xiii) C1-C12-alkyl substituted with heteroaryl, and optionally substituted heteroaryl
(xiv) heterocycloalkyl
(xv) NHC(O)R3 where R3 is as previously defined
(xvi) NHC(O)NR5R6 where R5 and R6 are as previously defined
(xvii) ═N—NR7R8 wherein R7 and R8 are as previously defined
(xviii) ═N—R4 wherein R4 as previously defined, and
(xix) ═N—NHC(O)R3 wherein R3 is as previously defined,
(4) C1-C10-alkenyl substituted with one or more substituents selected from the group consisting of
(i) halogen,
(ii) OR4 where R4 is as previously defined
(iii) —CHO
(iv) oxo
(v) —S(O)nR3 where n and R3 are as previously defined
(vi) —CN
(vii) —CO2R3 where R3 is as previously defined
(viii) NR7R8 wherein R7 and R8 are as previously defined
(ix) ═N—O—R4 where R4 is as previously defined
(x) —C(O)—R4 where R4 is as previously defined
(xi) —C(O)NR5R6 wherein R5 and R6 are as previously defined
(xii) aryl, and optionally substituted aryl
(xiii) heteroaryl, and optionally substituted heteroaryl
(xiv) C3-C7-cycloalkyl
(xv) C1-C12-alkyl substituted with heteroaryl
(xvi) NHC(O)R3 where R3 is as previously defined
(xvii) NHC(O)NR5R6 where R5 and R6 are as previously defined
(xviii) ═N—NR7R8 wherein le and R8 are as previously defined
(xix) ═N—R4 wherein R4 is as previously defined,
(xx) ═N—NHC(O)R3 wherein R3 is as previously defined, and
(xxi) ═N—NHC(O)NR5R6 wherein R5 and R6 are as previously defined,
(5) C2-C10-alkynyl, and
(6) C2-C10-alkynyl substituted with one or more substituents selected from the group consisting of
(i) halogen,
(ii) OR4 where R4 is defined as previously
(iii) —CHO
(iv) oxo
(v) —CO2R3 where R3 is as previously defined
(vi) —C(O)NR5R6 wherein R5 and R6 are as previously defined
(vii) —CN
(viii) NR7R8 wherein R7 and R8 are as previously defined
(ix) ═N—O—R4 where R4 is as previously defined
(x) —S(O)nR3 where n and R3 are as previously defined
(xi) aryl, and optionally substituted aryl
(xii) heteroaryl, and optionally substituted heteroaryl
(xiii) C3-C7-cycloalkyl
(xiv) C1-C12-alkyl substituted with heteroaryl
(xv) NHC(O)R3 where R3 is as previously defined
(xvi) NHC(O)NR5R6 where R5 and R6 are as previously defined
(xvii) ═N—NR7R8 wherein R7 and R8 are as previously defined
(xviii) ═N—R4 wherein R4 is as previously defined
(xix) ═N—NHC(O)R3 wherein R3 is as previously defined, and
(xx) ═N—NHC(O)NR5R6 wherein R5 and R6 are as previously defined;
R2 is selected from the group consisting of
(1) hydrogen
(2) OH
(3) OR3 where R3 is as previously defined
(4) OC(O)R3 where R3 is as previously defined, and
(5) O(CO)OR3 where R3 is as previously defined;
and X and Y taken together are selected from the group consisting of
(1) O
(2) NOR4 wherein R4 is as defined previously
(3) N—O C(R9)(CR10)—O—R4 where R4 is as previously defined and
(i) R9 and R10 are each independently defined as R4, or
(ii) R9 and R10 are taken together with the atom to which they are attached form a C3-C12 cycloalkyl ring,
(4) NR4 wherein R4 is as previously defined, and
(5) N—NR7R8 wherein R7 and R8 are as previously defined, or one of X and Y is hydrogen and the other is selected from the group consisting of
(1) OR4 wherein R4 is as previously defined, and
(2) —NR7R8 wherein R7 and R8 are as previously defined,
RP is selected from the group consisting of
(1) hydrogen
(2) R3 as previously defined
(3) COR3 where R3 is as previously defined;
subject to the proviso that when the structure is IV, Z and M are part of a five- or six-membered ring, said rings optionally being fully or partially unsaturated;
for the six- membered ring, the bonding between Z and M is through a carbonyl group;
for the five- membered ring, the bonding is directly between Z and M excluding CO;
Z and M are independently selected from the group consisting of carbon, oxygen or N;
and when M=N a second bridge may exist between this nitrogen and the oxygen of the 12-OH group whereby either an additional annulated oxazole or oxazine ring constitutes part of the molecule;
and subject to the proviso that when the structure is V, Z and M are part of a five- or six- membered ring, said rings optionally being fully saturated or fully or partially unsaturated;
for the six- membered ring, the bonding between Z and M is through a carbonyl group;
for the five-membered ring, the bonding is directly between Z and M excluding CO;
Z and M are independently selected from the group consisting of carbon, oxygen or nitrogen;
and when M=N a second bridge may exist between this nitrogen and the urethane nitrogen
wherein aryl groups have 5 to 10 ring atoms, and heteroaryl groups have 5 to 10 ring atoms including C and at least one of N, O and S.

210 more elements

Dependencies are inferred from the claim text.

Facts

Application: 12/569,926Filed 30 Sep 2009 · division
Priority: DK 2002 0195720 Dec 2002
Published: US 2010/0137234 A13 Jun 2010
Granted: 13 Dec 2011
Term ends: Not estimatedThe source records don’t support an estimate.

Classification6 codes

C07H 17/08
Heterocyclic radicals containing only oxygen as ring hetero atoms: hetero rings containing eight or more ring members, e.g. erythromycins
A61P 3/04
Drugs for disorders of the metabolism: anorexiants; Antiobesity agents
A61P 31/00
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
A61P 31/04
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics: antibacterial agents

Family

PCT/GB03/05659Parent of this division · filed 22 Dec 2003
US 2010/0137234 A1Pre-grant publication · published 3 Jun 2010
Application10/539,759Parent of this division
US 7,608,596 B2Parent of this division
US 2006/0241060 A1Published application
US 8,076,301 B2This patent

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

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Abstract

A 10-substituted-10-desmethyl macrolide of formula II, IV or V

wherein R is selected from the group consisting of
(1) methyl substituted with one or more substituents selected from the group consisting of
(i) CN,
(ii) F,
(iii) CO2R3 wherein R3 is selected from hydrogen, C1-C3-alkyl or aryl substituted C1-C3-alkyl, or heteroaryl substituted C1-C3-alkyl,
(iv) OR4 wherein R4 is selected from hydrogen, C1-C4-alkyl or aryl substituted C1-C4-alkyl, or heteroaryl substituted C1-C4-alkyl, heterocycloalkyl and optionally substituted cycloalkyl, C1-C3-alkoxy-C1-C3-alkoxy, C2-C4-alkenyl or aryl substituted C2-C4-alkenyl, or heteroaryl substituted C2-C4-alkenyl, heterocycloalkyl and optionally substituted cycloalkyl, aryl or optionally substituted aryl, heteroaryl or optionally substituted heteroaryl,
(v) S(O)nR3 wherein n=0, 1 or 2 and R3 is as previously defined
(vi) NR4C(O)R3 wherein R3 and R4 are as previously defined
(vii) NR4C(O)NR5R6 wherein R4 is defined as defined previously, and R5 and R6 are independently selected from hydrogen, C1-C3-alkyl, C1-C3 alkyl substituted with aryl, substituted aryl, heteroaryl, substituted heteroaryl
(viii) NR7R8 wherein R7 and R8 are independently selected from the group consisting of
(a) hydrogen
(b) C1-C12-alkyl, and optionally substituted C1-C12-alkyl
(c) C2-C12-alkenyl, and optionally substituted C2-C12-alkenyl
(d) C2-C12-alkynyl, and optionally substituted C2-C12-alkynyl
(e) aryl, and optionally substituted aryl
(f) heteroaryl, and optionally substituted heteroaryl
(g) heterocycloalkyl, and optionally substituted heterocycloalkyl
(h) C1-C12 alkyl substituted with aryl, and optionally substituted with substituted aryl
(i) C1-C12 alkyl substituted with heteroaryl, and optionally substituted with substituted heteroaryl
(j) C1-C12 alkyl substituted with heterocycloalkyl, and with optionally substituted heterocycloalkyl, and
(k) R7 and R8 taken together with the atom to which they are attached form a 3-10-membered heterocycloalkyl ring which may contain one or more additional heteroatoms and may be substituted with one or more substituents independently selected from the group consisting of
(aa) halogen, hydroxy, C1-C3-alkoxy, alkoxy-C1-C3- alkoxy, oxo, C1-C3-alkyl, aryl and optionally substituted aryl, heteroaryl and optional substituted heteroaryl
(bb) CO2R3 wherein R3 is as previously defined, and
(cc) C(O)NR5R6 wherein R5 and R6 are as previously defined,
(ix) aryl, and optionally substituted aryl, and
(x) heteroaryl, and optionally substituted heteroaryl,
(2) C2-C10-alkyl,
(3) C2-C10-alkyl substituted with one or more substituents selected from the group consisting of
(i) halogen,
(ii) OR4 wherein R4 is as defined previously
(iii) —CHO,
(iv) oxo,
(v) NR7R8 wherein R7 and R8 are defined as previously
(vi) ═N—O—R4 is wherein R3 is as previously defined
(vii) —CN
(viii) —S(O)nR3 wherein n=0, 1 or 2 and R3 is as previously defined
(ix) aryl, and optionally substituted aryl
(x) heteroaryl, and optionally substituted heteroaryl
(xi) C3-C8-cycloalkyl, and optionally substituted C3-C8-cycloalkyl
(xii) heterocycloalkyl, and optionally substituted heterocycloalkyl
(xiii) NR4C(O)R3 where R3 and R4 are as previously defined
(xiv) NR4C(O)NR5R6 wherein R4, R5 and R6 are as previously defined
(xv) ═N—NR7R8 wherein R7 and R8 are as previously defined
(xvi) ═N—R4 wherein R4 is as previously defined
(xvii) ═N—NR4C(O)R3 wherein R3 and R4 are as previously defined, and
(xviii) ═N—NR4C(O)NR5R6 wherein R4, R5 and R6 are as previously defined,
(4) C2-C10-alkenyl,
(5) C2-C10-alkenyl substituted with one or more substituents selected from the group consisting of
(i) halogen,
(ii) OR4 wherein R4 is as previously defined
(iii) O—S(O)nR3 where n and R3 are as previously defined
(iv) —CHO,
(v) oxo,
(vi) —CO2R3 where R3 is as previously defined
(vii) —C(O)—R4 where R4 is as previously defined
(viii) —CN
(ix) aryl, and optionally substituted aryl
(x) heteroaryl, and optionally substituted heteroaryl
(xi) C3-C7-cycloalkyl
(xii) C1-C12-alkyl substituted with heteroaryl
(xiii) NR7R8 wherein R7 and R8 are as previously defined
(xiv) NR4C(O)R3 where R3 and R4 are as previously defined
(xv) NR4C(O)NR5R6 where R4, R5 and R6 are as previously defined
(xvi) ═N—O—R4 where R4 is as previously defined
(xvii) ═N—NR7R8 wherein R7 and R8 are as previously defined
(xviii) ═N—NR4 wherein R4 is as previously defined
(xix) ═N—NR4C(O)R3 wherein R3 and R4 are as previously defined, and
(xx) ═N—NR4C(O)NR5R6 wherein R4, R5 and R6 are as previously defined,
(6) C2-C10-alkynyl
(7) C2-C10-alkynyl substituted with one or more substituents selected from the group consisting of
(i) trialkylsilyl
(ii) halogen,
(iii) —CN
(iv) OR4 where R4 is defined as previously
(v) —CHO,
(vi) oxo,
(vii) —CO2R3 where R3 is as previously defined
(viii) —C(O)NR5R6 wherein R5 and R6 are as previously defined
(ix) NR7R8 wherein R7 and R8 are as previously defined
(x) O—S(O)nR3 where n and R3 are as previously defined
(xi) C3-C7-cycloalkyl
(xii) C1-C12-alkyl substituted with heteroaryl
(xiii) aryl, and optionally substituted aryl
(xiv) heteroaryl, and optionally substituted heteroaryl
(xv) NR4C(O)R3 where R3 and R4 are as previously defined
(xvi) NR4C(O)NR5R6 where R4, R5 and R6 are as previously defined
(xvii) ═N—O—R4 where R4 is as previously defined
(xviii) ═N—NR7R8 wherein R7 and R8 are as previously defined
(xix) ═N—NR4C(O)R3 wherein R3 and R4 are as previously defined, and
(xx) ═N—NR4C(O)NR5R6 wherein R4, R5 and R6 are as previously defined,
(8) cyclic substituents
(i) aryl, and optionally substituted aryl
(ii) heteroaryl, and optionally substituted heteroaryl
(iii) heterocycloalkyl, and optionally substituted heterocycloalkyl, and
(iv) C3-C7-cycloalkyl, and optionally substituted C3-C7-cycloalkyl, and
(9) C1 substituents with the exception of 10-methyl derivatives which are part of the above definitions under (1)
(i) —CHO
(ii) —CN
(iii) CO2R3 wherein R3 is as previously defined
(iv) C(O)NR5R6 wherein R5 and R6 are as previously defined
(v) C(S)NR5R6 wherein R5 and R6 are as previously defined
(vi) C(NR4)NR5R6 wherein R4, N5 and R6 are as previously defined
(vii) CH═N—O—R4 wherein R4 is as previously defined
(viii) CH═N—R4 is wherein R4 is as previously defined
(ix) CH═N—NR7R8 wherein R7 and R8 are as previously defined
(x) CH═N—NR4C(O)R3 wherein R3 and R4 are as previously defined, and
(xi) CH═N-NR4C(O)NR5R6 wherein R4, R5 and R6 are as previously defined;
R1 is selected from the group consisting of
(1) H
(2) methyl
(3) methyl substituted with one or more substituents selected from the group consisting of
(i) F
(ii) —CN
(iii) —CO2R11 where R11 is C1-C3-alkyl or aryl substituted C1-C3-alkyl, or heteroalkyl substituted C1-C3-alkyl
(iv) —C(O)NR5R6 wherein R5 and R6 are defined as previously
(v) aryl, and optionally substituted aryl, and
(vi) heteroaryl, and optionally substituted heteroaryl
(4) C2-C10-alkyl
(5) substituted C2-C10-alkyl with one or more substituents selected from the group consisting of
(i) halogen,
(ii) OR4 where R4 is defined as previously
(iii) C1-C3-alkoxy-C1-C3-alkoxy
(iv) —CHO
(v) oxo
(vi) NR7R8 wherein R7 and R8 are as previously defined
(vii) ═N—O—R4 where R4 is as previously defined
(viii) —CN
(ix) —S(O)nR3 where n=0, 1, or 2 and R3 is as previously defined
(x) aryl, and optionally substituted aryl
(xi) heteroaryl, and optionally substituted heteroaryl
(xii) C3-C8-cycloalkyl, and optionally substituted C3-C8-cycloalkyl
(xiii) C1-C12-alkyl substituted with heteroaryl, and optionally substituted heteroaryl
(xiv) heterocycloalkyl
(xv) NHC(O)R3 where R3 is as previously defined
(xvi) NHC(O)NR5R6 where R5 and R6 are as previously defined
(xvii) ═N—NR7R8 wherein R7 and R8 are as previously defined
(xviii) ═N—R4 wherein R4 as previously defined, and
(xix) ═N—NHC(O)R3 wherein R3 is as previously defined,
(4) C1-C10-alkenyl substituted with one or more substituents selected from the group consisting of
(i) halogen,
(ii) OR4 where R4 is as previously defined
(iii) —CHO
(iv) oxo
(v) —S(O)nR3 where n and R3 are as previously defined
(vi) —CN
(vii) —CO2R3 where R3 is as previously defined
(viii) NR7R8 wherein R7 and R8 are as previously defined
(ix) ═N—O—R4 where R4 is as previously defined
(x) —C(O)—R4 where R4 is as previously defined
(xi) —C(O)NR5R6 wherein R5 and R6 are as previously defined
(xii) aryl, and optionally substituted aryl
(xiii) heteroaryl, and optionally substituted heteroaryl
(xiv) C3-C7-cycloalkyl
(xv) C1-C12-alkyl substituted with heteroaryl
(xvi) NHC(O)R3 where R3 is as previously defined
(xvii) NHC(O)NR5R6 where R5 and R6 are as previously defined
(xviii) ═N—NR7R8 wherein le and R8 are as previously defined
(xix) ═N—R4 wherein R4 is as previously defined,
(xx) ═N—NHC(O)R3 wherein R3 is as previously defined, and
(xxi) ═N—NHC(O)NR5R6 wherein R5 and R6 are as previously defined,
(5) C2-C10-alkynyl, and
(6) C2-C10-alkynyl substituted with one or more substituents selected from the group consisting of
(i) halogen,
(ii) OR4 where R4 is defined as previously
(iii) —CHO
(iv) oxo
(v) —CO2R3 where R3 is as previously defined
(vi) —C(O)NR5R6 wherein R5 and R6 are as previously defined
(vii) —CN
(viii) NR7R8 wherein R7 and R8 are as previously defined
(ix) ═N—O—R4 where R4 is as previously defined
(x) —S(O)nR3 where n and R3 are as previously defined
(xi) aryl, and optionally substituted aryl
(xii) heteroaryl, and optionally substituted heteroaryl
(xiii) C3-C7-cycloalkyl
(xiv) C1-C12-alkyl substituted with heteroaryl
(xv) NHC(O)R3 where R3 is as previously defined
(xvi) NHC(O)NR5R6 where R5 and R6 are as previously defined
(xvii) ═N—NR7R8 wherein R7 and R8 are as previously defined
(xviii) ═N—R4 wherein R4 is as previously defined
(xix) ═N—NHC(O)R3 wherein R3 is as previously defined, and
(xx) ═N—NHC(O)NR5R6 wherein R5 and R6 are as previously defined;
R2 is selected from the group consisting of
(1) hydrogen
(2) OH
(3) OR3 where R3 is as previously defined
(4) OC(O)R3 where R3 is as previously defined, and
(5) O(CO)OR3 where R3 is as previously defined;
and X and Y taken together are selected from the group consisting of
(1) O
(2) NOR4 wherein R4 is as defined previously
(3) N—O C(R9)(CR10)—O—R4 where R4 is as previously defined and
(i) R9 and R10 are each independently defined as R4, or
(ii) R9 and R10 are taken together with the atom to which they are attached form a C3-C12 cycloalkyl ring,
(4) NR4 wherein R4 is as previously defined, and
(5) N—NR7R8 wherein R7 and R8 are as previously defined, or one of X and Y is hydrogen and the other is selected from the group consisting of
(1) OR4 wherein R4 is as previously defined, and
(2) —NR7R8 wherein R7 and R8 are as previously defined,
RP is selected from the group consisting of
(1) hydrogen
(2) R3 as previously defined
(3) COR3 where R3 is as previously defined;
subject to the proviso that when the structure is IV, Z and M are part of a five- or six-membered ring, said rings optionally being fully or partially unsaturated;
for the six- membered ring, the bonding between Z and M is through a carbonyl group;
for the five- membered ring, the bonding is directly between Z and M excluding CO;
Z and M are independently selected from the group consisting of carbon, oxygen or N;
and when M=N a second bridge may exist between this nitrogen and the oxygen of the 12-OH group whereby either an additional annulated oxazole or oxazine ring constitutes part of the molecule;
and subject to the proviso that when the structure is V, Z and M are part of a five- or six- membered ring, said rings optionally being fully saturated or fully or partially unsaturated;
for the six- membered ring, the bonding between Z and M is through a carbonyl group;
for the five-membered ring, the bonding is directly between Z and M excluding CO;
Z and M are independently selected from the group consisting of carbon, oxygen or nitrogen;
and when M=N a second bridge may exist between this nitrogen and the urethane nitrogen
wherein aryl groups have 5 to 10 ring atoms, and heteroaryl groups have 5 to 10 ring atoms including C and at least one of N, O and S.

210 more elements

Facts

Application

12/569,926Filed 30 Sep 2009 · division

Priority

DK 2002 0195720 Dec 2002

Published

US 2010/0137234 A13 Jun 2010

Granted

13 Dec 2011

Term ends

Not estimatedThe source records don’t support an estimate.

Classification6 codes

C07H 17/08
Heterocyclic radicals containing only oxygen as ring hetero atoms: hetero rings containing eight or more ring members, e.g. erythromycins
A61P 3/04
Drugs for disorders of the metabolism: anorexiants; Antiobesity agents
A61P 31/00
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
A61P 31/04
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics: antibacterial agents

Family

PCT/GB03/05659Parent of this division · filed 22 Dec 2003

US 2010/0137234 A1Pre-grant publication · published 3 Jun 2010

Application10/539,759Parent of this division

US 7,608,596 B2Parent of this division

US 2006/0241060 A1Published application

US 8,076,301 B2This patent

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