US 6,274,715 B1Granted

Tricyclic erythromycin derivatives

AssigneeAbbott Laboratories

InventorsYat Sun Or, Ly Tam Phan, Daniel T. Chu, Kenneth P. Spina, Robert Hallas, Richard L. Elliott, Michael Tufano

Life of this patent

Estimating the term…

Abstract

Compounds, or pharmaceutically acceptable salts and esters thereof, of the formula: wherein A, B, D and E, R1, R2, and Z are specifically defined, having antibacterial activity, pharmaceutical compositions containing said compounds, treatment of bacterial infections with such compositions, and processes for the preparation of the compounds.

Claims29

Dependent claims

A compound having the formula:

or pharmaceutically acceptable salts and esters thereof, wherein a first substituent, optionally a second substituent, and optionally a third substituent selected from A, B, D and E are independently selected from the group consisting of:
(a) C1-C6 alkyl, substituted with one or more substituents selected from the group consisting of:
(i) aryl;
(ii) substituted-aryl;
(iii) heteroaryl;
(iv) substituted-heteroaryl;
(v) heterocycloalkyl;
(vi) hydroxy;
(vii) C1-C6 alkoxy;
(viii) halogen consisting of Br, Cl, F or I;
and
(ix) NR3R4, wherein R3 and R4 are independently selected from hydrogen and C1-C6-alkyl, or R3 and R4 taken together with a first hetero function, wherein said first hetero function is the nitrogen atom to which R3 and R4 are connected, form a non-aromatic 3- to 7-membered ring;
said ring optionally containing a second hetero function selected from the group consisting of —O—, —NH—, —N(C1-C6-alkyl-)-, —N(aryl-C1-C6-alkyl-)-, —N(substituted-aryl-C1-C6-alkyl-)-, —N(heteroaryl-C1-C6-alkyl-)-, —N(substituted-heteroaryl-C1-C6-alkyl-)-, —S— and —S(O)n—, wherein n is 1 or 2;
(b) C3-C7-cycloalkyl;
(c) aryl;
(d) substituted-aryl;
(e) heteroaryl;
(f) substituted-heteroaryl;
(g) heterocycloalkyl;
and
(h) C1-C6-alkyl-M—R5, wherein the C1-C6-alkyl group is optionally substituted with a substituent in group (a)(i)-(a)(ix), and wherein M is selected from the group consisting of:
(aa) —C(O)—NH—;
(bb) —NH—C(O)—;
(cc) —NH—;
(dd) —N(CH3)—;
(ee) —O—;
(ff) —S(O)n—, wherein n is 0, 1 or 2;
(gg) —C(═NH)—NH—;
(hh) —C(O)—O—;
(ii) —O—C(O)—;
(jj) —O—C(O)—NH—;
(kk) —NH—C(O)—O—;
and
(ll) —NH—C(O)—NH—;
R5 is selected from the group consisting of:
(aaa) C1-C6-alkyl, optionally substituted with a substituent selected from the group consisting of:
(i) aryl;
(ii) substituted-aryl;
(iii) heteroaryl;
and
(iv) substituted-heteroaryl;
(bbb) aryl;
(ccc) substituted-aryl;
(ddd) heteroaryl;
(eee) substituted-heteroaryl;
and
(fff) heterocycloalkyl;
said optional second and optional third substituents selected from a group (a)-(h) above and further selected from a group consisting of:
(i) hydrogen;
and
(j) C1-C6-alkyl;
a fourth substituent selected from A, B, D and E is hydrogen or C1-C6-alkyl;
R1 is selected from the group consisting of:
(a) hydrogen;
(b) —O—C1-C3-alkyl;
(c) —O—C3-C5-cycloalkyl;
(d) —O—C1-C3-alkyl-C3-C5-cycloalkyl;
(e) —O—C(O)—C1-C3-alkyl;
(f) —O—C(O)—O—C1-C3-alkyl;
and
(g) —O—C(O)—NH—C, C3-alkyl;
R2 is hydrogen or a hydroxy-protecting group;
and Z is hydroxy or protected-hydroxy.

60 more elements

A process for preparing a compound having the formula:

or pharmaceutically acceptable salts and esters thereof, wherein a first substituent, optionally a second substituent, and optionally a third substituent selected from A, B, D and E are independently selected from the group consisting of:
(a) C1-C6 alkyl, substituted with one or more substituents selected from the group consisting of:
(i) aryl;
(ii) substituted-aryl;
(iii) heteroaryl;
(iv) substituted-heteroaryl;
(v) heterocycloalkyl;
(vi) hydroxy;
(vii) C1-C6 alkoxy;
(viii) halogen consisting of Br, Cl, F or I;
and
(ix) NR3R4, wherein R3 and R4 are independently selected from hydrogen and C1-C6-alkyl, or R3 and R4 taken together with a first hetero function, wherein said first hetero function is the nitrogen atom to which R3 and R4 are connected, form a non-aromatic 3- to 7-membered ring;
said ring optionally containing a second hetero function selected from the group consisting of —O—, —NH—, —N(C1-C6-alkyl-)-, —N(aryl-C1-C6-alkyl-)-, —N(substituted-aryl-C1-C6-alkyl-)-, —N(heteroaryl-C1-C6-alkyl-)-, —N(substituted-heteroaryl-C1-C6-alkyl-)-, —S— and —S(O)n—, wherein n is 1 or 2;
(b) C3-C7-cycloalkyl;
(c) aryl;
(d) substituted-aryl;
(e) heteroaryl;
(f) substituted-heteroaryl;
(g) heterocycloalkyl;
and
(h) C1-C6-alkyl-M—R5, wherein the C1-C6-alkyl group is optionally substituted with a substituent in group (a)(i)-(a)(ix), and wherein M is selected from the group consisting of:
(aa) —C(O)—NH—;
(bb) —NH—C(O)—;
(cc) —NH—;
(dd) —N(CH3)—;
(ee) —O—;
(ff) —S(O)n—, wherein n is 0, 1 or 2;
(gg) —C(═NH)—NH—;
(hh) —C(O)—O—;
(ii) —O—C(O)—;
(jj) —O—C(O)—NH—;
(kk) —NH—C(O)—O—;
and
(ll) —NH—C(O)—NH—;
R5 is selected from the group consisting of:
(aaa) C1-C6-alkyl, optionally substituted with a substituent selected from the group consisting of:
(i) aryl;
(ii) substituted-aryl;
(iii) heteroaryl;
and
(iv) substituted-heteroaryl;
(bbb) aryl;
(ccc) substituted-aryl;
(ddd) heteroaryl;
(eee) substituted-heteroaryl;
and
(fff) heterocycloalkyl;
said optional second and optional third substituents selected from a group (a)-(h) above and further selected from a group consisting of:
(i) hydrogen;
and
(j) C1-C6-alkyl;
a fourth substituent selected from A, B, D and E is hydrogen or C1-C6-alkyl;
R1 is selected from the group consisting of:
(a) hydrogen;
(b) —O—C1-C3-alkyl;
(c) —O—C3-C5-cycloalkyl;
(d) —O—C1-C3-alkyl-C3-C5-cycloalkyl;
(e) —O—C(O)—C1-C3-alkyl;
(f) —O—C(O)—O—C1-C3-alkyl;
and
(g) —O—C(O)—NH—C, C3-alkyl;
R2 is hydrogen or a hydroxy-protecting group;
and Z is hydroxy or protected-hydroxy;
the method comprising:
(a) treating a compound having the formula:
respectively,
wherein R1 is as defined above and R2 is a hydroxy-protecting group;
with a base, followed by reaction with carbonyldiimidazole, in an aprotic solvent, to prepare first intermediate compounds having the formula:
respectively;
wherein R1 and R2 are as defined above;
(b) reacting said first intermediate compounds with a compound having the formula:
wherein A, B, D and E are as defined above, to give a bicyclic second intermediate compound having the formula:
respectively, wherein R1 and R2 are as defined above;
(c) deprotecting said second intermediate compounds by treatment with methanol or ethanol when OR2 is an ester or with fluoride in THFP or acetonitrile when R2 is a triaLkylsilyl group, for from 1 to 24 hours, to give the third intermediate compounds:
respectively;
(d) cyclizing said third intermediate compounds by treatment with dilute acid for a period of from 4 hours to 10 days to give the desired compounds (I), (II), (III) or (IV) above.

73 more elements

A process for preparing a compound having the formula:

or pharmaceutically acceptable salts or esters thereof,
wherein any one pair of substituents selected from a substituent A, B, D or E taken together with the atom or atoms to which they are attached form a pair AB, AD, AE, BD, BE or DE;
wherein each pair is taken together with the atom or atoms to which they are attached to form a 3- to 7-membered ring optionally containing a hetero function consisting of:
—O—;
—NH—;
—N(C1-C6-alkyl-)-;
—N(aryl)-;
—N(aryl-C1-C6-alkyl-)-;
—N(substituted-aryl-C1-C6-alkyl-)-;
—N(heteroaryl-C1-C6-alkyl-)-;
—N(substituted-heteroaryl-C1-C6-alkyl-)-;
—S(O)n—, wherein n is 0, 1 or 2;
—C(O)—NH—;
—C(O)—NR5—, wherein
R5 is selected from the group consisting of:
(aaa) C1-C6 akyl, optionally substituted with a substituent selected from the group consisting of:
(i) aryl;
(ii) substituted-aryl;
(iii) heteroaryl;
and
(iv) substituted-heteroaryl;
(bbb) aryl;
(ccc) substituted-aryl;
(ddd) heteroaryl;
(eee) substituted-heteroaryl;
and
(fff) heterocycloalkyl;
—NH—C(O)—;
—NR5—C(O)—, wherein R5 is as described above;
and
—C(═NH)—NH;
and wherein the remaining two, non-ring forming, substituents are each hydrogen;
R1 is selected from the group consisting of:
(a) hydrogen;
(b) —O—C1-C3-alkyl;
(c) —O—C3-C5-cycloalkyl;
(d) —O—C1-C3-alkyl-C3-C5-cycloalkyl;
(e) —O—C(O)—C1-C3-alkyl;
(f) —O—C(O)—O—C1-C3-alkyl;
and
(g) —O—C(O)—NH—C1-C3-alkyl;
R2 is hydrogen or a hydroxy-protecting group;
and
Z is hydroxy or protected-hydroxy;
the method comprising:
(a) treating a compound having the formula:
respectively,
wherein R1 is as defined above and R2 is a hydroxy-protecting group;
with a base, followed by reaction with carbonyldiimidazole, in an aprotic solvent, to prepare a first intermediate compound having the formula:
respectively;
wherein R1 and R2 are as defined above;
(b) reacting said first intermediate compounds with a compound having the formula:
wherein A, B, D and E are as defined above, to give a bicyclic second intermediate compound having the formula:
respectively, wherein R1 and R2 are as defined above;
(c) deprotecting said second intermediate compounds by treatment with methanol or ethanol when OR2 is an ester or with fluoride in nIF or acetonitrile when R2 is a trialkylsilyl group, for from 1 to 24 hours, to give the third intermediate compounds:
respectively;
(d) cychzing said third intermediate compounds by treatment with dilute acid for a period of from 4 hours to 10 days to give the desired compounds (I), (II), (III) or (IV) above.

54 more elements

A compound of Formula III

selecting from the group consisting of:
Compound of Formula (IV):
R1=methoxy;
R2=hydrogen;
A=B=D=E=hydrogen;
Compound of Formula (III):
A=B=E=H, D=benzyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=B=D=H, E=benzyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=benzyl, B=D=E=H, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
B=benzyl, A=D=E=H, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=E=phenyl, B=D=H, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
B=D=H;
A and E taken together is —CH2CH2CH2—, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
B=E=H;
A and D taken together is —CH2CH2CH2CH2—, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
R1=OCH3, R2=H;
A=B=D=H;
E=—CH2NH2;
Compound of Formula (III):
R1=OCH3, R2=H;
A=B=E=H;
D=—CH2NH2;
Compound of Formula (III):
R1=OCH3, R2=H;
B=E=H;
A and D taken together is —CH2CH2CH2—;
Compound of Formula (III):
R1=OCH3, R2=H;
B=E=H;
A and D taken together is —CH2OCH2—;
Compound of Formula (III):
R1=OCH3, R2=H;
B=E=H;
A and D taken together is —CH2—NH—CH2—;
Compound of Formula (III):
R1=OCH3, R2=H;
B=E=H;
A and D taken together is —CH2—N(benzyl)-CH2—;
Compound of Formula (III):
R1=OCH3, R2=H;
B=E=H;
A and D taken together is —CH2—N(phenyl-CH2—CH2—)—CH2—;
Compound of Formula (III):
R1=OCH3, R2=H;
B=E=H;
A and D taken together is —CH2—N(4-Cl-phenyl-CH2—)—CH2—;
Compound of Formula (III):
R1=OCH3, R2=H;
B=E=H;
A and D taken together is —CH2—N(4-pyridyl-CH2—)—CH2—;
Compound of Formula (III):
R1=OCH3, R2=H;
B=E=H;
A and D taken together is —CH2—N(2-pyridyl-CH2—)—CH2—;
Compound of Formula (III):
R1=OCH3, R2=H;
B=E=H;
A and D taken together is —CH2—NH(3-pyridyl-CH2—)—CH2—;
Compound of Formula (III):
R1=OCH3, R2=H;
B=E=H;
A and D taken together is —CH2—N(4-quinolyl-CH2—)—CH2—;
Compound of Formula (III):
R1=OCH3, R2=H;
B=E=H;
A=D=—CH2—O—CH2-phenyl;
Compound of Formula (III):
R1=OCH3, R2=H;
B=E=H;
A=D=—CH2—OH;
Compound of Formula (III):
R1=OCH3, R2=H;
B=E=H;
A=D=—CH2—O-phenyl;
Compound of Formula (III):
R1=OCH3, R2=H;
A=B=H;
D and E taken together is —CH2—CH2—CH2—CH2—;
Compound of Formula (III):
R1=OCH3, R2=H;
A and B taken together is —CH2—CH2—CH2—CH2—;
D=E=H;
Compound of Formula (III):
R1=OCH3, R2=H;
A=B=H;
D and E taken together is —CH2—O—CH2—;
Compound of Formula (III):
R1=OCH3, R2=H;
A=D=E=H;
B=—CH2—CH2-phenyl;
Compound of Formula (III):
R1=OCH3, R2=H;
A=D=E=H;
B=—CH2—CH2—CH2-phenyl;
Compound of Formula (III):
R1=OCH3, R2=H;
A=D=E=H;
B=—CH2—O—CH2-phenyl;
Compound of Formula (III):
R1=OCH3, R2=H;
A=D=E=H;
B=—CH2—CH2-(4-OCH3-phenyl);
Compound of Formula (III):
R1=OCH3, R2=H;
A=—CH2—CH2-phenyl;
B=D=E=H;
Compound of Formula (III):
R1=OCH3, R2=H;
A=—CH2—CH2—CH2-phenyl;
B=D=E=H;
Compound of Formula (III):
R1=OCH3, R2=H;
A=—CH2—O—CH2-phenyl;
B=D=E=H;
Compound of Formula (III):
R1=OCH3, R2=H;
A=D=E=H;
B=—CH2—CH2-(4-OCH3-phenyl);
Compound of Formula (III):
R1=OCH3, R2=H;
A=B=D=H;
E=—CH2CH2Ph;
Compound of Formula (III):
R1=OCH3, R2=H;
A=B=E=H;
D=—CH2CH2Ph;
Compound of Formula (III):
R1=OCH3, R2=H;
A=B=D=H;
E=—CH2CH2CH2Ph;
Compound of Formula (III):
R1=OCH3, R2=H;
A=B=E=H;
D=—CH2CH2CH2Ph;
Compound of Formula (III):
R1=OCH3, R2=H;
A=—CH2CH2OPh;
B=D=E=H;
Compound of Formula (III):
R1=OCH3, R2=H;
A=—CH2CH2NH2;
B=D=E=H;
Compound of Formula (III):
R1=OCH3, R2=H;
A=—CH2CH2NH2;
B=D=E=H;
Compound of Formula (III):
R1=OCH3, R2=H;
A=—CH2CH2OH;
B=D=E=H;
Compound of Formula (III):
R1=OCH3, R2=H;
A=—CH2COOH;
B=D=E=H;
Formula (III):
R1=OCH3, R2=H;
A=—CH2CH2OH;
B=D=E=H;
Compound of Formula (III):
R1=OCH3, R2=H;
A=—CH2CH2NH(4′-Pyridyl-);
B=D-E=H;
Compound of Formula (III):
R1=OCH3, R2=H;
A=B=D=H;
E=—CH2OH;
Compound of Formula (III):
R1=OCH3, R2=H;
A=B=E=H;
D=—CH2OH;
Compound of Formula (III):
R1=OCH3, R2=H;
A=B=E=H;
D=—CH2NHBenzoyl;
Compound of Formula (III):
R1=OCH3, R2=H;
A=B=E=H;
D=—CH2NHBenzyl;
Compound of Formula (III):
R1=OCH3, R2=H;
A=B=D=H;
E=—CH2NHBenzoyl;
Compound of Formula (III):
R1=OCH3, R2=H;
A=B=D=H;
E=—CH2NHBenzyl;
Compound of Formula (III):
R1=OCH3, R2=H;
B=D=H;
A=E=—CH2OCH2(4-Cl-phenyl-);
Compound of Formula (III):
R1=OCH3, R2=H;
A=B=E=H;
D=—CH2—N(CH3)-Benzyl;
Compound of Formula (III):
R1=OCH3, R2=H;
A=B-D=H;
E=—CH2—N(CH3)-Benzyl;
Compound of Formula (III):
R1=OCH3, R2=H;
A=B=D=H;
E=—CH2—NH-phenyl;
Compound of Formula (III):
R1=OCH3, R2=H;
A=B=E=H;
D=—CH2—NH-phenyl;
Compound of Formula (III):
A=4-ethoxybenzyloxymethyl, B=D=E=H, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=hydroxymethyl, B=D=E=H, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=4-benzyloxybenzyl, B=D=E=H, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=4-hydroxybenzyl, B=D=E=H, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=S-benzylthioxymethyl, B=D=E=H, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=3-indolylmethyl, B=D=E=H, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=4-thiazolylmethyl, B=D=E=H, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=4-iodobenzyl, B=D=E=H, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=4-fluorobenzyloxymethyl, B=D=E=H, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=3-fluorobenzyloxymethyl, B=D=E=H, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=2-fluorobenzyloxymethyl, B=D=E=H, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=B=E=H, D=(4-cyanobenzyloxy)methyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=B=E=H, D=(4-(t-butyloxycarbonyl)amino)benzyloxy)methyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=B=E=H, D=(4-(dimethylamino)benzyloxy)methyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=B=E=H, D=(4-pyridyl)methoxymethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=B=E=H, D=(2-chloro)benzyloxymethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=B=E=H, D=(4-chloro)benzyloxymethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=B=E=H, D=(3-chloro)benzyloxymethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=B=E=H, D=(2-pyridyl)methoxymethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=B=E=H, D=(3-pyidyl)methoxymethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=B=E=H, D=(4-methyl-2-quinolyl)methoxymethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=B=E=H, D=(4-(methoxycarbonyl)benzyl)oxymethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=B=E=H, D=(4-quinolyl)methoxymethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=B=D=H, E=(4-pyridyl)methoxymethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=B=E=H, D=(2-(N-morpholinyl)ethoxy)methyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=B=E=H, D=benzyloxymethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=B=D=H, E=benzyloxymethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=B=E=H, D=(4-methoxy)benzyloxymethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=B=E=H, D=2-phenoxyethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=B=E=H, D=2-(benzyloxy)ethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=B=E=H, D=(4-methyl-1-piperazinyl)methyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=B=E=H, D=N-methyl-N-benzylaminomethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=B=E=H, D=N-morpholinylmethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=B=E=H, D=(1-piperidinyl)methyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=B=E=H, D=(N,N-dimethyl)aminomethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (II):
A=B=E=H, D=hydroxymethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=B=E=H, D=(methylthioxy)methoxymethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=B=E=H, D=3,5-dimethoxybenzyloxymethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=B=E=H, D=4-fluorobenzyloxymethyl, R1=methoxy, R2=hydrogen;
Compound of Fonnula (III):
A=B=E=H, D=2-fluorobenzyloxymethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=B=E=H, D=4-bromobenzyloxymethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=B=E=H, D=2-bromobenzyloxymethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=B=E=H, D=3-bromobenzyloxymethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=D=H;
B and E taken together is —CH2CH2CH2CH2—, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=D=H;
B and E taken together is —CH2CH2CH2—, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=D=H;
B and E taken together is —CH2OCH2—, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=D=H;
B and E taken together is —CH2—NH—CH2—, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=D=H;
B and E taken together is —CH2—N(benzyl)-CH2—, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=D=H;
B and E taken together is —CH2—N(phenyl-CH2—CH2—CH2—)—CH2—, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
B=E=H;
A and D taken together is —CH2—N(phenyl-CH2—CH2—CH2—)—CH2—, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
B=E=H;
A and D taken together is —CH2—N(phenyl-CH(CH3)—)—CH2—, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
B=E=H;
A and D taken together is —CH2—N(CH3)—CH2—, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
B=E=H;
A and D taken together is —CH2—N(CH3CH2—)—CH2—, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
B=E=H;
A and D taken together is —CH2—N(allyl)-CH2—, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
B=E=H;
A and D taken together is —CH2—N(propargyl)-CH2—, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
B=E=H;
A and D taken together is —CH2—N(4-NO2-phenyl-CH2—CH2—)—CH2—, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
B=E=H;
A and D taken together is —CH2—N(2-NO2-phenyl-CH2—CH2—)—CH2—, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
B=E=H;
A and D taken together is —CH2—N(3-NO2-phenyl-CH2—CH2—)—CH2—, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
B=E=H;
A and D taken together is —CH2—N(4-NH2-phenyl-CH2—CH2—)—CH2—, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
B=E=H;
A and D taken together is —CH2—N(4-NH(acetyl)-phenyl-CH2—CH2—)—CH2—, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
B=E=H;
A and D taken together is —CH2—N(2-NO2-benzyl-SO2—)—CH2—, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
B=E=H;
A and D taken together is —CH2—N(CHO)—CH2—, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
B=E=H;
A and D taken together is —CH2—N(acetyl)-CH2—, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
B=E=H;
A and D taken together is —CH2—N(2-methoxyethyl)-CH2—, R1-methoxy, R2=hydrogen;
Compound of Formula (III):
B=E=H;
A and D taken together is —CH2—N(2,2-dimethoxyethyl)-CH2—, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
B=E=H;
A and D taken together is —CH2—N(2-phenoxyethyl)-CH2—, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
B=E=H;
A and D taken together is —CH2—N(2-(dimethylamino)ethyl)-CH2—, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
B=E=H;
A and D taken together is —CH2—N(2-(ethoxycarbonyl)ethyl)-CH2—, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
B=D=E=H, A=N-benzylaminomethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
B=D=E=H, A=N-benzyl-N-methylaminomethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
D=E=H, A=N-benzyl-N-methylaminomethyl, B=phenylthiomethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
D=E=H, A=N-benzyl-N-methylaminomethyl, B=methyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
D=E=H, A=dimethylaminomethyl, B=phenylthiomethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
D=E=H, A=dimethylaminomethyl, B=methyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
B=D=E=H, A=(4-quinolyl)carboxymethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
B=D=E=H, A=(4-pyridyl)carboxymethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
B=D=E=H, A=benzoyloxymethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
B=D=E=H, A=4-chlorobenzoyloxymethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
B=D=E=H, A=(2-quinolyl)carboxymethyl, R1=metboxy, R2=hydrogen;
Compound of Formula (III):
B=D=E=H, A=(1-methyl-2-indolyl)carboxymethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
B=D=E=H, A=(4-indolyl)carboxymethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
B=D=H, A=E=benzyloxymethyl, R1=methoxy, R2=hydrogen;
Compound of Formula (III):
A=E=H, B=D=(4-chloro)benzyloxymethyl, R1=methoxy, R2=hydrogen;
and
Compound of Formula (III):
B=E=H, A=D=(4-chloro)benzyloxymethyl, R1=methoxy, R2=hydrogen.

404 more elements

Dependencies are inferred from the claim text.

Facts

Application: 08/779,786Filed 7 Jan 1997 · continuation in part
Priority: 8 Nov 1995
Granted: 14 Aug 2001
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 31/00
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
A61P 31/04
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics: antibacterial agents
C07H 17/00
Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals

Family

Application08/555,246Parent of this continuation-in-part · filed 8 Nov 1995
US 6,274,715 B1This patent

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

Timeline

Citations

Open elsewhere

patentgrep

Loading patent…

Abstract

A compound having the formula:

or pharmaceutically acceptable salts and esters thereof, wherein a first substituent, optionally a second substituent, and optionally a third substituent selected from A, B, D and E are independently selected from the group consisting of:
(a) C1-C6 alkyl, substituted with one or more substituents selected from the group consisting of:
(i) aryl;
(ii) substituted-aryl;
(iii) heteroaryl;
(iv) substituted-heteroaryl;
(v) heterocycloalkyl;
(vi) hydroxy;
(vii) C1-C6 alkoxy;
(viii) halogen consisting of Br, Cl, F or I;
and
(ix) NR3R4, wherein R3 and R4 are independently selected from hydrogen and C1-C6-alkyl, or R3 and R4 taken together with a first hetero function, wherein said first hetero function is the nitrogen atom to which R3 and R4 are connected, form a non-aromatic 3- to 7-membered ring;
said ring optionally containing a second hetero function selected from the group consisting of —O—, —NH—, —N(C1-C6-alkyl-)-, —N(aryl-C1-C6-alkyl-)-, —N(substituted-aryl-C1-C6-alkyl-)-, —N(heteroaryl-C1-C6-alkyl-)-, —N(substituted-heteroaryl-C1-C6-alkyl-)-, —S— and —S(O)n—, wherein n is 1 or 2;
(b) C3-C7-cycloalkyl;
(c) aryl;
(d) substituted-aryl;
(e) heteroaryl;
(f) substituted-heteroaryl;
(g) heterocycloalkyl;
and
(h) C1-C6-alkyl-M—R5, wherein the C1-C6-alkyl group is optionally substituted with a substituent in group (a)(i)-(a)(ix), and wherein M is selected from the group consisting of:
(aa) —C(O)—NH—;
(bb) —NH—C(O)—;
(cc) —NH—;
(dd) —N(CH3)—;
(ee) —O—;
(ff) —S(O)n—, wherein n is 0, 1 or 2;
(gg) —C(═NH)—NH—;
(hh) —C(O)—O—;
(ii) —O—C(O)—;
(jj) —O—C(O)—NH—;
(kk) —NH—C(O)—O—;
and
(ll) —NH—C(O)—NH—;
R5 is selected from the group consisting of:
(aaa) C1-C6-alkyl, optionally substituted with a substituent selected from the group consisting of:
(i) aryl;
(ii) substituted-aryl;
(iii) heteroaryl;
and
(iv) substituted-heteroaryl;
(bbb) aryl;
(ccc) substituted-aryl;
(ddd) heteroaryl;
(eee) substituted-heteroaryl;
and
(fff) heterocycloalkyl;
said optional second and optional third substituents selected from a group (a)-(h) above and further selected from a group consisting of:
(i) hydrogen;
and
(j) C1-C6-alkyl;
a fourth substituent selected from A, B, D and E is hydrogen or C1-C6-alkyl;
R1 is selected from the group consisting of:
(a) hydrogen;
(b) —O—C1-C3-alkyl;
(c) —O—C3-C5-cycloalkyl;
(d) —O—C1-C3-alkyl-C3-C5-cycloalkyl;
(e) —O—C(O)—C1-C3-alkyl;
(f) —O—C(O)—O—C1-C3-alkyl;
and
(g) —O—C(O)—NH—C, C3-alkyl;
R2 is hydrogen or a hydroxy-protecting group;
and Z is hydroxy or protected-hydroxy.

60 more elements

Facts

Application

08/779,786Filed 7 Jan 1997 · continuation in part

Priority

8 Nov 1995

Granted

14 Aug 2001

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 31/00
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
A61P 31/04
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics: antibacterial agents
C07H 17/00
Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals