US 2003/0119860 A1 · METHOD FOR TRATMENT OF NON-RHEUMATOID ARTHRITIS

A method for treatment of a mammal afflicted with non-rheumatoid arthritis, said method comprising administering to said mammal a therapeutically effective amount of an sPLA2 inhibitor.

A method for treatment of a mammal to alleviate or prevent the pathological effects of the following types of non-rheumatoid arthritis (1-10):

1. Osteoarthritis
2. Gout
3. Spondylarthropathris
a. ankylosing spondylitis
b. Reiter's syndrome
c. Psoriatic arthropathy
d. Enterapathric spondylitis
e. Juvenile arthropathy or juvenile ankylosing spondylitis
f. Reactive arthropathy
4. Infectious or post-infectious arthritis
a. Gonoccocal arthritis
b. Tuberculous arthritis
c. Viral arthritis
d. Fungal arthritis
e. Syphilitic arthritis
f. Lyme disease
5. Arthritis associated with “vasculitic syndromes”
a. polyarteritis nodosa
b. hypersensitivity vasculitis
c. Luegenec's granulomatosis
d. polymyalgin rheumatica
e. joint cell arteritis
6. Calcium crystal deposition arthropathris
a. pseudo gout
7. Non-articular rheumatism
a. bursitis
b. tenosynomitis
c. epicondylitis (tennis elbow)
d. carpal tunnel syndrome
e. repetitive use injury (typing)
8. Miscellaneous forms of arthritis
a. neuropathic joint disease (charco and joint)
b. hemarthrosis (hemarthrosic)
c. Henoch-Schonlein Purpura
d. hypertrophic osteoarthropathy
e. Multicentric reticulohistiocytosis
9. Arthritis associated with certain diseases
a. surcoilosis
b. hemochromatosis
c. sickle cell disease and other hemoglobinopathries
d. hyperlipo proteineimia
e. hypogammaglobulinemia
f. hyperparathyroidism
g. acromegaly
h familial Mediterranean fever
i. Behat's Disease
j. Systemic lupus erythrematosis
k. hemophilia
10. Relapsing polychondritis;
wherein the method comprises administering to said mammal at least one sPLA2 inhibitor in a therapeutically effective amount.

47 more elements

A method for treatment of a human afflicted with a non-rheumatoid arthritis, said method comprising administering to said human a therapeutically effective amount of a 1H-indole-3-glyoxylamide of the invention represented by the formula (Ia), or a pharmaceutically acceptable salt or aliphatic ester prodrug derivative thereof;

120
wherein
both X are oxygen;
R1 is selected from the group consisting of
121
where R10 is a radical independently selected from halo, C1-C10 alkyl, C1-C10 alkoxy, —S—(C1-C10 alkyl) , and C1-C10 haloalkyl and t is a number from 0 to 5;
R2 is selected from the group;
halo, cyclopropyl, methyl, ethyl, and propyl;
R4 and R5 are independently selected from hydrogen, a non-interfering substituent, or the group, —(La)-(acidic group);
wherein —(La)— is an acid linker;
provided, the acid linker group, —(La)—, for R4 is selected from the group consisting of;
122
and provided, the acid linker, —(La)—, for R5 is selected from group consisting of;
123
wherein R84 and R85 are each independently selected from hydrogen, C1-C10 alkyl, aryl, C1-C10 alkaryl, C1-C10 aralkyl, carboxy, carbalkoxy, and halo;
and
provided, that at least one of R4 and R5 must be the group, —(La)-(acidic group) and wherein the (acidic group) on the group —(La)-(acidic group) of R4 or R5 is selected from —CO2H, —SO3H, or —P(O)(OH)2;
R6 and R7 are each independently selected form hydrogen and non-interfering substituents, with the non-interfering substituents being selected from the group consisting of the following:
C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C7-C12 aralkyl, C7-C12 alkaryl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, phenyl, tolulyl, xylenyl, biphenyl, C1-C6 alkoxy, C2-C6 alkenyloxy, C2-C6 alkynyloxy, C2-C12 alkoxyalkyl, C2-C12 alkoxyalkyloxy, C2-C12 alkylcarbonyl, C2-C12 alkylcarbonylamino, C2-C12 alkoxyamino, C2-C12 alkoxyaminocarbonyl, C2-C12 alkylamino, C1-C6 alkylthio, C2-C12 alkylthiocarbonyl, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C2-C6 haloalkoxy, C1-C6 haloalkylsulfonyl, C2-C6 haloalkyl, C1-C6 hydroxyalkyl, —C(O)O(C1-C6 alkyl), —(CH2)n—O—(C1-C6 alkyl), benzyloxy, phenoxy, phenylthio, —(CONHSO2R), —CHO, amino, amidino, bromo, carbamyl, carboxyl, carbalkoxy, —(CH2)n—CO2H, chloro, cyano, cyanoguanidinyl, fluoro, guanidino, hydrazide, hydrazino, hydrazido, hydroxy, hydroxyamino, iodo, nitro, phosphono, —SO3H, thioacetal, thiocarbonyl, and C1-C6 carbonyl;
where n is from 1 to 8.

17 more elements

A method for treatment of a human afflicted with non-rheumatoid arthritis, said method comprising administering to said human in need of such treatment, a therapeutically effective amount of a 1H-indole-3-glyoxylamide compound or a pharmaceutically acceptable salt, solvate, or a prodrug derivative thereof selected from the group consisting of compounds (A) through (P):

(A) [[3-(2-Amino-1,2-dioxoethyl)-2-methyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid,
(B) dl-2-[[3-(2-Amino-1,2-dioxoethyl)-2-methyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]propanoic acid,
(C) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-2-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(D) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-3-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(E) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-4-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(F) [[3-(2-Amino-1,2-dioxoethyl)-1-[(2,6-dichlorophenyl)methyl]-2-methyl-1H-indol-4-yl]oxy]acetic acid
(G) [[3-(2-Amino-1,2-dioxoethyl)-1-[4(-fluorophenyl)methyl]-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(H) [[3-(2-Amino-1,2-dioxoethyl)-2-methyl-1-[(1-naphthalenyl)methyl]-1H-indol-4-yl]oxy]acetic acid,
(I) [[3-(2-Amino-1,2-dioxoethyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid,
(J) [[3-(2-Amino-1,2-dioxoethyl)-1-[(3-chlorophenyl)methyl]-2-ethyl-1H-indol-4-yl]oxy]acetic acid,
(K) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-2-ylmethyl)-2-ethyl-1H-indol-4-yl]oxy]acetic acid,
(L) [[3-(2-amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-2-ylmethyl)-2-propyl-1H-indol-4-yl]oxy]acetic acid,
(M) [[3-(2-Amino-1,2-dioxoethyl)-2-cyclopropyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid,
(N) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-2-ylmethyl)-2-cyclopropyl-1H-indol-4-yl]oxy]acetic acid,
(O) 4-[[3-(2-Amino-1,2-dioxoethyl)-2-ethyl-1-(phenylmethyl)-1H-indol-5-yl]oxy]butanoic acid, and
(P) mixtures of (A) through (O).

13 more elements

A method for treatment of a human currently afflicted with non-rheumatoid arthritis, said method comprising administering to said human in need of such treatment, a therapeutically effective amount of a 1H-indole-3-acetic acid hydrazide represented by the formula† (Ib), or a pharmaceutically acceptable salt or prodrug derivative thereof;

126
wherein;
X is oxygen or sulfur;
R1 is selected from groups (i), (ii) and (iii) where;
(i) is C4-C20 alkyl, C4-C20 alkenyl, C4-C20 alkynyl, C4-C20 haloalkyl, C4-C12 cycloalkyl, or
(ii) is aryl or aryl substituted by halo, —CN, —CHO, —OH, —SH, C1-C10 alkylthio, C1-C10 alkoxy, C1-C10 alkyl, carboxyl, amino, or hydroxyamino;
(iii) is
127
where y is from 1 to 8, R74 is, independently, hydrogen or C1-C10 alkyl, and R75 is aryl or aryl substituted by halo, —CN, —CHO, —OH, nitro, phenyl, —SH, C1-C10 alkylthio, C1-C10 alkoxy, C1-C10 alkyl, amino, hydroxyamino or a substituted or unsubstituted 5 to 8 membered heterocyclic ring;
R2 is halo, C1-C3 alkyl, ethenyl, C1-C2 alkylthio, C1-C2 alkoxy, —CHO, —CN;
each R3 is independently hydrogen, C1-C3 alkyl, or halo;
R4, R5, R6, and R7 are each independently hydrogen, C1-C10 alkyl, C1-C10 alkenyl, C1-C10 alkynyl, C3-C8 cycloalkyl, aryl, aralkyl, or any two adjacent hydrocarbyl groups in the set R4, R5, R6, and R7 combined with the ring carbon atoms to which they are attached to form a 5 or 6 membered substituted or unsubstituted carbocyclic ring;
or C1-C10 haloalkyl, C1-C10 alkoxy, C1-C10 haloalkoxy, C4-C8 cycloalkoxy, phenoxy, halo, hydroxy, carboxyl, —SH, —CN, —S(C1-C10 alkyl), arylthio, thioacetal, —C(O)O(C1-C10 alkyl), hydrazino, hydrazido, —NH2, —NO2, —NR82R83, and —C(O)NR82R83, where, R82 and R83 are independently hydrogen, C1-C10 alkyl, C1-C10 hydroxyalkyl, or taken together with N, R82 and R83 form a 5 to 8 membered heterocyclic ring;
or a group having the formula;
128
where,
each R76 is independently selected from hydrogen, C1-C10 alkyl, hydroxy, or both R76 taken together are ═O;
p is 1 to 8,
Z is a bond, —O—, —N(C1-C10 alkyl)—, —NH, or —S—;
and
Q is —CON(R82R83), -5-tetrazolyl, —SO3H,
129
where R86 is independently selected from hydrogen, a metal, or C1-C10 alkyl.

20 more elements

A method for treatment of a human afflicted with non-rheumatoid arthritis, said method comprising administering to said human in need of such treatment, a therapeutically effective amount of a 1H-indole-3-acetamide sPLA2 inhibitor represented by formula (IIb), or a pharmaceutically acceptable salt or prodrug derivative thereof,

130
wherein;
X is oxygen or sulfur;
R11 is selected from groups (i), (ii) (iii) and (iv) where;
(i) is C6-C20 alkyl, C6-C20 alkenyl, C6-C20 alkynyl, C6-C20 haloalkyl, C4-C12 cycloalkyl, or
(ii) is aryl or aryl substituted by halo, nitro, —CN, —CHO, —OH, —SH, C1-C10 alkyl, C1-C10 alkylthio, C1-C10 alkoxyl, carboxyl, amino, or hydroxyamino;
or
(iii) is —(CH2)n—(R80), or —(NH)-(R81), where n is 1 to 8, and R80 is a group recited in (i), and R81 is selected from a group recited in (i) or (ii);
(iv) is
131
where R87 is hydrogen or C1-C10 alkyl, and R88 is selected from the group;
phenyl, naphthyl, indenyl, and biphenyl, unsubstituted or substituted by halo, —CN, —CHO, —OH, —SH, C1-C10 alkylthio, C1-C10 alkoxyl, phenyl, nitro, C1-C10 alkyl, C1-C10 haloalkyl, carboxyl, amino, hydroxyamino;
or a substituted or unsubstituted 5 to 8 membered heterocyclic ring;
R12 is halo, C1-C2 alkylthio, or C1-C2 alkoxy;
each R13 is independently hydrogen, halo, or methyl;
R14, R15, R16, and R17 are each independently hydrogen, C1-C10 alkyl, C1-C10 alkenyl, C1-C10 alkynyl, C3-C8 cycloalkyl, aryl, aralkyl, or any two adjacent hydrocarbyl groups in the set R14, R15, R16, and R17, combine with the ring carbon atoms to which they are attached to form a 5 or 6 membered substituted or unsubstituted carbocyclic ring;
or C1-C10 haloalkyl, C1-C10 alkoxy, C1-C10 haloalkoxy, C4-C8 cycloalkoxy, phenoxy, halo, hydroxy, carboxyl, —SH, —CN, C1-C10 alkylthio, arylthio, thioacetal, —C(O)O(C1-C10 alkyl), hydrazide, hydrazino, hydrazido, —NH2, —NO2, —NR82R83, and —C(O)NR82R83, where, R82 and R83 are independently hydrogen, C1-C10 alkyl, C1-C10 hydroxyalkyl, or taken together with N, R82 and R83 form a 5 to 8 membered heterocyclic ring;
or a group having the formula;
132
where,
Rνand R85 are each independently selected from hydrogen, C1-C10 alkyl, hydroxy, or R84 and R85 taken together are ═O;
p is 1 to 5,
Z is a bond, —O—, —N(C1-C10 alkyl)—, —NH—, or —S—;
and
Q is —CON(R82R83), -5-tetrazolyl, —SO3H,
133
where n is 1 to 8, R86 is independently selected from hydrogen, a metal, or C1-C10 alkyl, and R99 is selected from hydrogen or C1-C10 alkyl.

24 more elements

A method for treatment of a human afflicted with non-rheumatoid arthritis, said method comprising administering to said human in need of such treatment, a therapeutically effective amount of a A 1H-indole-1-acetamide compound or a pharmaceutically acceptable salt, solvate or prodrug derivative thereof;

wherein said compound is represented by the formula (Ic);
134
wherein for Formula (I);
X is oxygen or sulfur;
each R1 is independently hydrogen, or C1-C3 alkyl;
R3 is selected from groups (a), (b) and (c) where;
(a) is C7-C20 alkyl, C7-C20 alkenyl, C7-C20 alkynyl, carbocyclic radical, or heterocyclic radical, or
(b) is a member of (a) substituted with one or more independently selected non-interfering substituents;
or
(c) is the group —(L)—R80;
where, —(L)— is a divalent linking group of 1 to 12 atoms and where R80 is a group selected from (a) or (b);
R2 is hydrogen, halo, C1-C3 alkyl, C3-C4 cycloalkyl, C3-C4 cycloalkenyl, —O—(C1-C2 alkyl), —S—(C1-C2 alkyl), or a non-interfering substituent having a total of 1 to 3 atoms other than hydrogen;
R6 and R7 are independently selected from hydrogen, a non-interfering substituent, or the group, —(La)-(acidic group);
wherein —(La)—, is an acid linker having an acid linker length of 1 to 10;
provided, that at least one of R6 and R7 must be the group, —(La)-(acidic group);
R4 and R5 are each independently selected from hydrogen, non-interfering substituent, carbocyclic radical, carbocyclic radical substituted with non-interfering substituents, heterocyclic radical, and heterocyclic radical substituted with non-interfering substituents.

13 more elements

A method for treatment of a human afflicted with non-rheumatoid arthritis, said method comprising administering to said human in need of such treatment, a therapeutically effective amount of a 1H-indole-1-hydrazide compound or a pharmaceutically acceptable salt, solvate or prodrug derivative thereof;

wherein said compound is represented by the formula (IIc);
135
wherein for formula (II);
X is oxygen or sulfur;
each R1 is independently hydrogen, or C1-C3 alkyl;
R3 is selected from groups (a), (b) and (c) where;
(a) is C7-C20 alkyl, C7-C20 alkenyl, C7-C20 alkynyl, carbocyclic radical, or heterocyclic radical, or
(b) is a member of (a) substituted with one or more independently selected non-interfering substituent;
or
(c) is the group —(L)—R80;
where, —(L)— is a divalent linking group of 1 to 12 atoms and where R80 is a group selected from (a) or (b);
R2 is hydrogen, halo, C1-C3 alkyl, C3-C4 cycloalkyl, C3-C4 cycloalkenyl, —O—(C1-C2 alkyl), —S—(C1-C2 alkyl), or a non-interfering substituent having a total of 1 to 3 atoms other than hydrogen;
R6 and R7 are independently selected from hydrogen, a non-interfering substituent, or the group, —(La)-(acidic group);
wherein —(La)—, is an acid linker having an acid linker length of 1 to 10;
provided, that at least one of R6 and R7 must be the group, —(La)-(acidic group);
R4 and R5 are each independently selected from hydrogen, non-interfering substituent, carbocyclic radical, carbocyclic radical substituted with non-interfering substituents, heterocyclic radical, and heterocyclic radical substituted with non-interfering substituents.

13 more elements

A method for treatment of a human afflicted with non-rheumatoid arthritis, said method comprising administering to said human in need of such treatment, a therapeutically effective amount of an indolizine-1-acetamide compound or a pharmaceutically acceptable salt, solvate or prodrug derivative thereof;

wherein said compound is represented by the formula (Id);
136
wherein;
X is oxygen or sulfur;
each R11 is independently hydrogen, C1-C3 alkyl, or halo;
R13 is selected from groups (a), (b) and (c) where;
(a) is C7-C20 alkyl, C7-C20 alkenyl, C7-C20 alkynyl, carbocyclic radical, or heterocyclic radical, or
(b) is a member of (a) substituted with one or more independently selected non-interfering substituents;
or
(c) is the group —(L)—R80;
where, —(L)— is a divalent linking group of 1 to 12 atoms and where R80 is a group selected from (a) or (b);
R12 is hydrogen, halo, C1-C3 alkyl, C3-C4 cycloalkyl, C3-C4 cycloalkenyl, —O—(C1-C2 alkyl), —S—(C1-C2 alkyl), or a non-interfering substituent having a total of 1 to 3 atoms other than hydrogen;
R17 and R18 are independently selected from hydrogen, a non-interfering substituent, or the group, —(La)-(acidic group);
wherein —(La)—, is an acid linker having an acid linker length of 1 to 10;
provided, that at least one of R17 and R18 must be the group, —(La)-(acidic group);
and
R15 and R16 are each independently selected from hydrogen, non-interfering substituent, carbocyclic radical, carbocyclic radical substituted with non-interfering substituents, heterocyclic radical, and heterocyclic radical substituted with non-interfering substituents.

14 more elements

A method for treatment of a human afflicted with non-rheumatoid arthritis, said method comprising administering to said human in need of such treatment, a therapeutically effective amount of an indolizine-1-acetic acid hydrazide compound or a pharmaceutically acceptable salt, solvate or prodrug derivative thereof where said compound is represented by the formula (IId);

137
wherein;
X is oxygen or sulfur;
each R11 is independently hydrogen, C1-C3 alkyl, or halo;
R13 is selected from groups (a), (b) and (c) where;
(a) is C7-C20 alkyl, C7-C20 alkenyl, C7-C20 alkynyl, carbocyclic radical, or heterocyclic radical, or
(b) is a member of (a) substituted with one or more independently selected non-interfering substituents;
or
(c) is the group —(L)—R80;
where, —(L)— is a divalent linking group of 1 to 12 atoms and where R80 is a group selected from (a) or (b);
R12 is hydrogen, halo, C1-C3 alkyl, C3-C4 cycloalkyl, C3-C4 cycloalkenyl, —O—(C1-C2 alkyl), —S—(C1-C2 alkyl), or a non-interfering substituent having a total of 1 to 3 atoms other than hydrogen;
R17 and R18 are independently selected from hydrogen, a non-interfering substituent, or the group, —(La)-(acidic group);
wherein —(La)—, is an acid linker having an acid linker length of 1 to 10;
provided, that at least one of R17 and R18 must be the group, —(La)-(acidic group);
and
R15 and R16 are each independently selected from hydrogen, non-interfering substituent, carbocyclic radical, carbocyclic radical substituted with non-interfering substituents, heterocyclic radical, and heterocyclic radical substituted with non-interfering substituents.

13 more elements

A method for treatment of a human afflicted with non-rheumatoid arthritis, said method comprising administering to said human in need of such treatment, a therapeutically effective amount of an indolizine-1-glyoxylamide compound or a pharmaceutically acceptable salt, solvate or prodrug derivative thereof;

wherein said compound is represented by the formula (IIId);
138
wherein;
X is oxygen or sulfur;
each R11 is independently hydrogen, C1-C3 alkyl, or halo;
R13 is selected from groups (a), (b) and (c) where;
(a) is C7-C20 alkyl, C7-C20 alkenyl, C7-C20 alkynyl, carbocyclic radical, or heterocyclic radical, or
(b) is a member of (a) substituted with one or more independently selected noninterfering substituents;
or
(c) is the group —(L)—R80;
where, —(L)— is a divalent linking group of 1 to 12 atoms and where R80 is a group selected from (a) or b);
R12 is hydrogen, halo, C1-C3 alkyl, C3-C4 cycloalkyl, C3-C4 cycloalkenyl, —O—(C1-C2 alkyl), —S—(C1-C2 alkyl), or a non-interfering substituent having a total of 1 to 3 atoms other than hydrogen;
R17 and R18 are independently selected from hydrogen, a non-interfering substituent, or the group, —(La)-(acidic group);
wherein —(La)—, is an acid linker having an acid linker length of 1 to 10;
provided, that at least one of R17 and R18 must be the group, —(La)-(acidic group);
and
R15 and R16 are each independently selected from hydrogen, non-interfering substituent, carbocyclic radical, carbocyclic radical substituted with non-interfering substituents, heterocyclic radical, and heterocyclic radical substituted with non-interfering substituents.

14 more elements

A method for treatment of a human afflicted with non-rheumatoid arthritis, said method comprising administering to said human in need of such treatment, a therapeutically effective amount of an indolizine-3-acetamide compound or a pharmaceutically acceptable salt, solvate or prodrug derivative thereof;

wherein said compound is represented by the formula (IVd), as set out below:
139
wherein;
X is selected from oxygen or sulfur;
each R3 is independently hydrogen, C1-C3 alkyl, or halo;
R1 is selected from groups (a), (b) and (c) where;
(a) is C7-C20 alkyl, C7-C20 alkenyl, C7-C20 alkynyl, carbocyclic radical, or heterocyclic radical, or
(b) is a member of (a) substituted with one or more independently selected non-interfering substituents;
or
(c) is the group —(L)—R80;
where, —(L)— is a divalent linking group of 1 to 12 atoms and where R80 is a group selected from (a) or (b);
R2 is hydrogen, halo, C1-C3 alkyl, C3-C4 cycloalkyl, C3-C4 cycloalkenyl, —O—(C1-C2 alkyl), —S—(C1-C2 alkyl), or a non-interfering substituent having a total of 1 to 3 atoms other than hydrogen;
R5 and R6 are independently selected from hydrogen, a non-interfering substituent, or the group, —(La)-(acidic group);
wherein —(La)—, is an acid linker having an acid linker length of 1 to 10;
provided, that at least one of R5 and R6 must be the group, —(La)-(acidic group);
R7 and R8 are each independently selected from hydrogen, non-interfering substituent, carbocyclic radical, carbocyclic radical substituted with non-interfering substituents, heterocyclic radical, and heterocyclic radical substituted with non-interfering substituents.

13 more elements

A method for treatment of a human afflicted with non-rheumatoid arthritis, said method comprising administering to said human in need of such treatment, a therapeutically effective amount of an indolizine-3-hydrazide compound or a pharmaceutically acceptable salt, solvate or prodrug derivative thereof;

wherein said compound is represented by the formula (Vd), as set out below:
140
wherein;
X is selected from oxygen or sulfur;
each R3 is independently hydrogen, C1-C3 alkyl, or halo;
R1 is selected from groups (a), (b) and (c) where;
(a) is C7-C20 alkyl, C7-C20 alkenyl, C7-C20 alkynyl, carbocyclic radical, or heterocyclic radical, or
(b) is a member of (a) substituted with one or more independently selected non-interfering substituents;
or
(c) is the group —(L)—R80;
where, —(L)— is a divalent linking group of 1 to 12 atoms and where R80 is a group selected from (a) or (b);
R2 is hydrogen, halo, C1-C3 alkyl, C3-C4 cycloalkyl, C3-C4 cycloalkenyl, —O—(C1-C2 alkyl), —S—(C1-C2 alkyl), or a non-interfering substituent having a total of 1 to 3 atoms other than hydrogen;
R5 and R6 are independently selected from hydrogen, a non-interfering substituent, or the group, —(La)-(acidic group);
wherein —(La)—, is an acid linker having an acid linker length of 1 to 10;
provided, that at least one of R5 and R6 must be the group, —(La)-(acidic group);
R7 and R8 are each independently selected from hydrogen, non-interfering substituent, carbocyclic radical, carbocyclic radical substituted with non-interfering substituents, heterocyclic radical, and heterocyclic radical substituted with non-interfering substituents.

13 more elements

A method for treatment of a human afflicted with non-rheumatoid arthritis, said method comprising administering to said human in need of such treatment, a therapeutically effective amount of an indolizine-3-glyoxylamide compound or a pharmaceutically acceptable salt, solvate or prodrug derivative thereof;

wherein said compound is represented by the formula (VId), as set out below:
141
wherein;
X is selected from oxygen or sulfur;
each R3 is independently hydrogen, C1-C3 alkyl, or halo;
R1 is selected from groups (a), (b) and (c) where;
(a) is C7-C20 alkyl, C7-C20 alkenyl, C7-C20 alkynyl, carbocyclic radical, or heterocyclic radical, or
(b) is a member of (a) substituted with one or more independently selected non-interfering substituents;
or
(c) is the group —(L)—R80;
where, —(L)— is a divalent linking group of 1 to 12 atoms and where R80 is a group selected from (a) or (b);
R2 is hydrogen, halo, C1-C3 alkyl, C3-C4 cycloalkyl, C3-C4 cycloalkenyl, —O—(C1-C2 alkyl), —S—(C1-C2 alkyl), or a non-interfering substituent having a total of 1 to 3 atoms other than hydrogen;
R5 and R6 are independently selected from hydrogen, a non-interfering substituent, or the group, —(La)-(acidic group);
wherein —(La)—, is an acid linker having an acid linker length of 1 to 10;
provided, that at least one of R5 and R6 must be the group, —(La)-(acidic group);
R7 and R8 are each independently selected from hydrogen, non-interfering substituent, carbocyclic radical, carbocyclic radical substituted with non-interfering substituents, heterocyclic radical, and heterocyclic radical substituted with non-interfering substituents.

13 more elements

A method for treatment of a human afflicted with non-rheumatoid arthritis, said method comprising administering to said human in need of such treatment, a therapeutically effective amount of an indene-1-acetamide compound or a pharmaceutically acceptable salt, solvate or prodrug derivative thereof;

wherein said compound is represented by the formula (If);
142
wherein;
X is oxygen or sulfur;
each R1 is independently hydrogen, C1-C3 alkyl, or halo;
R3 is selected from groups (a), (b) and (c) where;
(a) is C7-C20 alkyl, C7-C20 alkenyl, C7-C20 alkynyl, carbocyclic radical, or heterocyclic radical, or
(b) is a member of (a) substituted with one or more independently selected non-interfering substituents;
or
(c) is the group —(L)—R80;
where, —(L)— is a divalent linking group of 1 to 12 atoms and where R80 is a group selected from (a) or (b);
R2 is hydrogen, halo, C1-C3 alkyl, C3-C4 cycloalkyl, C3-C4 cycloalkenyl, —O—(C1-C2 alkyl), —S—(C1-C2 alkyl), or a non-interfering substituent having a total of 1 to 3 atoms other than hydrogen;
R6 and R7 are independently selected from hydrogen, a non-interfering substituent, or the group, —(La)-(acidic group);
wherein —(La)—, is an acid linker having an acid linker length of 1 to 10;
provided, that at least one of R6 and R7 must be the group, —(La)-(acidic group);
and
R4 and R5 are each independently selected from hydrogen, non-interfering substituent, carbocyclic radical, carbocyclic radical substituted with non-interfering substituents, heterocyclic radical, and heterocyclic radical substituted with non-interfering substituents.

14 more elements

A method for treatment of a human afflicted with non-rheumatoid arthritis, said method comprising administering to said human in need of such treatment, a therapeutically effective amount of an indene-1-acetic acid hydrazide compound or a pharmaceutically acceptable salt, solvate or prodrug derivative thereof;

wherein said compound is represented by the formula (IIf);
143
wherein:
X is oxygen or sulfur;
each R1 is independently hydrogen, C1-C3 alkyl, or halo;
R3 is selected from groups (a), (b) and (c) where;
(a) is C7-C20 alkyl, C7-C20 alkenyl, C7-C20 alkynyl, carbocyclic radical, or heterocyclic radical, or
(b) is a member of (a) substituted with one or more independently selected non-interfering substituents;
or
(c) is the group —(L)—R80;
where, —(L)— is a divalent linking group of 1 to 12 atoms and where R80 is a group selected from (a) or (b);
R2 is hydrogen, halo, C1-C3 alkyl, C3-C4 cycloalkyl, C3-C4 cycloalkenyl, —O—(C1-C2 alkyl), —S—(C1-C2 alkyl), or a non-interfering substituent having a total of 1 to 3 atoms other than hydrogen;
R6 and R7 are independently selected from hydrogen, a non-interfering substituent, or the group, —(La)-(acidic group);
wherein —(La)—, is an acid linker having an acid linker length of 1 to 10;
provided, that at least one of R6 and R7 must be the group, —(La)-(acidic group);
and
R4 and R5 are each independently selected from hydrogen, non-interfering substituent, carbocyclic radical, carbocyclic radical substituted with non-interfering substituents, heterocyclic radical, and heterocyclic radical substituted with non-interfering substituents.

14 more elements

A method for treatment of a human afflicted with non-rheumatoid arthritis, said method comprising administering to said human in need of such treatment, a therapeutically effective amount of an indene-1-glyoxylamide compound or a pharmaceutically acceptable salt, solvate or prodrug derivative thereof;

wherein said compound is represented by the formula (IIIf);
144
where;
X is oxygen or sulfur;
R3 is selected from groups (a), (b) and (c) where;
(a) is C7-C20 alkyl, C7-C20 alkenyl, C7-C20 alkynyl, carbocyclic radical, or heterocyclic radical, or
(b) is a member of (a) substituted with one or more independently selected non-interfering substituents;
or
(c) is the group —(L)—R80;
where, —(L)— is a divalent linking group of 1 to 12 atoms and where R80 is a group selected from (a) or (b);
R2 is hydrogen, halo, C1-C3 alkyl, C3-C4 cycloalkyl, C3-C4 cycloalkenyl, —O—(C1-C2 alkyl), —S—(C1-C2 alkyl), or a non-interfering substituent having a total of 1 to 3 atoms other than hydrogen;
R6 and R7 are independently selected from hydrogen, a non-interfering substituent, or the group, —(La)-(acidic group);
wherein —(La)—, is an acid linker having an acid linker length of 1 to 10;
provided, that at least one of R6 and R7 must be the group, —(La)-(acidic group);
R4 and R5 are each independently selected from hydrogen, non-interfering substituent, carbocyclic radical, carbocyclic radical substituted with non-interfering substituents, heterocyclic radical, and heterocyclic radical substituted with non-interfering substituents.

12 more elements

A method for treatment of a human afflicted with non-rheumatoid arthritis, said method comprising administering to said human in need of such treatment, a therapeutically effective amount of a compound of the formula (Ie)

145
wherein;
A is phenyl or pyridyl wherein the nitrogen is at the 5-, 6-, 7- or 8-position;
one of B or D is nitrogen and the other is carbon;
Z is cyclohexenyl, phenyl, pyridyl, wherein the nitrogen is at the 1-, 2-, or 3-position, or a 6-membered heterocyclic ring having one heteroatom selected from the group consisting of sulfur or oxygen at the 1-, 2- or 3-position, and nitrogen at the 1-, 2-, 3- or 4-position;
is a double or single bond;
R20 is selected from groups (a), (b) and (c) where;
(a) is —(C5-C20)alkyl, —(C5-C20)alkenyl, (C5-C20)alkynyl, carbocyclic radicals, or heterocyclic radicals, or
(b) is a member of (a) substituted with one or more independently selected non-interfering substituents;
or
(c) is the group —(L)—R80;
where, —(L)— is a divalent linking group of 1 to 12 atoms selected from carbon, hydrogen, oxygen, nitrogen, and sulfur;
wherein the combination of atoms in —(L)— are selected from the group consisting of (i) carbon and hydrogen only, (ii) one sulfur only, (iii) one oxygen only, (iv) one or two nitrogen and hydrogen only, (v) carbon, hydrogen, and one sulfur only, and (vi) and carbon, hydrogen, and oxygen only;
and where R80 is a group selected from (a) or (b);
R21 is a non-interfering substituent;
R1′ is —NHNH2, —NH2 or —CONH2;
R2′ is selected from the group consisting of —OH, and —O(CH2)tR5′ where
R5′ is H, —CN, —NH2, —CONH2, —CONR9R10 —NHSO2R15;
—CONHSO2R15, where R15 is —(C1-C6)alkyl or —CF3;
phenyl or phenyl substituted with —CO2H or —CO2(C1-C4)alkyl;
and —(La)-(acidic group), wherein —(La)— is an acid linker having an acid linker length of 1 to 7 and t is 1-5;
R3′ is selected from non-interfering substituent, carbocyclic radicals, carbocyclic radicals substituted with non-interfering substituents, heterocyclic radicals, and heterocyclic radicals substituted with non-interfering substituents;
or a pharmaceutically acceptable racemate, solvate, tautomer, optical isomer, prodrug derivative or salt thereof;
provided that;
when R3′ is H, R20 is benzyl and m is 1 or 2;
R2′ cannot be —O(CH2)mH;
and
provided that when D is nitrogen, the heteroatom of Z is selected from the group consisting of sulfur or oxygen at the 1-, 2- or 3-position and nitrogen at the 1-, 2-, 3- or 4-position.

25 more elements

A method for treatment of a human afflicted with non-rheumatoid arthritis, said method comprising administering to said human in need of such treatment, a therapeutically effective amount of a compound represented by the formula (IIe):

146
wherein;
Z is cyclohexenyl, or phenyl;
R21 is a non-interfering substituent;
R1 is —NHNH2 or —NH2;
R2 is selected from the group consisting of —OH and —O(CH2)mR5 where
R5 is H, —CO2H, —CONH2, —CO2(C1-C4 alkyl);
147
where R6 and R7 are each independently —OH or —O(C1-C4)alkyl;
—SO3H, —SO3(C1-C4 alkyl), tetrazolyl, —CN, —NH2, —NHSO2R15;
—CONHSO2R15, where R15 is —(C1-C6)alkyl or —CF3, phenyl or phenyl substituted with —CO2H or —CO2(C1-C4)alkyl where m is 1-3;
R3 is H, —O(C1-C4)alkyl, halo, —(C1-C6)alkyl, phenyl, —(C1-C4)alkylphenyl;
phenyl substituted with —(C1-C6)alkyl, halo, or —CF3;
—CH2OSi(C1-C6)alkyl, furyl, thiophenyl, —(C1-C6)hydroxyalkyl;
or —(CH2)nR8 where R8 is H, —CONH2, —NR9R10, —CN or phenyl where R9 and R10 are independently —(C1-C4)alkyl or -phenyl(C1-C4)alkyl and n is 1 to 8;
R4 is H, —(C5-C14)alkyl, —(C3-C14)cycloalkyl, pyridyl, phenyl or phenyl substituted with —(C1-C6)alkyl, halo, —CF3, —OCF3, —(C1-C4)alkoxy, —CN, —(C1-C4)alkylthio, phenyl(C1-C4)alkyl, —(C1-C4)alkylphenyl, phenyl, phenoxy or naphthyl;
or a pharmaceutically acceptable racemate, solvate, tautomer, optical isomer, prodrug derivative or salt, thereof.

14 more elements

A method for treatment of a human afflicted with non-rheumatoid arthritis, wherein the method comprising administering to said human in need of such treatment, a therapeutically effective amount of a carbazole compound are selected from those represented by the formula (XXX):

148
wherein:
R1 is —NHNH2, or —NH2;
R2 is selected from the group consisting of —OH and —O(CH2)mR5 where
R5 is H, —CO2H, —CO2(C1-C4 alkyl);
149
where R6 and R7 are each independently —OH or —O(C1-C4)alkyl;
—SO3H, —SO3(C1-C4 alkyl), tetrazolyl, —CN, —NH2, —NHSO2R15;
—CONHSO2R15, where R15 is —(C1-C6)alkyl or —CF3, phenyl or phenyl substituted with —CO2H or —CO2(C1-C4)alkyl where m is 1-3;
R3 is H, —O(C1-C4)alkyl, halo, —(C1-C6)alkyl, phenyl, —(C1-C4)alkylphenyl;
phenyl substituted with —(C1-C6)alkyl, halo, or —CF3;
—CH2OSi(C1-C6)alkyl, furyl, thiophenyl, —(C1-C6)hydroxyalkyl;
or —(CH2)nR8 where R8 is H, —CONH2, —NR9R10, —CN or phenyl where R9 and R10 are independently —(C1-C4)alkyl or -phenyl(C1-C4)alkyl and n is 1 to 8;
R4 is H, —(C5-C14)alkyl, —(C3-C14)cycloalkyl, pyridyl, phenyl or phenyl substituted with —(C1-C6)alkyl, halo, —CF3, —OCF3, —(C1-C4)alkoxy, —CN, —(C1-C4)alkylthio, phenyl(C1-C4)alkyl, —(C1-C4)alkylphenyl, phenyl, phenoxy or naphthyl;
A is phenyl or pyridyl wherein the nitrogen is at the 5-, 6-, 7- or 8-position;
Z is cyclohexenyl, phenyl, pyridyl wherein the nitrogen is at the 1-, 2- or 3-position or a 6-membered heterocyclic ring having one heteroatom selected from the group consisting of sulfur or oxygen at the 1-, 2- or 3-position and nitrogen at the 1-, 2-, 3- or 4-position, or
wherein one carbon on the heterocyclic ring is optionally substituted with ═O;
or a pharmaceutically acceptable racemate, solvate, tautomer, optical isomer, prodrug derivative or salt thereof;
provided that one of A or Z is a heterocyclic ring.

16 more elements

A method for treatment of a human afflicted with non-rheumatoid arthritis, wherein the method comprising administering to said human in need of such treatment, a therapeutically effective amount of a compound selected from the following:

9-benzyl-5,7-dimethoxy-1,2,3,4-tetrahydrocarbazole-4-carboxylic acid hydrazide;
9-benzyl-5,7-dimethoxy-1,2,3,4-tetrahydrocarbazole-4-carboxamide;
[9-benzyl-4-carbamoyl-7-methoxy-1,2,3,4-tetrahydrocarbazol-5-yl]oxyacetic acid sodium salt;
[9-benzyl-4-carbamoyl-7-methoxycarbazol-5-yl]oxyacetic acid;
methyl [9-benzyl-4-carbamoyl-7-methoxycarbazol-5-yl]oxyacetic acid;
9-benzyl-7-methoxy-5-cyanomethyloxy-1,2,3,4-tetrahydrocarbazole-4-carboxamide;
9-benzyl-7-methoxy-5-(1H-tetrazol-5-yl-methyl)oxy)-1,2,3,4-tetrahydrocarbazole-4-carboxamide;
{9-[(phenyl)methyl]-5-carbamoyl-2-methyl-carbazol-4-yl}oxyacetic acid;
{9-[(3-fluorophenyl)methyl]-5-carbamoyl-2-methyl-carbazol-4-yl}oxyacetic acid;
{9-[(3-methylphenyl)methyl]-5-carbamoyl-2-methyl-carbazol-4-yl}oxyacetic acid;
{9-[(phenyl)methyl]-5-carbamoyl-2-(4-trifluoromethylphenyl)-carbazol-4-yl}oxyacetic acid;
9-benzyl-5-(2-methanesulfonamido)ethyloxy-7-methoxy-1,2,3,4-tetrahydrocarbazole-4-carboxamide;
9-benzyl-4-(2-methanesulfonamido)ethyloxy-2-methoxycarbazole-5-carboxamide;
9-benzyl-4-(2-trifluoromethanesulfonamido)ethyloxy-2-methoxycarbazole-5-carboxamide;
9-benzyl-5-methanesulfonamidoylmethyloxy-7-methoxy-1,2,3,4-tetrahydrocarbazole-4-carboxamide;
9-benzyl-4-methanesulfonamidoylmethyloxy-carbazole-5-carboxamide;
[5-carbamoyl-2-pentyl-9-(phenylmethyl)carbazol-4-yl]oxyacetic acid;
[5-carbamoyl-2-(1-methylethyl)-9-(phenylmethyl)carbazol-4-yl]oxyacetic acid;
[5-carbamoyl-9-(phenylmethyl)-2-[(tri(-1-methylethyl)silyl)oxymethyl]carbazol-4-yl]oxyacetic acid;
[5-carbamoyl-2-phenyl-9-(phenylmethyl)carbazol-4-yl]oxyacetic acid[5-carbamoyl-2-(4-chlorophenyl)-9-(phenylmethyl)carbazol-4-yl]oxyacetic acid;
[5-carbamoyl-2-(2-furyl)-9-(phenylmethyl)carbazol-4-yl]oxyacetic acid;
[5-carbamoyl-9-(phenylmethyl)-2-[(tri(-1-methylethyl)silyl)oxymethyl]carbazol-4-yl]oxyacetic acid, lithium salt;
{9-[(phenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid;
{9-[(3-fluorophenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid;
{9-[(3-phenoxyphenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid;
{9-[(2-Fluorophenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid;
{9-[(2-trifluoromethylphenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid;
{9-[(2-benzylphenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid;
{9-[(3-trifluoromethylphenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid;
{9-[(1-naphthyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid;
{9-[(2-cyanophenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid;
{9-[(3-cyanophenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid;
{9-[(2-methylphenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid;
{9-[(3-methylphenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid;
{9-[(3,5-dimethylphenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid;
{9-[(3-iodophenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid;
{9-[(2-Chlorophenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid;
{9-[(2,3-difluorophenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid;
{9-[(2,6-difluorophenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid;
{9-[(2,6-dichlorophenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid;
{9-[(3-trifluoromethoxyphenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid;
{9-[(2-biphenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid;
{9-[(2-Biphenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid;
the {9-[(2-Biphenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid;
[9-Benzyl-4-carbamoyl-1,2,3,4-tetrahydrocarbaole-5-yl]oxyacetic acid;
{9-[(2-Pyridyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid;
{9-[(3-Pyridyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid;
[9-benzyl-4-carbamoyl-8-methyl-1,2,3,4-tetrahydrocarbazol-5-yl]oxyacetic acid;
[9-benzyl-5-carbamoyl-1-methylcarbazol-4-yl]oxyacetic acid;
[9-benzyl-4-carbamoyl-8-fluoro-1,2,3,4-tetrahydrocarbazol-5-yl]oxyacetic acid;
[9-benzyl-5-carbamoyl-1-fluorocarbazol-4-yl]oxyacetic acid;
[9-benzyl-4-carbamoyl-8-chloro-1,2,3,4-tetrahydrocarbazol-5-yl]oxyacetic acid;
[9-benzyl-5-carbamoyl-1-chlorocarbazol-4-yl]oxyacetic acid;
[9-[(Cyclohexyl)methyl]-5-carbamoylcarbazol-4-yl]oxyacetic acid;
[9-[(Cyclopentyl)methyl]-5-carbamoylcarbazol-4-yl]oxyacetic acid;
5-carbamoyl-9-(phenylmethyl)-2-[[(propen-3-yl)oxy]methyl]carbazol-4-yl]oxyacetic acid;
[5-carbamoyl-9-(phenylmethyl)-2-[(propyloxy)methyl]carbazol-4-yl]oxyacetic acid;
9-benzyl-7-methoxy-5-((carboxamidomethyl)oxy)-1,2,3,4-tetrahydrocarbazole-4-carboxamide;
9-benzyl-7-methoxy-5-cyanomethyloxy-carbazole-4-carboxamide;
9-benzyl-7-methoxy-5-((1H-tetrazol-5-yl-methyl)oxy)-carbazole-4-carboxamide;
9-benzyl-7-methoxy-5-((carboxamidomethyl)oxy)-carbazole-4-carboxamide;
and
[9-Benzyl-4-carbamoyl-1,2,3,4-tetrahydrocarbaole-5-yl]oxyacetic acid
(R,S)-(9-benzyl-4-carbamoyl-1-oxo-3-thia-1,2,3,4-tetrahydrocarbazol-5-yl)oxyacetic acid;
(R,S)-(9-benzyl-4-carbamoyl-1-oxo-3-thia-1,2,3,4-tetrahydrocarbazol-5-yl)oxyacetic acid;
[N-benzyl-1-carbamoyl-1-aza-1,2,3,4-tetrahydrocarbazol-8-yl]oxyacetic acid;
4-methoxy-6-methoxycarbonyl-10-phenylmethyl-6,7,8,9-tetrahydropyrido[1,2-a]indole;
(4-carboxamido-9-phenylmethyl-4,5-dihydrothiopyrano[3,4-b]indol-5-yl)oxyacetic acid;
3,4-dihydro-4-carboxamidol-5-methoxy-9-phenylmethylpyrano[3,4-b]indole;
2-[(2,9 bis-benzyl-4-carbamoyl-1,2,3,4-tetrahydro-beta-carbolin-5-yl)oxy]acetic acid;
or a pharmaceutically acceptable racemate, solvate, tautomer, optical isomer, prodrug, or salt thereof.

68 more elements

A method for treatment of a human afflicted with non-rheumatoid arthritis, said method comprising administering to said human in need of such treatment, a therapeutically effective amount of a compound of the formula (Ih):

151
wherein:
R1 is phenyl, isoquinolin-3-yl, pyrazinyl, pyridin-2-yl, pyridin-2-yl substituted at the 4-position with —(C1-C4)alkyl, (C1-C4)alkoxyl, —CN or —(CH2)nCONH2 where n is 0-2;
R2 is phenyl;
phenyl substituted with 1 to 3 substituents selected from the group consisting of —(C1-C4)alkyl, —CN, halo, —NO2, CO2(C1-C4)alkyl and —CF3;
naphthyl;
thiophene or thiophene substituted with 1 to 3 halo groups;
R3 is hydrogen;
phenyl;
phenyl(C2-C6)alkenyl;
pyridyl;
naphthyl;
quinolinyl;
(C1-C4)alkylthiazolyl;
phenyl substituted with 1 to 2 substituents selected from the group consisting of —(C1-C4)alkyl, —CN, —CONH2, —NO2, —CF3, halo, (C1-C4)alkoxy, CO2(C1-C4)alkyl, phenoxy and SR4 where R4 is —(C1-C4)alkyl or halophenyl;
phenyl substituted with one substituent selected from the group consisting of
—O(CH2)pR5 where p is 1 to 3 and R5 is —CN, —CO2H, —CONH2, or tetrazolyl, phenyl and
—OR6 where R6 is cyclopentyl, cyclohexenyl, or phenyl substituted with halo or (C1-C4)alkoxy;
or phenyl substituted with two substituents which, when taken together with the phenyl ring to which they are attached form a methylenedioxy ring;
and
m is 1 to 5;
or a pharmaceutically acceptable salt thereof.

19 more elements

A method for treatment of a human afflicted with non-rheumatoid arthritis, said method comprising administering to said human in need of such treatment, a therapeutically effective amount of a compound of the formula (I):

153
R1 is hydrogen, (C1-C4)alkyl, phenyl or phenyl substituted with one or two substituents selected from the group consisting of —(C1-C4)alkyl, (C1-C4)alkoxy, phenyl(C1-C4)alkyl, (C1-C4)alkylthio, halo and phenyl;
R2 is hydrogen, —(C1-C4)alkyl, halo, (C1-C4)alkoxy or (C1-C4)alkylthio;
R3 and R4 are each hydrogen or when taken together are ═O;
R5 is —NH2 or —NHNH2;
R6 and R7 are each hydrogen or when one of R6 and R7 is hydrogen, the other is —(C1-C4)alkyl, —(CH2)nR10 where R10 is —CO2R11, —PO3(R11)2, —PO4(R11)2 or —SO3R11 where R11 is independently hydrogen or —(C1-C4)alkyl and n is 0 to 4;
or R6 and R7, taken together, are ═O or ═S;
X is R8(C1-C6)alkyl;
R8(C2-C6)alkenyl or phenyl substituted at the ortho position with R8 where R8 is (CH2)nR10 where R10 is —CO2R11, —PO3(R11)2, —PO4(R11) or —SO3R11, R11 and n is 1 to 4 as defined above, and additionally substituted with one or two substituents selected from the group consisting of hydrogen, —(C1-C4)alkyl, halo, (C1-C4)alkoxy, or two substituents which, when taken together with the phenyl ring to which they are attached, form a naphthyl group;
and
R9 is hydrogen or methyl or ethyl;
or a pharmaceutically acceptable salt thereof.

9 more elements

Method for tratment of non-rheumatoid arthritis

Life of this patent

Abstract

Claims42

Method for tratment of non-rheumatoid arthritis

Life of this patent

Abstract

Claims42