US2004147597A1PendingUtilityA1
Anti-mycobacterium compositions and methods of preparing and using same
Assignee: ADVANCED LIFE SCIENCES INCPriority: Sep 22, 1999Filed: Jan 12, 2004Published: Jul 29, 2004
Est. expirySep 22, 2019(expired)· nominal 20-yr term from priority
Inventors:Yuh-Meei Lin
A61K 31/12A61P 31/06A61K 31/352
57
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Claims
Abstract
The present invention relates to compounds, compositions and methods for the prevention or treatment of mycobacterium infections. The compounds are naturally occurring and synthetic biflavonoids, flavonoids, chalcones and chalcone like compounds. The compounds were screened for anti-mycobacterium activity. Of the compounds showing anti-mycobacterium activity, eight were identified as particularly potent, exhibiting greater than 90% inhibition of the growth of Mtb at a concentration of 12.5 Πg/mL. The actual minimum inhibitory concentrations (MIC), defined as the lowest concentration inhibiting 99% of the inoculum, for the preferred compounds ranged from 6.8 to 48.3 ΠM.
Claims
exact text as granted — not AI-modifiedWhat I claim:
1 . A composition for treating or preventing a mycobacterium infection comprising an effective anti-mycobacterium effective amount of a compound of formula i:
wherein R 1 -R 9 are independently comprised of H; OCH 3 ; EtO; OH; O-alkenyl;
phenyl; NH 2 ; COOH; F; Cl; Br; I; CONH 2 ; NO 2 ; NR 10 R 11 OCONR 10 R 11 wherein R 10 and R 11 independently comprise H alkyl or aryl; COR 12 wherein R 12 comprises H, OH, O-alkyl, O-aryl or amino; NHCOCH 3 ; O 2 − ; OCOR 13 wherein R 13 comprises alkyl or aryl; OAc; benzoyl; CONH 2 ; or NO 2 ; or a pharmaceutically acceptable derivative or salt thereof and a pharmaceutically acceptable carrier therefor.
2 . The composition of claim 1 wherein, R 1 =OH, R 5 , R 2 =R 4 =R 6 =R 7 =R 8 =R 9 =H.
3 . The composition of claim 2 wherein R 3 comprises OCH 3 , Cl, Br or I.
4 . The composition of claim 1 wherein, R 1 =OH, R 2 =R 3 =R 4 =R 6 =R 7 =R 9 =H and R 8 =OCH 3 .
5 . The composition of claim 4 wherein R 5 comprises OCH 3 or F.
6 . The composition of claim 1 wherein R 1 =OH; R 5 =R 3 =R 2 =R 6 =R 7 =R 8 =R 9 =H.
7 . The composition of claim 6 wherein R 4 comprises phenyl, NH 2 , Cl, Br or I.
8 . The composition of claim 1 wherein R 5 =R 2 =R 4 =R 1 =R 6 =R 7 =R 9 =H; R 3 =NO 2 ; and R 8 =OCH 3 .
9 . The composition of claim 1 wherein R 1 =OH; R 5 =R 2 =R 3 =R 4 =R 6 =R 8 =R 9 =H.
10 . The composition of claim 9 wherein R 7 comprises H, OH, NH 2 , Cl or I.
11 . The composition of claim 1 wherein, R 1 =R 4 =R 3 =R 5 =R 6 =R 9 =H; R 2 =OH; R 7 =OCH 2 − ; and R 8 =0.
12 . The composition of claim 1 wherein, R 1 =OH; R 2 =R 4 =R 6 =R 7 =R 9 =H; R 3 =R 8 =OCH 3 .
13 . The composition of claim 12 wherein R 5 comprises OCH 3 or H.
14 . The composition of claim 1 wherein, R 1 =OH; R 5 =R 2 =R 3 =R 4 =R 7 =R 8 =R 9 =H.
15 . The composition of claim 14 wherein R 6 comprises OCH 3 , Br or I.
16 . The composition of claim 1 wherein R 1 =R 2 =R 4 =R 5 =R 6 =R 7 =R 8 =R 9 =H; and R 3 =NH 2 .
17 . The composition of claim 1 wherein R 1 =OH; R 5 =R 3 =R 2 =R 6 =R 7 =R 9 =H; and R 8 =OCH 3 .
18 . The composition of claim 17 wherein R 4 comprises Cl or Br.
19 . The composition of claim 1 wherein R 1 =OH; and R 5 =R 2 =R 3 =R 4 =R 6 =R 7 =R 9 =H.
20 . The composition of claim 19 wherein R 8 comprises OCH 3 , Cl, Br or I.
21 . The composition of claim 1 wherein R 1 =F; R 5 =R 2 =R 3 =R 4 =R 6 =R 7 =R 9 =H; and R 8 =OCH 3 .
22 . The composition of claim 1 wherein R 1 =OH; R 5 =R 2 =R 4 =R 6 =R 7 =R 9 =H; and R 8 =OCH 3 .
23 . The composition of claim 22 wherein R 3 comprises F, Cl or Br.
24 . The composition of claim 1 wherein R 1 =OH; R 2 =F; R 5 =R 4 =R 3 =R 6 =R 7 =R 9 =H; and R 8 =OCH 3 .
25 . The composition of claim 1 wherein R 1 =OH; R 2 =Br; and R 5 =R 4 =R 3 =R 6 =R 7 =R 8 =R 9 =H.
26 . The composition of claim 1 wherein R 1 =OH; R 5 =R 2 =R 4 =R 7 =R 8 =R 9 =H; R 3 =Br; and R 6 =NH 2 .
27 . The composition of claim 1 wherein R 1 =OH; R 5 =R 3 =R 2 =R 7 =R 8 =R 9 =H; R 4 =Br; and R 6 =NH 2 .
28 . The composition of claim 1 wherein R 1 =R 4 =R 3 =R 5 =R 7 =R 8 =R 9 =H; R 2 =NH 2 ; and R 6 =I.
29 . The composition of claim 1 wherein R 1 =OH; R 5 =R 2 =R 4 =R 6 =R 8 =R 9 =H; R 3 =OCH 3 ; and R 7 =I.
30 . A method for preventing or treating a mycobacterium infection in a mammal comprising administering to a mammal in need of anti-mycobacterium prevention or treatment an effective anti-mycobacterium amount of at least one compound of formula i:
wherein R 1 -R 9 are independently comprised of H; OCH 3 ; EtO; OH; O-alkenyl; phenyl; NH 2 ; COOH; F; Cl; Br; I; CONH 2 ; NO 2 ; NR 10 R 11 OCONR 10 R 11 wherein R 10 and R 11 =I independently comprise H alkyl or aryl; COR 12 wherein R 12 comprises H, OH, O-alkyl, O-aryl or amino; NHCOCH 3 ; O 2 − ; OCOR 13 wherein R 13 comprises alkyl or aryl; OAc; benzoyl; CONH 2 ; or NO 2 ; or a pharmaceutically acceptable derivative or salt thereof and a pharmaceutically acceptable carrier therefor.
31 . The method of claim 30 wherein, R 1 =OH, R 5 =R 2 =R 4 =R 6 =R 7 =R 8 =R 9 =H.
32 . The method of claim 31 wherein R 3 comprises OCH 3 , Cl, Br or I.
33 . The method of claim 30 wherein, R 1 =OH, R 2 =R 3 =R 4 =R 6 =R 7 =R 9 =H and R 8 =OCH 3 .
34 . The method of claim 33 wherein R 5 comprises OCH 3 or F.
35 . The method of claim 30 wherein R 1 =OH; R 5 =R 3 =R 2 =R 6 =R 7 =R 8 =R 9 =H.
36 . The method of claim 35 wherein R 4 comprises phenyl, NH 2 , Cl, Br or I.
37 . The method of claim 30 wherein R 5 =R 2 =R 4 =R 6 =R 7 =R 9 =H; R 3 =NO 2 ; and R 8 =OCH 3 .
38 . The method of claim 30 wherein R 1 =OH; R 5 =R 2 =R 3 =R 4 =R 6 =R 8 =R 9 =H.
39 . The method of claim 38 wherein R 7 comprises H, OH, NH 2 , Cl or I.
40 . The method of claim 30 wherein, R 1 =R 4 =R 3 =R 5 =R 6 =R 9 =H; R 2 =OH; R 7 =OCH 2 − ; and R 8 =O − .
41 . The method of claim 30 wherein, R 1 =OH; R 2 =R 4 =R 6 =R 7 =R 9 =H; R 3 =R 8 =OCH 3 .
42 . The method of claim 41 wherein R 5 comprises OCH 3 or H.
43 . The method of claim 30 wherein, R 1 =OH; R 5 =R 2 =R 3 =R 4 =R 7 =R 8 =R 9 =H.
44 . The method of claim 43 wherein R 6 comprises OCH 3 , Br or I.
45 . The method of claim 30 wherein R 1 =R 2 =R 4 =R 5 =R 6 =R 7 =R 8 =R 9 =H; and R 3 =NH 2 .
46 . The method of claim 30 wherein R 1 =OH; R 5 =R 3 =R 2 =R 6 =R 7 =R 9 =H; and R 8 =OCH 3 .
47 . The method of claim 46 wherein R 4 comprises Cl or Br.
48 . The method of claim 30 wherein R 1 =OH; and R 5 =R 2 =R 3 =R 4 =R 6 =R 7 =R 9 =H.
49 . The method of claim 48 wherein R 8 comprises OCH 3 , Cl, Br or I.
50 . The method of claim 30 wherein R 1 =F; R 5 =R 2 =R 3 =R 4 =R 6 =R 7 =R 9 =H; and R 8 =OCH 3 .
51 . The method of claim 30 wherein R 1 =OH; R 5 =R 2 =R 4 =R 6 =R 7 =R 9 =H; and R 8 =OCH 3 .
52 . The method of claim 51 wherein R 3 comprises F, Cl or Br.
53 . The method of claim 30 wherein R 1 =OH; R 2 =F; R 5 =R 4 =R 3 =R 6 =R 7 =R 9 =H; and R 8 =OCH 3 .
54 . The method of claim 30 wherein R 1 =OH; R 2 =Br; and R 5 =R 4 =R 3 =R 6 =R 7 =R 8 =R 9 =H.
55 . The method of claim 30 wherein R 1 =OH; R 5 =R 2 =R 4 =R 7 =R 8 =R 9 =H; R 3 =Br; and R 6 =NH 2 .
56 . The method of claim 30 wherein R 1 =OH; R 5 =R 3 =R 2 =R 7 =R 8 =R 9 =H; R 4 =Br; and R 6 =NH 2 .
57 . The method of claim 30 wherein R 1 =R 4 =R 3 =R 5 =R 7 =R 8 =R 9 =H; R 2 =NH 2 ; and R 6 =I.
58 . The method of claim 30 wherein R 1 =OH; R 5 =R 2 =R 4 =R 6 =R 8 =R 9 =H; R 3 =OCH 3 ; and R 7 =I.
59 . A composition for treating or preventing a mycobacterium infection comprising an effective anti-mycobacterium effective amount of a compound of formula ii:
wherein R 1 =4-fluorophenyl-, 3-hydroxyphenyl-, pyridin-3-yl-, furan-2-yl-, phenanthren-2-yl-, 3-fluorenyl-, pyridin-2-yl-, naphthalen-1-yl-, pyridin-2-yl-, 4-bromo-2-hydroxyphenyl-, pyridin-4-yl-, 2-hydroxy-4-methoxyphenyl-, 4-aminophenyl-, pyridin-4-yl-, 2-hydroxy-5-methoxyphenyl-, 4-methoxyphenyl-, 4-methoxyphenyl-, 2-hydroxy-5-chlorophenyl-, 4-aminophenyl-, 3-hydroxynaphthalen-2-yl-, furan-2-yl- or pyridin-2-yl-; and
R 2 =pyridin-3-yl-, phenanthren-9-yl-, phenanthren-9-yl-, phenyl-, 2-aminopyridino-3-yl, 2-aminopyridino-3-yl-, pyridin-2-yl-, phenyl-, 4-dimethylaminophenyl-, furan-2-yl-, indol-2-yl-, furan-2-yl-, 2-aminopyridin-3-yl-, 4-dimethylaminophenyl-, furan-2-yl-, pyridin-4-yl-, pyridin-3-yl-, 2-amino-pyridin-3-yl-, 2-aminopyridin-3-yl-, 2-aminopyridin-3-yl-, pyridin-4-yl- or 4-methoxyphenyl-; or
a pharmaceutically acceptable derivative or salt thereof and a pharmaceutically acceptable carrier therefor.
60 . The composition of claim 59 wherein R 1 =4-fluorophenyl- and R 2 =pyridin-3-yl-.
61 . The composition of claim 59 wherein R 1 =3-hydroxyphenyl- and R 2 =phenanthren-9-yl-.
62 . The composition of claim 59 wherein R 1 =pyridin-3-yl- and R 2 =phenanthren-9-yl-.
63 . The composition of claim 59 wherein R 1 =furan-2-yl- and R 2 =phenyl-.
64 . The composition of claim 59 wherein R 1 =phenanthren-2-yl- and R 2 =2-aminopyridino-3-yl-.
65 . The composition of claim 59 wherein R 1 =3-fluorenyl- and R 2 =2-aminopyridino-3-yl-.
66 . The composition of claim 59 wherein R 1 =pyridin-2-yl- and R 2 =pyridin-2-yl-.
67 . The composition of claim 59 wherein R 1 =naphthalen-1-yl- and R 2 =phenyl-.
68 . The composition of claim 59 wherein R 1 =pyridin-2-yl- and R 2 =4-dimethylaminophenyl-.
69 . The composition of claim 59 wherein R 1 =4-bromo-2-hydroxyphenyl- and R 2 =furan-2-yl-.
70 . The composition of claim 59 wherein R 1 =pyridin-4-yl- and R 2 =indol-2-yl-.
71 . The composition of claim 59 wherein R 1 =2-hydroxy-4-methoxyphenyl- and R 2 =furan-2-yl-.
72 . The composition of claim 59 wherein R 1 =4-aminophenyl- and R 2 =2-aminopyridin-3-yl-.
73 . The composition of claim 59 wherein R 1 =pyridin-4-yl- and R 2 =4-dimethylaminophenyl-.
74 . A method for preventing or treating a mycobacterium infection in a mammal comprising administering to a mammal in need of anti-mycobacterium prevention or treatment an effective anti-mycobacterium amount of at least one compound of formula ii:
wherein R 1 =4-fluorophenyl-, 3-hydroxyphenyl-, pyridin-3-yl-, furan-2-yl-, phenanthren-2-yl-, 3-fluorenyl-, pyridin-2-yl-, naphthalen-1-yl-, pyridin-2-yl-, 4-bromo-2-hydroxyphenyl-, pyridin-4-yl-, 2-hydroxy-4-methoxyphenyl-, 4-aminophenyl-, pyridin-4-yl-, 2-hydroxy-5-methoxyphenyl-, 4-methoxyphenyl-, 4-methoxyphenyl-, 2-hydroxy-5-chlorophenyl-, 4-aminophenyl-, 3-hydroxynaphthalen-2-yl-, furan-2-yl- or pyridin-2-yl-; and
R 2 =pyridin-3-yl-, phenanthren-9-yl-, phenanthren-9-yl-, phenyl-, 2-aminopyridino-3-yl, 2-aminopyridino-3-yl-, pyridin-2-yl-, phenyl-, 4-dimethylaminophenyl-, furan-2-yl-, indol-2-yl-, furan-2-yl-, 2-aminopyridin-3-yl-, 4-dimethylaminophenyl-, furan-2-yl-, pyridin-4-yl-, pyridin-3-yl-, 2-amino-pyridin-3-yl-, 2-aminopyridin-3-yl-, 2-aminopyridin-3-yl-, pyridin-4-yl- or 4-methoxyphenyl-; or
a pharmaceutically acceptable derivative or salt thereof and a pharmaceutically acceptable carrier therefor.
75 . The method of claim 74 wherein R 1 =4-fluorophenyl- and R 2 =pyridin-3-yl-.
76 . The method of claim 74 wherein R 1 =3-hydroxyphenyl- and R 2 =phenanthren-9-yl-.
77 . The method of claim 74 wherein R 1 =pyridin-3-yl- and R 2 =phenanthren-9-yl-.
78 . The method of claim 74 wherein R 1 =furan-2-yl- and R 2 =phenyl-.
79 . The method of claim 74 wherein R 1 =phenanthren-2-yl- and R 2 =2-aminopyridino-3-yl-.
80 . The method of claim 74 wherein R 1 =3-fluorenyl- and R 2 =2-aminopyridino-3-yl-.
81 . The method of claim 74 wherein R 1 pyridin-2-yl- and R 2 pyridin-2-yl-.
82 . The method of claim 74 wherein R 1 =naphthalen-1-yl- and R 2 =phenyl-.
83 . The method of claim 74 wherein R 1 =pyridin-2-yl- and R 2 =4-dimethylaminophenyl-.
84 . The method of claim 74 wherein R 1 =4-bromo-2-hydroxyphenyl- and R 2 =furan-2-yl-.
85 . The method of claim 74 wherein R 1 =pyridin-4-yl- and R 2 =indol-2-yl-.
86 . The method of claim 74 wherein R 1 =2-hydroxy-4-methoxyphenyl- and R 2 furan-2-yl-.
87 . The method of claim 74 wherein R 1 =4-aminophenyl- and R 2 =2-aminopyridin-3-yl-.
88 . The method of claim 74 wherein R 1 =pyridin-4-yl- and R 2 =4-dimethylaminophenyl-.
89 . A composition for treating or preventing a mycobacterium infection comprising an effective anti-mycobacterium effective amount of a compound of formula iii:
wherein R 1 -R 8 are independently comprised of H; OCH 3 ; EtO; OH; O-alkenyl; phenyl; NH 2 ; COOH; F; Cl; Br; I; CONH 2 ; NO 2 ; NR 10 R 11 OCONR 10 R 11 wherein R 10 and R 11 independently comprise H alkyl or aryl; COR 12 wherein R 12 comprises H, OH, O-alkyl, O-aryl or amino; NHCOCH 3 ; O 2 ; OCOR 13 wherein R 13 comprises alkyl or aryl; OAc; benzoyl; CONH 2 ; or NO 2 ; or
a pharmaceutically acceptable derivative or salt thereof and a pharmaceutically acceptable carrier therefor.
90 . The composition of claim 89 wherein R 1 =R 2 , R 3 =R 4 =R 6 =R 7 =R 8 =H.
91 . The composition of claim 90 wherein R 5 comprises Br, Cl or I.
92 . The composition of claim 89 wherein R 1 =OH; R 2 =R 4 =R 5 =R 6 =R 7 =R 8 =H.
93 . The composition of claim 92 wherein R 3 comprises Br or I.
94 . The composition of claim 89 wherein R 1 =OH; R 2 =R 3 =R 4 =R 5 =R 6 =R 8 =H; and R 7 =Br.
95 . The composition of claim 89 wherein R 1 =OH; R 2 =R 3 =R 5 =R 6 =R 7 =R 8 =H; and R 4 =Cl.
96 . The composition of claim 89 wherein R 1 =R 2 =R 3 =R 4 =R 5 =R 6 =R 7 =H.
97 . The composition of claim 96 wherein R 8 comprises I, OCH 3 , Br, OH or Cl.
98 . The composition of claim 89 wherein R 1 =OH; R 2 =R 3 =R 5 =R 6 =R 7 =H; and R 8 =OCH 3 .
99 . The composition of claim 98 wherein R 4 comprises F or I.
100 . The composition of claim 89 wherein R 1 =OAc; R 2 =R 3 =R 5 =R 6 =R 7 =H; R 4 =F; and R 8 =OCH 3 .
101 . The composition of claim 89 wherein R 1 =OH; R 2 =R 4 =R 5 =R 6 =R 7 =H; and R 8 =OCH 3 .
102 . The composition of claim 101 wherein R 3 comprises F, Cl or Br.
103 . The composition of claim 89 wherein R 1 =OH; R 2 =R 3 =R 4 =R 5 =R 6 =R 7 =H.
104 . The composition of claim 103 wherein R 8 comprises H or OCH 3 .
105 . The composition of claim 89 wherein R 1 =OCH 3 ; R 2 =R 4 =R 5 =R 6 =R 7 =R 8 =H; and R 3 =Br.
106 . The composition of claim 89 wherein R 1 =OH; R 2 =R 3 =R 4 =R 6 =R 7 =R 8 =H; and R 5 =F.
107 . The composition of claim 89 wherein R 1 =R 2 =R 3 =R 4 =R 5 =R 6 =H; R 7 =NO 2 ; and R 8 =Cl.
108 . The composition of claim 89 wherein R 1 =Br; R 2 =R 3 =R 4 =R 5 =R 6 =R 7 =H.
109 . The composition of claim 108 wherein R 8 comprises H of OCH 3 .
110 . The composition of claim 89 wherein R 1 =R 2 =R 3 =R 4 =R 5 =R 7 , R 8 =H.
111 . The composition of claim 110 wherein R 6 comprises Br, I or OH.
112 . The composition of claim 89 wherein R 1 =R 2 =R 3 =R 4 =R 5 =R 6 =R 8 =H; and R 7 =I.
113 . The composition of claim 89 wherein R 1 =R 2 =R 3 =R 5 =R 6 =R 7 =R 8 =H.
114 . The composition of claim 113 wherein R 4 comprises I, F or Br.
115 . The composition of claim 89 wherein R 1 =R 3 =R 5 =R 6 =R 7 =H; and R 2 =R 4 =R 8 =OCH 3 .
116 . The composition of claim 89 wherein R 1 =Br; R 2 =R 3 =R 5 =R 6 =R 7 =H; R 4 =OCH 3 ; and R 8 =Cl.
117 . The composition of claim 89 wherein R 1 =R 2 =R 4 =R 5 =R 6 =R 7 =H; and R 8 =OCH 3 .
118 . The composition of claim 117 wherein R 3 comprises I or COOH.
119 . The composition of claim 89 wherein R 1 =R 4 =benzoyl; R 2 =R 3 =R 5 =R 6 =R 7 =R 8 =H.
120 . The composition of claim 89 wherein R 1 =R 2 =R 4 =R 5 =R 6 =R 7 =R 8 =H; and R 3 =F.
121 . The composition of claim 89 wherein R 1 =OH; R 2 =R 3 =R 4 =R 6 =R 7 =H; R 5 =I; and R 8 =OCH 3 .
122 . A method for preventing or treating a mycobacterium infection in a mammal comprising administering to a mammal in need of anti-mycobacterium prevention or treatment an effective anti-mycobacterium amount of at least one compound of formula iii:
wherein R 1 -R 8 are independently comprised of H; OCH 3 ; EtO; OH; O-alkenyl; phenyl; NH 2 ; COOH; F; Cl; Br; I; CONH 2 ; NO 2 ; NR 10 R 11 OCONR 10 R 11 wherein R 10 and R., independently comprise H allyl or aryl; COR 12 wherein R 12 comprises H, OH, O-alkyl, O-aryl or amino; NHCOCH 3 ; O 2 ; OCOR 13 wherein R 13 comprises alkyl or aryl; OAc; benzoyl; CONH 2 ; or NO 2 ; or
a pharmaceutically acceptable derivative or salt thereof and a pharmaceutically acceptable carrier therefor.
123 . The method of claim 122 wherein R 1 =R 2 =R 3 =R 4 =R 6 =R 7 =R 8 =H.
124 . The method of claim 123 wherein R 5 comprises Br, Cl or I.
125 . The method of claim 122 wherein R 1 =OH; R 2 =R 4 =R 5 =R 6 =R 7 =R 8 =H.
126 . The method of claim 125 wherein R 3 comprises Br or I.
127 . The method of claim 122 wherein R 1 =OH; R 2 =R 3 =R 4 =R 5 =R 6 =R 8 =H; and R 7 =Br.
128 . The method of claim 122 wherein R 1 =OH; R 2 =R 3 =R 5 =R 6 =R 7 =R 8 =H; and R 4 =Cl.
129 . The method of claim 122 wherein R 1 =R 2 =R 3 =R 4 =R 5 =R 6 =R 7 =H.
130 . The method of claim 129 wherein R 8 comprises I, OCH 3 , Br, OH or Cl.
131 . The method of claim 122 wherein R 1 =OH; R 2 =R 3 =R 5 =R 6 =R 7 =H; and R 8 =OCH 3 .
132 . The method of claim 131 wherein R 4 comprises F or I.
133 . The method of claim 122 wherein R 1 =OAc; R 2 =R 3 =R 5 =R 6 =R 7 =H; R 4 =F; and R 8 =OCH 3 .
134 . The method of claim 122 wherein R 1 =OH; R 2 =R 4 =R 5 =R 6 =R 7 =H; and R 8 =OCH 3 .
135 . The method of claim 134 wherein R 3 comprises F, Cl or Br.
136 . The method of claim 122 wherein R 1 =OH; R 2 =R 3 =R 4 =R 5 =R 6 =R 7 =H.
137 . The method of claim 136 wherein R 8 comprises H or OCH 3 .
138 . The method of claim 122 wherein R 1 =OCH 3 ; R 2 =R 4 =R 5 =R 6 =R 7 =R 8 =H; and R 3 =Br.
139 . The method of claim 122 wherein R 1 =OH; R 2 =R 3 =R 4 =R 6 =R 7 =R 8 =H; and R 5 =F.
140 . The method of claim 122 wherein R 1 =R 2 =R 3 =R 4 =R 5 =R 6 =H; R 7 =NO 2 ; and R 8 =Cl.
141 . The method of claim 122 wherein R 1 =Br; R 2 =R 3 =R 4 =R 5 =R 6 =R 7 =H.
142 . The method of claim 141 wherein R 8 comprises H of OCH 3 .
143 . The method of claim 122 wherein R 1 =R 2 =R 3 =R 4 =R 5 =R 7 =R 8 =H.
144 . The method of claim 143 wherein R 6 comprises Br, I or OH.
145 . The method of claim 122 wherein R 1 =R 2 =R 3 =R 4 =R 5 =R 6 =R 8 =H; and R 7 =I.
146 . The method of claim 122 wherein R 1 =R 2 =R 3 =R 5 =R 6 =R 7 =R 8 =H.
147 . The method of claim 146 wherein R 4 comprises I, F or Br.
148 . The method of claim 122 wherein R 1 =R 3 =R 5 =R 6 =R 7 =H; and R 2 =R 4 =R 8 =OCH 3 .
149 . The method of claim 122 wherein R 1 =Br; R 2 =R 3 =R 5 =R 6 =R 7 =H; R 4 =OCH 3 ; and R 8 =Cl.
150 . The method of claim 122 wherein R 1 =R 2 =R 4 =R 5 =R 6 =R 7 =H; and R 8 =OCH 3 .
151 . The method of claim 150 wherein R 3 comprises I or COOH.
152 . The method of claim 122 wherein R 1 =R 4 =benzoyl; R 2 =R 3 =R 5 =R 6 =R 7 =R 8 =H.
153 . The method of claim 122 wherein R 1 =R 2 =R 4 =R 5 =R 6 =R 7 , R 8 =H; and R 3 =F.
154 . The method of claim 122 wherein R 1 =OH; R 2 =R 3 =R 4 =R 6 =R 7 =H; R 5 =I; and R 8 =OCH 3 .
155 . A composition for treating or preventing a mycobacterium infection comprising an effective anti-mycobacterium effective amount of a compound selected from the group consisting of 6-6″-biagpigenin hexamethylether, volkensiflavone hexamethylether, GB-1a hexamethylether, 3′″-nitro-C3-O-C4′″-biflavone, 3′-8″-biflavone, 6-2′″-biflavone, 6-6″-binaringenin hexamethylether and 6-2′″-biapigenin; or derivative or salt thereof and a pharmaceutically acceptable carrier therefor.
156 . A method for preventing or treating a mycobacterium infection in a mammal comprising administering to a mammal in need of anti-mycobacterium prevention or treatment an effective anti-mycobacterium amount of at least one compound selected from the group consisting of 6-6″-biagpigenin hexamethylether, volkensiflavone hexamethylether, GB-1a hexamethylether, 3′″-nitro-C3-O-C4′″-biflavone, 3′-8″-biflavone, 6-2′″-biflavone, 6-6″-binaringenin hexamethylether and 6-2′″-biapigenin; or derivative or salt thereof and a pharmaceutically acceptable carrier therefor.
157 . A composition for treating or preventing a mycobacterium infection comprising an effective anti-mycobacterium effective amount of a compound of formula iv:
wherein R 1 -R 8 are independently comprised of H; OCH 3 ; EtO; OH; O-alkenyl; phenyl; NH 2 ; COOH; F; Cl; Br; I; CONH 2 ; NO 2 ; NR 10 R 11 OCONR 10 R 11 wherein R 10 and R 11 independently comprise H alkyl or aryl; COR 12 wherein R 12 comprises H, OH, O-alkyl, O-aryl or amino; NHCOCH 3 ; O 2 − ; OCOR 13 wherein R 13 comprises alkyl or aryl; OAc; benzoyl; CONH 2 ; or NO 2 , or
a pharmaceutically acceptable derivative or salt thereof and a pharmaceutically acceptable carrier therefor.
158 . The composition of claim 157 wherein R 1 =R 3 =R 4 =R 6 =R 7 =R 8 =H; R 2 =OCH 3 ; and R 5 =Br.
159 . The composition of claim 157 wherein R 1 =R 2 =R 3 =R 4 =R 5 =R 7 =R 8 =H; and R 6 =Br.
160 . The composition of claim 157 wherein R 1 =OH; R 2 =R 3 =R 4 =R 5 =R 7 =R 8 ; and R 6 =Cl.
161 . The composition of claim 157 wherein R 1 =R 2 =R 3 =R 5 =R 6 =R 7 =R 8 =H.
162 . The composition of claim 161 wherein R comprises Br, I or F.
163 . The composition of claim 157 wherein R 1 =R 2 =R 3 =R 5 =R 6 =R 8 =H; R 4 =OCH 3 ; and R 7 =Cl.
164 . The composition of claim 157 wherein R 1 =R 2 =R 4 =R 5 =R 6 =R 7 =R 8 =H.
165 . The composition of claim 164 wherein R 3 comprises Cl, I or Br.
166 . The composition of claim 157 wherein R 1 =Br; R 2 =R 4 =R 6 =R 7 =R 8 =OCH 3 ; and R 3 =R 5 =H.
167 . A method for preventing or treating a mycobacterium infection in a mammal comprising administering to a mammal in need of anti-mycobacterium prevention or treatment an effective anti-mycobacterium amount of at least one compound of formula iv:
wherein R 1 -R 8 are independently comprised of H; OCH 3 ; EtO; OH; O-alkenyl; phenyl; NH 2 ; COOH; F; Cl; Br; I; CONH 2 ; NO 2 ; NR 10 R 11 OCONR 10 R 11 wherein R 10 and R 11 independently comprise H alkyl or aryl; COR 12 wherein R 12 comprises H, OH, O-alkyl, O-aryl or amino; NHCOCH 3 ; O 2 − ; OCOR 13 wherein R 13 comprises alkyl or aryl; OAc; benzoyl; CONH 2 ; or NO 2 ; or
a pharmaceutically acceptable derivative or salt thereof and a pharmaceutically acceptable carrier therefor.
168 . The method of claim 167 wherein R 1 =R 3 =R 4 =R 6 =R 7 =R 8 =H; R 2 =OCH 3 ; and R 5 =Br.
169 . The method of claim 167 wherein R 1 =R 2 =R 3 =R 4 =R 5 =R 7 =R 8 =H; and R 6 =Br.
170 . The method of claim 167 wherein R 1 =OH; R 2 =R 3 =R 4 =R 5 =R 7 =R 8 ; and R 6 =Cl.
171 . The method of claim 167 wherein R 1 =R 2 =R 3 =R 5 =R 6 =R 7 =R 8 =H.
172 . The method of claim 171 wherein R 4 comprises Br, I or F.
173 . The method of claim 167 wherein R 1 =R 2 =R 3 =R 5 =R 6 =R 8 =H; R 4 =OCH 3 ; and R 7 =Cl.
174 . The method of claim 167 wherein R 1 =R 2 =R 4 =R 5 =R 6 =R 7 =R 8 =H.
175 . The method of claim 174 wherein R 3 comprises Cl, I or Br.
176 . The method of claim 167 wherein R 1 =Br; R 2 =R 4 =R 6 =R 7 =R 8 =OCH 3 ; and R 3 =R 5 =H.Cited by (0)
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