US2015337011A1PendingUtilityA1
Dendrimeric peptides, pharmaceutical compositions and methods of using the same
Est. expiryAug 27, 2030(~4.1 yrs left)· nominal 20-yr term from priority
A61P 31/00A61P 31/12A61K 38/00C07K 14/001C07K 19/00C07K 7/02C07K 5/06156Y02A50/30
30
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
Novel peptide compounds and pharmaceutical compositions thereof are disclosed that have a formula represented by the following formula (I) wherein L 1 , L 2 , L 3 , Z, R 1 , R 2 , R 4 and R 5 are as described herein. The compounds demonstrate antimicrobial activity and may be prepared as pharmaceutical compositions and used for the prevention and treatment of a variety of conditions in mammals including humans where microbial invasion is involved. The present peptides are particularly valuable as their effect is rapid, broad in spectrum and mostly indifferent to resistance provided by standard antibiotics.
Claims
exact text as granted — not AI-modified1 . (canceled)
2 . (canceled)
3 . (canceled)
4 . (canceled)
5 . (canceled)
6 . (canceled)
7 . (canceled)
8 . (canceled)
9 . (canceled)
10 . (canceled)
11 . (canceled)
12 . (canceled)
13 . (canceled)
14 . (canceled)
15 . (canceled)
16 . (canceled)
17 . (canceled)
18 . (canceled)
19 . (canceled)
20 . (canceled)
21 . (canceled)
22 . (canceled)
23 . A pharmaceutical composition for preventing, treating, ameliorating or managing a disease or condition caused by micro organisms; wherein the pharmaceutical composition comprises a peptide according to formula Ia:
wherein
L 3 is substituted or unsubstituted C 2-5 alkylene;
R 3 is substituted or unsubstituted alkyl, aralkyl, heteroarylalkyl, aminoalkyl, or guanidinoalkyl;
R 4 is R 5 , or
and each R 5 , R 6 , and R 7 is independently —NH—(B′) n —Z, or
each B′ is independently an peptide residue selected from R, W, W*, F, Y, K, 2-Nal, H*, and Tta;
n is 2, 3, or 4; each Z is independently H, Ac, or any other conventional N-protecting group; and
Tta is 2,5,7-trialkyltryptophan residue;
or a pharmaceutically acceptable salt, solvate or prodrug thereof; and stereoisomers, isotopic variants and tautomers thereof;
provided that at least one of B's is Tta.
24 . (canceled)
25 . The pharmaceutical composition according to claim 23 , wherein the compound is according to formula VIa or VIb:
wherein R 4 is R 5 ;
each R 5 , R 6 , and R 7 is independently —NH—(B′) n —Z,
each B′ is independently an peptide residue selected from R, W, W*, F, Y, K, 2-Nal, H*, and Tta;
n is 2, 3, or 4; each Z is independently H, Ac, or any other conventional N-protecting group; and
Tta is 2,5,7-trialkyltryptophan residue;
or a pharmaceutically acceptable salt, solvate or prodrug thereof; and stereoisomers, isotopic variants and tautomers thereof;
provided that at least one of B's is Tta.
26 . (canceled)
27 . (canceled)
28 . (canceled)
29 . The pharmaceutical composition according to claim 23 , wherein each R 5 , R 6 , and R 7 is independently selected from —NH—(RW)—Z, —NH—(RTtb)-Z, —NH—(WR)—Z, —NH—(WTtb)-Z, —NH-(TtbR)—Z, —NH-(TtbW)—Z, —NH—(RWR)—Z, —NH—(RTtbR)—Z, —NH—(WTtbR)—Z, —NH—(WTtbW)—Z, —NH—(RTtbW)—Z, —NH-(TtbRW)—Z, —NH-(TtbWR)—Z, —NH-(TtbRR)—Z, —NH-(TtbWW)—Z, —NH—(RTtbTtb)-Z, —NH—(WTtbTtb)-Z, —NH-(TtbTtbR)—Z, —NH-(TtbTtbW)—Z, —NH-(TtbRTtb)-Z, —NH-(TtbWTtb)-Z, and —NH-(TtbTtbTtb)-Z; and Z is H, or Ac; and Ttb is 2,5,7-tri-t-butyltryptophan residue;
provided that at least one of R 4 and R 5 ; and at least one of R 5 , R 6 , and R 7 , contains Ttb residue.
30 . The pharmaceutical composition according to claim 23 , wherein the peptide is according to formula VIIa, VIIb, VIIc, VIId, VIIe, VIIf, VIIIa VIIIb, VIIIc, VIIId, VIIIe, or VIIIf:
wherein each Z is independently H, or Ac.
31 . (canceled)
32 . (canceled)
33 . (canceled)
34 . (canceled)
35 . (canceled)
36 . (canceled)
37 . (canceled)
38 . (canceled)
39 . (canceled)
40 . (canceled)
41 . (canceled)
42 . (canceled)
43 . (canceled)
44 . (canceled)
45 . (canceled)
46 . (canceled)
47 . (canceled)
48 . (canceled)
49 . (canceled)
50 . (canceled)
51 . (canceled)
52 . (canceled)
53 . (canceled)
54 . (canceled)
55 . (canceled)
56 . (canceled)
57 . (canceled)
58 . (canceled)
59 . (canceled)
60 . (canceled)
61 . (canceled)
62 . (canceled)
63 . (canceled)
64 . (canceled)
65 . (canceled)
66 . (canceled)
67 . (canceled)
68 . (canceled)
69 . A peptide according to formula Ia:
wherein
L 3 is substituted or unsubstituted C 2-5 alkylene;
R 3 is substituted or unsubstituted alkyl, aralkyl, heteroarylalkyl, aminoalkyl, or guanidinoalkyl;
R 4 is R 5 , or
and each R 5 , R 6 , and R 7 is independently —NH—(B′) n —Z, or
each B′ is independently an peptide residue selected from R, W, W*, F, Y, K, 2-Nal, H*, and Tta;
n is 2, 3, or 4; each Z is independently H, Ac, or any other conventional N-protecting group; and
Tta is 2,5,7-trialkyltryptophan residue;
or a pharmaceutically acceptable salt, solvate or prodrug thereof; and stereoisomers, isotopic variants and tautomers thereof;
provided that at least one of B's is Tta.
70 . (canceled)
71 . The peptide according to claim 69 , wherein the peptide is according to formula VIa or VIb:
wherein R 4 is R 5 ;
each R 5 , R 6 , and R 7 is independently —NH—(B′) n —Z,
each B′ is independently an peptide residue selected from R, W, W*, F, Y, K, 2-Nal, H*, and Tta;
n is 2, 3, or 4; each Z is independently H, Ac, or any other conventional N-protecting group; and
Tta is 2,5,7-trialkyltryptophan residue;
or a pharmaceutically acceptable salt, solvate or prodrug thereof; and stereoisomers, isotopic variants and tautomers thereof;
provided that at least one of B's is Tta.
72 . (canceled)
73 . (canceled)
74 . (canceled)
75 . The peptide according to claim 69 , wherein each R 5 , R 6 , and R 7 is independently selected from —NH—(RW)—Z, —NH—(RTtb)-Z, —NH—(WR)—Z, —NH—(WTtb)-Z, —NH-(TtbR)—Z, —NH-(TtbW)—Z, —NH—(RWR)—Z, —NH—(RTtbR)—Z, —NH—(WTtbR)—Z, —NH—(WTtbW)—Z, —NH—(RTtbW)—Z, —NH-(TtbRW)—Z, —NH-(TtbWR)—Z, —NH-(TtbRR)—Z, —NH-(TtbWW)—Z, —NH—(RTtbTtb)-Z, —NH—(WTtbTtb)-Z, —NH-(TtbTtbR)—Z, —NH-(TtbTtbW)—Z, —NH-(TtbRTtb)-Z, —NH-(TtbWTtb)-Z, and —NH-(TtbTtbTtb)-Z; and Z is H, or Ac; and Ttb is 2,5,7-tri-t-butyltryptophan residue;
provided that at least one of R 4 and R 5 ; and at least one of R 5 , R 6 , and R 7 , contains Ttb residue.
76 . The peptide according to claim 69 , wherein the peptide is according to formula VIIa, VIIb, VIIc, VIId, VIIe, VIIf, VIIIa, VIIIb, VIIIc, VIIId, VIIIe, or VIIIf:
wherein each Z is independently H, or Ac.
77 . (canceled)
78 . (canceled)
79 . (canceled)
80 . (canceled)
81 . (canceled)
82 . A method for preventing, treating, ameliorating or managing a disease or condition associated with infection by a gram positive or gram negative bacteria which comprises administering to a patient in need of such prevention, treatment, amelioration or management, a prophylactically or therapeutically effective amount of the pharmaceutical composition of claim 23 .
83 . (canceled)
84 . (canceled)
85 . (canceled)
86 . (canceled)
87 . (canceled)
88 . (canceled)
89 . (canceled)
90 . (canceled)
91 . (canceled)
92 . (canceled)
93 . (canceled)
94 . (canceled)
95 . (canceled)
96 . The pharmaceutical composition of claim 23 , wherein L 3 is selected from —CH 2 —CH 2 —, —CH 2 —CH 2 —CH 2 —, and —CH 2 —CH 2 —CH 2 —CH 2 —.
97 . The pharmaceutical composition according to claim 23 , wherein Z is H.
98 . The pharmaceutical composition according to claim 23 , wherein n is 2, 3, or 4; and each B′ is independently selected from R, W, W*, F, Y, K, 2-Nal, H*, and Tta.
99 . The pharmaceutical composition according to claim 23 , wherein n is 2, 3, or 4; and each B′ is independently selected from R, W, Ttm, Tte, Ttip, and Ttb; and wherein Ttm is 2,5,7-trimethyltryptophan residue; Tte is 2,5,7-triethyltryptophan residue; Ttip is 2,5,7-tri-iso-propyl-tryptophan residue; and Ttb is 2,5,7-tri-t-butyltryptophan residue.
100 . The pharmaceutical composition according to claim 23 , wherein n is 2, 3, or 4; and each B′ is independently selected from R, W, and Ttb.
101 . The method of claim 82 , wherein the gram positive bacteria is Staphylococcus aureus.
102 . The method of claim 99 , wherein the Staphylococcus aureus is methicillin-resistant Staphylococcus aureus (MRSA).
103 . The method of claim 82 , wherein the gram positive bacteria is Bacillus subtilis.
104 . The method of claim 82 , wherein the gram negative bacteria is Escherichia coli ( E. coli ).
105 . The method of claim 104 , wherein the E. coli is E. coli D31.Join the waitlist — get patent alerts
Track US2015337011A1 — get alerts on status changes and closely related new filings.
We store only your email — no account needed. See our privacy policy.