The present invention relates to compounds having activity at both the human
5 glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1)
receptors. The present invention also relates to compounds having an extended duration
of action at each of these receptors. Furthermore, the present invention relates to
compounds that may be administered orally. These compounds may be useful in the
treatment of type 2 diabetes mellitus (“T2DM”). Also, the compounds may be useful in
10 the treatment of obesity.
Over the past several decades, the prevalence of diabetes has continued to rise.
T2DM is the most common form of diabetes accounting for approximately 90% of all
diabetes. T2DM is characterized by high blood glucose levels associated mainly with
insulin resistance. The current standard of care for T2DM includes diet and exercise,
15 treatment with oral medications, and injectable glucose lowering drugs, including
incretin-based therapies, such as GLP-1 receptor agonists. A variety of GLP-1 receptor
agonists are currently available for treatment of T2DM, although currently marketed
GLP-1 receptor agonists are generally dose-limited by gastrointestinal side effects such as
nausea and vomiting. Subcutaneous injection is the typical route of administration for the
20 available GLP-1 receptor agonists. When treatment with oral medications and incretinbased therapies are insufficient, insulin treatment is considered. Despite the advances in
treatment available today, many patients with T2DM are unable to reach their glycemic
control goals. Uncontrolled diabetes leads to several conditions associated with increased
morbidity and mortality of patients. There is a need for a treatment to enable more
25 patients with T2DM to reach their glycemic treatment goal.
Obesity is a complex medical disorder resulting in excessive accumulation of
adipose tissue mass. Today obesity is a global public health concern that is associated
with undesired health outcomes and morbidities. Desired treatments for patients with
obesity strive to reduce excess body weight, improve obesity-related co-morbidities, and
30 maintain long-term weight reduction. Available treatments for obesity are particularly
3
unsatisfactory for patients with severe obesity. There is a need for alternative treatment
options to induce therapeutic weight loss in patients in need of such treatment.
WO2016/111971 describes peptides stated to have GLP-1 and GIP activity.
WO2013/164483 also discloses compounds stated to have GLP-1 and GIP activity.
5 There is a need for T2DM treatments capable of providing effective glucose
control for a larger portion of the patients in need of such treatment. There is a further
need for T2D treatments capable of providing effective glucose control and with a
favorable side effect profile. There is a need for alternate treatment options to provide
therapeutic weight loss in a patient in need of such treatment. There is a need for an
10 alternate treatment option for a patient in need of treatment for severe obesity.
There is a desire for compounds having agonist activity at the GIP and GLP-1
receptors that are suitable for oral administration. Compounds with extended duration of
action at each of the GIP and GLP-1 receptors are desirable to allow for less frequent
dosing of the compound. Compounds with two acylation modifications in combination
15 with an amino acid sequence to provide GLP-1 and GIP activity from a single compound
are desired.
Accordingly, provided are a compound of Formula I
X1X2EGTX6TSDX10X11X12X13LDX16X17AQX20X21X22IX24X25LIX28GX30
(SEQ ID NO:505)
20 wherein
X1 is selected from the group consisting of Y and R1Y;
R1 is an Ac modification of the N-terminal amino group;
X2 is Aib;
X6 is selected from the group consisting of αMeF and αMeF(2F);
25 X10 is selected from the group consisting of 4Pal, Y, αMeF, αMeF(2F), αMeL,
αMeV, Ac4c, Ac5c, Ac6c, Bip, 1Nal, 2Nal, OMeY, hTyr, Nle, V, 4CPhe, ChG,
ChA, Bzt, 2FA, 4TAA, 2TA, 3TA, and KZ1;
X11 is selected from the group consisting of S, αMeS, Aib, G, Dap, Ac5c, and Tle;
X12 is selected from the group consisting of I and KZ1;
30 X13 is selected from the group consisting of αMeL and αMeF;
4
X16 is Orn;
X17 is selected from the group consisting of Q, I, and KZ1;
X20 is selected from the group consisting of Aib, Orn, 4Pal, αMeF, Ac5c, and
Ac6c;
5 X21 is selected from the group consisting of E, KZ1, G, Orn, and 4Pal;
X22 is selected from the group consisting of F, 2ClPhe, 3ClPhe, 2FPhe, 3FPhe,
3,5FPhe, 1Nal, 2Nal, αMeF(2F), ChA, Bzt, and αMeF;
X24 is selected from the group consisting of D-Glu, E, G, and KZ1;
X25 is selected from the group consisting of Y, αMeY, αMeF, and KZ1;
10 X28 is selected from the group consisting of E, Orn, and KZ1;
X30 is selected from the group consisting of G, Orn, KZ1, K(Z1)R6, OrnR2, and
GR2;
R2 is selected from the group consisting of X31, X31SSG (SEQ ID NO:5), X31SSGR3 (SEQ ID NO:6), X31SSGX35PPPX39 (SEQ ID NO:7), X31SSGX35PPPX39R3
15 (SEQ ID NO:8), X31SSGX35PPPX39X40 (SEQ ID NO:9), X31SSGX35PPPX39X40R3
(SEQ ID NO:10), and a modification of the c-terminal group wherein the
modification is NH2;
R6 is selected from the group consisting of PSSG (SEQ ID NO:506), PSSG-R3
(SEQ ID NO:507), PSSGX35PPPX39 (SEQ ID NO:508), PSSGX35PPPX39R3 (SEQ
20 ID NO:509), PSSGX35PPPX39X40 (SEQ ID NO:510), PSSGX35PPPX39X40R3
(SEQ ID NO:511), and a modification of the c-terminal group wherein the
modification is NH2;
X31 is selected from the group consisting of P and KZ1;
X35 is selected from the group consisting of A and Orn;
25 X39 is selected from the group consisting of S and Orn;
X40 is KZ1;
R3 is a modification of the C-terminal group, wherein the modification is NH2;
wherein two, and only two, of X10, X12, X17, X21, X24, X25, X28, X30, X31, and X40
are KZ1 or K(Z1)R6;
30 Z1 is selected from the group consisting of R5 and -R4R5;
5
R4 is a linker; and
R5 is a fatty acid; or
a pharmaceutically acceptable salt thereof.
Provided is a compound of Formula II:
5 X1X2EGTX6TSDX10X11X12X13LDX16X17AQX20X21X22IX24X25LIX28GX30 (SEQ
ID NO:4)
wherein
X1 is selected from the group consisting of Y and R1Y;
R1 is an Ac modification of the N-terminal amino group;
10 X2 is Aib;
X6 is selected from the group consisting of αMeF and αMeF(2F);
X10 is selected from the group consisting of 4Pal, Y, αMeF, αMeF(2F), αMeL,
αMeV, Ac4c, Ac5c, Ac6c, Bip, 1Nal, 2Nal, OMeY, hTyr, Nle, V, 4CPhe, ChG,
ChA, Bzt, 2FA, 4TAA, 2TA, 3TA, and KZ1;
15 X11 is selected from the group consisting of Ac5c, S, αMeS, Aib, G, Dap, and Tle;
X12 is selected from the group consisting of I and KZ1;
X13 is selected from the group consisting of αMeL and αMeF;
X16 is Orn;
X17 is selected from the group consisting of Q, I, and KZ1;
20 X20 is selected from the group consisting of Aib, Orn, 4Pal, αMeF, Ac5c, and
Ac6c;
X21 is selected from the group consisting of E, KZ1, G, Orn, and 4Pal;
X22 is selected from the group consisting of F, 2ClPhe, 3ClPhe, 2FPhe, 3FPhe,
3,5FPhe, 1Nal, 2Nal, αMeF(2F), ChA, Bzt, and αMeF;
25 X24 is selected from the group consisting of D-Glu, E, G, and KZ1;
X25 is selected from the group consisting of Y, αMeY, αMeF, and KZ1;
X28 is selected from the group consisting of E, Orn, and KZ1;
X30 is selected from the group consisting of G, Orn, KZ1, and GR2;
R2 is selected from the group consisting of X31SSG (SEQ ID NO:5), X31SSG-R3
30 (SEQ ID NO:6), X31SSGX35PPPX39 (SEQ ID NO:7), X31SSGX35PPPX39R3 (SEQ
6
ID NO:8), X31SSGX35PPPX39X40 (SEQ ID NO:9), X31SSGX35PPPX39X40R3 (SEQ
ID NO:10), and a modification of the c-terminal group wherein the modification is
NH2;
X31 is selected from the group consisting of P and KZ1;
5 X35 is selected from the group consisting of A and Orn;
X39 is selected from the group consisting of S and Orn;
X40 is KZ1;
R3 is a modification of the C-terminal group, wherein the modification is NH2;
wherein two, and only two, of X10, X12, X17, X21, X24, X25, X28, X30, X31, and X40
10 are KZ1;
Z1 is selected from the group consisting of R5 and -R4R5; and
R4 is a linker;
R5 is a fatty acid; or
a pharmaceutically acceptable salt thereof.
15 Provided is a peptide of Formula I, or a pharmaceutically acceptable salt thereof,
wherein Z1 is selected from the group consisting of
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-CO-(CH2)10-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-(10-(4-
20 carboxyphenoxy)decanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-(4-(4-iodophenyl)butanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-(4-(4-tertbutylphenyl)butanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-CO-(CH2)14-CH3,
25 -(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-CO-(CH2)12-CH3,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-CO-(CH2)10-CH3,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(10-(4-carboxyphenoxy)decanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-CO-(CH2)12-CO2H,
7
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-(10-(4-
carboxyphenoxy)decanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-CO-(CH2)14-CH3,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-CO-(CH2)10-CH3,
5 -(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)3-(-Glu)-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)3-(-Glu)-CO-(CH2)14-CH3,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(K)-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(K)-(-Glu)-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(K)-(-Glu)-CO-(CH2)12-CO2H,
10 -(K)-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-CO-(CH2)12-CO2H,
-(K)-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-CO-(CH2)12-CO2H,
-(K)-(-Glu)-CO-(CH2)12-CO2H,
-(K)-(-Glu)-(-Glu)-CO-(CH2)12-CO2H,
-(-Glu)-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-CO-(CH2)12-CO2H,
15 -(K)-(K)-(-Glu)-CO-(CH2)12-CO2H,
-(-Glu)-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-(2-[2-(2-Amino-ethoxy)-
ethoxy]-acetyl)-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-(7-(4-
20 carboxyphenoxy)heptanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-(8-(4-
carboxyphenoxy)octanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-(4-(4-tertbutylphenyl)butanoyl),
25 -(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-(11-(4-
carboxyphenoxy)undecanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)3-(-Glu)-(10-(4-
carboxyphenoxy)decanoyl),
8
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-(2-[2-(2-Amino-ethoxy)-
ethoxy]-acetyl)-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-(2-[2-(2-Amino-ethoxy)-
ethoxy]-acetyl)2-CO-(CH2)12-CO2H,
5 -PEG3-(-Glu)-CO-(CH2)12-CO2H,
-PEG4-(-Glu)-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)3-(-Glu)-CO-(CH2)10-CH3,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-(11-(4-
carboxyphenoxy)undecanoyl,
10 -(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-CO-(CH2)14-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-Ahx-(-Glu)-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-Aoc-(-Glu)-CO-(CH2)12-CO2H,
-Ahx-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-CO-(CH2)12-CO2H,
-Aoc-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-CO-(CH2)12-CO2H,
15 -(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-Ahx-(-Glu)-(10-(4-
carboxyphenoxy)decanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-Aoc-(-Glu)-(10-(4-
carboxyphenoxy)decanoyl),
-Ahx-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-(10-(4-
20 carboxyphenoxy)decanoyl),
-Aoc-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-(10-(4-
carboxyphenoxy)decanoyl),
-PEG4-(-Glu)-(10-(4-carboxyphenoxy)decanoyl),
-PEG3-(-Glu)-(10-(4-carboxyphenoxy)decanoyl),
25 -(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-Aoc-CO-(CH2)12-CO2H,
-PEG6-(-Glu)-CO-(CH2)12-CO2H,
-PEG5-(-Glu)-CO-(CH2)12-CO2H,
-PEG6-(-Glu)-(10-(4-carboxyphenoxy)decanoyl),
-PEG5-(-Glu)-(10-(4-carboxyphenoxy)decanoyl),
9
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-Trx-(-Glu)-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-Trx-(-Glu)-(10-(4-
carboxyphenoxy)decanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-Trx-(-Glu)-CO-(CH2)12-CO2H,
5 -(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-Trx-(-Glu)-(10-(4-
carboxyphenoxy)decanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)2-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)2-(10-(4-
carboxyphenoxy)decanoyl),
10 -(-Glu)-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-CO-(CH2)12-CO2H,
-(-Glu)-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-(10-(4-
carboxyphenoxy)decanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-(2-[2-(2-Amino-ethoxy)-
ethoxy]-acetyl)-(-Glu)-CO-(CH2)12-CO2H, and
15 -(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-(2-[2-(2-Amino-ethoxy)-
ethoxy]-acetyl)-(-Glu)-(10-(4-carboxyphenoxy)decanoyl).
Provided is a peptide of Formula I, or a pharmaceutically acceptable salt thereof,
wherein Z1 is selected from the group consisting of
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-CO-(CH2)12-CO2H,
20 -(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-CO-(CH2)10-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-(10-(4-
carboxyphenoxy)decanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-(4-(4-iodophenyl)butanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-(4-(4-tert25 butylphenyl)butanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-CO-(CH2)14-CH3,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-CO-(CH2)12-CH3,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-CO-(CH2)10-CH3,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-CO-(CH2)12-CO2H,
10
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(10-(4-carboxyphenoxy)decanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-(10-(4-
carboxyphenoxy)decanoyl),
5 -(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-CO-(CH2)14-CH3,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-CO-(CH2)10-CH3,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)3-(-Glu)-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)3-(-Glu)-CO-(CH2)14-CH3,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(K)-CO-(CH2)12-CO2H,
10 -(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(K)-(-Glu)-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(K)-(-Glu)-CO-(CH2)12-CO2H,
-(K)-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-CO-(CH2)12-CO2H,
-(K)-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-CO-(CH2)12-CO2H,
-(K)-(-Glu)-CO-(CH2)12-CO2H,
15 -(K)-(-Glu)-(-Glu)-CO-(CH2)12-CO2H,
-(-Glu)-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-CO-(CH2)12-CO2H,
-(K)-(K)-(-Glu)-CO-(CH2)12-CO2H,
-(-Glu)-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-CO-(CH2)12-CO2H
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-(2-[2-(2-Amino-ethoxy)-
20 ethoxy]-acetyl)-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-(7-(4-
carboxyphenoxy)heptanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-(8-(4-
carboxyphenoxy)octanoyl), and
25 -(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-(4-(4-tertbutylphenyl)butanoyl).
Provided is a peptide of Formula I, or a pharmaceutically acceptable salt thereof,
wherein Z1 is selected from the group consisting of
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-CO-(CH2)12-CO2H,
11
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-CO-(CH2)10-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-(10-(4-
carboxyphenoxy)decanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-(4-(4-iodophenyl)butanoyl),
5 -(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-(4-(4-tertbutylphenyl)butanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-CO-(CH2)14-CH3,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-CO-(CH2)12-CH3,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-CO-(CH2)10-CH3,
10 -(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(10-(4-carboxyphenoxy)decanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-(10-(4-
carboxyphenoxy)decanoyl),
15 -(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-CO-(CH2)14-CH3,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-CO-(CH2)10-CH3,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)3-(-Glu)-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)3-(-Glu)-CO-(CH2)14-CH3,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(K)-CO-(CH2)12-CO2H,
20 -(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(K)-(-Glu)-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(K)-(-Glu)-CO-(CH2)12-CO2H,
-(K)-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-CO-(CH2)12-CO2H,
-(K)-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-CO-(CH2)12-CO2H,
-(K)-(-Glu)-CO-(CH2)12-CO2H,
25 -(K)-(-Glu)-(-Glu)-CO-(CH2)12-CO2H,
-(-Glu)-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-CO-(CH2)12-CO2H,
-(K)-(K)-(-Glu)-CO-(CH2)12-CO2H,
-(-Glu)-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-CO-(CH2)12-CO2H,
12
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-(2-[2-(2-Amino-ethoxy)-
ethoxy]-acetyl)-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-(7-(4-
carboxyphenoxy)heptanoyl),
5 -(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-(8-(4-
carboxyphenoxy)octanoyl), and
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-(4-(4-tertbutylphenyl)butanoyl).
Provided is a compound of Formula I, or a pharmaceutically acceptable salt
10 thereof, wherein R5 is selected from the group consisting of
-CO-(CH2)12-CO2H, -CO-(CH2)10-CO2H, -(10-(4-carboxyphenoxy)decanoyl), -(4-(4-
iodophenyl)butanoyl), -(4-(4-tert-butylphenyl)butanoyl), -CO-(CH2)14-CH3, -CO-(CH2)12-
CH3, -CO-(CH2)10-CH3, -(7-(4-carboxyphenoxy)heptanoyl), -(8-(4-
carboxyphenoxy)octanoyl), (11-(4-carboxyphenoxy)undecanoyl), -(12-(4-
15 carboxyphenoxy)dodecanoyl), and CO-(CH2)14-CO2H.
Provided is a compound of Formula I, or a pharmaceutically acceptable salt
thereof, wherein R5 is selected from the group consisting of
-CO-(CH2)12-CO2H, -CO-(CH2)10-CO2H, -(10-(4-carboxyphenoxy)decanoyl), -(4-(4-
iodophenyl)butanoyl), -(4-(4-tert-butylphenyl)butanoyl), -CO-(CH2)14-CH3, -CO-(CH2)12-
20 CH3, -CO-(CH2)10-CH3, -(7-(4-carboxyphenoxy)heptanoyl), and -(8-(4-
carboxyphenoxy)octanoyl).

WE CLAIM:
1. A compound of the formula:
X1X2EGTX6TSDX10X11X12X13LDX16X17AQX20X21X22IX24X25LIX28GX30
5 (SEQ ID NO:505)
wherein
X1 is selected from the group consisting of Y and R1Y;
R1 is an Ac modification of the N-terminal amino group;
X2 is Aib;
10 X6 is selected from the group consisting of αMeF and αMeF(2F);
X10 is selected from the group consisting of 4Pal, Y, αMeF, αMeF(2F), αMeL,
αMeV, Ac4c, Ac5c, Ac6c, Bip, 1Nal, 2Nal, OMeY, hTyr, Nle, V, 4CPhe, ChG,
ChA, Bzt, 2FA, 4TAA, 2TA, 3TA, and KZ1;
X11 is selected from the group consisting of S, αMeS, Aib, G, Dap, Ac5c, and Tle;
15 X12 is selected from the group consisting of I and KZ1;
X13 is selected from the group consisting of αMeL and αMeF;
X16 is Orn;
X17 is selected from the group consisting of Q, I, and KZ1;
X20 is selected from the group consisting of Aib, Orn, 4Pal, αMeF, Ac5c, and
20 Ac6c;
X21 is selected from the group consisting of E, KZ1, G, Orn, and 4Pal;
X22 is selected from the group consisting of F, 2ClPhe, 3ClPhe, 2FPhe, 3FPhe,
3,5FPhe, 1Nal, 2Nal, αMeF(2F), ChA, Bzt, and αMeF;
X24 is selected from the group consisting of D-Glu, E, G, and KZ1;
25 X25 is selected from the group consisting of Y, αMeY, αMeF, and KZ1;
X28 is selected from the group consisting of E, Orn, and KZ1;
X30 is selected from the group consisting of G, Orn, KZ1, K(Z1)R6, OrnR2, and
GR2;
R2 is selected from the group consisting of X31, X31SSG (SEQ ID NO:5), X31SSG30 R3 (SEQ ID NO:6), X31SSGX35PPPX39 (SEQ ID NO:7), X31SSGX35PPPX39R3
(SEQ ID NO:8), X31SSGX35PPPX39X40 (SEQ ID NO:9), X31SSGX35PPPX39X40R3
155
(SEQ ID NO:10), and a modification of the c-terminal group wherein the
modification is NH2;
R6 is selected from the group consisting of PSSG (SEQ ID NO:506), PSSG-R3
(SEQ ID NO:507), PSSGX35PPPX39 (SEQ ID NO:508), PSSGX35PPPX39R3 (SEQ
5 ID NO:509), PSSGX35PPPX39X40 (SEQ ID NO:510), PSSGX35PPPX39X40R3
(SEQ ID NO:511), and a modification of the c-terminal group wherein the
modification is NH2;
X31 is selected from the group consisting of P, and KZ1;
X35 is selected from the group consisting of A and Orn;
10 X39 is selected from the group consisting of S and Orn;
X40 is KZ1;
R3 is a modification of the C-terminal group, wherein the modification is NH2;
wherein two, and only two, of X10, X12, X17, X21, X24, X25, X28, X30, X31, and X40
are KZ1 or K(Z1)R6;
15 Z1 is selected from the group consisting of R5 and -R4R5;
R4 is a linker; and
R5 is a fatty acid; or
a pharmaceutically acceptable salt thereof.
2. A compound, or a pharmaceutically acceptable salt thereof, as claimed by Claim
20 1 wherein
X30 is selected from the group consisting of G, Orn, KZ1, and GR2; and
R2 is selected from the group consisting of X31SSG (SEQ ID NO:5), X31SSG-R3
(SEQ ID NO:6), X31SSGX35PPPX39 (SEQ ID NO:7), X31SSGX35PPPX39R3 (SEQ
ID NO:8), X31SSGX35PPPX39X40 (SEQ ID NO:9), X31SSGX35PPPX39X40R3 (SEQ
25 ID NO:10), and a modification of the c-terminal group wherein the modification is
NH2.
3. A compound, or pharmaceutically acceptable salt thereof, as claimed by Claim 1
or 2, wherein Z1 is -R4R5.
4. A compound, or a pharmaceutically acceptable salt thereof, as claimed by any one
30 of Claims 1 to 3 wherein R5 is selected from the group consisting of -CO-(CH2)12-
156
CO2H, CO-(CH2)14-CO2H, -CO-(CH2)10-CO2H, -(10-(4-
carboxyphenoxy)decanoyl), -(4-(4-iodophenyl)butanoyl), -(4-(4-tertbutylphenyl)butanoyl), -CO-(CH2)14-CH3, -CO-(CH2)12-CH3, -CO-(CH2)10-CH3, -
(7-(4-carboxyphenoxy)heptanoyl), -(11-(4-carboxyphenoxy)undecanoyl), -(12-(4-
5 carboxyphenoxy)dodecanoyl), and -(8-(4-carboxyphenoxy)octanoyl).
5. A compound, or a pharmaceutically acceptable salt thereof, as claimed by any one
of Claims 1 to 4 wherein R5 is selected from the group consisting of
-CO-(CH2)12-CO2H, -CO-(CH2)10-CO2H, -(10-(4-carboxyphenoxy)decanoyl), -(4-
(4-iodophenyl)butanoyl), -(4-(4-tert-butylphenyl)butanoyl), -CO-(CH2)14-CH3, -
10 CO-(CH2)12-CH3, -CO-(CH2)10-CH3, -(7-(4-carboxyphenoxy)heptanoyl), and -(8-
(4-carboxyphenoxy)octanoyl).
6. A compound, or a pharmaceutically acceptable salt thereof, as claimed by any one
of Claims 1 to 4 wherein R5 is selected from the group consisting of
CO-(CH2)14-CO2H, -(11-(4-carboxyphenoxy)undecanoyl), and -(12-(4-
15 carboxyphenoxy)dodecanoyl).
7. A compound, or a pharmaceutically acceptable salt thereof, as claimed by any one
of Claims 1 to 6 wherein R4 is -(K)a1-(γ-Glu)a2-(2-[2-(2-Amino-ethoxy)-
ethoxy]-acetyl)a3-(K)b1-(γ-Glu)b2-;
a1 is selected from the group consisting of 0, 1, and 2;
20 a2 is selected from the group consisting of 0, 1, and 2;
a3 is selected from the group consisting of 0, 1, 2, and 3;
b1 is 0 or 1; and
b2 is 0 or 1.
8. A compound, or a pharmaceutically acceptable salt thereof, as claimed by any one
25 of Claims 1 to 6 wherein R4 is selected from the group consisting of
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)2)-,
30 -(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)3-(-Glu)-,
157
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(K)-,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(K)-(-Glu)-,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(K)-(-Glu)-,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-Trx-(-Glu)-,
5 -(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-Trx-(-Glu)-,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-Aoc-,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-Aoc-(-Glu)-,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-Ahx-(-Glu)-,
-PEG3-(-Glu)-,
10 -PEG4-(-Glu)-,
-PEG5-(-Glu)-,
-PEG6-(-Glu)-,
-Ahx-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-,
-Aoc-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-,
15 -(K)-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-,
-(K)-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-,
-(K)-(-Glu)-,
-(K)-(-Glu)-(-Glu)-,
-(-Glu)-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-,
20 -(K)-(K)-(-Glu)-,
-(-Glu)-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-,
-(-Glu)-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-(2-[2-(2-Amino-ethoxy)-
ethoxy]-acetyl)-,
25 -(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-(2-[2-(2-Amino-ethoxy)-
ethoxy]-acetyl)-,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-(2-[2-(2-Amino-ethoxy)-
ethoxy]-acetyl)2-, and
158
(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-(2-[2-(2-Amino-ethoxy)-ethoxy]-
acetyl)-(-Glu)-.
9. A compound, or a pharmaceutically acceptable salt thereof, as claimed by any one
of Claims 1 to 6 wherein R4 is selected from the group consisting of
5 -(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)3-(-Glu)-,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(K)-,
10 -(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(K)-(-Glu)-,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(K)-(-Glu)-,
-(K)-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-,
-(K)-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-,
-(K)-(-Glu)-,
15 -(K)-(-Glu)-(-Glu)-,
-(-Glu)-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-,
-(K)-(K)-(-Glu)-,
-(-Glu)-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-, and
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-(2-[2-(2-Amino-ethoxy)-
20 ethoxy]-acetyl)-.
10. A compound, or pharmaceutically acceptable salt thereof, as claimed by any one
of Claims 2, and 4 to 9, wherein Z1 is selected from the group consisting of
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-CO-(CH2)10-CO2H,
25 -(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-(10-(4-
carboxyphenoxy)decanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-(4-(4-iodophenyl)butanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-(4-(4-tertbutylphenyl)butanoyl),
159
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-CO-(CH2)14-CH3,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-CO-(CH2)12-CH3,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-CO-(CH2)10-CH3,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-CO-(CH2)12-CO2H,
5 -(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(10-(4-carboxyphenoxy)decanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-(10-(4-
carboxyphenoxy)decanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-CO-(CH2)14-CH3,
10 -(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-CO-(CH2)10-CH3,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)3-(-Glu)-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)3-(-Glu)-CO-(CH2)14-CH3,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(K)-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(K)-(-Glu)-CO-(CH2)12-CO2H,
15 -(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(K)-(-Glu)-CO-(CH2)12-CO2H,
-(K)-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-CO-(CH2)12-CO2H,
-(K)-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-CO-(CH2)12-CO2H,
-(K)-(-Glu)-CO-(CH2)12-CO2H,
-(K)-(-Glu)-(-Glu)-CO-(CH2)12-CO2H,
20 -(-Glu)-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-CO-(CH2)12-CO2H,
-(K)-(K)-(-Glu)-CO-(CH2)12-CO2H,
-(-Glu)-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-(2-[2-(2-Amino-ethoxy)-
ethoxy]-acetyl)-CO-(CH2)12-CO2H,
25 -(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-(7-(4-
carboxyphenoxy)heptanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-(8-(4-
carboxyphenoxy)octanoyl),
160
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-(4-(4-tertbutylphenyl)butanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-(11-(4-
carboxyphenoxy)undecanoyl),
5 -(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)3-(-Glu)-(10-(4-
carboxyphenoxy)decanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-(2-[2-(2-Amino-ethoxy)-
ethoxy]-acetyl)-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-(2-[2-(2-Amino-ethoxy)-
10 ethoxy]-acetyl)2-CO-(CH2)12-CO2H,
-PEG3-(-Glu)-CO-(CH2)12-CO2H,
-PEG4-(-Glu)-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)3-(-Glu)-CO-(CH2)10-CH3,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-(11-(4-
15 carboxyphenoxy)undecanoyl,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-CO-(CH2)14-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-Ahx-(-Glu)-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-Aoc-(-Glu)-CO-(CH2)12-CO2H,
-Ahx-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-CO-(CH2)12-CO2H,
20 -Aoc-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-Ahx-(-Glu)-(10-(4-
carboxyphenoxy)decanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-Aoc-(-Glu)-(10-(4-
carboxyphenoxy)decanoyl),
25 -Ahx-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-(10-(4-
carboxyphenoxy)decanoyl),
-Aoc-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-(10-(4-
carboxyphenoxy)decanoyl),
-PEG4-(-Glu)-(10-(4-carboxyphenoxy)decanoyl),
161
-PEG3-(-Glu)-(10-(4-carboxyphenoxy)decanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-Aoc-CO-(CH2)12-CO2H,
-PEG6-(-Glu)-CO-(CH2)12-CO2H,
-PEG5-(-Glu)-CO-(CH2)12-CO2H,
5 -PEG6-(-Glu)-(10-(4-carboxyphenoxy)decanoyl),
-PEG5-(-Glu)-(10-(4-carboxyphenoxy)decanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-Trx-(-Glu)-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-Trx-(-Glu)-(10-(4-
carboxyphenoxy)decanoyl),
10 -(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-Trx-(-Glu)-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-Trx-(-Glu)-(10-(4-
carboxyphenoxy)decanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)2-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)2-(10-(4-
15 carboxyphenoxy)decanoyl),
-(-Glu)-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-CO-(CH2)12-CO2H,
-(-Glu)-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-(10-(4-
carboxyphenoxy)decanoyl),
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-(2-[2-(2-Amino-ethoxy)-
20 ethoxy]-acetyl)-(-Glu)-CO-(CH2)12-CO2H, and
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)-(-Glu)-(2-[2-(2-Amino-ethoxy)-
ethoxy]-acetyl)-(-Glu)-(10-(4-carboxyphenoxy)decanoyl).
11. A compound, or a pharmaceutically acceptable salt thereof, as claimed by Claim
10 wherein Z1 is selected from the group consisting of:
25 -(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-CO-(CH2)12-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-CO-(CH2)10-CO2H,
-(2-[2-(2-Amino-ethoxy)-ethoxy]-acetyl)2-(-Glu)-(10-(4-
carboxyphenoxy)decanoyl),