Peptidic dual GLP-1/glucagon receptor agonists derived from exendin-4
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Abstract
The present invention relates to dual GLP-1/glucagon receptor agonists or optionally trigonal GLP-1/glucagon/GIP receptor agonists and their medical use, for example in the treatment of disorders of the metabolic syndrome, including diabetes and obesity, as well as for reduction of excess food intake.
636 Citations
31 Claims
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1. A peptidic compound having the formula (I):
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31)
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2. The compound or salt or solvate thereof of claim 1, wherein R1 is NH2.
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3. The compound or salt or solvate thereof of claim 1, wherein the peptidic compound has a relative activity of at least 0.1% compared to that of natural glucagon at the glucagon receptor.
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4. The compound or salt or solvate thereof of claim 1, wherein the peptidic compound exhibits a relative activity of at least 0.1% compared to that of GLP-1 (7-36)-amide at the GLP-1 receptor.
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5. The compound or salt or solvate thereof of claim 1, wherein
X14 is Lys wherein the — - NH2 side chain group is functionalized with a group —
Z—
C(O)R5, whereinZ is a group selected from the group consisting of γ
E, γ
E-γ
E, AEEAc-AEEAc-γ
E, and AEEAc-AEEAc-AEEAc, andR5 is a group selected from the group consisting of pentadecanyl, heptadecanyl, and 16-carboxy hexadecanyl.
- NH2 side chain group is functionalized with a group —
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6. The compound or salt or solvate thereof of claim 5, wherein
X14 is Lys wherein the — - NH2 side chain group is functionalized with a group —
Z—
C(O)R5, whereinZ is a group selected from the group consisting of γ
E, γ
E-γ
E, AEEAc-AEEAc-γ
E, and AEEAc-AEEAc-AEEAc, andR5 is a group selected from the group consisting of pentadecanyl and heptadecanyl.
- NH2 side chain group is functionalized with a group —
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7. The compound or salt or solvate thereof of claim 1, wherein
X2 is Ser, X3 is an amino acid residue selected from the group consisting of Gln and His, X14 is Lys wherein the — - NH2 side chain group is functionalized by a group selected from the group consisting of (S)-4-Carboxy-4-octadecanoylamino-butyryl- and (S)-4-Carboxy-4-((S)-4-carboxy-4-hexadecanoylamino-butyrylamino)-butyryl-,
X15 is Glu, X28 is Ala, and R1 is NH2.
- NH2 side chain group is functionalized by a group selected from the group consisting of (S)-4-Carboxy-4-octadecanoylamino-butyryl- and (S)-4-Carboxy-4-((S)-4-carboxy-4-hexadecanoylamino-butyrylamino)-butyryl-,
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8. The compound or salt or solvate thereof of claim 1, wherein
X2 is D-Ser, X3 is an amino acid residue selected from the group consisting of Gln and His, X14 is Lys wherein the — - NH2 side chain group is functionalized by a group selected from the group consisting of (S)-4-Carboxy-4-hexadecanoylamino-butyryl-, (S)-4-Carboxy-4-octadecanoylamino-butyryl- and (S)-4-Carboxy-4-((S)-4-carboxy-4-hexadecanoylamino-butyrylamino)-butyryl,
X15 is an amino acid residue selected from the group consisting of Glu and Asp, X28 is an amino acid residue selected from the group consisting of Ala and Lys, and R1 is NH2.
- NH2 side chain group is functionalized by a group selected from the group consisting of (S)-4-Carboxy-4-hexadecanoylamino-butyryl-, (S)-4-Carboxy-4-octadecanoylamino-butyryl- and (S)-4-Carboxy-4-((S)-4-carboxy-4-hexadecanoylamino-butyrylamino)-butyryl,
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9. The compound or salt or solvate thereof of claim 1, wherein
X2 is Aib, X3 is an amino acid residue selected from the group consisting of Gln and His, X14 is Lys wherein the — - NH2 side chain group is functionalized by a group selected from the group consisting of (S)-4-Carboxy-4-hexadecanoylamino-butyryl-, (S)-4-Carboxy-4-octadecanoylamino-butyryl-, (S)-4-Carboxy-4-((S)-4-carboxy-4-hexadecanoylamino-butyrylamino)-butyryl-, (2-{2-[2-(2-{2-[(4S)-4-Carboxy-4-hexadecanoylamino-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetyl, (2-{2-[2-(2-{2-[(4S)-4-Carboxy-4-octadecanoylamino-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetyl, and [2-(2-{2-[2-(2-{2-[2-(2-Octadecanoylamino-ethoxy)-ethoxy]-acetylamino}-ethoxy)-ethoxy]-acetylamino}-ethoxy)-ethoxy]-acetyl-,
X15 is an amino acid residue selected from the group consisting of Glu and Asp, X28 is an amino acid residue selected from the group consisting of Ala and Lys, and R1 is NH2.
- NH2 side chain group is functionalized by a group selected from the group consisting of (S)-4-Carboxy-4-hexadecanoylamino-butyryl-, (S)-4-Carboxy-4-octadecanoylamino-butyryl-, (S)-4-Carboxy-4-((S)-4-carboxy-4-hexadecanoylamino-butyrylamino)-butyryl-, (2-{2-[2-(2-{2-[(4S)-4-Carboxy-4-hexadecanoylamino-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetyl, (2-{2-[2-(2-{2-[(4S)-4-Carboxy-4-octadecanoylamino-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetyl, and [2-(2-{2-[2-(2-{2-[2-(2-Octadecanoylamino-ethoxy)-ethoxy]-acetylamino}-ethoxy)-ethoxy]-acetylamino}-ethoxy)-ethoxy]-acetyl-,
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10. The compound or salt or solvate thereof of claim 1, wherein
X2 is an amino acid residue selected from the group consisting of Ser, D-Ser, and Aib, X3 is Gln, X14 is Lys wherein the — - NH2 side chain group is functionalized by a group selected from the group consisting of (S)-4-Carboxy-4-hexadecanoylamino-butyryl-, (S)-4-Carboxy-4-octadecanoylamino-butyryl-, and (S)-4-Carboxy-4-((S)-4-carboxy-4-hexadecanoylamino-butyrylamino)-butyryl-,
X15 is an amino acid residue selected from the group consisting of Glu and Asp, X28 is an amino acid residue selected from the group consisting of Ala and Lys, and R1 is NH2.
- NH2 side chain group is functionalized by a group selected from the group consisting of (S)-4-Carboxy-4-hexadecanoylamino-butyryl-, (S)-4-Carboxy-4-octadecanoylamino-butyryl-, and (S)-4-Carboxy-4-((S)-4-carboxy-4-hexadecanoylamino-butyrylamino)-butyryl-,
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11. The compound or salt or solvate thereof of claim 1, wherein
X2 is an amino acid residue selected from the group consisting of Ser, D-Ser, and Aib, X3 is His, X14 is Lys wherein the — - NH2 side chain group is functionalized by a group selected from the group consisting of (S)-4-Carboxy-4-hexadecanoylamino-butyryl-, (S)-4-Carboxy-4-octadecanoylamino-butyryl-, (S)-4-Carboxy-4-((S)-4-carboxy-4-hexadecanoylamino-butyrylamino)-butyryl-, (2-{2-[2-(2-{2-[(4S)-4-Carboxy-4-hexadecanoylamino-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetyl, (2-{2-[2-(2-{2-[(4S)-4-Carboxy-4-octadecanoylamino-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetyl, and [2-(2-{2-[2-(2-{2-[2-(2-Octadecanoylamino-ethoxy)-ethoxy]-acetylamino}-ethoxy)-ethoxy]-acetylamino}-ethoxy)-ethoxy]-acetyl-,
X15 is an amino acid residue selected from the group consisting of Glu and Asp, X28 is an amino acid residue selected from the group consisting of Ala and Lys, and R1 is NH2.
- NH2 side chain group is functionalized by a group selected from the group consisting of (S)-4-Carboxy-4-hexadecanoylamino-butyryl-, (S)-4-Carboxy-4-octadecanoylamino-butyryl-, (S)-4-Carboxy-4-((S)-4-carboxy-4-hexadecanoylamino-butyrylamino)-butyryl-, (2-{2-[2-(2-{2-[(4S)-4-Carboxy-4-hexadecanoylamino-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetyl, (2-{2-[2-(2-{2-[(4S)-4-Carboxy-4-octadecanoylamino-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetyl, and [2-(2-{2-[2-(2-{2-[2-(2-Octadecanoylamino-ethoxy)-ethoxy]-acetylamino}-ethoxy)-ethoxy]-acetylamino}-ethoxy)-ethoxy]-acetyl-,
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12. The compound or salt or solvate thereof of claim 1, wherein
X2 is an amino acid residue selected from the group consisting of Ser, D-Ser, and Aib, X3 is an amino acid residue selected from the group consisting of Gln and His, X14 is Lys wherein the — - NH2 side chain group is functionalized by a group selected from the group consisting of (S)-4-Carboxy-4-hexadecanoylamino-butyryl-, (S)-4-Carboxy-4-octadecanoylamino-butyryl-, (S)-4-Carboxy-4-((S)-4-carboxy-4-hexadecanoylamino-butyrylamino)-butyryl-, (2-{2-[2-(2-{2-[(4S)-4-Carboxy-4-hexadecanoylamino-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetyl, (2-{2-[2-(2-{2-[(4S)-4-Carboxy-4-octadecanoylamino-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetyl, and [2-(2-{2-[2-(2-{2-[2-(2-Octadecanoylamino-ethoxy)-ethoxy]-acetylamino}-ethoxy)-ethoxy]-acetylamino}-ethoxy)-ethoxy]-acetyl-,
X15 is Glu, X28 is an amino acid residue selected from the group consisting of Ala and Lys, and R1 is NH2.
- NH2 side chain group is functionalized by a group selected from the group consisting of (S)-4-Carboxy-4-hexadecanoylamino-butyryl-, (S)-4-Carboxy-4-octadecanoylamino-butyryl-, (S)-4-Carboxy-4-((S)-4-carboxy-4-hexadecanoylamino-butyrylamino)-butyryl-, (2-{2-[2-(2-{2-[(4S)-4-Carboxy-4-hexadecanoylamino-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetyl, (2-{2-[2-(2-{2-[(4S)-4-Carboxy-4-octadecanoylamino-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetyl, and [2-(2-{2-[2-(2-{2-[2-(2-Octadecanoylamino-ethoxy)-ethoxy]-acetylamino}-ethoxy)-ethoxy]-acetylamino}-ethoxy)-ethoxy]-acetyl-,
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13. The compound or salt or solvate thereof of claim 1, wherein
X2 is an amino acid residue selected from the group consisting of D-Ser and Aib, X3 is an amino acid residue selected from the group consisting of Gln and His, X14 is Lys wherein the — - NH2 side chain group is functionalized by a group selected from the group consisting of (S)-4-Carboxy-4-octadecanoylamino-butyryl- and (S)-4-Carboxy-4-((S)-4-carboxy-4-hexadecanoylamino-butyrylamino)-butyryl-,
X15 is Asp, X28 is Ala, and R1 is NH2.
- NH2 side chain group is functionalized by a group selected from the group consisting of (S)-4-Carboxy-4-octadecanoylamino-butyryl- and (S)-4-Carboxy-4-((S)-4-carboxy-4-hexadecanoylamino-butyrylamino)-butyryl-,
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14. The compound or salt or solvate thereof of claim 1, wherein
X2 is an amino acid residue selected from the group consisting of Ser, D-Ser, and Aib, X3 is an amino acid residue selected from the group consisting of Gln and His, X14 is Lys wherein the — - NH2 side chain group is functionalized by a group selected from the group consisting of (S)-4-Carboxy-4-hexadecanoylamino-butyryl-, (S)-4-Carboxy-4-octadecanoylamino-butyryl-, (S)-4-Carboxy-4-((S)-4-carboxy-4-hexadecanoylamino-butyrylamino)-butyryl-, (2-{2-[2-(2-{2-[(4S)-4-Carboxy-4-hexadecanoylamino-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetyl, (2-{2-[2-(2-{2-[(4S)-4-Carboxy-4-octadecanoylamino-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetyl, and [2-(2-{2-[2-(2-{2-[2-(2-Octadecanoylamino-ethoxy)-ethoxy]-acetylamino}-ethoxy)-ethoxy]-acetylamino}-ethoxy)-ethoxy]-acetyl-,
X15 is an amino acid residue selected from the group consisting of Glu and Asp, X28 is Ala, and R1 is NH2.
- NH2 side chain group is functionalized by a group selected from the group consisting of (S)-4-Carboxy-4-hexadecanoylamino-butyryl-, (S)-4-Carboxy-4-octadecanoylamino-butyryl-, (S)-4-Carboxy-4-((S)-4-carboxy-4-hexadecanoylamino-butyrylamino)-butyryl-, (2-{2-[2-(2-{2-[(4S)-4-Carboxy-4-hexadecanoylamino-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetyl, (2-{2-[2-(2-{2-[(4S)-4-Carboxy-4-octadecanoylamino-butyrylamino]-ethoxy}-ethoxy)-acetylamino]-ethoxy}-ethoxy)-acetyl, and [2-(2-{2-[2-(2-{2-[2-(2-Octadecanoylamino-ethoxy)-ethoxy]-acetylamino}-ethoxy)-ethoxy]-acetylamino}-ethoxy)-ethoxy]-acetyl-,
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15. The compound or salt or solvate thereof of claim 1, wherein
X2 is an amino acid residue selected from the group consisting of D-Ser and Aib, X3 is an amino acid residue selected from the group consisting of Gln and His, X14 is Lys wherein the — - NH2 side chain group is functionalized by a group selected from the group consisting of (S)-4-Carboxy-4-octadecanoylamino-butyryl- and (S)-4-Carboxy-4-((S)-4-carboxy-4-hexadecanoylamino-butyrylamino)-butyryl-,
X15 is Glu, X28 is Lys, and R1 is NH2.
- NH2 side chain group is functionalized by a group selected from the group consisting of (S)-4-Carboxy-4-octadecanoylamino-butyryl- and (S)-4-Carboxy-4-((S)-4-carboxy-4-hexadecanoylamino-butyrylamino)-butyryl-,
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16. The compound or salt or solvate thereof of claim 1, wherein
X2 is Aib, X3 is His, X14 is Lys wherein the — - NH2 side chain group is functionalized by a group selected from the group consisting of (S)-4-Carboxy-4-hexadecanoylamino-butyryl-, (S)-4-Carboxy-4-octadecanoylamino-butyryl-, and (S)-4-Carboxy-4-((S)-4-carboxy-4-hexadecanoylamino-butyrylamino)-butyryl,
X15 is an amino acid residue selected from the group consisting of Glu and Asp, X28 is Ala, and R1 is NH2.
- NH2 side chain group is functionalized by a group selected from the group consisting of (S)-4-Carboxy-4-hexadecanoylamino-butyryl-, (S)-4-Carboxy-4-octadecanoylamino-butyryl-, and (S)-4-Carboxy-4-((S)-4-carboxy-4-hexadecanoylamino-butyrylamino)-butyryl,
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17. The compound or salt or solvate thereof of claim 1, selected from any one of the compounds of SEQ ID NOs:
- 6-31.
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18. The compound or salt or solvate thereof of claim 17, selected from any one of the compounds of SEQ ID NOs:
- 6-29 and 31.
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19. The compound, salt or solvate of claim 1, consisting of the amino acid sequence of SEQ ID NO:
- 11, or a salt or solvate thereof.
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20. The compound, salt or solvate of claim 1, consisting of the amino acid sequence of SEQ ID NO:
- 12, or a salt or solvate thereof.
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21. The compound, salt or solvate of claim 1, consisting of the amino acid sequence of SEQ ID NO:
- 20, or a salt or solvate thereof.
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22. A solvate of a compound of claim 1.
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23. A hydrate of a compound of claim 1.
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24. A pharmaceutical composition comprising one or more compounds of claim 1 or a salt or solvate thereof as an active ingredient and at least one pharmaceutically acceptable carrier.
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25. The pharmaceutical composition of claim 24, further comprising at least one additional therapeutically active agent, wherein the additional therapeutically active agent is selected from the group consisting of:
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insulin and insulin derivatives selected from the group consisting of;
insulin glargine, insulin glusiline, insulin detemir, insulin lispro, insulin degludec, insulin aspart, basal insulin and analogues thereof, pegylated insulin, recombinant human insulin, polysialated insulins, long-acting insulin, NN1045, insulin in combination with pramlintide, PE0139, fast-acting and short-acting insulins, insulin hydrogel, oral insulin, inhalable insulin, transdermal insulin and sublingual insulin, and insulin derivatives which are bonded to albumin or another protein by a bifunctional linker;GLP-1, GLP-1 analogues, and GLP-1 receptor agonists selected from the group consisting of;
lixisenatide, exenatide, exendin-4, ITCA 650, AC-2993, liraglutide, semaglutide, taspoglutide, albiglutide, dulaglutide, rExendin-4, CJC-1134-PC, PB-1023, TTP-054, Langlenatide, HM-11260C, CM-3, ORMD-0901, NN-9924, NN-9926, NN-9927, CVX-096, ZYOG-1, ZYD-1, GSK-2374697, DA-3091, MAR-701, MAR709, ZP-2929, ZP-3022, TT-401, BHM-034, MOD-6030, CAM-2036, DA-15864, ARI-2651, ARI-2255, xtenylated exenatide, xtenylated glucagon, and polymer bound derivatives thereof;dual GLP-1/GIP receptor agonists;
dual GLP-1/glucagon receptor agonists;
protein YY3-36 (PYY3-36);
pancreatic polypeptide;
glucagon receptor agonists;
GIP receptor agonists or antagonists;
ghrelin receptor antagonists or inverse agonists;
xenin;
dipeptidyl peptidase IV (DPP-IV) inhibitors;
sodium glucose cotransporter 2 (SGLT2) inhibitors;
dual SGLT2/SGLT1 inhibitors;
biguanides;
thiazolidinediones;
dual peroxisome proliferator-activated receptor (PPAR) agonists;
sulfonylureas;
meglitinides;
alpha-glucosidase inhibitors;
amylin;
pramlintide;
G protein-coupled receptor 119 (GPR119) agonists;
GPR40 agonists;
GPR120 agonists;
GPR142 agonists;
systemic or low-absorbable transmembrane G protein-coupled receptor 5 (TGR5) agonists;
bromocriptine mesylate;
inhibitors of 11-beta-hydroxysteroid dehydrogenase (HSD);
activators of glucokinase;
inhibitors of diacylglycerol acyltransferase (DGAT);
inhibitors of protein tyrosinephosphatase 1;
inhibitors of glucose-6-phosphatase;
inhibitors of fructose-1,6-bisphosphatase;
inhibitors of glycogen phosphorylase;
inhibitors of phosphoenol pyruvate carboxykinase;
inhibitors of glycogen synthase kinase;
inhibitors of pyruvate dehydrogenase kinase;
alpha2-antagonists;
C-C motif receptor (CCR-2) antagonists;
modulators of glucose transporter-4;
somatostatin receptor 3 agonists;
3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA)-reductase inhibitors;
fibrates;
nicotinic acid and derivatives thereof;
nicotinic acid receptor 1 agonists;
PPAR-alpha, gamma, or alpha/gamma agonists or modulators;
PPAR-delta agonists;
acyl-CoA cholesterol acyltransferase (ACAT) inhibitors;
cholesterol absorption inhibitors;
bile acid-binding substances;
ileal bile acid transporter (IBAT) inhibitors;
microsomal triglyceride transfer protein (MTP) inhibitors;
modulators of proprotein convertase subtilisin/kinexin type 9 (PCSK9);
low-density lipoprotein (LDL) receptor up-regulators by liver selective thyroid hormone receptor β
agonists;
high-density lipoprotein (HDL)-raising compounds;
lipid metabolism modulators;
phospholipase A2 (PLA2) inhibitors;
apolipoprotein A1 (ApoA-1) enhancers;
thyroid hormone receptor agonists;
cholesterol synthesis inhibitors; and
omega-3 fatty acids and derivatives thereof;substances for the treatment of obesity selected from the group consisting of;
sibutramine, tesofensine, tetrahydrolipstatin, cannabinoid-1 (CB-1) receptor antagonists, melanin-concentrating hormone-1 (MCH-1) antagonists, melanocortin 4 (MC4) receptor agonists or partial agonists, neuropeptide Y5 (NPY5) or NPY2 antagonists, NPY4 agonists, beta-3-agonists, leptin or leptin mimetics, agonists of the 5HT2c receptor, combinations of bupropione/naltrexone, combinations of bupropione/zonisamide, combinations of bupropione/phentermine, combinations of pramlintide/metreleptin, and combinations of phentermine/topiramate;lipase inhibitors;
angiogenesis inhibitors;
H3 antagonists;
Agouti-related protein (AgRP) inhibitors;
triple monoamine uptake inhibitors;
methionine aminopeptidase type 2 (MetAP2) inhibitors;
nasal formulation of the calcium channel blocker diltiazem;
antisense molecules against production of fibroblast growth factor receptor 4; and
prohibitin targeting peptide-1; anddrugs for influencing high blood pressure, chronic heart failure, or atherosclerosis selected from the groups consisting of;
angiotensin II receptor antagonists, angiotensin-converting-enzyme (ACE) inhibitors, endothelin-converting-enzyme (ECE) inhibitors, diuretics, beta-blockers, calcium antagonists, centrally acting hypertensives, antagonists of the alpha-2-adrenergic receptor, inhibitors of neutral endopeptidase, and thrombocyte aggregation inhibitors.
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26. A method for the treatment of hyperglycemia, type 1 diabetes, type 2 diabetes,
or obesity, or any combination of these individual disease components, the method comprising administering to a patient in need of such treatment an effective amount of one or more compounds, salts or solvates of claim 1. -
27. The method of claim 26, for the treatment of hyperglycemia, or type 2 diabetes.
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28. A method for the simultaneous treatment of diabetes and obesity which comprises administering to a patient in need of such treatment an effective amount of one or more compounds, salts or solvates of claim 1.
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29. A method for the treatment of hyperglycemia, type 2 diabetes, type 1 diabetes, or obesity, or any combination of these individual disease components, the method comprising administering to a patient in need of such treatment an effective amount of a pharmaceutical composition of claim 24.
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30. The method of claim 29, for the treatment of hyperglycemia or type 2 diabetes.
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31. A method for the simultaneous treatment of diabetes and obesity, the method comprising administering to a patient in need of such treatment an effective amount of a pharmaceutical composition of claim 24.
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2. The compound or salt or solvate thereof of claim 1, wherein R1 is NH2.
Specification
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Current AssigneeSanofi
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Original AssigneeSanofi
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InventorsBossart, Martin, Elvert, Ralf, Evers, Andreas, Haack, Torsten, Stengelin, Siegfried, Wagner, Michael, Lorenz, Katrin
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Primary Examiner(s)Ha, Julie
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Assistant Examiner(s)Hellman, Kristina M
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Application NumberUS14/679,777Publication NumberTime in Patent Office904 DaysField of SearchNoneUS Class CurrentCPC Class CodesA61K 38/26 GlucagonsA61K 45/06 Mixtures of active ingredie...A61P 3/04 Anorexiants; Antiobesity ag...A61P 3/06 AntihyperlipidemicsA61P 3/10 for hyperglycaemia, e.g. an...A61P 5/50 for increasing or potentiat...A61P 9/00 Drugs for disorders of the ...A61P 9/10 for treating ischaemic or a...A61P 9/12 AntihypertensivesC07K 14/57563 Vasoactive intestinal pepti...C07K 14/605 Glucagons