CA2443229A1 - Treatment of type 2 diabetes with inhibitors of dipeptidyl peptidase iv - Google Patents
Treatment of type 2 diabetes with inhibitors of dipeptidyl peptidase iv Download PDFInfo
- Publication number
- CA2443229A1 CA2443229A1 CA002443229A CA2443229A CA2443229A1 CA 2443229 A1 CA2443229 A1 CA 2443229A1 CA 002443229 A CA002443229 A CA 002443229A CA 2443229 A CA2443229 A CA 2443229A CA 2443229 A1 CA2443229 A1 CA 2443229A1
- Authority
- CA
- Canada
- Prior art keywords
- inhibitor
- dipeptidyl peptidase
- het
- aminoacyl
- general formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000003112 inhibitor Substances 0.000 title claims abstract description 48
- 102000016622 Dipeptidyl Peptidase 4 Human genes 0.000 title claims abstract description 25
- 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 title claims abstract description 25
- 208000001072 type 2 diabetes mellitus Diseases 0.000 title claims abstract description 23
- 238000011282 treatment Methods 0.000 title claims description 21
- 238000000034 method Methods 0.000 claims abstract description 22
- 229940002612 prodrug Drugs 0.000 claims abstract description 15
- 239000000651 prodrug Substances 0.000 claims abstract description 15
- 201000010099 disease Diseases 0.000 claims abstract description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 14
- 150000001875 compounds Chemical class 0.000 claims description 38
- 239000000203 mixture Substances 0.000 claims description 23
- 238000009472 formulation Methods 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 6
- -1 5-cyano-2-pyridyl group Chemical group 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
- 241001465754 Metazoa Species 0.000 description 10
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 10
- 206010012601 diabetes mellitus Diseases 0.000 description 7
- 238000013293 zucker diabetic fatty rat Methods 0.000 description 7
- IOVCWXUNBOPUCH-UHFFFAOYSA-M nitrite group Chemical group N(=O)[O-] IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 6
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 6
- 102000004877 Insulin Human genes 0.000 description 5
- 108090001061 Insulin Proteins 0.000 description 5
- 201000001421 hyperglycemia Diseases 0.000 description 5
- 229940125396 insulin Drugs 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 235000021588 free fatty acids Nutrition 0.000 description 4
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- VLJNHYLEOZPXFW-BYPYZUCNSA-N L-prolinamide Chemical compound NC(=O)[C@@H]1CCCN1 VLJNHYLEOZPXFW-BYPYZUCNSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000002255 enzymatic effect Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 150000003140 primary amides Chemical group 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
- LSTRKXWIZZZYAS-UHFFFAOYSA-N 2-bromoacetyl bromide Chemical compound BrCC(Br)=O LSTRKXWIZZZYAS-UHFFFAOYSA-N 0.000 description 1
- NIUAJYOMWZYSQR-UHFFFAOYSA-N 6-(2-aminoethylamino)pyridine-3-carbonitrile Chemical compound NCCNC1=CC=C(C#N)C=N1 NIUAJYOMWZYSQR-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 208000002249 Diabetes Complications Diseases 0.000 description 1
- 206010012655 Diabetic complications Diseases 0.000 description 1
- 102100025101 GATA-type zinc finger protein 1 Human genes 0.000 description 1
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 description 1
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 125000000266 alpha-aminoacyl group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 229940125708 antidiabetic agent Drugs 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 125000006165 cyclic alkyl group Chemical group 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000009200 high fat diet Nutrition 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000001127 hyperphagic effect Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 239000000859 incretin Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 206010036067 polydipsia Diseases 0.000 description 1
- 230000000291 postprandial effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- ALSCEGDXFJIYES-UHFFFAOYSA-N pyrrolidine-2-carbonitrile Chemical compound N#CC1CCCN1 ALSCEGDXFJIYES-UHFFFAOYSA-N 0.000 description 1
- QSJTUXCBPTVKQZ-UHFFFAOYSA-N pyrrolidine-2-carbonitrile;hydrochloride Chemical compound Cl.N#CC1CCCN1 QSJTUXCBPTVKQZ-UHFFFAOYSA-N 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/426—1,3-Thiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Plant Substances (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0109146.1 | 2001-04-11 | ||
| GBGB0109146.1A GB0109146D0 (en) | 2001-04-11 | 2001-04-11 | Treatment of type 2 diabetes |
| PCT/GB2002/001674 WO2002083109A1 (en) | 2001-04-11 | 2002-04-10 | Treatment of type 2 diabetes with inhibitors of dipeptidyl peptidase iv |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2443229A1 true CA2443229A1 (en) | 2002-10-24 |
Family
ID=9912727
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002443229A Abandoned CA2443229A1 (en) | 2001-04-11 | 2002-04-10 | Treatment of type 2 diabetes with inhibitors of dipeptidyl peptidase iv |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US20040209891A1 (https=) |
| EP (1) | EP1377278B1 (https=) |
| JP (1) | JP2004525179A (https=) |
| KR (1) | KR20040025915A (https=) |
| CN (1) | CN1248683C (https=) |
| AT (1) | ATE344029T1 (https=) |
| AU (1) | AU2002244860B2 (https=) |
| CA (1) | CA2443229A1 (https=) |
| CZ (1) | CZ20032927A3 (https=) |
| DE (1) | DE60215787T2 (https=) |
| GB (1) | GB0109146D0 (https=) |
| HU (1) | HUP0303876A3 (https=) |
| IL (1) | IL157821A0 (https=) |
| MX (1) | MXPA03009224A (https=) |
| NO (1) | NO20034549L (https=) |
| NZ (1) | NZ528172A (https=) |
| PL (1) | PL366633A1 (https=) |
| RU (1) | RU2328283C2 (https=) |
| UA (1) | UA76452C2 (https=) |
| WO (1) | WO2002083109A1 (https=) |
| ZA (1) | ZA200307156B (https=) |
Families Citing this family (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2296979T3 (es) | 2001-06-27 | 2008-05-01 | Smithkline Beecham Corporation | Fluoropirrolidinas como inhibidores de dipeptidil peptidasa. |
| GB0125445D0 (en) * | 2001-10-23 | 2001-12-12 | Ferring Bv | Protease Inhibitors |
| AU2002952946A0 (en) * | 2002-11-27 | 2002-12-12 | Fujisawa Pharmaceutical Co., Ltd. | Dpp-iv inhibitor |
| US7550590B2 (en) | 2003-03-25 | 2009-06-23 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| WO2004103993A1 (en) | 2003-05-14 | 2004-12-02 | Syrrx, Inc. | Dipeptidyl peptidase inhibitors |
| US6995183B2 (en) | 2003-08-01 | 2006-02-07 | Bristol Myers Squibb Company | Adamantylglycine-based inhibitors of dipeptidyl peptidase IV and methods |
| KR20060041309A (ko) | 2003-08-13 | 2006-05-11 | 다케다 야쿠힌 고교 가부시키가이샤 | ４-피리미돈 유도체 및 펩티딜 펩티다제 저해제로서의 그의용도 |
| US7169926B1 (en) | 2003-08-13 | 2007-01-30 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| US7678909B1 (en) | 2003-08-13 | 2010-03-16 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| US7790734B2 (en) | 2003-09-08 | 2010-09-07 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| US20070149451A1 (en) * | 2003-11-17 | 2007-06-28 | Holmes David G | Combination of a dpp IV inhibitor and an antiobesity or appetite regulating agent |
| KR20120008093A (ko) | 2003-11-17 | 2012-01-25 | 노파르티스 아게 | 디펩티딜 펩티다제 ⅳ 억제제의 용도 |
| DK1715893T3 (da) | 2004-01-20 | 2009-11-09 | Novartis Pharma Ag | Direkte kompressionsformulering og fremgangsmåde |
| US7732446B1 (en) | 2004-03-11 | 2010-06-08 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| CN102127057A (zh) | 2004-03-15 | 2011-07-20 | 武田药品工业株式会社 | 二肽基肽酶抑制剂 |
| JP2008501714A (ja) | 2004-06-04 | 2008-01-24 | 武田薬品工業株式会社 | ジペプチジルペプチダーゼインヒビター |
| WO2006019965A2 (en) | 2004-07-16 | 2006-02-23 | Takeda San Diego, Inc. | Dipeptidyl peptidase inhibitors |
| ATE553077T1 (de) * | 2004-07-23 | 2012-04-15 | Nuada Llc | Peptidaseinhibitoren |
| WO2006068978A2 (en) | 2004-12-21 | 2006-06-29 | Takeda Pharmaceutial Company Limited | Dipeptidyl peptidase inhibitors |
| DOP2006000008A (es) | 2005-01-10 | 2006-08-31 | Arena Pharm Inc | Terapia combinada para el tratamiento de la diabetes y afecciones relacionadas y para el tratamiento de afecciones que mejoran mediante un incremento de la concentración sanguínea de glp-1 |
| AU2006239929B2 (en) | 2005-04-22 | 2011-11-03 | Alantos Pharmaceuticals Holding, Inc. | Dipeptidyl peptidase-IV inhibitors |
| AU2006278039B2 (en) * | 2005-08-11 | 2010-10-21 | F. Hoffmann-La Roche Ag | Pharmaceutical composition comprising a DPP-lV inhibitor |
| GEP20135838B (en) | 2005-09-14 | 2013-06-10 | Takeda Pharmaceutical | Dipeptidyl peptidase inhibitors usage at diabetes treatment |
| CN101360723A (zh) | 2005-09-16 | 2009-02-04 | 武田药品工业株式会社 | 制备嘧啶二酮衍生物的方法 |
| GB0526291D0 (en) | 2005-12-23 | 2006-02-01 | Prosidion Ltd | Therapeutic method |
| WO2007112347A1 (en) | 2006-03-28 | 2007-10-04 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| PE20071221A1 (es) | 2006-04-11 | 2007-12-14 | Arena Pharm Inc | Agonistas del receptor gpr119 en metodos para aumentar la masa osea y para tratar la osteoporosis y otras afecciones caracterizadas por masa osea baja, y la terapia combinada relacionada a estos agonistas |
| US8324383B2 (en) | 2006-09-13 | 2012-12-04 | Takeda Pharmaceutical Company Limited | Methods of making polymorphs of benzoate salt of 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-benzonitrile |
| TW200838536A (en) | 2006-11-29 | 2008-10-01 | Takeda Pharmaceutical | Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor |
| US8093236B2 (en) | 2007-03-13 | 2012-01-10 | Takeda Pharmaceuticals Company Limited | Weekly administration of dipeptidyl peptidase inhibitors |
| EP2108960A1 (en) | 2008-04-07 | 2009-10-14 | Arena Pharmaceuticals, Inc. | Methods of using A G protein-coupled receptor to identify peptide YY (PYY) secretagogues and compounds useful in the treatment of conditons modulated by PYY |
| FR2938999B1 (fr) * | 2008-11-24 | 2011-07-01 | Oreal | Procede de preparation d'un parfum au sein d'un systeme comportant une pluralite de terminaux interactifs de formulation de parfums et un serveur agence pour echanger des donnees avec la pluralite de terminaux |
| AR077642A1 (es) | 2009-07-09 | 2011-09-14 | Arena Pharm Inc | Moduladores del metabolismo y el tratamiento de trastornos relacionados con el mismo |
| AU2011237775A1 (en) | 2010-04-06 | 2012-11-22 | Arena Pharmaceuticals, Inc. | Modulators of the GPR119 receptor and the treatment of disorders related thereto |
| PH12013500547A1 (en) | 2010-09-22 | 2013-06-10 | Arena Pharm Inc | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| US20140018371A1 (en) | 2011-04-01 | 2014-01-16 | Arena Pharmaceuticals, Inc. | Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto |
| US20140066369A1 (en) | 2011-04-19 | 2014-03-06 | Arena Pharmaceuticals, Inc. | Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto |
| US20140038889A1 (en) | 2011-04-22 | 2014-02-06 | Arena Pharmaceuticals, Inc. | Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto |
| WO2012145604A1 (en) | 2011-04-22 | 2012-10-26 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| WO2012170702A1 (en) | 2011-06-08 | 2012-12-13 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| WO2013055910A1 (en) | 2011-10-12 | 2013-04-18 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| WO2014074668A1 (en) | 2012-11-08 | 2014-05-15 | Arena Pharmaceuticals, Inc. | Modulators of gpr119 and the treatment of disorders related thereto |
| GB201415598D0 (en) | 2014-09-03 | 2014-10-15 | Univ Birmingham | Elavated Itercranial Pressure Treatment |
| EA201791982A1 (ru) | 2015-03-09 | 2020-02-17 | Интекрин Терапьютикс, Инк. | Способы лечения неалкогольной жировой болезни печени и/или липодистрофии |
| WO2018162722A1 (en) | 2017-03-09 | 2018-09-13 | Deutsches Institut Für Ernährungsforschung Potsdam-Rehbrücke | Dpp-4 inhibitors for use in treating bone fractures |
| AU2018249822A1 (en) | 2017-04-03 | 2019-10-31 | Coherus Biosciences Inc. | PPArgamma agonist for treatment of progressive supranuclear palsy |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL111785A0 (en) * | 1993-12-03 | 1995-01-24 | Ferring Bv | Dp-iv inhibitors and pharmaceutical compositions containing them |
| DE19616486C5 (de) * | 1996-04-25 | 2016-06-30 | Royalty Pharma Collection Trust | Verfahren zur Senkung des Blutglukosespiegels in Säugern |
| TW492957B (en) * | 1996-11-07 | 2002-07-01 | Novartis Ag | N-substituted 2-cyanopyrrolidnes |
| US6011155A (en) * | 1996-11-07 | 2000-01-04 | Novartis Ag | N-(substituted glycyl)-2-cyanopyrrolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV |
| DE19823831A1 (de) * | 1998-05-28 | 1999-12-02 | Probiodrug Ges Fuer Arzneim | Neue pharmazeutische Verwendung von Isoleucyl Thiazolidid und seinen Salzen |
| CO5150173A1 (es) * | 1998-12-10 | 2002-04-29 | Novartis Ag | Compuestos n-(glicilo sustituido)-2-cianopirrolidinas inhibidores de peptidasa de dipeptidilo-iv (dpp-iv) los cuales son efectivos en el tratamiento de condiciones mediadas por la inhibicion de dpp-iv |
| DE60045030D1 (de) * | 1999-02-10 | 2010-11-11 | Curis Inc | Peptid yy (pyy) zur behandlung von glukose stoffwechselkrankheiten |
| GB9906714D0 (en) * | 1999-03-23 | 1999-05-19 | Ferring Bv | Compositions for improving fertility |
| US6110949A (en) * | 1999-06-24 | 2000-08-29 | Novartis Ag | N-(substituted glycyl)-4-cyanothiazolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV |
| US6107317A (en) * | 1999-06-24 | 2000-08-22 | Novartis Ag | N-(substituted glycyl)-thiazolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV |
| EP1228061A4 (en) * | 1999-11-12 | 2004-12-15 | Guilford Pharm Inc | DIPEPTIDYL PEPTIDASE IV INHIBITORS; METHODS OF MANUFACTURE AND USE OF SAID INHIBITORS |
| GB9928330D0 (en) * | 1999-11-30 | 2000-01-26 | Ferring Bv | Novel antidiabetic agents |
| HU229042B1 (en) * | 2000-03-31 | 2013-07-29 | Prosidion Ltd | Method for the improvement of islet signaling in diabetes mellitus and for its prevention |
| GB0010188D0 (en) * | 2000-04-26 | 2000-06-14 | Ferring Bv | Inhibitors of dipeptidyl peptidase IV |
| GB0014969D0 (en) * | 2000-06-19 | 2000-08-09 | Smithkline Beecham Plc | Novel method of treatment |
-
2001
- 2001-04-11 GB GBGB0109146.1A patent/GB0109146D0/en not_active Ceased
-
2002
- 2002-04-10 CN CNB028080955A patent/CN1248683C/zh not_active Expired - Fee Related
- 2002-04-10 DE DE60215787T patent/DE60215787T2/de not_active Expired - Fee Related
- 2002-04-10 AT AT02713070T patent/ATE344029T1/de not_active IP Right Cessation
- 2002-04-10 CZ CZ20032927A patent/CZ20032927A3/cs unknown
- 2002-04-10 NZ NZ528172A patent/NZ528172A/en unknown
- 2002-04-10 JP JP2002580913A patent/JP2004525179A/ja not_active Withdrawn
- 2002-04-10 AU AU2002244860A patent/AU2002244860B2/en not_active Ceased
- 2002-04-10 MX MXPA03009224A patent/MXPA03009224A/es active IP Right Grant
- 2002-04-10 RU RU2003132687/14A patent/RU2328283C2/ru not_active IP Right Cessation
- 2002-04-10 US US10/474,676 patent/US20040209891A1/en not_active Abandoned
- 2002-04-10 KR KR10-2003-7013350A patent/KR20040025915A/ko not_active Ceased
- 2002-04-10 WO PCT/GB2002/001674 patent/WO2002083109A1/en not_active Ceased
- 2002-04-10 CA CA002443229A patent/CA2443229A1/en not_active Abandoned
- 2002-04-10 PL PL02366633A patent/PL366633A1/xx unknown
- 2002-04-10 IL IL15782102A patent/IL157821A0/xx unknown
- 2002-04-10 EP EP02713070A patent/EP1377278B1/en not_active Expired - Lifetime
- 2002-04-10 HU HU0303876A patent/HUP0303876A3/hu unknown
- 2002-10-04 UA UA2003109184A patent/UA76452C2/uk unknown
-
2003
- 2003-09-12 ZA ZA200307156A patent/ZA200307156B/en unknown
- 2003-10-09 NO NO20034549A patent/NO20034549L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| RU2328283C2 (ru) | 2008-07-10 |
| RU2003132687A (ru) | 2005-04-10 |
| KR20040025915A (ko) | 2004-03-26 |
| HUP0303876A2 (hu) | 2004-03-01 |
| NZ528172A (en) | 2004-09-24 |
| US20040209891A1 (en) | 2004-10-21 |
| CN1501796A (zh) | 2004-06-02 |
| DE60215787D1 (de) | 2006-12-14 |
| IL157821A0 (en) | 2004-03-28 |
| EP1377278B1 (en) | 2006-11-02 |
| NO20034549D0 (no) | 2003-10-09 |
| ATE344029T1 (de) | 2006-11-15 |
| CN1248683C (zh) | 2006-04-05 |
| AU2002244860B2 (en) | 2006-11-16 |
| DE60215787T2 (de) | 2007-08-30 |
| HK1059213A1 (en) | 2004-06-25 |
| UA76452C2 (en) | 2006-08-15 |
| EP1377278A1 (en) | 2004-01-07 |
| JP2004525179A (ja) | 2004-08-19 |
| PL366633A1 (en) | 2005-02-07 |
| NO20034549L (no) | 2003-10-09 |
| WO2002083109A1 (en) | 2002-10-24 |
| GB0109146D0 (en) | 2001-05-30 |
| MXPA03009224A (es) | 2004-01-29 |
| HUP0303876A3 (en) | 2005-06-28 |
| CZ20032927A3 (cs) | 2004-06-16 |
| ZA200307156B (en) | 2004-06-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2002244860B2 (en) | Treatment of type 2 diabetes with inhibitors of dipeptidyl peptidase IV | |
| AU2002244860A1 (en) | Treatment of type 2 diabetes with inhibitors of dipeptidyl peptidase IV | |
| US9119843B2 (en) | Method of using dopamine reuptake inhibitors and their analogs for treating diabetes symptoms and delaying or preventing diabetes-associated pathologic conditions | |
| AU2003201577B2 (en) | Use of phosphodiesterase antagonists to treat insulin resistance | |
| NO314065B1 (no) | Farmasöytisk sammensetning omfattende en insulinsensitivitetsenhancer og etbiguanid ved behandling av diabetes | |
| PT654264E (pt) | Tratamento de incontinencia com venlafaxina ou com um composto de ariloxi propanamina | |
| EA015382B1 (ru) | Применение рофлумиласта для лечения сахарного диабета типа 2 | |
| JP2826379B2 (ja) | チアゾリジン誘導体を有効成分とする肥満性高血圧症治療剤 | |
| US20090118225A1 (en) | 1-Methyl Nicotinamide and Derivatives for Treatment of Gastric Injury | |
| US20070287685A1 (en) | Medicinal composition containing FBPase inhibitor | |
| US20060246131A1 (en) | Use of metformin to counteract weight gain associated with psychotropic medications | |
| US20140329844A1 (en) | Method of restoring the incretin effect | |
| MX2014014316A (es) | Método de reducción de peso. | |
| JPWO2007007757A1 (ja) | ＰＰＡＲγアゴニストを含有する医薬組成物 | |
| AU2004269923A2 (en) | Use of PDE4 inhibitors for the treatment of diabetes mellitus | |
| HK1059213B (en) | Treatment of type 2 diabetes with inhibitors of dipeptidyl peptidase iv | |
| WO2024226995A1 (en) | Compositions and methods for treating post-traumatic stress disorder | |
| US20070208080A1 (en) | A composition containing a thiourea derivative for preventing or treating pruritic or irritant skin diseases | |
| CN119584967A (zh) | 用甘氨酸转运抑制剂治疗肝性卟啉症的组合物和方法 | |
| JP2006193516A (ja) | ＦＢＰａｓｅ阻害剤を含有する医薬組成物 | |
| HK1104477A (en) | Medicinal composition containing fbpase inhibitor | |
| WO2005117853A1 (ja) | 高脂血症治療剤及び糖尿病治療剤 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |