ZA200406332B - ACC inhibitors. - Google Patents

ACC inhibitors. Download PDF

Info

Publication number: ZA200406332B
Authority: ZA; South Africa
Prior art keywords: insulin; moiety; human; patient; conjugate
Prior art date: 2002-02-27

Application number

ZA200406332A

Other languages

English (en)

Inventor

David Austen Perry

Harwood Harold James Jr

Original Assignee

Pfizer Prod Inc

Priority date (The priority date 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 date listed.)

2002-02-27

Filing date

2004-08-10

Publication date

2005-09-28

2004-08-10 Application filed by Pfizer Prod Inc filed Critical Pfizer Prod Inc

2005-09-28 Publication of ZA200406332B publication Critical patent/ZA200406332B/en

Links

229940121373 acetyl-coa carboxylase inhibitor Drugs 0.000 title 1
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 claims description 1341
102000004877 Insulin Human genes 0.000 claims description 793
108090001061 Insulin Proteins 0.000 claims description 793
229940125396 insulin Drugs 0.000 claims description 658
238000000034 method Methods 0.000 claims description 343
241000282414 Homo sapiens Species 0.000 claims description 251
206010012601 diabetes mellitus Diseases 0.000 claims description 149
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 claims description 127
239000008103 glucose Substances 0.000 claims description 124
125000000217 alkyl group Chemical group 0.000 claims description 103
239000003814 drug Substances 0.000 claims description 98
229920001515 polyalkylene glycol Polymers 0.000 claims description 94
125000003827 glycol group Chemical group 0.000 claims description 91
229940079593 drug Drugs 0.000 claims description 89
235000012054 meals Nutrition 0.000 claims description 81
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 67
230000002093 peripheral effect Effects 0.000 claims description 65
239000000203 mixture Substances 0.000 claims description 63
230000037406 food intake Effects 0.000 claims description 59
125000004432 carbon atom Chemical group C* 0.000 claims description 58
230000002440 hepatic effect Effects 0.000 claims description 57
230000009229 glucose formation Effects 0.000 claims description 56
210000004369 blood Anatomy 0.000 claims description 52
239000008280 blood Substances 0.000 claims description 52
125000005313 fatty acid group Chemical group 0.000 claims description 49
150000001408 amides Chemical group 0.000 claims description 47
ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 claims description 46
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 44
210000003240 portal vein Anatomy 0.000 claims description 44
235000000346 sugar Nutrition 0.000 claims description 44
229920001223 polyethylene glycol Polymers 0.000 claims description 43
239000002202 Polyethylene glycol Substances 0.000 claims description 42
KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims description 41
150000002148 esters Chemical group 0.000 claims description 41
125000005587 carbonate group Chemical group 0.000 claims description 35
235000012000 cholesterol Nutrition 0.000 claims description 33
125000001033 ether group Chemical group 0.000 claims description 33
XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 30
150000007970 thio esters Chemical group 0.000 claims description 28
125000003158 alcohol group Chemical group 0.000 claims description 27
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
239000008194 pharmaceutical composition Substances 0.000 claims description 27
230000000291 postprandial effect Effects 0.000 claims description 25
125000003545 alkoxy group Chemical group 0.000 claims description 24
239000004472 Lysine Substances 0.000 claims description 21
239000004026 insulin derivative Substances 0.000 claims description 21
230000009467 reduction Effects 0.000 claims description 16
125000006850 spacer group Chemical group 0.000 claims description 15
125000005647 linker group Chemical group 0.000 claims description 14
210000005259 peripheral blood Anatomy 0.000 claims description 13
239000011886 peripheral blood Substances 0.000 claims description 13
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical group OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 11
108010076181 Proinsulin Proteins 0.000 claims description 10
230000037396 body weight Effects 0.000 claims description 10
238000002360 preparation method Methods 0.000 claims description 8
239000004202 carbamide Substances 0.000 claims description 5
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 2
150000003558 thiocarbamic acid derivatives Chemical group 0.000 claims 24
101100400201 Drosophila melanogaster LysB gene Proteins 0.000 claims 2
241000478345 Afer Species 0.000 claims 1
101150078948 proB2 gene Proteins 0.000 claims 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 83
-1 antibodies Proteins 0.000 description 79
210000004185 liver Anatomy 0.000 description 33
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 26
PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 description 26
230000000694 effects Effects 0.000 description 25
229920006395 saturated elastomer Polymers 0.000 description 21
238000007920 subcutaneous administration Methods 0.000 description 21
235000001014 amino acid Nutrition 0.000 description 20
101000976075 Homo sapiens Insulin Proteins 0.000 description 19
229940024606 amino acid Drugs 0.000 description 19
150000001413 amino acids Chemical class 0.000 description 19
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 15
229920001451 polypropylene glycol Polymers 0.000 description 15
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 14
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 14
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 14
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 14
239000000243 solution Substances 0.000 description 14
235000014113 dietary fatty acids Nutrition 0.000 description 13
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 13
239000000194 fatty acid Substances 0.000 description 13
229930195729 fatty acid Natural products 0.000 description 13
238000010521 absorption reaction Methods 0.000 description 12
VKOBVWXKNCXXDE-UHFFFAOYSA-N ethyl stearic acid Natural products CCCCCCCCCCCCCCCCCCCC(O)=O VKOBVWXKNCXXDE-UHFFFAOYSA-N 0.000 description 11
229920001184 polypeptide Polymers 0.000 description 11
108090000765 processed proteins & peptides Proteins 0.000 description 11
102000004196 processed proteins & peptides Human genes 0.000 description 11
239000007787 solid Substances 0.000 description 10
125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 9
125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 9
125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 9
125000005916 2-methylpentyl group Chemical group 0.000 description 9
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 9
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 9
125000005917 3-methylpentyl group Chemical group 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical group CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Chemical group CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 9
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 9
125000001204 arachidyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 9
125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 9
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 9
230000014101 glucose homeostasis Effects 0.000 description 9
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 9
239000007788 liquid Substances 0.000 description 9
125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
125000001196 nonadecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 9
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
210000000496 pancreas Anatomy 0.000 description 9
125000002958 pentadecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
229940083608 sodium hydroxide Drugs 0.000 description 9
235000011121 sodium hydroxide Nutrition 0.000 description 9
125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
125000002889 tridecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 9
229920002554 vinyl polymer Polymers 0.000 description 9
125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 8
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 8
OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 8
150000004665 fatty acids Chemical class 0.000 description 8
238000002347 injection Methods 0.000 description 8
239000007924 injection Substances 0.000 description 8
239000000902 placebo Substances 0.000 description 8
229940068196 placebo Drugs 0.000 description 8
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical group CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 7
YZXBAPSDXZZRGB-DOFZRALJSA-M Arachidonate Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC([O-])=O YZXBAPSDXZZRGB-DOFZRALJSA-M 0.000 description 7
241000282472 Canis lupus familiaris Species 0.000 description 7
239000004480 active ingredient Substances 0.000 description 7
MBMBGCFOFBJSGT-KUBAVDMBSA-N all-cis-docosa-4,7,10,13,16,19-hexaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCC(O)=O MBMBGCFOFBJSGT-KUBAVDMBSA-N 0.000 description 7
125000003275 alpha amino acid group Chemical group 0.000 description 7
229940114078 arachidonate Drugs 0.000 description 7
229940116224 behenate Drugs 0.000 description 7
UKMSUNONTOPOIO-UHFFFAOYSA-M behenate Chemical group CCCCCCCCCCCCCCCCCCCCCC([O-])=O UKMSUNONTOPOIO-UHFFFAOYSA-M 0.000 description 7
XMHIUKTWLZUKEX-UHFFFAOYSA-M cerotate Chemical group CCCCCCCCCCCCCCCCCCCCCCCCCC([O-])=O XMHIUKTWLZUKEX-UHFFFAOYSA-M 0.000 description 7
GHVNFZFCNZKVNT-UHFFFAOYSA-M decanoate Chemical group CCCCCCCCCC([O-])=O GHVNFZFCNZKVNT-UHFFFAOYSA-M 0.000 description 7
229940000640 docosahexaenoate Drugs 0.000 description 7
POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical group CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 7
ZQPPMHVWECSIRJ-MDZDMXLPSA-M elaidate Chemical compound CCCCCCCC\C=C\CCCCCCCC([O-])=O ZQPPMHVWECSIRJ-MDZDMXLPSA-M 0.000 description 7
238000009472 formulation Methods 0.000 description 7
239000012634 fragment Substances 0.000 description 7
IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical group CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 7
FUZZWVXGSFPDMH-UHFFFAOYSA-M hexanoate Chemical group CCCCCC([O-])=O FUZZWVXGSFPDMH-UHFFFAOYSA-M 0.000 description 7
230000002218 hypoglycaemic effect Effects 0.000 description 7
229940070765 laurate Drugs 0.000 description 7
229940049918 linoleate Drugs 0.000 description 7
DTOSIQBPPRVQHS-PDBXOOCHSA-M linolenate Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC([O-])=O DTOSIQBPPRVQHS-PDBXOOCHSA-M 0.000 description 7
229940040452 linolenate Drugs 0.000 description 7
229940105132 myristate Drugs 0.000 description 7
WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical group CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 7
229940049964 oleate Drugs 0.000 description 7
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 7
SECPZKHBENQXJG-FPLPWBNLSA-N palmitoleic acid Chemical compound CCCCCC\C=C/CCCCCCCC(O)=O SECPZKHBENQXJG-FPLPWBNLSA-N 0.000 description 7
238000006467 substitution reaction Methods 0.000 description 7
230000002194 synthesizing effect Effects 0.000 description 7
239000003826 tablet Substances 0.000 description 7
QZZGJDVWLFXDLK-UHFFFAOYSA-M tetracosanoate Chemical group CCCCCCCCCCCCCCCCCCCCCCCC([O-])=O QZZGJDVWLFXDLK-UHFFFAOYSA-M 0.000 description 7
TUNFSRHWOTWDNC-UHFFFAOYSA-N tetradecanoic acid Chemical group CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 7
125000004417 unsaturated alkyl group Chemical group 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
208000013016 Hypoglycemia Diseases 0.000 description 6
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 6
206010067584 Type 1 diabetes mellitus Diseases 0.000 description 6
238000006243 chemical reaction Methods 0.000 description 6
201000010099 disease Diseases 0.000 description 6
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
239000004615 ingredient Substances 0.000 description 6
125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
208000001072 type 2 diabetes mellitus Diseases 0.000 description 6
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 5
ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 5
241000699670 Mus sp. Species 0.000 description 5
GNVMUORYQLCPJZ-UHFFFAOYSA-M Thiocarbamate Chemical group NC([S-])=O GNVMUORYQLCPJZ-UHFFFAOYSA-M 0.000 description 5
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 5
239000002775 capsule Substances 0.000 description 5
239000007963 capsule composition Substances 0.000 description 5
231100000673 dose–response relationship Toxicity 0.000 description 5
239000000796 flavoring agent Substances 0.000 description 5
238000004128 high performance liquid chromatography Methods 0.000 description 5
239000012071 phase Substances 0.000 description 5
239000000047 product Substances 0.000 description 5
108090000623 proteins and genes Proteins 0.000 description 5
230000004044 response Effects 0.000 description 5
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
239000007983 Tris buffer Substances 0.000 description 4
YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 4
239000000872 buffer Substances 0.000 description 4
150000001875 compounds Chemical class 0.000 description 4
GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 4
POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 4
ZQPPMHVWECSIRJ-MDZDMXLPSA-N elaidic acid Chemical compound CCCCCCCC\C=C\CCCCCCCC(O)=O ZQPPMHVWECSIRJ-MDZDMXLPSA-N 0.000 description 4
238000010828 elution Methods 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
235000013355 food flavoring agent Nutrition 0.000 description 4
239000007903 gelatin capsule Substances 0.000 description 4
230000010030 glucose lowering effect Effects 0.000 description 4
KEMQGTRYUADPNZ-UHFFFAOYSA-N heptadecanoic acid Chemical compound CCCCCCCCCCCCCCCCC(O)=O KEMQGTRYUADPNZ-UHFFFAOYSA-N 0.000 description 4
IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 4
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 4
QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
230000003278 mimic effect Effects 0.000 description 4
150000002772 monosaccharides Chemical group 0.000 description 4
WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 4
229910052757 nitrogen Inorganic materials 0.000 description 4
WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 4
239000000843 powder Substances 0.000 description 4
235000018102 proteins Nutrition 0.000 description 4
102000004169 proteins and genes Human genes 0.000 description 4
239000001488 sodium phosphate Substances 0.000 description 4
229910000162 sodium phosphate Inorganic materials 0.000 description 4
SZHOJFHSIKHZHA-UHFFFAOYSA-N tridecanoic acid Chemical compound CCCCCCCCCCCCC(O)=O SZHOJFHSIKHZHA-UHFFFAOYSA-N 0.000 description 4
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 4
ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 4
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
239000004475 Arginine Substances 0.000 description 3
DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 3
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
108010010803 Gelatin Proteins 0.000 description 3
206010060378 Hyperinsulinaemia Diseases 0.000 description 3
DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 3
AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 3
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 3
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 3
229930195725 Mannitol Natural products 0.000 description 3
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
229930006000 Sucrose Natural products 0.000 description 3
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 3
239000004473 Threonine Substances 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
230000004913 activation Effects 0.000 description 3
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
229960001230 asparagine Drugs 0.000 description 3
235000009582 asparagine Nutrition 0.000 description 3
229940009098 aspartate Drugs 0.000 description 3
239000011230 binding agent Substances 0.000 description 3
230000004071 biological effect Effects 0.000 description 3
230000036765 blood level Effects 0.000 description 3
210000005178 buccal mucosa Anatomy 0.000 description 3
239000006172 buffering agent Substances 0.000 description 3
239000001913 cellulose Substances 0.000 description 3
235000010980 cellulose Nutrition 0.000 description 3
229920002678 cellulose Polymers 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
239000011248 coating agent Substances 0.000 description 3
238000007796 conventional method Methods 0.000 description 3
230000007423 decrease Effects 0.000 description 3
239000003623 enhancer Substances 0.000 description 3
239000008273 gelatin Substances 0.000 description 3
229920000159 gelatin Polymers 0.000 description 3
235000019322 gelatine Nutrition 0.000 description 3
235000011852 gelatine desserts Nutrition 0.000 description 3
229930195712 glutamate Natural products 0.000 description 3
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 3
239000008187 granular material Substances 0.000 description 3
229940088597 hormone Drugs 0.000 description 3
239000005556 hormone Substances 0.000 description 3
201000001421 hyperglycemia Diseases 0.000 description 3
230000003451 hyperinsulinaemic effect Effects 0.000 description 3
201000008980 hyperinsulinism Diseases 0.000 description 3
238000001802 infusion Methods 0.000 description 3
230000002452 interceptive effect Effects 0.000 description 3
238000001990 intravenous administration Methods 0.000 description 3
229960000310 isoleucine Drugs 0.000 description 3
AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 3
239000008101 lactose Substances 0.000 description 3
239000000594 mannitol Substances 0.000 description 3
235000010355 mannitol Nutrition 0.000 description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
239000002245 particle Substances 0.000 description 3
229920001748 polybutylene Polymers 0.000 description 3
229920005862 polyol Polymers 0.000 description 3
150000003077 polyols Chemical class 0.000 description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
230000002829 reductive effect Effects 0.000 description 3
230000001105 regulatory effect Effects 0.000 description 3
238000004007 reversed phase HPLC Methods 0.000 description 3
210000002966 serum Anatomy 0.000 description 3
239000000600 sorbitol Substances 0.000 description 3
235000010356 sorbitol Nutrition 0.000 description 3
229960004793 sucrose Drugs 0.000 description 3
150000005846 sugar alcohols Polymers 0.000 description 3
150000008163 sugars Chemical class 0.000 description 3
239000000725 suspension Substances 0.000 description 3
239000004474 valine Substances 0.000 description 3
WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 2
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 2
QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 2
244000215068 Acacia senegal Species 0.000 description 2
229920000945 Amylopectin Chemical class 0.000 description 2
241000283690 Bos taurus Species 0.000 description 2
239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 2
239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 description 2
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical group NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
102000003670 Carboxypeptidase B Human genes 0.000 description 2
108090000087 Carboxypeptidase B Proteins 0.000 description 2
239000004471 Glycine Substances 0.000 description 2
229920000084 Gum arabic Polymers 0.000 description 2
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
239000005639 Lauric acid Substances 0.000 description 2
239000005642 Oleic acid Substances 0.000 description 2
235000021314 Palmitic acid Nutrition 0.000 description 2
208000017442 Retinal disease Diseases 0.000 description 2
206010038923 Retinopathy Diseases 0.000 description 2
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
235000021355 Stearic acid Nutrition 0.000 description 2
GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
102000004142 Trypsin Human genes 0.000 description 2
108090000631 Trypsin Proteins 0.000 description 2
QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
239000000205 acacia gum Substances 0.000 description 2
235000010489 acacia gum Nutrition 0.000 description 2
230000003213 activating effect Effects 0.000 description 2
125000002252 acyl group Chemical group 0.000 description 2
230000002411 adverse Effects 0.000 description 2
235000004279 alanine Nutrition 0.000 description 2
150000001298 alcohols Chemical class 0.000 description 2
125000002947 alkylene group Chemical group 0.000 description 2
125000005336 allyloxy group Chemical group 0.000 description 2
239000000427 antigen Substances 0.000 description 2
102000036639 antigens Human genes 0.000 description 2
108091007433 antigens Proteins 0.000 description 2
229940114079 arachidonic acid Drugs 0.000 description 2
235000021342 arachidonic acid Nutrition 0.000 description 2
125000005251 aryl acyl group Chemical group 0.000 description 2
230000008901 benefit Effects 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
229920001400 block copolymer Polymers 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
150000005829 chemical entities Chemical class 0.000 description 2
238000011260 co-administration Methods 0.000 description 2
238000000576 coating method Methods 0.000 description 2
229920001577 copolymer Polymers 0.000 description 2
235000018417 cysteine Nutrition 0.000 description 2
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 2
235000013681 dietary sucrose Nutrition 0.000 description 2
150000002016 disaccharides Chemical group 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
230000000081 effect on glucose Effects 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
235000019441 ethanol Nutrition 0.000 description 2
125000005290 ethynyloxy group Chemical group C(#C)O* 0.000 description 2
235000019197 fats Nutrition 0.000 description 2
239000000945 filler Substances 0.000 description 2
238000001914 filtration Methods 0.000 description 2
235000013305 food Nutrition 0.000 description 2
235000003599 food sweetener Nutrition 0.000 description 2
230000004153 glucose metabolism Effects 0.000 description 2
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
230000003914 insulin secretion Effects 0.000 description 2
238000010255 intramuscular injection Methods 0.000 description 2
239000007927 intramuscular injection Substances 0.000 description 2
YAQXGBBDJYBXKL-UHFFFAOYSA-N iron(2+);1,10-phenanthroline;dicyanide Chemical compound [Fe+2].N#[C-].N#[C-].C1=CN=C2C3=NC=CC=C3C=CC2=C1.C1=CN=C2C3=NC=CC=C3C=CC2=C1 YAQXGBBDJYBXKL-UHFFFAOYSA-N 0.000 description 2
208000017169 kidney disease Diseases 0.000 description 2
KQQKGWQCNNTQJW-UHFFFAOYSA-N linolenic acid Natural products CC=CCCC=CCC=CCCCCCCCC(O)=O KQQKGWQCNNTQJW-UHFFFAOYSA-N 0.000 description 2
235000019359 magnesium stearate Nutrition 0.000 description 2
230000014759 maintenance of location Effects 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
238000005259 measurement Methods 0.000 description 2
230000004060 metabolic process Effects 0.000 description 2
150000002734 metacrylic acid derivatives Chemical class 0.000 description 2
229930182817 methionine Natural products 0.000 description 2
229920000609 methyl cellulose Polymers 0.000 description 2
239000001923 methylcellulose Substances 0.000 description 2
235000010981 methylcellulose Nutrition 0.000 description 2
210000003205 muscle Anatomy 0.000 description 2
210000002850 nasal mucosa Anatomy 0.000 description 2
230000012666 negative regulation of transcription by glucose Effects 0.000 description 2
201000001119 neuropathy Diseases 0.000 description 2
230000007823 neuropathy Effects 0.000 description 2
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
229960002446 octanoic acid Drugs 0.000 description 2
239000003921 oil Substances 0.000 description 2
125000004430 oxygen atom Chemical group O* 0.000 description 2
208000033808 peripheral neuropathy Diseases 0.000 description 2
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
229920000642 polymer Polymers 0.000 description 2
150000003839 salts Chemical class 0.000 description 2
125000005471 saturated fatty acid group Chemical group 0.000 description 2
230000011664 signaling Effects 0.000 description 2
239000002904 solvent Substances 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
239000007858 starting material Substances 0.000 description 2
239000008117 stearic acid Substances 0.000 description 2
239000000758 substrate Substances 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
239000000454 talc Substances 0.000 description 2
229910052623 talc Inorganic materials 0.000 description 2
235000012222 talc Nutrition 0.000 description 2
TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 2
238000004448 titration Methods 0.000 description 2
239000012588 trypsin Substances 0.000 description 2
208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 2
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
125000005314 unsaturated fatty acid group Chemical group 0.000 description 2
210000003462 vein Anatomy 0.000 description 2
230000002618 waking effect Effects 0.000 description 2
MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
RUDATBOHQWOJDD-UHFFFAOYSA-N (3beta,5beta,7alpha)-3,7-Dihydroxycholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 RUDATBOHQWOJDD-UHFFFAOYSA-N 0.000 description 1
OYHQOLUKZRVURQ-NTGFUMLPSA-N (9Z,12Z)-9,10,12,13-tetratritiooctadeca-9,12-dienoic acid Chemical compound C(CCCCCCC\C(=C(/C\C(=C(/CCCCC)\[3H])\[3H])\[3H])\[3H])(=O)O OYHQOLUKZRVURQ-NTGFUMLPSA-N 0.000 description 1
QLEWEHIYERWUFK-UHFFFAOYSA-N 1-[2-[2-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]propan-2-ol Chemical class CC(O)COCCOCCOCCOCCOCCOCCO QLEWEHIYERWUFK-UHFFFAOYSA-N 0.000 description 1
OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
206010002091 Anaesthesia Diseases 0.000 description 1
241000272525 Anas platyrhynchos Species 0.000 description 1
208000023275 Autoimmune disease Diseases 0.000 description 1
201000004569 Blindness Diseases 0.000 description 1
241000283153 Cetacea Species 0.000 description 1
239000004380 Cholic acid Substances 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
229920002261 Corn starch Chemical class 0.000 description 1
108020004414 DNA Proteins 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
238000002965 ELISA Methods 0.000 description 1
239000001692 EU approved anti-caking agent Substances 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
241000283073 Equus caballus Species 0.000 description 1
239000001856 Ethyl cellulose Substances 0.000 description 1
ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
241000287828 Gallus gallus Species 0.000 description 1
229920002527 Glycogen Polymers 0.000 description 1
101001126414 Homo sapiens Proteolipid protein 2 Proteins 0.000 description 1
208000031226 Hyperlipidaemia Diseases 0.000 description 1
LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 1
ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
SMEROWZSTRWXGI-UHFFFAOYSA-N Lithocholsaeure Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 SMEROWZSTRWXGI-UHFFFAOYSA-N 0.000 description 1
208000019693 Lung disease Diseases 0.000 description 1
206010054805 Macroangiopathy Diseases 0.000 description 1
GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
101001129122 Mannheimia haemolytica Outer membrane lipoprotein 2 Proteins 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
MQUQNUAYKLCRME-INIZCTEOSA-N N-tosyl-L-phenylalanyl chloromethyl ketone Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N[C@H](C(=O)CCl)CC1=CC=CC=C1 MQUQNUAYKLCRME-INIZCTEOSA-N 0.000 description 1
206010067482 No adverse event Diseases 0.000 description 1
208000008589 Obesity Diseases 0.000 description 1
101000642171 Odontomachus monticola U-poneritoxin(01)-Om2a Proteins 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
241001494479 Pecora Species 0.000 description 1
239000004698 Polyethylene Substances 0.000 description 1
108010076504 Protein Sorting Signals Proteins 0.000 description 1
102100030486 Proteolipid protein 2 Human genes 0.000 description 1
108020004511 Recombinant DNA Proteins 0.000 description 1
206010038731 Respiratory tract irritation Diseases 0.000 description 1
229920001800 Shellac Polymers 0.000 description 1
241000282898 Sus scrofa Species 0.000 description 1
WBWWGRHZICKQGZ-UHFFFAOYSA-N Taurocholic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(=O)NCCS(O)(=O)=O)C)C1(C)C(O)C2 WBWWGRHZICKQGZ-UHFFFAOYSA-N 0.000 description 1
GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
230000003187 abdominal effect Effects 0.000 description 1
239000008351 acetate buffer Substances 0.000 description 1
239000002253 acid Substances 0.000 description 1
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
239000000853 adhesive Substances 0.000 description 1
239000000556 agonist Substances 0.000 description 1
150000001346 alkyl aryl ethers Chemical class 0.000 description 1
DTOSIQBPPRVQHS-PDBXOOCHSA-N alpha-linolenic acid Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 description 1
235000020661 alpha-linolenic acid Nutrition 0.000 description 1
125000000539 amino acid group Chemical group 0.000 description 1
230000037354 amino acid metabolism Effects 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
230000037005 anaesthesia Effects 0.000 description 1
238000004873 anchoring Methods 0.000 description 1
230000000181 anti-adherent effect Effects 0.000 description 1
239000003831 antifriction material Substances 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
239000007961 artificial flavoring substance Substances 0.000 description 1
239000008122 artificial sweetener Substances 0.000 description 1
230000002238 attenuated effect Effects 0.000 description 1
239000012752 auxiliary agent Substances 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
239000003613 bile acid Substances 0.000 description 1
230000008827 biological function Effects 0.000 description 1
230000033228 biological regulation Effects 0.000 description 1
230000008512 biological response Effects 0.000 description 1
239000004067 bulking agent Substances 0.000 description 1
125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
239000000378 calcium silicate Substances 0.000 description 1
229910052918 calcium silicate Inorganic materials 0.000 description 1
CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
239000008116 calcium stearate Substances 0.000 description 1
235000013539 calcium stearate Nutrition 0.000 description 1
OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
210000004027 cell Anatomy 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
235000019416 cholic acid Nutrition 0.000 description 1
BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
229960002471 cholic acid Drugs 0.000 description 1
208000020832 chronic kidney disease Diseases 0.000 description 1
230000021615 conjugation Effects 0.000 description 1
230000001276 controlling effect Effects 0.000 description 1
239000008120 corn starch Chemical class 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
229960003067 cystine Drugs 0.000 description 1
230000002939 deleterious effect Effects 0.000 description 1
KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
229960003964 deoxycholic acid Drugs 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000037213 diet Effects 0.000 description 1
239000011363 dried mixture Substances 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
230000000857 drug effect Effects 0.000 description 1
238000001035 drying Methods 0.000 description 1
239000000975 dye Substances 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
208000028208 end stage renal disease Diseases 0.000 description 1
201000000523 end stage renal failure Diseases 0.000 description 1
235000019325 ethyl cellulose Nutrition 0.000 description 1
229920001249 ethyl cellulose Polymers 0.000 description 1
230000001610 euglycemic effect Effects 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
230000005714 functional activity Effects 0.000 description 1
230000004190 glucose uptake Effects 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
229940096919 glycogen Drugs 0.000 description 1
239000003979 granulating agent Substances 0.000 description 1
208000019622 heart disease Diseases 0.000 description 1
210000003494 hepatocyte Anatomy 0.000 description 1
XPJRQAIZZQMSCM-UHFFFAOYSA-N heptaethylene glycol Chemical compound OCCOCCOCCOCCOCCOCCOCCO XPJRQAIZZQMSCM-UHFFFAOYSA-N 0.000 description 1
150000002433 hydrophilic molecules Chemical class 0.000 description 1
239000002933 immunoreactive insulin Substances 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
230000002608 insulinlike Effects 0.000 description 1
230000003993 interaction Effects 0.000 description 1
230000000968 intestinal effect Effects 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
230000000622 irritating effect Effects 0.000 description 1
210000004153 islets of langerhan Anatomy 0.000 description 1
239000004922 lacquer Substances 0.000 description 1
238000011542 limb amputation Methods 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 1
229960004488 linolenic acid Drugs 0.000 description 1
150000002632 lipids Chemical class 0.000 description 1
150000002634 lipophilic molecules Chemical class 0.000 description 1
239000012669 liquid formulation Substances 0.000 description 1
SMEROWZSTRWXGI-HVATVPOCSA-N lithocholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 SMEROWZSTRWXGI-HVATVPOCSA-N 0.000 description 1
210000005229 liver cell Anatomy 0.000 description 1
230000007774 longterm Effects 0.000 description 1
210000003141 lower extremity Anatomy 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
238000007726 management method Methods 0.000 description 1
239000003550 marker Substances 0.000 description 1
210000004379 membrane Anatomy 0.000 description 1
239000012528 membrane Substances 0.000 description 1
HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
208000030159 metabolic disease Diseases 0.000 description 1
230000037353 metabolic pathway Effects 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
231100000017 mucous membrane irritation Toxicity 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
230000023830 negative regulation of catabolic process Effects 0.000 description 1
231100000957 no side effect Toxicity 0.000 description 1
239000012457 nonaqueous media Substances 0.000 description 1
235000020824 obesity Nutrition 0.000 description 1
239000006186 oral dosage form Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
210000003300 oropharynx Anatomy 0.000 description 1
125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
238000010647 peptide synthesis reaction Methods 0.000 description 1
210000003200 peritoneal cavity Anatomy 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
230000003285 pharmacodynamic effect Effects 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
229920000233 poly(alkylene oxides) Polymers 0.000 description 1
229920001281 polyalkylene Polymers 0.000 description 1
229920000768 polyamine Polymers 0.000 description 1
229920000573 polyethylene Polymers 0.000 description 1
229920001592 potato starch Chemical class 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000037452 priming Effects 0.000 description 1
239000000651 prodrug Substances 0.000 description 1
229940002612 prodrug Drugs 0.000 description 1
125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
LZFIOSVZIQOVFW-UHFFFAOYSA-N propyl 2-hydroxybenzoate Chemical class CCCOC(=O)C1=CC=CC=C1O LZFIOSVZIQOVFW-UHFFFAOYSA-N 0.000 description 1
229960004063 propylene glycol Drugs 0.000 description 1
235000013772 propylene glycol Nutrition 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
230000028503 regulation of lipid metabolic process Effects 0.000 description 1
238000005070 sampling Methods 0.000 description 1
230000000276 sedentary effect Effects 0.000 description 1
239000004208 shellac Substances 0.000 description 1
ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
229940113147 shellac Drugs 0.000 description 1
235000013874 shellac Nutrition 0.000 description 1
238000010532 solid phase synthesis reaction Methods 0.000 description 1
241000894007 species Species 0.000 description 1
238000010183 spectrum analysis Methods 0.000 description 1
239000007921 spray Substances 0.000 description 1
230000006641 stabilisation Effects 0.000 description 1
238000011105 stabilization Methods 0.000 description 1
229910001220 stainless steel Inorganic materials 0.000 description 1
239000010935 stainless steel Substances 0.000 description 1
239000008107 starch Chemical class 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
238000003756 stirring Methods 0.000 description 1
238000003860 storage Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
230000001629 suppression Effects 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
230000001839 systemic circulation Effects 0.000 description 1
WBWWGRHZICKQGZ-GIHLXUJPSA-N taurocholic acid Chemical compound C([C@@H]1C[C@H]2O)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@@H]([C@@H](CCC(=O)NCCS(O)(=O)=O)C)[C@@]2(C)[C@H](O)C1 WBWWGRHZICKQGZ-GIHLXUJPSA-N 0.000 description 1
ADUQGQSOYWRHCA-UHFFFAOYSA-J tetrasodium;hydroxide;phosphate Chemical compound [OH-].[Na+].[Na+].[Na+].[Na+].[O-]P([O-])([O-])=O ADUQGQSOYWRHCA-UHFFFAOYSA-J 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
239000004408 titanium dioxide Substances 0.000 description 1
235000010215 titanium dioxide Nutrition 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
238000011144 upstream manufacturing Methods 0.000 description 1
210000002700 urine Anatomy 0.000 description 1
RUDATBOHQWOJDD-UZVSRGJWSA-N ursodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-UZVSRGJWSA-N 0.000 description 1
229960001661 ursodiol Drugs 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
239000001993 wax Substances 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
239000000811 xylitol Substances 0.000 description 1
HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
235000010447 xylitol Nutrition 0.000 description 1
229960002675 xylitol Drugs 0.000 description 1
DTOSIQBPPRVQHS-UHFFFAOYSA-N α-Linolenic acid Chemical compound CCC=CCC=CCC=CCCCCCCCC(O)=O DTOSIQBPPRVQHS-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Diabetes (AREA)
Hematology (AREA)
Obesity (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Engineering & Computer Science (AREA)
Life Sciences & Earth Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Inorganic Insulating Materials (AREA)
Magnetic Heads (AREA)
Polishing Bodies And Polishing Tools (AREA)

ZA200406332A 2002-02-27 2004-08-10 ACC inhibitors. ZA200406332B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US36535802P	2002-02-27	2002-02-27

Publications (1)

Publication Number	Publication Date
ZA200406332B true ZA200406332B (en)	2005-09-28

Family

ID=27766270

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ZA200406332A ZA200406332B (en)	2002-02-27	2004-08-10	ACC inhibitors.

Country Status (20)

Country	Link
US (1)	US6979741B2 (fr)
EP (1)	EP1478437B1 (fr)
KR (1)	KR20040095239A (fr)
CN (1)	CN1642599A (fr)
AT (1)	ATE303178T1 (fr)
AU (1)	AU2003248354A1 (fr)
CO (1)	CO5601002A2 (fr)
DE (1)	DE60301491T2 (fr)
EA (1)	EA200400980A1 (fr)
ES (1)	ES2246481T3 (fr)
HR (1)	HRP20040716A2 (fr)
IL (1)	IL163659A0 (fr)
IS (1)	IS7391A (fr)
MA (1)	MA27178A1 (fr)
NO (1)	NO20044034L (fr)
NZ (1)	NZ534582A (fr)
PL (1)	PL372887A1 (fr)
TN (1)	TNSN04164A1 (fr)
WO (1)	WO2003072197A1 (fr)
ZA (1)	ZA200406332B (fr)

Families Citing this family (137)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP1474132A1 (fr) *	2002-01-11	2004-11-10	Abbott Laboratories	Ligands de recepteur d'histamine-3 pour traiter des etats diabetiques
US7884189B2 (en) *	2003-01-10	2011-02-08	The Trustees Of Columbia University In The City Of New York	Carboxyltransferase domain of acetyl-CoA carboxylase
AU2004212004B2 (en)	2003-02-13	2008-01-10	Albert Einstein College Of Medicine Of Yeshiva University	Regulation of food intake and glucose production by modulation of long-chain fatty acyl-coa levels in the hypothalamus
US20040242566A1 (en)	2003-03-25	2004-12-02	Syrrx, Inc.	Dipeptidyl peptidase inhibitors
EP1625122A1 (fr)	2003-05-14	2006-02-15	Takeda San Diego, Inc.	Inhibiteurs de dipeptidyl peptidase
US7169926B1 (en)	2003-08-13	2007-01-30	Takeda Pharmaceutical Company Limited	Dipeptidyl peptidase inhibitors
CA2535619A1 (fr)	2003-08-13	2005-02-24	Takeda Pharmaceutical Company Limited	Derives de 4-pyrimidone et leur utilisation en tant qu'inhibiteurs de la peptidyle peptidase
JP2007505121A (ja)	2003-09-08	2007-03-08	武田薬品工業株式会社	ジペプチジルぺプチダーゼ阻害剤
US7371759B2 (en)	2003-09-25	2008-05-13	Bristol-Myers Squibb Company	HMG-CoA reductase inhibitors and method
WO2005044814A1 (fr) *	2003-11-07	2005-05-19	F. Hoffmann-La Roche Ag	Derives de benzo [b][1,4] dioxepine
GB0326029D0 (en) *	2003-11-07	2003-12-10	Astrazeneca Ab	Chemical compounds
US7420059B2 (en)	2003-11-20	2008-09-02	Bristol-Myers Squibb Company	HMG-CoA reductase inhibitors and method
US7732446B1 (en)	2004-03-11	2010-06-08	Takeda Pharmaceutical Company Limited	Dipeptidyl peptidase inhibitors
GEP20094679B (en)	2004-03-15	2009-05-10	Takeda Pharmaceuticals Co	Dipeptidyl peptidase inhibitors
WO2005113069A2 (fr) *	2004-05-14	2005-12-01	Research Development Foundation	Utilisation de curcumine et d'analogues de curcumine comme inhibiteurs de l'acc2
US7687638B2 (en)	2004-06-04	2010-03-30	Takeda San Diego, Inc.	Dipeptidyl peptidase inhibitors
EP1750862B1 (fr)	2004-06-04	2011-01-05	Teva Pharmaceutical Industries Ltd.	Composition pharmaceutique contenant de l'irbesartan
US7150969B2 (en) *	2004-06-04	2006-12-19	Rosetta Inpharmatics Llc	Alternatively spliced isoform of acetyl-CoA carboxylase 2 (ACC2)
WO2006012226A2 (fr) *	2004-06-24	2006-02-02	Incyte Corporation	Piperidines a substitution n et utilisation de ces dernieres en tant que substances pharmaceutiques
US7572805B2 (en)	2004-07-14	2009-08-11	Bristol-Myers Squibb Company	Pyrrolo(oxo)isoquinolines as 5HT ligands
US7618980B2 (en) *	2004-07-14	2009-11-17	Bristol-Myers Squibb Company	Pyrrolo(oxo)quinolines as 5HT ligands
WO2006019965A2 (fr)	2004-07-16	2006-02-23	Takeda San Diego, Inc.	Inhibiteurs de la dipeptidyl peptidase
US7872124B2 (en)	2004-12-21	2011-01-18	Takeda Pharmaceutical Company Limited	Dipeptidyl peptidase inhibitors
BRPI0519288A2 (pt)	2004-12-24	2009-01-06	Astrazeneca Ab	compostos heterocÍclicos como antagonistas de ccr2b
ATE421518T1 (de)	2005-02-10	2009-02-15	Bristol Myers Squibb Co	Dihydrochinazolinone als 5ht-modulatoren
CA2614963C (fr) *	2005-07-19	2014-10-07	Merck & Co., Inc.	Derives de spirochromanone utilises en tant quinhibiteurs d'acetyle coenzyme a carboxylase
US20100160255A1 (en) *	2005-07-29	2010-06-24	Takeda Pharmaceutical Company Limited	Spiro-cyclic compound
US7795436B2 (en)	2005-08-24	2010-09-14	Bristol-Myers Squibb Company	Substituted tricyclic heterocycles as serotonin receptor agonists and antagonists
ME02005B (fr)	2005-09-14	2012-08-31	Takeda Pharmaceuticals Co	Inhibiteurs de la dipeptidyl peptidase permettant de traiter le diabete
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
WO2007053498A1 (fr)	2005-11-01	2007-05-10	Millennium Pharmaceuticals, Inc.	Composés pouvant être employés en tant qu'antagonistes de ccr2
US8067415B2 (en)	2005-11-01	2011-11-29	Millennium Pharmaceuticals, Inc.	Compounds useful as antagonists of CCR2
WO2007053495A2 (fr) *	2005-11-01	2007-05-10	Millennium Pharmaceuticals, Inc.	Composes utiles en tant qu’antagonistes de ccr2
CN101384568B (zh) *	2006-02-15	2012-12-12	雅培制药有限公司	乙酰辅酶a羧化酶(acc)抑制剂及其在糖尿病、肥胖症和代谢综合征中的应用
JP5369257B2 (ja) *	2006-02-15	2013-12-18	アッヴィ・インコーポレイテッド	新規なアセチル−ＣｏＡカルボキシラーゼ（ＡＣＣ）阻害薬およびそれらの糖尿病、肥満および代謝症候群での使用
WO2007112347A1 (fr)	2006-03-28	2007-10-04	Takeda Pharmaceutical Company Limited	Inhibiteurs de la dipeptidyl peptidase
JPWO2007119833A1 (ja)	2006-04-14	2009-08-27	武田薬品工業株式会社	含窒素複素環化合物
JP2010500300A (ja)	2006-08-08	2010-01-07	サノフィ−アベンティス	アリールアミノアリール−アルキル−置換イミダゾリジン−２，４−ジオン、それらの製造法、それらの化合物を含有する薬剤、およびそれらの使用
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
DK2073810T3 (da) *	2006-09-13	2011-10-31	Takeda Pharmaceutical	Anvendelse af 2-6-(3-aminio-piperidin-l-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-l-ylmethyl-4-fluor-benzonitril til behandling af diabetes, cancer, autoimmune sygdomme og HIV infektion
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
AU2008205642B2 (en)	2007-01-12	2013-06-06	Msd K.K.	Spirochromanon derivatives
PE20081559A1 (es)	2007-01-12	2008-11-20	Merck & Co Inc	DERIVADOS DE ESPIROCROMANONA SUSTITUIDOS COMO INHIBIDORES DE ACETIL CoA CARBOXILASA
EP2128163A1 (fr)	2007-01-25	2009-12-02	Takeda Pharmaceutical Company Limited	Composé à cycle spiro
WO2008103382A1 (fr) *	2007-02-20	2008-08-28	Sergey Kozmin	Procédé permettant d'assembler des bibliothèques chimiques de grande pureté, composés supprimant les activités de l'acétyl coenzyme a carboxylase découverts grâce à ce procédé
US8093236B2 (en)	2007-03-13	2012-01-10	Takeda Pharmaceuticals Company Limited	Weekly administration of dipeptidyl peptidase inhibitors
CA2685380A1 (fr) *	2007-05-14	2008-11-20	Neuera Pharmaceuticals, Inc.	Inhibiteurs de l'acetyl-coa carboxylase pour le traitement de l'hypometabolisme neuronal
CN101820757A (zh)	2007-06-01	2010-09-01	普林斯顿大学托管委员会	通过调节宿主细胞代谢途径治疗病毒感染
US8969514B2 (en)	2007-06-04	2015-03-03	Synergy Pharmaceuticals, Inc.	Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases
WO2008151257A2 (fr)	2007-06-04	2008-12-11	Synergy Pharmaceuticals Inc.	Agonistes de guanylase cyclase utiles pour le traitement de troubles gastro-intestinaux, d'inflammation, de cancer et d'autres troubles
EP2025674A1 (fr)	2007-08-15	2009-02-18	sanofi-aventis	Tetrahydronaphthaline substituée, son procédé de fabrication et son utilisation en tant que médicament
US7981904B2 (en)	2008-03-20	2011-07-19	Takeda Pharmaceutical Company Limited	Acetyl CoA carboxylase inhibitors
CA2724774C (fr)	2008-05-28	2013-06-25	Pfizer Inc.	Inhibiteurs de la pyrazolospirocetone acetl-coa carboxylase
WO2009149279A2 (fr)	2008-06-04	2009-12-10	Synergy Pharmaceuticals Inc.	Agonistes de guanylate cyclase utile dans le traitement de troubles gastro-intestinaux, d'une inflammation, d'un cancer et d'autres troubles
WO2010002010A1 (fr)	2008-07-04	2010-01-07	Banyu Pharmaceutical Co.,Ltd.	Nouveaux acides spirochromanone carboxyliques
WO2010003624A2 (fr)	2008-07-09	2010-01-14	Sanofi-Aventis	Composés hétérocycliques, leurs procédés de préparation, médicaments comprenant lesdits composés et leur utilisation
CA2730603C (fr)	2008-07-16	2019-09-24	Synergy Pharmaceuticals Inc.	Agonistes de la guanylate cyclase utiles dans le traitement des affections gastro-intestinales, de l'inflammation gastro-intestinale, du cancer gastro-intestinal et d'autres affections
US20100113473A1 (en)	2008-10-30	2010-05-06	Player Mark R	Aryl amide compound as an acetyl coenzyme a carboxylase inhibitor
WO2010068601A1 (fr)	2008-12-08	2010-06-17	Sanofi-Aventis	Hydrate de fluoroglycoside hétéroaromatique cristallin, ses procédés de fabrication, ses procédés d'utilisation et compositions pharmaceutiques le contenant
KR20120060207A (ko)	2009-08-26	2012-06-11	사노피	신규한 결정성 헤테로방향족 플루오로글리코시드 수화물, 이들 화합물을 포함하는 약제 및 이들의 용도
NZ599815A (en)	2009-11-10	2013-04-26	Pfizer	N1-pyrazolospiroketone acetyl-coa carboxylase inhibitors
SI2547679T1 (sl)	2010-03-19	2015-12-31	Pfizer Inc.	Derivati 2,3 dihidro-1H-inden-1-il-2,7-diazaspiro(3.6)nonana in njihova uporaba kot antagonisti ali inverzni agonisti grelinskega receptorja
MA34245B1 (fr) *	2010-04-27	2013-05-02	Takeda Pharmaceutcal Company Ltd	Dérivés de composés bicycliques et leur utilisation en tant qu'inhibiteurs de l'acc.
WO2011157827A1 (fr)	2010-06-18	2011-12-22	Sanofi	Dérivés d'azolopyridin-3-one en tant qu'inhibiteurs de lipases et de phospholipases
US9616097B2 (en)	2010-09-15	2017-04-11	Synergy Pharmaceuticals, Inc.	Formulations of guanylate cyclase C agonists and methods of use
JP5824055B2 (ja)	2010-09-30	2015-11-25	ファイザー・インク	Ｎ１−ピラゾロスピロケトンアセチル−ＣｏＡカルボキシラーゼ阻害剤
HUE025078T2 (en)	2010-10-29	2016-01-28	Pfizer	N1 / N2-lactam-acetyl-CoA carboxylase inhibitors
WO2012120057A1 (fr)	2011-03-08	2012-09-13	Sanofi	Nouveaux dérivés phényl-oxathiazine substitués, procédé pour leur préparation, agent pharmaceutique contenant ces composés et leur utilisation
WO2012120055A1 (fr)	2011-03-08	2012-09-13	Sanofi	Dérivés oxathiazine di- et tri-substitués, procédé pour leur préparation, utilisation en tant que médicament, agent pharmaceutique contenant ces dérivés et utilisation
WO2012120056A1 (fr)	2011-03-08	2012-09-13	Sanofi	Dérivés oxathiazine tétra-substitués, procédé pour leur préparation, utilisation en tant que médicament, agent pharmaceutique contenant ces dérivés et utilisation
WO2012120051A1 (fr)	2011-03-08	2012-09-13	Sanofi	Dérivés benzyl-oxathiazine substitués avec adamantane ou noradamantane, médicaments contenant ces composés et leur utilisation
US8828995B2 (en)	2011-03-08	2014-09-09	Sanofi	Branched oxathiazine derivatives, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof
EP2683702B1 (fr)	2011-03-08	2014-12-24	Sanofi	Nouveaux dérivés de phényle-oxathiazine substitués, leur procédé de fabrication, médicament contenant ces liaisons et son utilisation
EP2683701B1 (fr)	2011-03-08	2014-12-24	Sanofi	Dérivés d'oxathiazine substitués par des groupes de benzyle-méthyles ou d'hétéro-méthyles, leur procédé de fabrication, leur utilisation comme médicament ainsi que médicaments en étant pourvu et leur utilisation
EP2766349B1 (fr)	2011-03-08	2016-06-01	Sanofi	Dérivés d'oxathiazine substitués par des carbocycles ou des hétérocycles, leur procédé de préparation, médicaments contenant ces composés et leur utilisation
US8828994B2 (en)	2011-03-08	2014-09-09	Sanofi	Di- and tri-substituted oxathiazine derivatives, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof
MX348860B (es)	2011-04-22	2017-06-30	Pfizer	Derivados de pirazoloespirocetona para usarse como inhibidores de acetil-coa carboxilasa.
CA2841757A1 (fr)	2011-07-15	2013-01-24	Etzer Darout	Modulateurs de gpr 119
BR112014000288A2 (pt)	2011-07-22	2017-01-10	Pfizer	moduladores do receptor de glucagon de quinolinila
WO2013030713A1 (fr)	2011-08-31	2013-03-07	Pfizer Inc.	Hexahydropyrano[3,4-d][1,3]thiazine-2-amines
EP2567959B1 (fr)	2011-09-12	2014-04-16	Sanofi	Dérivés d'amide d'acide 6-(4-hydroxy-phényl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylique en tant qu'inhibiteurs de kinase
LT2776038T (lt)	2011-11-11	2018-04-25	Gilead Apollo, Llc	Acc inhibitoriai ir jų panaudojimas
CN103917529B (zh)	2011-11-11	2016-08-17	辉瑞大药厂	2-硫代嘧啶酮类
US8530460B2 (en) *	2011-12-19	2013-09-10	Boehringer Ingelheim International Gmbh	Azetidine derivatives
US8530461B2 (en)	2011-12-29	2013-09-10	Boehringer Ingelheim International Gmbh	Azetidine derivatives
US8623860B2 (en)	2011-12-30	2014-01-07	Boehringer Ingelheim International Gmbh	Azetidine derivatives, pharmaceutical compositions and uses thereof
AP2014007953A0 (en)	2012-04-06	2014-09-30	Pfizer	Diacylglycerol acyltransferase 2 inhibitors
US8889730B2 (en)	2012-04-10	2014-11-18	Pfizer Inc.	Indole and indazole compounds that activate AMPK
WO2013164730A1 (fr)	2012-05-04	2013-11-07	Pfizer Inc.	Composés d'hexahydropyrano[3,4-d][1,3]thiazin-2-amine substitués par des hétérocycliques à titre d'inhibiteurs d'app, bace1 et bace2
EP2897964A1 (fr)	2012-09-20	2015-07-29	Pfizer Inc.	Composés de hexahydropyrano [3,4-d][1,3]thiazin-2-amine substitués par alkyle
CA2893256A1 (fr)	2012-12-11	2014-06-19	Pfizer Inc.	Composes d'hexahydropyrano [3,4-d][1,3]thiazin-2-amine en tant qu'inhibiteurs de bace1
JP6162820B2 (ja)	2012-12-19	2017-07-12	ファイザー・インク	炭素環式および複素環式置換ヘキサヒドロピラノ［３，４−ｄ］［１，３］チアジン−２−アミン化合物
WO2014125394A1 (fr)	2013-02-13	2014-08-21	Pfizer Inc.	Composés hexahydropyrano [3,4-d][1,3] thiazin-2-amine substitués par un hétéroaryle
US9233981B1 (en)	2013-02-15	2016-01-12	Pfizer Inc.	Substituted phenyl hexahydropyrano[3,4-d][1,3]thiazin-2-amine compounds
WO2014151200A2 (fr)	2013-03-15	2014-09-25	Synergy Pharmaceuticals Inc.	Compositions utiles pour le traitement de troubles gastro-intestinaux
EP2970384A1 (fr)	2013-03-15	2016-01-20	Synergy Pharmaceuticals Inc.	Agonistes de la guanylate cyclase et leurs utilisations
KR20150132192A (ko) *	2013-03-18	2015-11-25	제노사이언스 파마	신규한 항암제로서의 퀴놀린 유도체
AU2014274812B2 (en)	2013-06-05	2018-09-27	Bausch Health Ireland Limited	Ultra-pure agonists of guanylate cyclase C, method of making and using same
WO2015036892A1 (fr)	2013-09-12	2015-03-19	Pfizer Inc.	Utilisation d'inhibiteurs de l'acétyl-coa carboxylase pour traiter l'acné vulgaire
JP6348582B2 (ja)	2013-10-09	2018-06-27	ファイザー・インク	プロスタグランジンｅｐ３受容体の拮抗薬
JPWO2015137496A1 (ja)	2014-03-14	2017-04-06	武田薬品工業株式会社	複素環化合物の製造法
SI3119757T1 (en)	2014-03-17	2018-08-31	Pfizer Inc.	Diacylglycerol acyltransferase 2 inhibitors for use in the treatment of metabolic and related disorders
RS58597B1 (sr)	2014-04-04	2019-05-31	Pfizer	Biciklično-spojena heteroaril ili aril jedinjenja i njihova upotreba kao irak4 inhibitora
CN106459088A (zh)	2014-04-10	2017-02-22	辉瑞公司	2‑氨基‑6‑甲基‑4，4a，5，6‑四氢吡喃并[3，4‑d][1，3]噻嗪‑8a(8H)‑基‑1，3‑噻唑‑4‑基酰胺
WO2016092413A1 (fr)	2014-12-10	2016-06-16	Pfizer Inc.	Composés indoliques et indazoliques qui activent l'ampk
JP2017538769A (ja)	2014-12-22	2017-12-28	ファイザー・インク	プロスタグランジンｅｐ３受容体の拮抗薬
MA42035A (fr)	2015-05-05	2018-03-14	Pfizer	2-thiopyrimidinones
CA2987179C (fr)	2015-05-29	2020-08-25	Pfizer Inc.	Composes heterocycliques comme inhibiteurs de l'enzyme vanine-1
PL3310784T3 (pl)	2015-06-17	2021-03-08	Pfizer Inc.	Związki tricykliczne i ich zastosowanie jako inhibitory fosfodiesterazy
WO2016203335A1 (fr)	2015-06-18	2016-12-22	Pfizer Inc.	Nouvelles pyrido [2,3-b] pyrazinones utilisées en tant qu'inhibiteurs de bromodomaines de la famille bet
JP2018527337A (ja)	2015-08-13	2018-09-20	ファイザー・インク	二環式縮合ヘテロアリールまたはアリール化合物
ES2865199T3 (es)	2015-08-27	2021-10-15	Pfizer	Compuestos de heteroarilo o arilo condensados bicíclicos como moduladores de IRAK4
WO2017037567A1 (fr)	2015-09-03	2017-03-09	Pfizer Inc.	Régulateurs de la frataxine
JP2018531924A (ja)	2015-09-24	2018-11-01	ファイザー・インク	テトラヒドロピラノ［３，４−ｄ］［１，３］オキサジン誘導体、およびｂａｃｅ阻害剤としてのその使用
WO2017051294A1 (fr)	2015-09-24	2017-03-30	Pfizer Inc.	N-[2-(3-amino-2,5-diméthyl-1,1-dioxido-5,6-dihydro-2h-1,2,4-thiadiazin-5-yl)-1,3-thiazol-4-yl] amides utiles comme inhibiteurs de bace
BR112018003489A2 (pt)	2015-09-24	2018-09-25	Pfizer	n-[2-(2-amino-6,6-dissubstituído-4,4a,5,6-tetra-hidropirano[3,4-d][1,3]tiazin-8a(8h)-il)-1,3-tiazol-4-il]amidas
AR106472A1 (es)	2015-10-26	2018-01-17	Gilead Apollo Llc	Inhibidores de acc y usos de los mismos
CN108347939B (zh)	2015-11-25	2021-09-28	吉利德阿波罗公司	含有2,4-二氧代-1,4-二氢噻吩并[2,3-d]嘧啶的衍生物的杀真菌组合物
WO2017091602A1 (fr)	2015-11-25	2017-06-01	Gilead Apollo, Llc	Inhibiteurs de l'acc à base d'esters et utilisations associées
EA201890913A1 (ru)	2015-11-25	2018-11-30	Джилид Аполло, Ллс	Пиразоловые соединения в качестве ингибиторов акк и их применение
MX2018006287A (es)	2015-11-25	2018-09-07	Gilead Apollo Llc	Inhibidores de acc de triazol y usos de los mismos.
DK3397631T3 (da)	2015-12-29	2021-05-25	Pfizer	Substituerede 3-azabicyclo[3.1.0]hexaner som ketohexokinase-inhibitorer
BR112018067408A2 (pt)	2016-03-02	2018-12-26	Gilead Apollo Llc	formas sólidas de um inibidor de acc de tienopirimidinadiona e métodos para a produção das mesmas
EP3266454A1 (fr) *	2016-07-07	2018-01-10	Forschungszentrum Borstel Leibniz-Zentrum für Medizin und Biowissenschaften	Inhibiteurs d'acc pour leur utilisation dans le traitement de maladies mycobactériennes
AU2017296338A1 (en)	2016-07-14	2019-01-03	Pfizer Inc.	Novel pyrimidine carboxamides as inhibitors of vanin-1 enzyme
AR109179A1 (es)	2016-08-19	2018-11-07	Pfizer	Inhibidores de diacilglicerol aciltransferasa 2
EP4122464B1 (fr)	2017-03-28	2024-05-15	Gilead Sciences, Inc.	Combinaisons thérapeutiques pour le traitement des maladies du foie
WO2019133445A1 (fr)	2017-12-28	2019-07-04	Inception Ibd, Inc.	Aminothiazoles utilisés en tant qu'inhibiteurs de vanin-1
US11254660B2 (en)	2018-08-31	2022-02-22	Pfizer Inc.	Combinations for treatment of NASH/NAFLD and related diseases
WO2020102575A1 (fr)	2018-11-16	2020-05-22	Inception Ibd, Inc.	Aminothiazoles hétérocycliques et leurs utilisations
EP3972596B1 (fr)	2019-05-20	2025-07-16	Pfizer Inc.	Combinaisons comprenant du benzodioxol en tant qu'agonistes de glp-1r destinées à être utilisées dans le traitement de la nash/nafld et de maladies associées
WO2021155841A1 (fr)	2020-02-07	2021-08-12	Gasherbrum Bio, Inc.	Agonistes hétérocycliques de glp-1
CN114105947B (zh) *	2020-08-27	2025-04-22	鲁南制药集团股份有限公司	一类喹啉衍生物
EP4490155A1 (fr)	2022-03-09	2025-01-15	Gasherbrum Bio, Inc.	Agonistes hétérocycliques de glp-1
EP4508047A1 (fr)	2022-04-14	2025-02-19	Gasherbrum Bio, Inc.	Agonistes hétérocycliques de glp-1
WO2024118524A1 (fr)	2022-11-28	2024-06-06	Cerevel Therapeutics, Llc	Composés d'azaindole et leur utilisation en tant qu'inhibiteurs de phosphodiestérase
EP4634180A1 (fr)	2022-12-15	2025-10-22	Gasherbrum Bio, Inc.	Sels et formes solides d'un composé ayant une activité agoniste de glp-1

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA2325358C (fr) *	1999-11-10	2005-08-02	Pfizer Products Inc.	Amides de l'acide 7-¬(4'-trifluoromethylbiphenyl-2-carbonyl)amino\|-quinoleine-3-carboxylique et methodes pour inhiber la secretion d'apolipoproteine b
US6509358B2 (en) *	2000-07-17	2003-01-21	Wyeth	Piperidino-phenyl amino squarate and thiadiazole dioxide beta-3 adrenergic receptor agonists
US20030171588A1 (en) *	2002-03-07	2003-09-11	Kahl Jeffrey D.	1,2-disubstituted-6-oxo-3-phenyl-piperidine-3-carboxamides and combinatorial libraries thereof

2003
- 2003-02-17 PL PL03372887A patent/PL372887A1/xx not_active Application Discontinuation
- 2003-02-17 DE DE60301491T patent/DE60301491T2/de not_active Expired - Fee Related
- 2003-02-17 NZ NZ534582A patent/NZ534582A/xx unknown
- 2003-02-17 KR KR10-2004-7013482A patent/KR20040095239A/ko not_active Ceased
- 2003-02-17 EA EA200400980A patent/EA200400980A1/ru unknown
- 2003-02-17 ES ES03742882T patent/ES2246481T3/es not_active Expired - Lifetime
- 2003-02-17 WO PCT/IB2003/000573 patent/WO2003072197A1/fr not_active Ceased
- 2003-02-17 CN CNA038069903A patent/CN1642599A/zh active Pending
- 2003-02-17 EP EP03742882A patent/EP1478437B1/fr not_active Expired - Lifetime
- 2003-02-17 IL IL16365903A patent/IL163659A0/xx unknown
- 2003-02-17 AT AT03742882T patent/ATE303178T1/de not_active IP Right Cessation
- 2003-02-17 HR HR20040716A patent/HRP20040716A2/hr not_active Application Discontinuation
- 2003-02-17 AU AU2003248354A patent/AU2003248354A1/en not_active Abandoned
- 2003-02-20 US US10/370,844 patent/US6979741B2/en not_active Expired - Fee Related
2004
- 2004-08-09 IS IS7391A patent/IS7391A/is unknown
- 2004-08-10 ZA ZA200406332A patent/ZA200406332B/en unknown
- 2004-08-18 MA MA27830A patent/MA27178A1/fr unknown
- 2004-08-25 TN TNP2004000164A patent/TNSN04164A1/fr unknown
- 2004-08-26 CO CO04083409A patent/CO5601002A2/es not_active Application Discontinuation
- 2004-09-24 NO NO20044034A patent/NO20044034L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
PL372887A1 (en)	2005-08-08
IS7391A (is)	2004-08-09
CN1642599A (zh)	2005-07-20
US6979741B2 (en)	2005-12-27
NZ534582A (en)	2006-03-31
NO20044034L (no)	2004-11-24
AU2003248354A1 (en)	2003-09-09
DE60301491T2 (de)	2006-05-18
DE60301491D1 (en)	2005-10-06
EP1478437A1 (fr)	2004-11-24
KR20040095239A (ko)	2004-11-12
HRP20040716A2 (en)	2005-02-28
EA200400980A1 (ru)	2005-02-24
ES2246481T3 (es)	2006-02-16
TNSN04164A1 (fr)	2007-03-12
MA27178A1 (fr)	2005-01-03
CO5601002A2 (es)	2006-01-31
IL163659A0 (en)	2005-12-18
WO2003072197A1 (fr)	2003-09-04
EP1478437B1 (fr)	2005-08-31
US20030187254A1 (en)	2003-10-02
ATE303178T1 (de)	2005-09-15

Publication	Publication Date	Title
CA2437940C (fr)	2012-07-10	Procedes de traitement du diabete sucre
ZA200406332B (en)	2005-09-28	ACC inhibitors.
AU2002244020A1 (en)	2003-02-27	Methods of treating diabetes mellitus
TWI596110B (zh)	2017-08-21	新穎升糖素類似物
CN114901682B (zh)	2024-04-16	胰岛素衍生物
US5124314A (en)	1992-06-23	Pharmaceutical compositions containing amylin
ES2542146T3 (es)	2015-07-31	Insulinas extendidas PEGiladas.
US5175145A (en)	1992-12-29	Treatment of diabetes mellitus with amylin agonists
US12152059B2 (en)	2024-11-26	Method of treating nash using a long-acting mutant human fibroblast growth factor
US5939387A (en)	1999-08-17	Method of treating insulin resistance
US7601688B2 (en)	2009-10-13	Methods of reducing hypoglycemic episodes in the treatment of diabetes mellitus
US20100196330A1 (en)	2010-08-05	Pharmaceutical compositions comprising unacylated ghrelin and therapeutical uses thereof
CN115947822A (zh)	2023-04-11	一种长效酰化胰岛素衍生物及其药物组合物和应用
JP2023514992A (ja)	2023-04-12	Ｇｌｐ－１ｒおよびｇｃｇｒアゴニスト、製剤、ならびに使用方法
JPS63303930A (ja)	1988-12-12	インシユリンおよびインシユリン誘導体の混合結晶
CN119431514A (zh)	2025-02-14	一种gcgr、gipr和glp-1r三重靶向激动作用的多肽衍生物
SK1702004A3 (sk)	2005-03-04	Farmaceutický prostriedok na liečenie diabetu, jeho použitie a súprava obsahujúca tento prostriedok
EP3653639B1 (fr)	2022-11-09	Polypeptide et composition de celui-ci pour le traitement de maladies du système métabolique
WO2024230819A1 (fr)	2024-11-14	Compositions pharmaceutiques et leurs utilisations, et procédés pour améliorer la stabilité au stockage de compositions pharmaceutiques
Scarpignato	1994	Somatostatin Analogues in the Management
WO2023143458A1 (fr)	2023-08-03	Insuline acylée