HRP20110068T1 - Postupci uporabe receptora gpr119 za identifikaciju spojeva korisnih za povećanje koštane mase jedne osobe - Google Patents
Postupci uporabe receptora gpr119 za identifikaciju spojeva korisnih za povećanje koštane mase jedne osobe Download PDFInfo
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- 150000001875 compounds Chemical class 0.000 title claims abstract 54
- 238000000034 method Methods 0.000 title claims 43
- 210000000988 bone and bone Anatomy 0.000 title 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 claims abstract 44
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 claims abstract 44
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract 43
- 102000005962 receptors Human genes 0.000 claims abstract 41
- 108020003175 receptors Proteins 0.000 claims abstract 41
- 210000004027 cell Anatomy 0.000 claims abstract 29
- 102000040430 polynucleotide Human genes 0.000 claims abstract 18
- 108091033319 polynucleotide Proteins 0.000 claims abstract 18
- 239000002157 polynucleotide Substances 0.000 claims abstract 18
- 230000000580 secretagogue effect Effects 0.000 claims abstract 16
- 150000001413 amino acids Chemical class 0.000 claims abstract 14
- 238000003752 polymerase chain reaction Methods 0.000 claims abstract 14
- 108091006027 G proteins Proteins 0.000 claims abstract 11
- 102000030782 GTP binding Human genes 0.000 claims abstract 11
- 108091000058 GTP-Binding Proteins 0.000 claims abstract 11
- 238000000338 in vitro Methods 0.000 claims abstract 10
- DGBKNTVAKIFYNU-UHFFFAOYSA-N n-(2-fluoro-4-methylsulfonylphenyl)-5-nitro-6-[4-(3-propan-2-yl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]pyrimidin-4-amine Chemical compound CC(C)C1=NOC(C2CCN(CC2)C=2C(=C(NC=3C(=CC(=CC=3)S(C)(=O)=O)F)N=CN=2)N(=O)=O)=N1 DGBKNTVAKIFYNU-UHFFFAOYSA-N 0.000 claims abstract 7
- 210000000170 cell membrane Anatomy 0.000 claims abstract 4
- 102100034154 Guanine nucleotide-binding protein G(i) subunit alpha-2 Human genes 0.000 claims 39
- AJJISMLYIMQAKP-OAHLLOKOSA-N 5-[4-[(2r)-4-(3-fluoro-4-methylsulfonylphenoxy)butan-2-yl]piperidin-1-yl]-3-propan-2-yl-1,2,4-oxadiazole Chemical compound CC(C)C1=NOC(N2CCC(CC2)[C@H](C)CCOC=2C=C(F)C(=CC=2)S(C)(=O)=O)=N1 AJJISMLYIMQAKP-OAHLLOKOSA-N 0.000 claims 32
- 229940100607 GPR119 agonist Drugs 0.000 claims 32
- 241000251539 Vertebrata <Metazoa> Species 0.000 claims 25
- 230000028327 secretion Effects 0.000 claims 14
- 230000000694 effects Effects 0.000 claims 13
- 210000003158 enteroendocrine cell Anatomy 0.000 claims 9
- 239000013604 expression vector Substances 0.000 claims 8
- 239000003446 ligand Substances 0.000 claims 8
- 150000003384 small molecules Chemical class 0.000 claims 7
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 claims 6
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 claims 6
- 229940095074 cyclic amp Drugs 0.000 claims 6
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 claims 4
- MMWCIQZXVOZEGG-HOZKJCLWSA-N [(1S,2R,3S,4S,5R,6S)-2,3,5-trihydroxy-4,6-diphosphonooxycyclohexyl] dihydrogen phosphate Chemical compound O[C@H]1[C@@H](O)[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H](O)[C@H]1OP(O)(O)=O MMWCIQZXVOZEGG-HOZKJCLWSA-N 0.000 claims 4
- ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 claims 4
- 150000001982 diacylglycerols Chemical class 0.000 claims 4
- 210000003574 melanophore Anatomy 0.000 claims 4
- 101000996752 Homo sapiens Glucose-dependent insulinotropic receptor Proteins 0.000 claims 3
- 102000056352 human GPR119 Human genes 0.000 claims 3
- 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 claims 2
- 108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 claims 2
- 102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 claims 2
- 108091000080 Phosphotransferase Proteins 0.000 claims 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims 2
- 239000000556 agonist Substances 0.000 claims 2
- 238000004458 analytical method Methods 0.000 claims 2
- 239000012528 membrane Substances 0.000 claims 2
- 102000020233 phosphotransferase Human genes 0.000 claims 2
- XOFLBQFBSOEHOG-UUOKFMHZSA-N γS-GTP Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=S)[C@@H](O)[C@H]1O XOFLBQFBSOEHOG-UUOKFMHZSA-N 0.000 claims 2
- 238000005259 measurement Methods 0.000 claims 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 abstract 4
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Abstract
Uporaba receptora vezanih G-proteina za identifikaciju GIP sekretogoga, na način in vitro, naznačena time, da se sastoji od sljedećih koraka: (a) stavljanje u doticaj test spoja sa stanicom domaćina ili s membranom stanice domaćina koji obuhvaća spomenuti receptor vezanih G-proteina, pri čemu receptor vezanih G-proteina sadrži sekvencu amino kiseline odabranu iz skupine koja sadrži: (i) amino kiseline 1-335 od SEQ ID NO:2; (ii) amino kiseline 2-335 od SEQ ID NO:2; (iii) sekvencu amino kiseline od receptora vezanih G-proteina kodiranu s polinukleotidima koji su pojačani lančanom reakcijom polimeraze (PCR) na humanom DNA uzorku koristeći specifične primere SEQ ID NO:3 i SEQ ID NO:4; (iv) sekvencu amino kiseline od receptora vezanih G-proteina kodiranu s polinukleotidima koji su hibridizirani pod uvjetima visoke oskudice prema dodatku od SEQ ID NO:1; (v) sekvencu amino kiseline od receptora vezanih G-proteina koja ima najmanje oko 80% identiteta od SEQ ID NO:2; (vi) sekvencu amino kiseline od tvorbene aktivne verzije receptora vezanih G-proteina koja ima SEQ ID NO:2; i (vii) biološki aktivni dio od (i) ili (ii), pri čemu je spomenuti biološki aktivni dio sposoban za vezanje na (2-fluoro-4-metansulfonil-fenil)-{6-[4-(3-izopropil-[1,2,4]oksadiazol-5-il)-piperidin-1-il]-5-nitro-pirimidin-4-il}-amin; i (b) određivanje sposobnosti test spoja za stimulaciju djelotvornosti receptora; pri čemu sposobnost test spoja za stimulaciju djelotvornosti receptora pokazuje da li je test spoj postao GIP sekretogog. Patent sadrži još 68 patentnih zahtjeva.
Claims (69)
1. Uporaba receptora vezanih G-proteina za identifikaciju GIP sekretogoga, na način in vitro, naznačena time, da se sastoji od sljedećih koraka:
(a) stavljanje u doticaj test spoja sa stanicom domaćina ili s membranom stanice domaćina koji obuhvaća spomenuti receptor vezanih G-proteina, pri čemu receptor vezanih G-proteina sadrži sekvencu amino kiseline odabranu iz skupine koja sadrži:
(i) amino kiseline 1-335 od SEQ ID NO:2;
(ii) amino kiseline 2-335 od SEQ ID NO:2;
(iii) sekvencu amino kiseline od receptora vezanih G-proteina kodiranu s polinukleotidima koji su pojačani lančanom reakcijom polimeraze (PCR) na humanom DNA uzorku koristeći specifične primere SEQ ID NO:3 i SEQ ID NO:4;
(iv) sekvencu amino kiseline od receptora vezanih G-proteina kodiranu s polinukleotidima koji su hibridizirani pod uvjetima visoke oskudice prema dodatku od SEQ ID NO:1;
(v) sekvencu amino kiseline od receptora vezanih G-proteina koja ima najmanje oko 80% identiteta od SEQ ID NO:2;
(vi) sekvencu amino kiseline od tvorbene aktivne verzije receptora vezanih G-proteina koja ima SEQ ID NO:2; i
(vii) biološki aktivni dio od (i) ili (ii), pri čemu je spomenuti biološki aktivni dio sposoban za vezanje na (2-fluoro-4-metansulfonil-fenil)-{6-[4-(3-izopropil-[1,2,4]oksadiazol-5-il)-piperidin-1-il]-5-nitro-pirimidin-4-il}-amin; i
(b) određivanje sposobnosti test spoja za stimulaciju djelotvornosti receptora;
pri čemu sposobnost test spoja za stimulaciju djelotvornosti receptora pokazuje da li je test spoj postao GIP sekretogog.
2. Uporaba prema zahtjevu 1, naznačena time, da nadalje ima sljedeće korake:
(c) stavljanje u doticaj spoja koji stimulira djelotvornost receptora iz koraka (b) in vitro sa enteroendokrinom stanicom kralježnjaka ili sa stanicom sposobnom za GIP sekreciju;
(d) određivanje da li spoj stimulira GIP sekreciju iz enteroendokrine stanice kralježnjaka ili da li je stanica sposobna za GIP sekreciju;
pri čemu sposobnost da test spoj stimulira GIP sekreciju iz enteroendokrine stanice kralježnjaka ili sposobnost stanice za GIP sekreciju, pokazuje da li je test spoj postao GIP sekretogog.
3. Uporaba prema zahtjevu 1, naznačena time, da nadalje ima sljedeći korak:
(e) određivanje da li spoj povećava GIP razinu kod kralježnjaka, mjerenjem GIP razine u uzorku dobivenom od kralježnjaka na kojemu je prethodno primijenjen spoj koji stimulira djelotvornost receptora iz koraka (b);
pri čemu sposobnost test spoja da poveća GIP razinu kod kralježnjaka pokazuje da li je test spoj postao GIP sekretogog.
4. Uporaba prema zahtjevu 3, naznačena time, da kralježnjak nije humani kralježnjak.
5. Uporaba prema bilo kojem zahtjevu od 1 do 4, naznačena time, da receptor je rekombinant.
6. Uporaba prema bilo kojem zahtjevu od 1 do 5, naznačena time, da stanica domaćina obuhvaća vektor ekspresije, dok spomenuti vektor ekspresije sadrži polinukleotid koji kodira receptor vezanih G-proteina.
7. Uporaba prema bilo kojem zahtjevu od 1 do 6, naznačena time, da spomenuto određivanje proizlazi iz mjerenja razine drugog dostavljača.
8. Uporaba prema zahtjevu 7, naznačena time, da je drugi dostavljač odabran iz skupine koja sadrži ciklički AMP (cAMP), ciklički GMP (cGMP), inositol 1,4,5-trifosfat (IP3), diacilglicerol (DAG), MAP aktivnost kinaze, MAPK/ERK aktivnost kinaza-1 kinaze (MEKK1), te Ca2+.
9. Uporaba prema zahtjevu 8, naznačena time, da se razina cAMP povećava.
10. Uporaba prema bilo kojem zahtjevu od 1 do 6, naznačena time, da se spomenuto određivanje provodi kroz uporabu Melanophore uzorka, kroz mjerenje GTPγS vezivanja za membranu koja sadrži spomenuti GPCR, ili kroz analizu reportera.
11. Uporaba prema bilo kojem zahtjevu od 1 do 10, naznačena time, da stanica domaćina je stanica domaćina sisavaca.
12. Uporaba prema bilo kojem zahtjevu od 1 do 10, naznačena time, da stanica domaćina je stanica domaćina kvasca.
13. Uporaba prema bilo kojem zahtjevu od 1 do 10, naznačena time, da stanica domaćina je stanica domaćina Melanophore.
14. Uporaba prema bilo kojem zahtjevu od 1 do 13, naznačena time, da je test spoj mala molekula koja ima molekularnu masu manju od oko 5.000 gram/mol.
15. Uporaba prema bilo kojem zahtjevu od 1 do 14, naznačena time, da receptor sadrži sekvencu amino kiseline receptora vezanih G-proteina koja ima najmanje oko 80% identiteta od SEQ ID NO:2.
16. Uporaba prema bilo kojem zahtjevu od 1 do 15, naznačena time, da receptor sadrži sekvencu amino kiseline od SEQ ID NO:2.
17. Postupak za identifikaciju GIP sekretogoga, naznačen time, da obuhvaća sljedeće korake:
(a) stavljanje u doticaj agonista GPR119 in vitro sa enteroendokrinom stanicom kralježnjaka ili stanice sposobne za GIP sekreciju; i
(b) određivanje da li agonist GPR119 stimulira GIP sekreciju iz enteroendokrine stanice kralježnjaka ili iz stanice sposobne za GIP sekreciju;
pri čemu sposobnost agonista GPR119 da stimulira GIP sekreciju iz enteroendokrine stanice kralježnjaka ili iz stanice sposobne za GIP sekreciju, pokazuje da li je agonist GPR119 postao GIP sekretogog.
18. Postupak za identifikaciju GIP sekretogoga, naznačen time, da obuhvaća sljedeće korake:
(a) određivanje da li agonist GPR119 povećava GIP razinu kod kralježnjaka, pomoću mjerenja GIP razine u uzorku dobivenom iz kralježnjaka na kojemu je prethodno primijenjen agonist GPT119;
pri čemu sposobnost agonista GPR119 da povećava GIP razinu kod kralježnjaka, pokazuje da li je agonist GPR119 postao GIP sekretogog.
19. Postupak prema zahtjevu 18, naznačen time, da kralježnjak je čovjek.
20. Postupak prema zahtjevu 18, naznačen time, da kralježnjak nije čovjek.
21. Postupak prema bilo kojem zahtjevu od 17 do 20, naznačen time, da agonist GPR119 je mala molekula koja ima molekularnu masu manju od oko 5.000 gram/mol.
22. Postupak prema bilo kojem zahtjevu od 17 do 21, naznačen time, da agonist GPR119 je agonist humanog GPR119.
23. Postupak prema bilo kojem zahtjevu od 17 do 22, naznačen time, da agonist GPR119 je selektivni agonist GPR119.
24. Postupak prema bilo kojem zahtjevu od 17 do 23, naznačen time, da agonist GPR119 ima EC50 u količini manjoj od 10 μM.
25. Postupak prema bilo kojem zahtjevu od 17 do 23, naznačen time, da agonist GPR119 ima EC50 u količini manjoj od 1 μM.
26. Postupak prema bilo kojem zahtjevu od 17 do 23, naznačen time, da agonist GPR119 ima EC50 u količini manjoj od 100 nM.
27. Postupak prema zahtjevu 17, naznačen time, da prije koraka (a) obuhvaća dodatne korake in vitro kako slijedi:
(x) stavljanje u doticaj test spoja sa stanicom domaćina ili s membranom stanice domaćina, koji sadrži receptor vezanih G-proteina, pri čemu receptor vezanih G-proteina sadrži sekvencu amino kiseline odabranu iz skupine koja sadrži:
(i) amino kiseline 1-335 od SEQ ID NO:2;
(ii) amino kiseline 2-335 od SEQ ID NO:2;
(iii) sekvencu amino kiseline od receptora vezanih G-proteina kodiranu s polinukleotidima koji su pojačani lančanom reakcijom polimeraze (PCR) na humanom DNA uzorku koristeći specifične primere SEQ ID NO:3 i SEQ ID NO:4;
(iv) sekvencu amino kiseline od receptora vezanih G-proteina kodiranu s polinukleotidima koji su hibridizirani pod uvjetima visoke oskudice prema dodatku od SEQ ID NO:1;
(v) sekvencu amino kiseline od receptora vezanih G-proteina koja ima najmanje oko 80% identiteta od SEQ ID NO:2;
(vi) sekvencu amino kiseline od tvorbene aktivne verzije receptora vezanih G-proteina koja ima SEQ ID NO:2; i
(vii) biološki aktivni dio od (i) ili (ii), pri čemu je spomenuti biološki aktivni dio sposoban za vezanje na (2-fluoro-4-metansulfonil-fenil)-{6-[4-(3-izopropil-[1,2,4]oksadiazol-5-il)-piperidin-1-il]-5-nitro-pirimidin-4-il}-amin; i
(y) određivanje sposobnosti test spoja da stimulira djelotvornost receptora;
pri čemu sposobnost test spoja da stimulira djelotvornost receptora, pokazuje da li je test spoj postao GIP sekretogog, i pri čemu agonist GPR119 iz koraka (a) je test spoj identificiran kao stimulator djelotvornosti receptora u koraku (y).
28. Postupak prema zahtjevu 18, naznačen time, da prije koraka (a) obuhvaća sljedeće dodatne korake in vitro:
(x) stavljanje u doticaj test spoja sa stanicom domaćina ili s membranom stanice domaćina, koji sadrži receptor vezanih G-proteina, pri čemu receptor vezanih G-proteina sadrži sekvencu amino kiseline odabranu iz skupine koja sadrži:
(i) amino kiseline 1-335 od SEQ ID NO:2;
(ii) amino kiseline 2-335 od SEQ ID NO:2;
(iii) sekvencu amino kiseline od receptora vezanih G-proteina kodiranu s polinukleotidima koji su pojačani lančanom reakcijom polimeraze (PCR) na humanom DNA uzorku koristeći specifične primere SEQ ID NO:3 i SEQ ID NO:4;
(iv) sekvencu amino kiseline od receptora vezanih G-proteina kodiranu s polinukleotidima koji su hibridizirani pod uvjetima visoke oskudice prema dodatku od SEQ ID NO:1;
(v) sekvencu amino kiseline od receptora vezanih G-proteina koja ima najmanje oko 80% identiteta od SEQ ID NO:2;
(vi) sekvencu amino kiseline od tvorbene aktivne verzije receptora vezanih G-proteina koja ima SEQ ID NO:2; i
(vii) biološki aktivni dio od (i) ili (ii), pri čemu je spomenuti biološki aktivni dio sposoban za vezanje na (2-fluoro-4-metansulfonil-fenil)-{6-[4-(3-izopropil-[1,2,4]oksadiazol-5-il)-piperidin-1-il]-5-nitro-pirimidin-4-il}-amin; i
(y) određivanje sposobnosti test spoja da stimulira djelotvornost receptora;
pri čemu sposobnost test spoja da stimulira djelotvornost receptora, pokazuje da li je test spoj postao GIP sekretogog, i pri čemu agonist GPR119 iz koraka (a) je test spoj identificiran kao stimulator djelotvornosti receptora u koraku (y).
29. Postupak prema zahtjevu 28, naznačen time, da kralježnjak je čovjek.
30. Postupak prema zahtjevu 28, naznačen time, da kralježnjak nije čovjek.
31. Postupak prema bilo kojem zahtjevu od 27 do 30, naznačen time, da receptor je rekombinant.
32. Postupak prema bilo kojem zahtjevu od 27 do 31, naznačen time, da stanica domaćina sadrži vektor ekspresije, dok spomenuti vektor ekspresije sadrži polinukleotid koji kodira receptor vezanih G-proteina.
33. Postupak prema bilo kojem zahtjevu od 27 do 32, naznačen time, da se spomenuto određivanje provodi putem mjerenja razine drugog dostavljača.
34. Postupak prema zahtjevu 33, naznačen time, da je drugi dostavljač odabran iz skupine koja sadrži ciklički AMP (cAMP), ciklički GMP (cGMP), inositol 1,4,5-trifosfat (IP3), diacilglicerol (DAG), aktivitet MAP kinaze, aktivitet MAPK/ERK kinaza-1 kinaze (MEKK1), te Ca2+.
35. Postupak prema zahtjevu 34, naznačen time, da se povećava razina cAMP.
36. Postupak prema bilo kojem zahtjevu od 27 do 32, naznačen time, da se spomenuto određivanje provodi putem uporabe Melanophore uzorka, kroz mjerenje GTPγS vezivanja za membranu koja sadrži spomenuti GPCR, ili kroz analizu reportera.
37. Postupak prema bilo kojem zahtjevu od 27 do 36, naznačen time, da stanica domaćina je stanica domaćina sisavaca.
38. Postupak prema bilo kojem zahtjevu od 27 do 36, naznačen time, da stanica domaćina je stanica domaćina kvasca.
39. Postupak prema bilo kojem zahtjevu od 27 do 36, naznačen time, da stanica domaćina je stanica domaćina Melanophore.
40. Postupak prema bilo kojem zahtjevu od 27 do 39, naznačen time, da je test spoj mala molekula koja ima molekularnu masu manju od oko 5.000 gram/mol.
41. Postupak prema bilo kojem zahtjevu od 27 do 40, naznačen time, da receptor sadrži sekvencu amino kiseline receptora vezanih G-proteina koja ima najmanje oko 80% identiteta od SEQ ID NO:2.
42. Postupak prema bilo kojem zahtjevu od 27 do 41, naznačen time, da receptor sadrži sekvencu amino kiseline od SEQ ID NO:2.
43. Uporaba receptora vezanih G-proteina, naznačena time, da služi za identifikaciju GIP sekretogoga, postupkom in vitro koji obuhvaća sljedeće korake:
(a) stavljanje u doticaj receptora vezanih G-proteina sa opcijski obilježenim poznatim ligandom za receptor, u prisutnosti ili u odsutnosti test spoja, pri čemu receptor vezanih G-proteina sadrži sekvencu amino kiseline odabranu iz skupine koja sadrži:
(i) amino kiseline 1-335 od SEQ ID NO:2;
(ii) amino kiseline 2-335 od SEQ ID NO:2;
(iii) sekvencu amino kiseline od receptora vezanih G-proteina kodiranu s polinukleotidima koji su pojačani lančanom reakcijom polimeraze (PCR) na humanom DNA uzorku koristeći specifične primere SEQ ID NO:3 i SEQ ID NO:4;
(iv) sekvencu amino kiseline od receptora vezanih G-proteina kodiranu s polinukleotidima koji su hibridizirani pod uvjetima visoke oskudice prema dodatku od SEQ ID NO:1;
(v) sekvencu amino kiseline od receptora vezanih G-proteina koja ima najmanje oko 80% identiteta od SEQ ID NO:2;
(vi) sekvencu amino kiseline od tvorbene aktivne verzije receptora vezanih G-proteina koja ima SEQ ID NO:2; i
(vii) biološki aktivni dio od (i) ili (ii), pri čemu je spomenuti biološki aktivni dio sposoban za vezanje na (2-fluoro-4-metansulfonil-fenil)-{6-[4-(3-izopropil-[1,2,4]oksadiazol-5-il)-piperidin-1-il]-5-nitro-pirimidin-4-il}-amin; i
(b) otkrivanje kompleksa između spomenutog poznatog liganda i spomenutog receptora; i
(c) određivanje da li je formirano manje spomenutog kompleksa u prisutnosti test spoja nego li u odsutnosti test spoja.
44. Uporaba prema zahtjevu 43, naznačena time, da spomenuti postupak nadalje obuhvaća:
(d) stavljanje u doticaj onoga spoja u čijoj je prisutnosti formirano manje kompleksa u koraku (c) in vitro sa enteroendokrinom stanicom kralježnjaka ili sa stanicom sposobnom za GIP sekreciju; i
(e) određivanje da li spoj stimulira GIP sekreciju iz enteroendokrine stanice kralježnjaka ili iz stanice sposobne za GIP sekreciju;
pri čemu sposobnost test spoja za stimuliranje GIP sekrecije iz enteroendokrine stanice kralježnjaka ili iz stanice sposobne za GIP sekreciju, pokazuje da li je test spoj postao GIP sekretogog.
45. Uporaba prema zahtjevu 43, naznačena time, da spomenuti postupak nadalje obuhvaća:
(d) određivanje da li spoj povećava GIP razinu kod kralježnjaka, pomoću mjerenja GIP razine u uzorku dobivenom iz kralježnjaka na kojemu je prethodno primijenjen spoj u čijem je prisustvu formirano manje spomenutog kompleksa u koraku (c);
pri čemu sposobnost test spoja za povećanje GIP razine kod kralježnjaka, pokazuje da li je test spoj postao GIP sekretogog.
46. Uporaba prema zahtjevu 45, naznačena time, da kralježnjak nije čovjek.
47. Uporaba prema bilo kojem zahtjevu od 43 do 46, naznačena time, da receptor je rekombinant.
48. Uporaba prema bilo kojem zahtjevu od 43 do 47, naznačena time, da stanica domaćina sadrži vektor ekspresije, dok spomenuti vektor ekspresije sadrži polinukleotid koji kodira receptor vezanih G-proteina.
49. Uporaba prema bilo kojem zahtjevu od 43 do 48, naznačena time, da poznati ligand je agonist GPR119.
50. Uporaba prema zahtjevu 49, naznačena time, da agonist GPR119 je agonist humanog GPR119.
51. Uporaba prema zahtjevu 49 ili zahtjevu 50, naznačena time, da agonist GPR119 je selektivni agonist GPR119.
52. Uporaba prema bilo kojem zahtjevu od 49 do 51, naznačena time, da agonist GPR119 ima EC50 u vrijednosti manjoj od one odabrane iz skupine koja se sastoji od 10 μM, 1 μM i 100 nM.
53. Uporaba prema bilo kojem zahtjevu od 49 do 52, naznačena time, da agonist GPR119 je mala molekula koja ima molekularnu masu manju od oko 5.000 gram/mol.
54. Uporaba prema bilo kojem zahtjevu od 43 do 53, naznačena time, da test spoj je mala molekula koja ima molekularnu masu manju od oko 5.000 gram/mol.
55. Uporaba prema bilo kojem zahtjevu od 43 do 54, naznačena time, da receptor sadrži sekvencu amino kiseline od receptora vezanih G-proteina koja ima najmanje oko 80% identiteta od SEQ ID NO:2.
56. Uporaba prema bilo kojem zahtjevu od 43 do 55, naznačena time, da receptor sadrži sekvencu amino kiseline od SEQ ID NO:2.
57. Postupak prema zahtjevu 17, naznačen time, da prije koraka (a) obuhvaća dodatne korake in vitro kako slijedi:
(x) stavljanje u doticaj receptora vezanih G-proteina sa opcijski obilježenim poznatim ligandom za receptor u prisutnosti ili u odsutnosti test spoja, pri čemu receptor vezanih G-proteina sadrži sekvencu amino kiseline odabranu iz skupine koja sadrži:
(i) amino kiseline 1-335 od SEQ ID NO:2;
(ii) amino kiseline 2-335 od SEQ ID NO:2;
(iii) sekvencu amino kiseline od receptora vezanih G-proteina kodiranu s polinukleotidima koji su pojačani lančanom reakcijom polimeraze (PCR) na humanom DNA uzorku koristeći specifične primere SEQ ID NO:3 i SEQ ID NO:4;
(iv) sekvencu amino kiseline od receptora vezanih G-proteina kodiranu s polinukleotidima koji su hibridizirani pod uvjetima visoke oskudice prema dodatku od SEQ ID NO:1;
(v) sekvencu amino kiseline od receptora vezanih G-proteina koja ima najmanje oko 80% identiteta od SEQ ID NO:2;
(vi) sekvencu amino kiseline od tvorbene aktivne verzije receptora vezanih G-proteina koja ima SEQ ID NO:2; i
(vii) biološki aktivni dio od (i) ili (ii), pri čemu je spomenuti biološki aktivni dio sposoban za vezanje na (2-fluoro-4-metansulfonil-fenil)-{6-[4-(3-izopropil-[1,2,4]oksadiazol-5-il)-piperidin-1-il]-5-nitro-pirimidin-4-il}-amin; i
(y) otkrivanje kompleksa između spomenutog poznatog liganda i spomenutog receptora; i
(z) određivanje da li je manje spomenutog kompleksa formirano u prisutnosti test spoja nego li u odsutnosti test spoja;
pri čemu spomenuto određivanje pokazuje da li je test spoj postao GIP sekretogog, te pri čemu agonist GPR119 iz koraka (a) je test spoj određen u koraku (z) da bude spoj u čijoj prisutnosti je formirano manje spomenutog kompleksa.
58. Postupak prema zahtjevu 18, naznačen time, da prije koraka (a) obuhvaća dodatne korake in vitro kako slijedi:
(x) stavljanje u doticaj receptora vezanih G-proteina sa opcijski obilježenim poznatim ligandom za receptor u prisutnosti ili u odsutnosti test spoja, pri čemu receptor vezanih G-proteina sadrži sekvencu amino kiseline odabranu iz skupine koja sadrži:
(i) amino kiseline 1-335 od SEQ ID NO:2;
(ii) amino kiseline 2-335 od SEQ ID NO:2;
(iii) sekvencu amino kiseline od receptora vezanih G-proteina kodiranu s polinukleotidima koji su pojačani lančanom reakcijom polimeraze (PCR) na humanom DNA uzorku koristeći specifične primere SEQ ID NO:3 i SEQ ID NO:4;
(iv) sekvencu amino kiseline od receptora vezanih G-proteina kodiranu s polinukleotidima koji su hibridizirani pod uvjetima visoke oskudice prema dodatku od SEQ ID NO:1;
(v) sekvencu amino kiseline od receptora vezanih G-proteina koja ima najmanje oko 80% identiteta od SEQ ID NO:2;
(vi) sekvencu amino kiseline od tvorbene aktivne verzije receptora vezanih G-proteina koja ima SEQ ID NO:2; i
(vii) biološki aktivni dio od (i) ili (ii), pri čemu je spomenuti biološki aktivni dio sposoban za vezanje na (2-fluoro-4-metansulfonil-fenil)-{6-[4-(3-izopropil-[1,2,4]oksadiazol-5-il)-piperidin-1-il]-5-nitro-pirimidin-4-il}-amin; i
(y) otkrivanje kompleksa između spomenutog poznatog liganda i spomenutog receptora; i
(z) određivanje da li je manje spomenutog kompleksa formirano u prisutnosti test spoja nego li u odsutnosti test spoja;
pri čemu spomenuto određivanje pokazuje da li je test spoj postao GIP sekretogog, te pri čemu agonist GPR119 iz koraka (a) je test spoj određen u koraku (z) da bude spoj u čijoj prisutnosti je formirano manje spomenutog kompleksa.
59. Postupak prema zahtjevu 58, naznačen time, da kralježnjak nije čovjek.
60. Postupak prema bilo kojem zahtjevu od 57 do 59, naznačen time, da receptor je rekombinant.
61. Postupak prema bilo kojem zahtjevu od 57 do 60, naznačen time, da stanica domaćina sadrži vektor ekspresije, pri čemu taj vektor ekspresije sadrži polinukleotid koji kodira receptor vezanih G-proteina.
62. Postupak prema bilo kojem zahtjevu od 57 do 61, naznačen time, da poznati ligand je agonist GPR119.
63. Postupak prema zahtjevu 62, naznačen time, da agonist GPR119 je agonist humanog GPR119.
64. Postupak prema zahtjevu 62 ili zahtjevu 63, naznačen time, da spomenuti agonist GPR119 je selektivni agonist.
65. Postupak prema bilo kojem zahtjevu od 62 do 64, naznačen time, da agonist GPR119 ima EC50 u vrijednosti manjoj nego što je odabrana iz skupine koja se sastoji od 10 μM, 1 μM i 100 nM.
66. Postupak prema bilo kojem zahtjevu od 62 do 65, naznačen time, da agonist GPR119 je mala molekula koja ima molekularnu masu manju od oko 5.000 gram/mol.
67. Postupak prema bilo kojem zahtjevu od 57 do 66, naznačen time, da test spoj je mala molekula koja ima molekularnu masu manju od oko 5.000 gram/mol.
68. Postupak prema bilo kojem zahtjevu od 57 do 67, naznačen time, da receptor sadrži sekvencu amino kiseline receptora vezanih G-proteina koja ima najmanje oko 80% identiteta od SEQ ID NO:2.
69. Postupak prema bilo kojem zahtjevu od 57 do 68, naznačen time, da receptor sadrži sekvencu amino kiseline od SEQ ID NO:2.
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Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK1599468T3 (da) | 2003-01-14 | 2008-02-04 | Arena Pharm Inc | 1,2,3-trisubstituerede aryl- og heteroarylderivater som modulatorer af metabolisme og forebyggelse og behandling af forstyrrelser forbundet dermed såsom diabetes og hyperglykæmi |
| 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 |
| 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 |
| SI1971862T1 (sl) | 2006-04-11 | 2011-02-28 | Arena Pharm Inc | Postopki uporabe GPR119 receptorja za identificiranje spojin, uporabnih za povečanje kostne mase pri posamezniku |
| BRPI0817211A2 (pt) | 2007-09-20 | 2017-05-16 | Irm Llc | composto composições como moduladores da atividade de gpr119 |
| EP2146210A1 (en) * | 2008-04-07 | 2010-01-20 | Arena Pharmaceuticals, Inc. | Methods of using A G protein-coupled receptor to identify peptide YY (PYY) secretagogues and compounds useful in the treatment of conditions modulated by PYY |
| TW201111361A (en) | 2009-06-24 | 2011-04-01 | Boehringer Ingelheim Int | New compounds, pharmaceutical composition and methods relating thereto |
| AR077214A1 (es) | 2009-06-24 | 2011-08-10 | Neurocrine Biosciences Inc | Heterociclos nitrogenados y composiciones farmaceuticas que los contienen |
| AR077642A1 (es) | 2009-07-09 | 2011-09-14 | Arena Pharm Inc | Moduladores del metabolismo y el tratamiento de trastornos relacionados con el mismo |
| US20130109703A1 (en) | 2010-03-18 | 2013-05-02 | Boehringer Ingelheim International Gmbh | Combination of a GPR119 Agonist and the DPP-IV Inhibitor Linagliptin for Use in the Treatment of Diabetes and Related Conditions |
| US20130023494A1 (en) | 2010-04-06 | 2013-01-24 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| WO2012025811A1 (en) | 2010-08-23 | 2012-03-01 | Lupin Limited | Indolylpyrimidines as modulators of gpr119 |
| EP3323818A1 (en) | 2010-09-22 | 2018-05-23 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| EP2643311A1 (en) | 2010-11-26 | 2013-10-02 | Lupin Limited | Bicyclic gpr119 modulators |
| WO2012135570A1 (en) | 2011-04-01 | 2012-10-04 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| WO2012145361A1 (en) | 2011-04-19 | 2012-10-26 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| US20140051714A1 (en) | 2011-04-22 | 2014-02-20 | Arena Pharmaceuticals, Inc. | Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto |
| WO2012145603A1 (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 |
| CA2836487A1 (en) | 2011-06-09 | 2012-12-13 | Rhizen Pharmaceuticals Sa | Novel compounds as modulators of gpr-119 |
| WO2013055910A1 (en) | 2011-10-12 | 2013-04-18 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| AR091739A1 (es) | 2012-07-11 | 2015-02-25 | Elcelyx Therapeutics Inc | Composiciones y metodos para reducir el riesgo cardiometabolico |
| WO2014074668A1 (en) | 2012-11-08 | 2014-05-15 | Arena Pharmaceuticals, Inc. | Modulators of gpr119 and the treatment of disorders related thereto |
| EP3242666B1 (en) | 2015-01-06 | 2024-10-16 | Arena Pharmaceuticals, Inc. | Compound for use in treating conditions related to the s1p1 receptor |
| KR200481746Y1 (ko) | 2015-01-21 | 2016-11-04 | 큰길엔터프라이즈 주식회사 | 가습대 |
| PT3310760T (pt) | 2015-06-22 | 2022-11-10 | Arena Pharm Inc | Sal cristalino de l-arginina de ácido (r)-2-(7-(4-ciclopentil-3-(trifluorometil)benziloxi)-1,2,3,4-tetrahidrociclo-penta[b]indol-3-il)acético para utilização em distúrbios associados a recetores de s1p1 |
| CA3053418A1 (en) | 2017-02-16 | 2018-08-23 | Arena Pharmaceuticals, Inc. | Compounds and methods for treatment of primary biliary cholangitis |
| MA49456A (fr) | 2017-06-19 | 2020-04-29 | Arena Pharm Inc | Composés et procédés pour le traitement de nafld et de nash |
| CN116323608A (zh) | 2020-05-19 | 2023-06-23 | 卡尔优普公司 | Ampk活化剂 |
| CN116390925A (zh) | 2020-06-26 | 2023-07-04 | 卡尔优普公司 | Ampk活化剂 |
Family Cites Families (191)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4166452A (en) | 1976-05-03 | 1979-09-04 | Generales Constantine D J Jr | Apparatus for testing human responses to stimuli |
| US4256108A (en) | 1977-04-07 | 1981-03-17 | Alza Corporation | Microporous-semipermeable laminated osmotic system |
| US4704362A (en) | 1977-11-08 | 1987-11-03 | Genentech, Inc. | Recombinant cloning vehicle microbial polypeptide expression |
| US4265874A (en) | 1980-04-25 | 1981-05-05 | Alza Corporation | Method of delivering drug with aid of effervescent activity generated in environment of use |
| US4495002A (en) * | 1981-05-27 | 1985-01-22 | Westinghouse Electric Corp. | Three-step treatment of stainless steels having metastable austenitic and martensitic phases to increase resistance to chloride corrosion |
| US5462856A (en) | 1990-07-19 | 1995-10-31 | Bunsen Rush Laboratories, Inc. | Methods for identifying chemicals that act as agonists or antagonists for receptors and other proteins involved in signal transduction via pathways that utilize G-proteins |
| CA2121369C (en) | 1991-10-22 | 2003-04-29 | William W. Bachovchin | Inhibitors of dipeptidyl-aminopeptidase type iv |
| MX9206628A (es) | 1991-11-22 | 1993-05-01 | Boehringer Ingelheim Pharma | Ester de prolinaboronato y metodo para su preparacion. |
| US6100042A (en) | 1993-03-31 | 2000-08-08 | Cadus Pharmaceutical Corporation | Yeast cells engineered to produce pheromone system protein surrogates, and uses therefor |
| US20020006899A1 (en) | 1998-10-06 | 2002-01-17 | Pospisilik Andrew J. | Use of dipeptidyl peptidase IV effectors for lowering blood pressure in mammals |
| DE122010000020I1 (de) | 1996-04-25 | 2010-07-08 | Prosidion Ltd | Verfahren zur Senkung des Blutglukosespiegels in Säugern |
| TW492957B (en) | 1996-11-07 | 2002-07-01 | Novartis Ag | N-substituted 2-cyanopyrrolidnes |
| US6040145A (en) | 1997-05-07 | 2000-03-21 | Tufts University | Potentiation of the immune response |
| US6100234A (en) | 1997-05-07 | 2000-08-08 | Tufts University | Treatment of HIV |
| US6183974B1 (en) | 1997-07-31 | 2001-02-06 | The General Hospital Corporation | Screening assays for G protein coupled receptor agonists and antagonists |
| GB9719496D0 (en) | 1997-09-13 | 1997-11-19 | Glaxo Group Ltd | G protien chimeras |
| EP1043328B1 (en) | 1997-11-18 | 2008-03-19 | Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai | Novel physiologically active substance sulphostin, process for producing the same, and use thereof |
| EP2823812A1 (en) | 1998-02-02 | 2015-01-14 | Trustees Of Tufts College | Dipeptidylpeptidase IV inhibitors for use in the treatment of Type II diabetes |
| US5922576A (en) | 1998-02-27 | 1999-07-13 | The John Hopkins University | Simplified system for generating recombinant adenoviruses |
| US6304621B1 (en) | 1998-05-13 | 2001-10-16 | Broadcom Corporation | Multi-mode variable rate digital cable receiver |
| DE19823831A1 (de) | 1998-05-28 | 1999-12-02 | Probiodrug Ges Fuer Arzneim | Neue pharmazeutische Verwendung von Isoleucyl Thiazolidid und seinen Salzen |
| DE19828113A1 (de) | 1998-06-24 | 2000-01-05 | Probiodrug Ges Fuer Arzneim | Prodrugs von Inhibitoren der Dipeptidyl Peptidase IV |
| DE19828114A1 (de) | 1998-06-24 | 2000-01-27 | Probiodrug Ges Fuer Arzneim | Produgs instabiler Inhibitoren der Dipeptidyl Peptidase IV |
| DE19834591A1 (de) | 1998-07-31 | 2000-02-03 | Probiodrug Ges Fuer Arzneim | Verfahren zur Steigerung des Blutglukosespiegels in Säugern |
| WO2000007658A1 (en) | 1998-08-06 | 2000-02-17 | Shmuel Peltz | Method and appliances for electrostimulation |
| WO2000010549A1 (en) | 1998-08-21 | 2000-03-02 | Point Therapeutics, Inc. | Regulation of substrate activity |
| WO2000012705A2 (en) | 1998-09-01 | 2000-03-09 | Basf Aktiengesellschaft | Methods for improving the function of heterologous g protein-coupled receptors |
| JP2002526554A (ja) | 1998-10-07 | 2002-08-20 | メディカル カレッジ オブ ジョージア リサーチ インスティチュート，インコーポレイテッド | 骨親和性ホルモンとして用いられるグルコース依存性インスリン親和性ペプチド |
| US6242422B1 (en) | 1998-10-22 | 2001-06-05 | Idun Pharmacueticals, Inc. | (Substituted)Acyl dipeptidyl inhibitors of the ice/ced-3 family of cysteine proteases |
| DK1133559T3 (da) | 1998-11-20 | 2006-04-10 | Arena Pharm Inc | Human-G-protein-koblet orphan receptor RUP3 |
| 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 |
| JP2000191616A (ja) | 1998-12-24 | 2000-07-11 | Senju Pharmaceut Co Ltd | 新規ジペプチジルアルデヒド誘導体およびそれを含有する医薬 |
| US6221660B1 (en) | 1999-02-22 | 2001-04-24 | Synaptic Pharmaceutical Corporation | DNA encoding SNORF25 receptor |
| US20030125539A1 (en) | 1999-02-22 | 2003-07-03 | Synaptic Pharmaceutical Corporation | DNA encoding SNORF25 receptor |
| JP4121215B2 (ja) | 1999-05-17 | 2008-07-23 | 財団法人微生物化学研究会 | スルフォスチン類縁体、並びにスルフォスチン及びその類縁体の製造方法 |
| JP4028135B2 (ja) | 1999-05-27 | 2007-12-26 | 本田技研工業株式会社 | 物体検出装置 |
| US6617340B1 (en) | 1999-07-29 | 2003-09-09 | Novartis Ag | N-(substituted glycyl)-pyrrolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV |
| DE19940130A1 (de) | 1999-08-24 | 2001-03-01 | Probiodrug Ges Fuer Arzneim | Neue Effektoren der Dipeptidyl Peptidase IV zur topischen Anwendung |
| US6653064B1 (en) | 1999-09-23 | 2003-11-25 | Boehringer Ingelheim International Gmbh | Method for identifying compounds useful in the therapy of bone disorders |
| GB9923177D0 (en) | 1999-09-30 | 1999-12-01 | Pfizer Ltd | Novel polypeptide |
| AU1916401A (en) | 1999-11-12 | 2001-06-06 | Guilford Pharmaceuticals Inc. | Dipeptidyl peptidase iv inhibitors and methods of making and using dipeptidyl peptidase iv inhibitors |
| US6380398B2 (en) | 2000-01-04 | 2002-04-30 | Novo Nordisk A/S | Therapeutically active and selective heterocyclic compounds that are inhibitors of the enzyme DPP-IV |
| DK1741445T3 (da) | 2000-01-21 | 2013-11-04 | Novartis Ag | Kombinationer omfattende dipeptidylpeptidase-IV-inhibitorer og antidiabetiske midler |
| US6395767B2 (en) | 2000-03-10 | 2002-05-28 | Bristol-Myers Squibb Company | Cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV and method |
| US6608038B2 (en) | 2000-03-15 | 2003-08-19 | Novartis Ag | Methods and compositions for treatment of diabetes and related conditions via gene therapy |
| US6864229B2 (en) | 2000-04-21 | 2005-03-08 | New England Medical Center Hospitals, Inc. | G protein coupled receptor (GPCR) agonists and antagonists and methods of activating and inhibiting GPCR using the same |
| GB0010188D0 (en) | 2000-04-26 | 2000-06-14 | Ferring Bv | Inhibitors of dipeptidyl peptidase IV |
| GB0010183D0 (en) | 2000-04-26 | 2000-06-14 | Ferring Bv | Inhibitors of dipeptidyl peptidase IV |
| EP1287133B1 (en) | 2000-05-18 | 2006-12-13 | Bayer HealthCare AG | Regulation of human dopamine-like g protein-coupled receptor |
| TW583185B (en) | 2000-06-13 | 2004-04-11 | Novartis Ag | N-(substituted glycyl)-2-cyanopyrrolidines and pharmaceutical composition for inhibiting dipeptidyl peptidase-IV (DPP-IV) or for the prevention or treatment of diseases or conditions associated with elevated levels of DPP-IV comprising the same |
| US6432969B1 (en) | 2000-06-13 | 2002-08-13 | Novartis Ag | N-(substituted glycyl)-2 cyanopyrrolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV |
| AU2001268958B2 (en) | 2000-07-04 | 2006-03-09 | Novo Nordisk A/S | Heterocyclic compounds, which are inhibitors of the enzyme dpp-iv |
| JP2004513076A (ja) * | 2000-07-25 | 2004-04-30 | メルク エンド カムパニー インコーポレーテッド | 糖尿病治療で有用なｎ−置換インドール類 |
| DK1308439T3 (da) | 2000-08-10 | 2009-01-12 | Mitsubishi Tanabe Pharma Corp | Prolinderivater og anvendelse af disse som lægemidler |
| US20040005555A1 (en) | 2000-08-31 | 2004-01-08 | Rothman Richard E. | Molecular diagnosis of bactermia |
| JP2004035574A (ja) | 2000-10-06 | 2004-02-05 | Tanabe Seiyaku Co Ltd | 脂肪族含窒素五員環化合物 |
| JP4329290B2 (ja) | 2000-10-06 | 2009-09-09 | 田辺三菱製薬株式会社 | 脂肪族含窒素五員環化合物 |
| JP4329291B2 (ja) | 2000-10-06 | 2009-09-09 | 田辺三菱製薬株式会社 | 含窒素五員環化合物 |
| WO2002030890A1 (fr) | 2000-10-06 | 2002-04-18 | Tanabe Seiyaku Co., Ltd. | Composes azotes a noyau a cinq elements |
| TWI243162B (en) | 2000-11-10 | 2005-11-11 | Taisho Pharmaceutical Co Ltd | Cyanopyrrolidine derivatives |
| AU1989002A (en) | 2000-11-27 | 2002-06-03 | Arena Pharm Inc | Endogenous and non-endogenous versions of human g protein-coupled receptors |
| EP1338651B9 (en) | 2000-12-01 | 2007-05-09 | Astellas Pharma Inc. | Method of screening remedy for diabetes |
| EP1354882A1 (en) | 2000-12-27 | 2003-10-22 | Kyowa Hakko Kogyo Co., Ltd. | Dipeptidyl peptidase iv inhibitor |
| JP4823431B2 (ja) | 2001-01-30 | 2011-11-24 | 東レ・ダウコーニング株式会社 | 室温硬化性シリコーンゴム組成物 |
| JP4213390B2 (ja) | 2001-02-02 | 2009-01-21 | 武田薬品工業株式会社 | 縮合複素環化合物 |
| RS50955B (sr) | 2001-02-24 | 2010-08-31 | Boehringer Ingelheim Pharma Gmbh. & Co.Kg. | Derivati ksantina, njihovo dobijanje i njihova primena kao lekova |
| JP2002265439A (ja) | 2001-03-08 | 2002-09-18 | Mitsubishi Pharma Corp | シアノピロリジン誘導体およびその医薬用途 |
| US6911474B2 (en) | 2001-03-27 | 2005-06-28 | The Regents Of The University Of California | Methods, compounds, and compositions for reducing body fat and modulating fatty acid metabolism |
| AU2002306823B2 (en) | 2001-03-27 | 2006-05-11 | Merck & Co., Inc. | Dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes |
| FR2822826B1 (fr) | 2001-03-28 | 2003-05-09 | Servier Lab | Nouveaux derives sulfonyles d'alpha-amino-acides, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| US6573287B2 (en) | 2001-04-12 | 2003-06-03 | Bristo-Myers Squibb Company | 2,1-oxazoline and 1,2-pyrazoline-based inhibitors of dipeptidyl peptidase IV and method |
| US20020192206A1 (en) | 2001-05-05 | 2002-12-19 | Kozarov Emil V. | Methods and compositions for angioproliferative disorder treatment |
| FR2824825B1 (fr) | 2001-05-15 | 2005-05-06 | Servier Lab | Nouveaux derives d'alpha-amino-acides, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| JP2003000977A (ja) | 2001-06-26 | 2003-01-07 | Juki Corp | 玉縁縫製用ミシンの袋布地供給装置 |
| US20030130199A1 (en) | 2001-06-27 | 2003-07-10 | Von Hoersten Stephan | Dipeptidyl peptidase IV inhibitors and their uses as anti-cancer agents |
| US7368421B2 (en) | 2001-06-27 | 2008-05-06 | Probiodrug Ag | Use of dipeptidyl peptidase IV inhibitors in the treatment of multiple sclerosis |
| US6869947B2 (en) | 2001-07-03 | 2005-03-22 | Novo Nordisk A/S | Heterocyclic compounds that are inhibitors of the enzyme DPP-IV |
| UA74912C2 (en) | 2001-07-06 | 2006-02-15 | Merck & Co Inc | Beta-aminotetrahydroimidazo-(1,2-a)-pyrazines and tetratriazolo-(4,3-a)-pyrazines as inhibitors of dipeptylpeptidase for the treatment or prevention of diabetes |
| US6740250B2 (en) | 2001-07-13 | 2004-05-25 | Hazard Control Technologies | Fire suppressant having foam stabilizer |
| US6844316B2 (en) | 2001-09-06 | 2005-01-18 | Probiodrug Ag | Inhibitors of dipeptidyl peptidase I |
| DE10143840A1 (de) | 2001-09-06 | 2003-03-27 | Probiodrug Ag | Neue Inhibitoren der Dipeptidylpeptidase I |
| WO2003026661A1 (fr) | 2001-09-14 | 2003-04-03 | Yamanouchi Pharmaceutical Co., Ltd. | Accelerateur de secretion de l'insuline et nouveau derive de pyrimidine |
| CN100341862C (zh) | 2001-09-14 | 2007-10-10 | 三菱制药株式会社 | 噻唑烷衍生物及其医药用途 |
| JP2005509603A (ja) | 2001-09-19 | 2005-04-14 | ノボ ノルディスク アクティーゼルスカブ | Ｄｐｐ−ｉｖ酵素の阻害剤であるヘテロ環化合物 |
| EP1572892A4 (en) | 2001-10-18 | 2007-08-22 | Bristol Myers Squibb Co | HUMAN GLUCAGON-LIKE-PEPTIDE-1 MIMICS AND THEIR USE IN THE TREATMENT OF DIABETES AND RELATED CONDITIONS |
| US7238671B2 (en) | 2001-10-18 | 2007-07-03 | Bristol-Myers Squibb Company | Human glucagon-like-peptide-1 mimics and their use in the treatment of diabetes and related conditions |
| GB0125446D0 (en) | 2001-10-23 | 2001-12-12 | Ferring Bv | Novel anti-diabetic agents |
| US6861440B2 (en) | 2001-10-26 | 2005-03-01 | Hoffmann-La Roche Inc. | DPP IV inhibitors |
| US20030125304A1 (en) | 2001-11-09 | 2003-07-03 | Hans-Ulrich Demuth | Substituted amino ketone compounds |
| AU2002360453C1 (en) | 2001-11-26 | 2009-06-18 | The Brigham And Women's Hospital, Inc. | Methods for treating autoimmune disorders, and reagents related thereto |
| US7727964B2 (en) | 2001-11-26 | 2010-06-01 | Trustees Of Tufts College | Peptidomimetic inhibitors of post-proline cleaving enzymes |
| WO2003057144A2 (en) | 2001-12-26 | 2003-07-17 | Guilford Pharmaceuticals | Change inhibitors of dipeptidyl peptidase iv |
| US6727261B2 (en) | 2001-12-27 | 2004-04-27 | Hoffman-La Roche Inc. | Pyrido[2,1-A]Isoquinoline derivatives |
| EP1480999A2 (en) | 2002-02-08 | 2004-12-01 | Idun Pharmaceuticals | (substituted)acyl dipeptidyl inhibitors of the ice/ced-3 family of cysteine proteases |
| BR0307576A (pt) | 2002-02-13 | 2005-01-11 | Hoffmann La Roche | Compostos; processo para a fabricação de compostos; composições farmacêuticas; método para o tratamento e/ou profilaxia de doenças associadas com o dpp iv; e uso de compostos |
| JP4359146B2 (ja) | 2002-02-13 | 2009-11-04 | エフ．ホフマン−ラ ロシュ アーゲー | 新規なピリジン−およびピリミジン−誘導体 |
| US6906074B2 (en) | 2002-02-22 | 2005-06-14 | Nippon Zoki Pharmaceutical Co., Ltd. | 2-phenylpiperazine derivatives |
| EP1338595B1 (en) | 2002-02-25 | 2006-05-03 | Eisai Co., Ltd. | Xanthine derivatives as DPP-IV inhibitors |
| JP2004043429A (ja) | 2002-02-25 | 2004-02-12 | Eisai Co Ltd | 新規キサンチン誘導体およびｄｐｐｉｖ阻害剤 |
| EP1480961B1 (en) | 2002-02-28 | 2006-12-27 | Prosidion Ltd. | Glutaminyl based dpiv inhibitors |
| HUP0200849A2 (hu) * | 2002-03-06 | 2004-08-30 | Sanofi-Synthelabo | N-aminoacetil-2-ciano-pirrolidin-származékok, e vegyületeket tartalmazó gyógyszerkészítmények és eljárás előállításukra |
| CA2479898A1 (en) | 2002-03-25 | 2003-10-02 | Masatoshi Abe | Novel .alpha.-amino-n-(diaminophosphinyl)lactam derivatives |
| ATE373660T1 (de) | 2002-03-25 | 2007-10-15 | Merck & Co Inc | Heterocyclische beta-aminoverbindungen als inhibitoren der dipeptidylpeptidase zur behandlung bzw. prävention von diabetes |
| JP4329381B2 (ja) | 2002-04-04 | 2009-09-09 | 田辺三菱製薬株式会社 | 医薬組成物 |
| JP4329382B2 (ja) | 2002-04-04 | 2009-09-09 | 田辺三菱製薬株式会社 | 医薬組成物 |
| AU2003214534B2 (en) | 2002-04-08 | 2006-08-31 | Torrent Pharmaceuticals Ltd. | Thiazolidine-4-carbonitriles and analogues and their use as dipeptidyl-peptidas inhibitors |
| JP2003300977A (ja) | 2002-04-10 | 2003-10-21 | Sumitomo Pharmaceut Co Ltd | キサンチン誘導体 |
| JP2004026820A (ja) | 2002-05-09 | 2004-01-29 | Taisho Pharmaceut Co Ltd | ジペプチジルペプチダーゼｉｖ阻害剤 |
| JP2003327532A (ja) | 2002-05-10 | 2003-11-19 | Takeda Chem Ind Ltd | ペプチダーゼ阻害剤 |
| WO2003101449A2 (en) | 2002-06-04 | 2003-12-11 | Pfizer Products Inc. | Process for the preparation of 3,3,4,4-tetrafluoropyrrolidine and derivatives thereof |
| US6710040B1 (en) | 2002-06-04 | 2004-03-23 | Pfizer Inc. | Fluorinated cyclic amides as dipeptidyl peptidase IV inhibitors |
| RU2297418C9 (ru) | 2002-06-06 | 2009-01-27 | Эйсай Ко., Лтд. | Новые конденсированные производные имидазола, ингибитор дипептидилпептидазы iv, фармацевтическая композиция, способ лечения и применение на их основе |
| JP2004026678A (ja) | 2002-06-24 | 2004-01-29 | Microbial Chem Res Found | ２型糖尿病治療剤 |
| US6833973B2 (en) | 2002-06-27 | 2004-12-21 | International Business Machines Corporation | Apparatus and method to calibrate a servo sensor |
| CA2490818A1 (en) | 2002-07-15 | 2004-01-22 | Merck & Co., Inc. | Piperidino pyrimidine dipeptidyl peptidase inhibitors for the treatment of diabetes |
| JP4542757B2 (ja) | 2002-08-08 | 2010-09-15 | 武田薬品工業株式会社 | 縮合複素環化合物 |
| AU2003296895A1 (en) | 2002-08-20 | 2004-05-04 | The Regents Of The University Of California | Combination therapy for controlling appetites |
| US7407955B2 (en) | 2002-08-21 | 2008-08-05 | Boehringer Ingelheim Pharma Gmbh & Co., Kg | 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions |
| DE10238243A1 (de) | 2002-08-21 | 2004-03-04 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | 8-[3-Amino-piperidin-1-yl]-xanthine, deren Herstellung und deren Verwendung als Arzneimittel |
| DE10238470A1 (de) | 2002-08-22 | 2004-03-04 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Xanthinderivate, deren Herstellung und deren Verwendung als Arzneimittel |
| DE10238477A1 (de) | 2002-08-22 | 2004-03-04 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Purinderivate, deren Herstellung und deren Verwendung als Arzneimittel |
| AU2003262042A1 (en) | 2002-09-11 | 2004-04-30 | Yamanouchi Pharmaceutical Co., Ltd. | Method of screening insulin content enhancer |
| US20060039974A1 (en) | 2002-09-11 | 2006-02-23 | Takeda Pharmaceutical Company Limited | Sustained release preparation |
| DE10251927A1 (de) | 2002-11-08 | 2004-05-19 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Xanthinderivate, deren Herstellung und deren Verwendung als Arzneimittel |
| US7482337B2 (en) | 2002-11-08 | 2009-01-27 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Xanthine derivatives, the preparation thereof and their use as pharmaceutical compositions |
| BR0316327A (pt) | 2002-11-18 | 2005-09-27 | Pfizer Prod Inc | Amidas cìclicas fluorinadas inibidoras de dipeptidilpeptidase iv |
| DE10256264A1 (de) | 2002-12-03 | 2004-06-24 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue substituierte Imidazo-pyridinone und Imidazo-pyridazinone, ihre Herstellung und ihre Verwendung als Arzneimittel |
| EP1578414A4 (en) | 2002-12-04 | 2007-10-24 | Merck & Co Inc | PHENYLALANINE DERIVATIVES ALSDIPEPTIDYL-PEPTIDASE INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES |
| JP4504924B2 (ja) | 2002-12-20 | 2010-07-14 | メルク・シャープ・エンド・ドーム・コーポレイション | 糖尿病の治療および予防のためのジペプチジルペプチダーゼ阻害薬としての３−アミノ−４−フェニルブタン酸誘導体 |
| DK1599468T3 (da) | 2003-01-14 | 2008-02-04 | Arena Pharm Inc | 1,2,3-trisubstituerede aryl- og heteroarylderivater som modulatorer af metabolisme og forebyggelse og behandling af forstyrrelser forbundet dermed såsom diabetes og hyperglykæmi |
| WO2004064778A2 (en) | 2003-01-17 | 2004-08-05 | Merck & Co. Inc. | 3-amino-4-phenylbutanoic acid derivatives as dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes |
| JP2004244412A (ja) | 2003-01-20 | 2004-09-02 | Kotobuki Seiyaku Kk | ４位に置換基を有する２−シアノピロリジン誘導体及びその製造方法並びにそれを含有する薬剤 |
| JP2006516573A (ja) | 2003-01-31 | 2006-07-06 | メルク エンド カムパニー インコーポレーテッド | 糖尿病の治療および予防のためのジペプチジルペプチダーゼ阻害薬としての３−アミノ−４−フェニルブタン酸誘導体 |
| BRPI0407620A (pt) | 2003-02-24 | 2006-02-21 | Arena Pharm Inc | derivados de arila e heteroarila substituìdos como moduladores do metabolismo da glicose e a profilaxia e tratamento de seus distúrbios |
| JP2004269468A (ja) | 2003-03-12 | 2004-09-30 | Yamanouchi Pharmaceut Co Ltd | ピリミジン誘導体又はその塩 |
| JP2004269469A (ja) | 2003-03-12 | 2004-09-30 | Yamanouchi Pharmaceut Co Ltd | ピリミジン誘導体又はその塩 |
| DE602004026289D1 (de) | 2003-05-05 | 2010-05-12 | Probiodrug Ag | Glutaminylcyclase-hemmer |
| US7083933B1 (en) | 2003-05-09 | 2006-08-01 | Prosidion Limited | Methods for identification of modulators of OSGPR116 activity |
| US7638638B2 (en) | 2003-05-14 | 2009-12-29 | Takeda San Diego, Inc. | Dipeptidyl peptidase inhibitors |
| DE602004023932D1 (de) | 2003-05-14 | 2009-12-17 | Merck & Co Inc | 3-amino-4-phenylbutansäurederivate als dipeptidylpeptidase-hemmer zur behandlung oder vorbeugung von diabetes |
| KR20060009933A (ko) | 2003-05-15 | 2006-02-01 | 다이쇼 세이야꾸 가부시끼가이샤 | 시아노플루오로피롤리딘 유도체 |
| DE10327439A1 (de) | 2003-06-18 | 2005-01-05 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Imidazopyridazinon- und Imidazopyridonderivate, deren Herstellung und deren Verwendung als Arzneimittel |
| ATE489387T1 (de) | 2003-06-20 | 2010-12-15 | Hoffmann La Roche | Pyridoä2,1-aü-isochinolinderivate als dpp-iv inhibitoren |
| KR100744893B1 (ko) | 2003-06-20 | 2007-08-01 | 에프. 호프만-라 로슈 아게 | Ｄｐｐ-ｉｖ 저해제로서 헥사하이드로피리도아이소퀴놀린 |
| JP2005019000A (ja) | 2003-06-23 | 2005-01-20 | Inter Media:Kk | 照明制御システム |
| JO2625B1 (en) | 2003-06-24 | 2011-11-01 | ميرك شارب اند دوم كوربوريشن | Phosphoric acid salts of dipeptidyl betidase inhibitor 4 |
| JP2005018412A (ja) | 2003-06-26 | 2005-01-20 | Toppan Printing Co Ltd | 電子購買システム及び方法 |
| JP2005023038A (ja) | 2003-07-04 | 2005-01-27 | Taisho Pharmaceut Co Ltd | 慢性腎疾患治療薬 |
| AR045047A1 (es) | 2003-07-11 | 2005-10-12 | Arena Pharm Inc | Derivados arilo y heteroarilo trisustituidos como moduladores del metabolismo y de la profilaxis y tratamiento de desordenes relacionados con los mismos |
| EP1644375A2 (en) | 2003-07-14 | 2006-04-12 | Arena Pharmaceuticals, Inc. | Fused-aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto |
| US7008957B2 (en) | 2003-07-25 | 2006-03-07 | Sanofi-Aventis Deutschland Gmbh | Bicyclic cyanoheterocycles, process for their preparation and their use as medicaments |
| US7094800B2 (en) | 2003-07-25 | 2006-08-22 | Sanofi-Aventis Deutschland Gmbh | Cyanopyrrolidides, process for their preparation and their use as medicaments |
| DE10333935A1 (de) | 2003-07-25 | 2005-02-24 | Aventis Pharma Deutschland Gmbh | Neue bicyclische Cyanoheterocyclen, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| US6995183B2 (en) | 2003-08-01 | 2006-02-07 | Bristol Myers Squibb Company | Adamantylglycine-based inhibitors of dipeptidyl peptidase IV and methods |
| WO2005019168A2 (en) | 2003-08-20 | 2005-03-03 | Pfizer Products Inc. | Fluorinated lysine derivatives as dipeptidyl peptidase iv inhibitors |
| HU227684B1 (en) | 2003-08-29 | 2011-11-28 | Sanofi Aventis | Adamantane and azabicyclo-octane and nonane derivatives and their use as dpp-iv inhibitors |
| WO2005021550A1 (ja) | 2003-08-29 | 2005-03-10 | Dainippon Sumitomo Pharma Co., Ltd. | 二環性ピラゾール誘導体 |
| CA2540741A1 (en) | 2003-10-03 | 2005-04-14 | Takeda Pharmaceutical Company Limited | Agent for treating diabetes |
| DE10355304A1 (de) | 2003-11-27 | 2005-06-23 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue 8-(Piperazin-1-yl)-und 8-([1,4]Diazepan-1-yl)-xanthine, deren Herstellung und deren Verwendung als Arzneimittel |
| US7217711B2 (en) | 2003-12-17 | 2007-05-15 | Boehringer Ingelheim International Gmbh | Piperazin-1-yl and 2-([1,4]diazepan-1-yl)-imidazo[4,5-d]-pyridazin-4-ones, the preparation thereof and their use as pharmaceutical compositions |
| CN1898235A (zh) | 2003-12-24 | 2007-01-17 | 普罗西迪恩有限公司 | 作为gpcr受体激动剂的杂环衍生物 |
| US7501426B2 (en) | 2004-02-18 | 2009-03-10 | Boehringer Ingelheim International Gmbh | 8-[3-amino-piperidin-1-yl]-xanthines, their preparation and their use as pharmaceutical compositions |
| DE102004009039A1 (de) | 2004-02-23 | 2005-09-08 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | 8-[3-Amino-piperidin-1-yl]-xanthine, deren Herstellung und Verwendung als Arzneimittel |
| UA92150C2 (ru) | 2004-06-04 | 2010-10-11 | Арена Фармасьютикалз, Инк. | Замещенные производные арила и гетероарила как модуляторы метаболизма и для профилактики и лечения связанных с ним расстройств |
| JP2008503229A (ja) | 2004-06-24 | 2008-02-07 | ガラパゴス・ナムローゼ・フェンノートシャップ | 骨ホメオスタシスを促進させる方法及び組成物 |
| US20060024313A1 (en) | 2004-07-06 | 2006-02-02 | Xin Chen | Agents that disrupt dimer formation in DPP-IV family of prolyl dipeptidases |
| WO2006019965A2 (en) | 2004-07-16 | 2006-02-23 | Takeda San Diego, Inc. | Dipeptidyl peptidase inhibitors |
| US20060046978A1 (en) | 2004-08-31 | 2006-03-02 | Morphochem Ag | Novel compounds that inhibit dipeptidyl peptidase (DPP-IV) and neprilysin (NEP) and/or angiotensin converting enzyme (ACE) |
| DE102004044221A1 (de) | 2004-09-14 | 2006-03-16 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue 3-Methyl-7-butinyl-xanthine, deren Herstellung und deren Verwendung als Arzneimittel |
| US20080076805A1 (en) * | 2004-10-07 | 2008-03-27 | Lin Linus S | Acyclic Hydrazides as Cannabinoid Receptor Modulators |
| JP4862654B2 (ja) | 2004-10-08 | 2012-01-25 | アステラス製薬株式会社 | 芳香環縮合ピリミジン誘導体 |
| TW200621257A (en) | 2004-10-20 | 2006-07-01 | Astellas Pharma Inc | Pyrimidine derivative fused with nonaromatic ring |
| US7411093B2 (en) | 2004-12-20 | 2008-08-12 | Hoffman-La Roche Inc. | Aminocycloalkanes as DPP-IV inhibitors |
| EP1828192B1 (en) | 2004-12-21 | 2014-12-03 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| CA2591922A1 (en) | 2004-12-24 | 2006-06-29 | Prosidion Limited | G-protein coupled receptor (gpr116) agonists and use thereof for treating obesity and diabetes |
| WO2006067532A1 (en) | 2004-12-24 | 2006-06-29 | Prosidion Ltd | G-protein coupled receptor agonists |
| US7589088B2 (en) | 2004-12-29 | 2009-09-15 | Bristol-Myers Squibb Company | Pyrimidine-based inhibitors of dipeptidyl peptidase IV and methods |
| GB0428514D0 (en) | 2004-12-31 | 2005-02-09 | Prosidion Ltd | Compounds |
| MY148521A (en) | 2005-01-10 | 2013-04-30 | Arena Pharm Inc | Substituted pyridinyl and pyrimidinyl derivatives as modulators of metabolism and the treatment of disorders related thereto |
| 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 |
| WO2006086727A2 (en) | 2005-02-09 | 2006-08-17 | Entelos, Inc. | Treating diabetes with glucagon-like peptide-1 secretagogues |
| WO2006132406A1 (ja) | 2005-06-09 | 2006-12-14 | Banyu Pharmaceutical Co., Ltd. | 下痢を伴う疾患の治療剤としてのnpy y2アゴニスト |
| WO2007003961A2 (en) | 2005-06-30 | 2007-01-11 | Prosidion Limited | Gpcr agonists |
| CA2613235A1 (en) | 2005-06-30 | 2007-01-11 | Prosidion Limited | Gpcr agonists |
| JP2008545010A (ja) | 2005-06-30 | 2008-12-11 | プロシディオン・リミテッド | Ｇタンパク質共役受容体アゴニスト |
| EP1907383A1 (en) | 2005-06-30 | 2008-04-09 | Prosidion Limited | Gpcr agonists |
| US7708191B2 (en) * | 2005-07-28 | 2010-05-04 | Edwin Vega | Telebanking apparatus for transferring money or cash value between two parties in the same country or across national borders, for paying bills and browsing the internet |
| SI1971862T1 (sl) | 2006-04-11 | 2011-02-28 | Arena Pharm Inc | Postopki uporabe GPR119 receptorja za identificiranje spojin, uporabnih za povečanje kostne mase pri posamezniku |
| 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 |
| JP2010501629A (ja) | 2006-08-30 | 2010-01-21 | ビオヴィトルム・アクチボラゲット（プブリクト） | Ｇｐｒ１１９関連障害を治療するためのピリジン化合物 |
| EP2146210A1 (en) | 2008-04-07 | 2010-01-20 | Arena Pharmaceuticals, Inc. | Methods of using A G protein-coupled receptor to identify peptide YY (PYY) secretagogues and compounds useful in the treatment of conditions modulated by PYY |
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