HRP980360A2 - Dipeptide derivatives - Google Patents
Dipeptide derivativesInfo
- Publication number
- HRP980360A2 HRP980360A2 HR60/050,764A HRP980360A HRP980360A2 HR P980360 A2 HRP980360 A2 HR P980360A2 HR P980360 A HRP980360 A HR P980360A HR P980360 A2 HRP980360 A2 HR P980360A2
- Authority
- HR
- Croatia
- Prior art keywords
- compound
- alkyl
- mixture
- isomer
- group
- Prior art date
Links
- 108010016626 Dipeptides Proteins 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims description 723
- 239000000203 mixture Substances 0.000 claims description 288
- 239000000651 prodrug Substances 0.000 claims description 270
- 229940002612 prodrug Drugs 0.000 claims description 270
- 229910052739 hydrogen Inorganic materials 0.000 claims description 197
- 239000001257 hydrogen Substances 0.000 claims description 191
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 177
- 125000001424 substituent group Chemical group 0.000 claims description 170
- 150000003839 salts Chemical class 0.000 claims description 142
- -1 hydroxy, nitro, amino, cyano, phenyl Chemical group 0.000 claims description 137
- 125000000217 alkyl group Chemical group 0.000 claims description 133
- 239000000122 growth hormone Substances 0.000 claims description 132
- 102000018997 Growth Hormone Human genes 0.000 claims description 130
- 108010051696 Growth Hormone Proteins 0.000 claims description 129
- 125000001153 fluoro group Chemical group F* 0.000 claims description 112
- 238000000034 method Methods 0.000 claims description 109
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 107
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 104
- 239000000460 chlorine Substances 0.000 claims description 102
- 229910052801 chlorine Inorganic materials 0.000 claims description 95
- 229910052731 fluorine Inorganic materials 0.000 claims description 95
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 93
- 229920006395 saturated elastomer Polymers 0.000 claims description 93
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 88
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 87
- 238000011282 treatment Methods 0.000 claims description 77
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 75
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 75
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 74
- 229910052760 oxygen Inorganic materials 0.000 claims description 74
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 65
- 241001465754 Metazoa Species 0.000 claims description 64
- 125000005843 halogen group Chemical group 0.000 claims description 55
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 55
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 52
- 229910052757 nitrogen Inorganic materials 0.000 claims description 51
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 48
- 239000001301 oxygen Substances 0.000 claims description 47
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 45
- 229910052717 sulfur Inorganic materials 0.000 claims description 45
- 239000011593 sulfur Substances 0.000 claims description 45
- 125000005842 heteroatom Chemical group 0.000 claims description 43
- 125000004076 pyridyl group Chemical group 0.000 claims description 42
- 125000003118 aryl group Chemical group 0.000 claims description 40
- 210000000988 bone and bone Anatomy 0.000 claims description 37
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 36
- 208000001132 Osteoporosis Diseases 0.000 claims description 36
- 229910052799 carbon Inorganic materials 0.000 claims description 35
- 125000000335 thiazolyl group Chemical group 0.000 claims description 34
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 31
- 230000001965 increasing effect Effects 0.000 claims description 31
- 230000002265 prevention Effects 0.000 claims description 31
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 28
- 150000001721 carbon Chemical group 0.000 claims description 28
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 26
- 229940011871 estrogen Drugs 0.000 claims description 26
- 239000000262 estrogen Substances 0.000 claims description 26
- 230000028327 secretion Effects 0.000 claims description 26
- 125000001544 thienyl group Chemical group 0.000 claims description 25
- 239000000556 agonist Substances 0.000 claims description 22
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 22
- 241000282412 Homo Species 0.000 claims description 19
- 241000282326 Felis catus Species 0.000 claims description 18
- 239000005557 antagonist Substances 0.000 claims description 18
- 241000124008 Mammalia Species 0.000 claims description 16
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 16
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims description 15
- 208000008589 Obesity Diseases 0.000 claims description 15
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 15
- 229910052794 bromium Inorganic materials 0.000 claims description 15
- 238000006243 chemical reaction Methods 0.000 claims description 15
- 239000003937 drug carrier Substances 0.000 claims description 15
- 230000012010 growth Effects 0.000 claims description 15
- 229910052740 iodine Inorganic materials 0.000 claims description 15
- 238000004519 manufacturing process Methods 0.000 claims description 15
- 235000020824 obesity Nutrition 0.000 claims description 15
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 15
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 14
- 239000012442 inert solvent Substances 0.000 claims description 14
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 14
- 101710142969 Somatoliberin Proteins 0.000 claims description 13
- 239000000384 adrenergic alpha-2 receptor agonist Substances 0.000 claims description 13
- 102000004169 proteins and genes Human genes 0.000 claims description 13
- 108090000623 proteins and genes Proteins 0.000 claims description 13
- 150000003254 radicals Chemical class 0.000 claims description 13
- 229940122361 Bisphosphonate Drugs 0.000 claims description 12
- 125000004429 atom Chemical group 0.000 claims description 12
- 230000015572 biosynthetic process Effects 0.000 claims description 12
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 125000002883 imidazolyl group Chemical group 0.000 claims description 12
- 238000001356 surgical procedure Methods 0.000 claims description 12
- 201000010099 disease Diseases 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- 210000003205 muscle Anatomy 0.000 claims description 11
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 11
- 125000006709 (C5-C7) cycloalkenyl group Chemical group 0.000 claims description 10
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 10
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 10
- 239000000095 Growth Hormone-Releasing Hormone Substances 0.000 claims description 10
- 206010019280 Heart failures Diseases 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 9
- 206010022489 Insulin Resistance Diseases 0.000 claims description 9
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 230000013632 homeostatic process Effects 0.000 claims description 9
- 238000011084 recovery Methods 0.000 claims description 9
- 230000004044 response Effects 0.000 claims description 9
- 208000010392 Bone Fractures Diseases 0.000 claims description 8
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 claims description 8
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 claims description 8
- 239000003623 enhancer Substances 0.000 claims description 8
- 125000000623 heterocyclic group Chemical group 0.000 claims description 8
- 125000006536 (C1-C2)alkoxy group Chemical group 0.000 claims description 7
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 claims description 7
- 125000004423 acyloxy group Chemical group 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 230000001925 catabolic effect Effects 0.000 claims description 7
- 229960002896 clonidine Drugs 0.000 claims description 7
- HRLIOXLXPOHXTA-UHFFFAOYSA-N medetomidine Chemical compound C=1C=CC(C)=C(C)C=1C(C)C1=CN=C[N]1 HRLIOXLXPOHXTA-UHFFFAOYSA-N 0.000 claims description 7
- 229960002140 medetomidine Drugs 0.000 claims description 7
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 7
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 claims description 7
- 229960001600 xylazine Drugs 0.000 claims description 7
- WKDBMZQECSVNDS-UHFFFAOYSA-N (2,6-difluorophenyl)-pyrrolidin-1-ylmethanone Chemical compound FC1=CC=CC(F)=C1C(=O)N1CCCC1 WKDBMZQECSVNDS-UHFFFAOYSA-N 0.000 claims description 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 6
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 6
- 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims description 6
- UCZGQLWFDZVBER-UHFFFAOYSA-N 8a-(pyridin-2-ylmethyl)-2-(2,2,2-trifluoroethyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine-1,3-dione Chemical compound O=C1N(CC(F)(F)F)C(=O)N2CCNCC21CC1=CC=CC=N1 UCZGQLWFDZVBER-UHFFFAOYSA-N 0.000 claims description 6
- 208000017667 Chronic Disease Diseases 0.000 claims description 6
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 6
- 102000005157 Somatostatin Human genes 0.000 claims description 6
- 108010056088 Somatostatin Proteins 0.000 claims description 6
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 claims description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
- 125000002541 furyl group Chemical group 0.000 claims description 6
- 125000005059 halophenyl group Chemical group 0.000 claims description 6
- 230000002503 metabolic effect Effects 0.000 claims description 6
- 125000004043 oxo group Chemical group O=* 0.000 claims description 6
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 claims description 6
- 229960000553 somatostatin Drugs 0.000 claims description 6
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 6
- 230000029663 wound healing Effects 0.000 claims description 6
- NWQWNCILOXTTHF-HLCSKTDOSA-N (2s)-6-amino-2-[[(2r)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-[[(2s)-2-[[(2s)-2-aminopropanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]propanoyl]amino]-3-(1h-indol-3-yl)propanoyl]amino]-3-phenylpropanoyl]amino]hexanamide Chemical compound C([C@H](NC(=O)[C@@H](N)C)C(=O)N[C@H](CC=1C=C2C=CC=CC2=CC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCCN)C(N)=O)C1=CNC=N1 NWQWNCILOXTTHF-HLCSKTDOSA-N 0.000 claims description 5
- WZHKXNSOCOQYQX-FUAFALNISA-N (2s)-6-amino-2-[[(2r)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-[[(2s)-2-amino-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(1h-indol-3-yl)propanoyl]amino]propanoyl]amino]-3-(1h-indol-3-yl)propanoyl]amino]-3-phenylpropanoyl]amino]hexanamide Chemical compound C([C@H](N)C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCCN)C(N)=O)C1=CN=CN1 WZHKXNSOCOQYQX-FUAFALNISA-N 0.000 claims description 5
- DHSSDEDRBUKTQY-UHFFFAOYSA-N 6-prop-2-enyl-4,5,7,8-tetrahydrothiazolo[4,5-d]azepin-2-amine Chemical compound C1CN(CC=C)CCC2=C1N=C(N)S2 DHSSDEDRBUKTQY-UHFFFAOYSA-N 0.000 claims description 5
- 206010006895 Cachexia Diseases 0.000 claims description 5
- 102000055006 Calcitonin Human genes 0.000 claims description 5
- 108060001064 Calcitonin Proteins 0.000 claims description 5
- 241000283073 Equus caballus Species 0.000 claims description 5
- 102000048143 Insulin-Like Growth Factor II Human genes 0.000 claims description 5
- 108090001117 Insulin-Like Growth Factor II Proteins 0.000 claims description 5
- 108010083553 alanyl-histidyl-(2-naphthyl)alanyl-tryptophyl-phenylalanyl-lysinamide Proteins 0.000 claims description 5
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 claims description 5
- 229960004015 calcitonin Drugs 0.000 claims description 5
- 108010015153 growth hormone releasing hexapeptide Proteins 0.000 claims description 5
- DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 claims description 4
- RVWNMGKSNGWLOL-GIIHNPQRSA-N (2s)-6-amino-2-[[(2r)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-[[(2s)-2-amino-3-(1h-imidazol-5-yl)propanoyl]amino]-3-(2-methyl-1h-indol-3-yl)propanoyl]amino]propanoyl]amino]-3-(1h-indol-3-yl)propanoyl]amino]-3-phenylpropanoyl]amino]hexanamide Chemical compound C([C@H](N)C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCCN)C(N)=O)C1=CN=CN1 RVWNMGKSNGWLOL-GIIHNPQRSA-N 0.000 claims description 4
- HMBSMLATJKWAHH-UHFFFAOYSA-N 2-phenyl-1-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-3,4-dihydro-1h-isoquinolin-6-ol Chemical compound C1CC2=CC(O)=CC=C2C(C=2C=CC(OCCN3CCCC3)=CC=2)N1C1=CC=CC=C1 HMBSMLATJKWAHH-UHFFFAOYSA-N 0.000 claims description 4
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- ZQZFYGIXNQKOAV-OCEACIFDSA-N Droloxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=C(O)C=CC=1)\C1=CC=C(OCCN(C)C)C=C1 ZQZFYGIXNQKOAV-OCEACIFDSA-N 0.000 claims description 4
- 206010056438 Growth hormone deficiency Diseases 0.000 claims description 4
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
- 150000007942 carboxylates Chemical class 0.000 claims description 4
- 229960001270 d- tartaric acid Drugs 0.000 claims description 4
- 229950004203 droloxifene Drugs 0.000 claims description 4
- JKKFKPJIXZFSSB-CBZIJGRNSA-N estrone 3-sulfate Chemical compound OS(=O)(=O)OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 JKKFKPJIXZFSSB-CBZIJGRNSA-N 0.000 claims description 4
- 108010070965 hexarelin Proteins 0.000 claims description 4
- 235000013336 milk Nutrition 0.000 claims description 4
- 239000008267 milk Substances 0.000 claims description 4
- 210000004080 milk Anatomy 0.000 claims description 4
- 229940063238 premarin Drugs 0.000 claims description 4
- 239000000186 progesterone Substances 0.000 claims description 4
- 229960003387 progesterone Drugs 0.000 claims description 4
- 230000001737 promoting effect Effects 0.000 claims description 4
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 claims description 4
- 229960004622 raloxifene Drugs 0.000 claims description 4
- 230000008439 repair process Effects 0.000 claims description 4
- OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 claims description 3
- 208000036119 Frailty Diseases 0.000 claims description 3
- 208000002705 Glucose Intolerance Diseases 0.000 claims description 3
- MPBVHIBUJCELCL-UHFFFAOYSA-N Ibandronate Chemical compound CCCCCN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O MPBVHIBUJCELCL-UHFFFAOYSA-N 0.000 claims description 3
- 229940062527 alendronate Drugs 0.000 claims description 3
- 206010003549 asthenia Diseases 0.000 claims description 3
- 201000001421 hyperglycemia Diseases 0.000 claims description 3
- 229940015872 ibandronate Drugs 0.000 claims description 3
- QJEAKIUFGOHGQJ-ZBLYBZFDSA-N n-[(2r)-1-[(8as)-1,3-dioxo-8a-(pyridin-2-ylmethyl)-2-(2,2,2-trifluoroethyl)-6,8-dihydro-5h-imidazo[1,5-a]pyrazin-7-yl]-1-oxo-3-phenylmethoxypropan-2-yl]-2-amino-2-methylpropanamide Chemical compound C([C@@H](NC(=O)C(C)(N)C)C(=O)N1C[C@@]2(CC=3N=CC=CC=3)C(=O)N(CC(F)(F)F)C(=O)N2CC1)OCC1=CC=CC=C1 QJEAKIUFGOHGQJ-ZBLYBZFDSA-N 0.000 claims description 3
- 229960001603 tamoxifen Drugs 0.000 claims description 3
- UYMYXIDXGCBSET-QNLPTKCRSA-N tert-butyl n-[1-[[(2r)-1-[(8as)-1,3-dioxo-8a-(pyridin-2-ylmethyl)-2-(2,2,2-trifluoroethyl)-6,8-dihydro-5h-imidazo[1,5-a]pyrazin-7-yl]-1-oxo-3-phenylmethoxypropan-2-yl]amino]-2-methyl-1-oxopropan-2-yl]carbamate Chemical compound C([C@@H](NC(=O)C(C)(C)NC(=O)OC(C)(C)C)C(=O)N1C[C@@]2(CC=3N=CC=CC=3)C(=O)N(CC(F)(F)F)C(=O)N2CC1)OCC1=CC=CC=C1 UYMYXIDXGCBSET-QNLPTKCRSA-N 0.000 claims description 3
- MSSOZMTZHUAWDU-UHFFFAOYSA-N 2-[[2-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]-3-phenylmethoxypropanoic acid Chemical compound CC(C)(C)OC(=O)NC(C)(C)C(=O)NC(C(O)=O)COCC1=CC=CC=C1 MSSOZMTZHUAWDU-UHFFFAOYSA-N 0.000 claims description 2
- UHSCEBCQSSOHAI-XJQHNOHDSA-N 2-amino-2-methyl-N-[(2R)-1-[2-methyl-1,3-dioxo-8a-(pyridin-2-ylmethyl)-6,8-dihydro-5H-imidazo[1,5-a]pyrazin-7-yl]-1-oxo-3-phenylmethoxypropan-2-yl]propanamide Chemical compound O=C1N(C)C(=O)N2CCN(C(=O)[C@@H](COCC=3C=CC=CC=3)NC(=O)C(C)(C)N)CC21CC1=CC=CC=N1 UHSCEBCQSSOHAI-XJQHNOHDSA-N 0.000 claims description 2
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- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical group [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 210000001875 somatotroph Anatomy 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
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- 238000007619 statistical method Methods 0.000 description 1
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- 230000001954 sterilising effect Effects 0.000 description 1
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- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
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- 239000006188 syrup Substances 0.000 description 1
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- BXDKFDKGBNIHPI-SFHVURJKSA-N tert-butyl (8as)-1,3-dioxo-8a-(pyridin-2-ylmethyl)-2-(2,2,2-trifluoroethyl)-6,8-dihydro-5h-imidazo[1,5-a]pyrazine-7-carboxylate Chemical compound C([C@]12C(=O)N(CC(F)(F)F)C(=O)N1CCN(C2)C(=O)OC(C)(C)C)C1=CC=CC=N1 BXDKFDKGBNIHPI-SFHVURJKSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 229940034199 thyrotropin-releasing hormone Drugs 0.000 description 1
- 229940019375 tiludronate Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000007070 tosylation reaction Methods 0.000 description 1
- 238000009901 transfer hydrogenation reaction Methods 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 1
- 238000011870 unpaired t-test Methods 0.000 description 1
- 229960003726 vasopressin Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
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Classifications
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- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0202—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0205—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-(X)3-C(=0)-, e.g. statine or derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0207—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-(X)4-C(=0), e.g. 'isosters', replacing two amino acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/021—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-(X)n-C(=0)-, n being 5 or 6; for n > 6, classification in C07K5/06 - C07K5/10, according to the moiety having normal peptide bonds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US5076497P | 1997-06-25 | 1997-06-25 |
Publications (1)
Publication Number | Publication Date |
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HRP980360A2 true HRP980360A2 (en) | 1999-04-30 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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HR60/050,764A HRP980360A2 (en) | 1997-06-25 | 1998-06-25 | Dipeptide derivatives |
Country Status (13)
Country | Link |
---|---|
US (9) | USRE38524E1 (de) |
EP (1) | EP1001970B1 (de) |
JP (4) | JP3514774B2 (de) |
AP (1) | AP9801270A0 (de) |
AT (1) | ATE356139T1 (de) |
AU (1) | AU7445498A (de) |
DE (1) | DE69837264T2 (de) |
ES (1) | ES2283055T3 (de) |
HR (1) | HRP980360A2 (de) |
MA (1) | MA24580A1 (de) |
PA (1) | PA8453501A1 (de) |
TN (1) | TNSN98112A1 (de) |
WO (1) | WO1998058947A1 (de) |
Families Citing this family (56)
Publication number | Priority date | Publication date | Assignee | Title |
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UA64751C2 (uk) * | 1997-06-25 | 2004-03-15 | Пфайзер Продактс Інк. | Спосіб лікування інсулінової толерантності речовинами, які посилюють секрецію гормону росту (варіанти) та фармацевтична композиція (варіанти) |
JP3514774B2 (ja) * | 1997-06-25 | 2004-03-31 | ファイザー・インク | 成長ホルモン分泌促進薬としてのジペプチド誘導体 |
US6358951B1 (en) | 1998-08-21 | 2002-03-19 | Pfizer Inc. | Growth hormone secretagogues |
US6194578B1 (en) * | 1998-11-20 | 2001-02-27 | Pfizer Inc. | Dipeptide derivatives |
US6297380B1 (en) * | 1998-11-23 | 2001-10-02 | Pfizer Inc. | Process and intermediates for growth hormone secretagogues |
EP1486498A1 (de) * | 1998-11-23 | 2004-12-15 | Pfizer Products Inc. | Verfahren und Zwischenprodukte für Sekretionsfördermittel für Wachstumshormone |
WO2000048623A1 (en) | 1999-02-18 | 2000-08-24 | Kaken Pharmaceutical Co., Ltd. | Novel amide derivatives as growth hormone secretagogues |
US6541634B2 (en) | 1999-02-26 | 2003-04-01 | Pfizer Inc. | Process for preparing growth hormone secretagogues |
DE60034571T2 (de) * | 1999-06-15 | 2007-12-27 | Aventis Pharmaceuticals Inc. | Festphasensynthese von n,n-disubstituierten diazacycloalkylcarboxy-derivaten |
US6897225B1 (en) | 1999-10-20 | 2005-05-24 | Tanabe Seiyaku Co., Ltd. | Inhibitors of αLβ2 mediated cell adhesion |
DOP2001000154A (es) * | 2000-05-25 | 2002-05-15 | Pfizer Prod Inc | Combinación de secretagogos de hormona del crecimiento y antidepresivos |
WO2001091752A1 (en) | 2000-05-30 | 2001-12-06 | Merck & Co., Inc. | Melanocortin receptor agonists |
EP1159964B1 (de) | 2000-05-31 | 2009-10-28 | Pfizer Products Inc. | Verwendung von Wachstumshormonsekretagoga zur Förderung der Beweglichkeit des Verdauungstrakts |
IL143690A0 (en) * | 2000-06-19 | 2002-04-21 | Pfizer Prod Inc | The use of growth hormone secretagogues to treat systemic lupus erythematosus and inflammatory bowel disease |
EP1181933A3 (de) * | 2000-06-29 | 2002-04-10 | Pfizer Products Inc. | Verwendung von wachstumshormonsekretion-fördernden mitteln zur appetit erholung |
IL144468A0 (en) * | 2000-07-27 | 2002-05-23 | Pfizer Prod Inc | Use of growth hormone secretagogues for improvement of functional health status |
AP2001002264A0 (en) | 2000-08-30 | 2001-09-30 | Pfizer Prod Inc | Sustained release formulations for growth hormone secretagogues. |
IL145106A0 (en) * | 2000-08-30 | 2002-06-30 | Pfizer Prod Inc | Intermittent administration of a geowth hormone secretagogue |
EP1192943A3 (de) * | 2000-09-28 | 2002-11-27 | Pfizer Products Inc. | Verwendung von Sekretionsfördermitteln für Wachstumshormone in Verbindung mit Körpertraining |
CA2347330C (en) * | 2001-05-10 | 2002-03-12 | Pharmaceutical Partners Of Canada Inc. | Liquid injectable formulation of disodium pamidronate |
EP1312363A1 (de) * | 2001-09-28 | 2003-05-21 | Pfizer Products Inc. | Behandlungsverfahren und kits bestehend aus Wachstumshormonsekretionsförderern |
TW200303200A (en) | 2002-02-07 | 2003-09-01 | Tanabe Seiyaku Co | Inhibitors of α L β 2 integrin mediated cell adhesion |
US8018817B2 (en) * | 2002-05-20 | 2011-09-13 | Samsung Electronics Co., Ltd. | Method of recording erase pattern information on an optical recording medium, erasing information on the optical recording medium based on the erase pattern information, and optical recording medium therefor |
MXPA05002991A (es) * | 2002-09-18 | 2005-10-05 | Univ Montreal Ct Hospitalier Chum | Analogos de ghrh. |
US7390809B2 (en) * | 2002-10-07 | 2008-06-24 | Merck & Co., Inc. | Beta-amino heterocyclic dipeptidyl peptidase inhibitors for diabetes |
WO2004058266A1 (en) * | 2002-12-20 | 2004-07-15 | Merck & Co., Inc. | 3-amino-4-phenylbutanoic acid derivatives as dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes |
DE502004011328D1 (de) * | 2003-02-13 | 2010-08-12 | Sanofi Aventis Deutschland | Substituierte hexahydro-pyrazino(1,2-a)pyrimidin-4,7-dionderivate, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
US7390814B2 (en) * | 2003-02-13 | 2008-06-24 | Sanofi-Aventis Deutschland Gmbh | Substituted hexahydropyrazino [1,2-a] pyrimidine-4,7-dione derivatives, process for their preparation and their use as medicaments |
KR20050100686A (ko) * | 2003-02-13 | 2005-10-19 | 사노피-아벤티스 도이칠란트 게엠베하 | 질소-치환된헥사하이드로피라지노[1,2-a]피리미딘-4,7-디온 유도체,이의 제조방법 및 의약으로서의 이의 용도 |
US7652007B2 (en) | 2003-02-13 | 2010-01-26 | Sanofi-Aventis Deutschland Gmbh | Nitrogen-substituted hexahydropyrazino[1,2-A]pyrimidine-4,7-dione derivatives, processes for their preparation and their use as medicaments |
US7476653B2 (en) | 2003-06-18 | 2009-01-13 | Tranzyme Pharma, Inc. | Macrocyclic modulators of the ghrelin receptor |
MXPA06000852A (es) * | 2003-07-24 | 2006-03-30 | Smithkline Beecham Corp | Peliculas que se disuelven oralmente. |
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