OA10702A - Growth-hormone secretagogues. - Google Patents

Growth-hormone secretagogues. Download PDF

Info

Publication number: OA10702A
Authority: OA; OAPI
Prior art keywords: alkyl; oxo; phenyl; compound; optionally substituted
Prior art date: 1995-12-28

Application number

OA9800090A

Other languages

English (en)

Inventor

Philip A Carpino

Jardine Paul A Dasilva

Bruce A Lefker

John A Ragan

Original Assignee

Pfizer

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1995-12-28

Filing date

1998-06-19

Publication date

2001-05-07

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=21737850&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=OA10702(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1998-06-19 Application filed by Pfizer filed Critical Pfizer

2001-05-07 Publication of OA10702A publication Critical patent/OA10702A/en

Links

239000003324 growth hormone secretagogue Substances 0.000 title abstract description 9
150000001875 compounds Chemical class 0.000 claims abstract description 385
-1 bisphosphonate compound Chemical class 0.000 claims abstract description 129
102000018997 Growth Hormone Human genes 0.000 claims abstract description 80
108010051696 Growth Hormone Proteins 0.000 claims abstract description 80
239000000122 growth hormone Substances 0.000 claims abstract description 80
238000011282 treatment Methods 0.000 claims abstract description 54
208000001132 Osteoporosis Diseases 0.000 claims abstract description 30
241001465754 Metazoa Species 0.000 claims abstract description 29
229940011871 estrogen Drugs 0.000 claims abstract description 19
239000000262 estrogen Substances 0.000 claims abstract description 19
239000000556 agonist Substances 0.000 claims abstract description 17
239000005557 antagonist Substances 0.000 claims abstract description 13
229940122361 Bisphosphonate Drugs 0.000 claims abstract description 9
108090000723 Insulin-Like Growth Factor I Proteins 0.000 claims abstract description 9
102000004218 Insulin-Like Growth Factor I Human genes 0.000 claims abstract description 8
101710142969 Somatoliberin Proteins 0.000 claims abstract description 8
102000004169 proteins and genes Human genes 0.000 claims abstract description 8
108090000623 proteins and genes Proteins 0.000 claims abstract description 8
238000011084 recovery Methods 0.000 claims abstract description 8
150000003839 salts Chemical class 0.000 claims abstract description 8
239000000095 Growth Hormone-Releasing Hormone Substances 0.000 claims abstract description 7
206010019280 Heart failures Diseases 0.000 claims abstract description 7
210000003205 muscle Anatomy 0.000 claims abstract description 7
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
208000010392 Bone Fractures Diseases 0.000 claims abstract description 6
230000032683 aging Effects 0.000 claims abstract description 6
230000008439 repair process Effects 0.000 claims abstract description 6
238000001356 surgical procedure Methods 0.000 claims abstract description 6
230000013632 homeostatic process Effects 0.000 claims abstract description 5
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 abstract description 4
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 abstract 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 abstract description 4
206010006895 Cachexia Diseases 0.000 claims abstract description 4
108090001117 Insulin-Like Growth Factor II Proteins 0.000 claims abstract description 4
102000048143 Insulin-Like Growth Factor II Human genes 0.000 claims abstract description 4
208000008589 Obesity Diseases 0.000 claims abstract description 4
108010083553 alanyl-histidyl-(2-naphthyl)alanyl-tryptophyl-phenylalanyl-lysinamide Proteins 0.000 claims abstract description 4
229940062527 alendronate Drugs 0.000 claims abstract description 4
108010015153 growth hormone releasing hexapeptide Proteins 0.000 claims abstract description 4
238000012423 maintenance Methods 0.000 claims abstract description 4
230000002503 metabolic effect Effects 0.000 claims abstract description 4
235000020824 obesity Nutrition 0.000 claims abstract description 4
230000004044 response Effects 0.000 claims abstract description 4
DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 claims abstract description 3
208000017667 Chronic Disease Diseases 0.000 claims abstract description 3
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 abstract description 3
229940063238 premarin Drugs 0.000 claims abstract description 3
102000038461 Growth Hormone-Releasing Hormone Human genes 0.000 claims abstract 4
239000000203 mixture Substances 0.000 claims description 243
125000000217 alkyl group Chemical group 0.000 claims description 206
239000001257 hydrogen Substances 0.000 claims description 157
229910052739 hydrogen Inorganic materials 0.000 claims description 157
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 112
239000000460 chlorine Substances 0.000 claims description 111
238000000034 method Methods 0.000 claims description 104
229920006395 saturated elastomer Polymers 0.000 claims description 99
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 89
125000001424 substituent group Chemical group 0.000 claims description 80
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 76
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 73
229910052757 nitrogen Inorganic materials 0.000 claims description 66
229910052760 oxygen Inorganic materials 0.000 claims description 62
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 62
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 59
229940047889 isobutyramide Drugs 0.000 claims description 57
229910052731 fluorine Inorganic materials 0.000 claims description 52
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 50
229910052801 chlorine Inorganic materials 0.000 claims description 48
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 46
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 45
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 42
239000001301 oxygen Substances 0.000 claims description 42
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 38
229910052717 sulfur Inorganic materials 0.000 claims description 38
239000011593 sulfur Substances 0.000 claims description 38
150000002431 hydrogen Chemical class 0.000 claims description 36
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 35
150000002148 esters Chemical class 0.000 claims description 32
125000005842 heteroatom Chemical group 0.000 claims description 30
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 29
229910052736 halogen Inorganic materials 0.000 claims description 29
150000002367 halogens Chemical class 0.000 claims description 29
229910052799 carbon Inorganic materials 0.000 claims description 27
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 24
125000001153 fluoro group Chemical group F* 0.000 claims description 23
125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims description 22
150000001721 carbon Chemical group 0.000 claims description 21
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 21
125000003545 alkoxy group Chemical group 0.000 claims description 20
125000000335 thiazolyl group Chemical group 0.000 claims description 19
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 18
125000002883 imidazolyl group Chemical group 0.000 claims description 18
125000004429 atom Chemical group 0.000 claims description 16
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 16
230000012010 growth Effects 0.000 claims description 16
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 16
125000000753 cycloalkyl group Chemical group 0.000 claims description 15
125000003118 aryl group Chemical group 0.000 claims description 14
230000003287 optical effect Effects 0.000 claims description 14
230000001737 promoting effect Effects 0.000 claims description 13
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 13
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 12
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 12
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
229910052794 bromium Inorganic materials 0.000 claims description 9
125000004432 carbon atom Chemical group C* 0.000 claims description 9
125000004093 cyano group Chemical group *C#N 0.000 claims description 9
201000010099 disease Diseases 0.000 claims description 9
229940088597 hormone Drugs 0.000 claims description 9
239000005556 hormone Substances 0.000 claims description 9
125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
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 8
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
125000002541 furyl group Chemical group 0.000 claims description 8
229910052740 iodine Inorganic materials 0.000 claims description 8
239000000651 prodrug Substances 0.000 claims description 8
229940002612 prodrug Drugs 0.000 claims description 8
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
125000004076 pyridyl group Chemical group 0.000 claims description 7
125000001544 thienyl group Chemical group 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
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 6
125000006709 (C5-C7) cycloalkenyl group Chemical group 0.000 claims description 6
125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 claims description 6
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
230000000580 secretagogue effect Effects 0.000 claims description 6
LJCZNYWLQZZIOS-UHFFFAOYSA-N 2,2,2-trichlorethoxycarbonyl chloride Chemical compound ClC(=O)OCC(Cl)(Cl)Cl LJCZNYWLQZZIOS-UHFFFAOYSA-N 0.000 claims description 5
125000004423 acyloxy group Chemical group 0.000 claims description 5
125000005907 alkyl ester group Chemical group 0.000 claims description 5
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 5
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 5
125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims description 4
125000001309 chloro group Chemical group Cl* 0.000 claims description 4
230000007812 deficiency Effects 0.000 claims description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 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
229960001603 tamoxifen Drugs 0.000 claims description 4
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 claims description 3
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 3
JJKOTMDDZAJTGQ-DQSJHHFOSA-N Idoxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN2CCCC2)=CC=1)/C1=CC=C(I)C=C1 JJKOTMDDZAJTGQ-DQSJHHFOSA-N 0.000 claims description 3
241000124008 Mammalia Species 0.000 claims description 3
125000001891 dimethoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
229950004203 droloxifene Drugs 0.000 claims description 3
125000005059 halophenyl group Chemical group 0.000 claims description 3
229940015872 ibandronate Drugs 0.000 claims description 3
229950002248 idoxifene Drugs 0.000 claims description 3
WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical compound CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 claims description 3
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
206010011416 Croup infectious Diseases 0.000 claims description 2
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 2
241001296405 Tiso Species 0.000 claims description 2
125000005037 alkyl phenyl group Chemical group 0.000 claims description 2
201000010549 croup Diseases 0.000 claims description 2
125000001041 indolyl group Chemical group 0.000 claims description 2
208000019116 sleep disease Diseases 0.000 claims description 2
SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 59
LHHCSNFAOIFYRV-DOVBMPENSA-N boceprevir Chemical compound O=C([C@@H]1[C@@H]2[C@@H](C2(C)C)CN1C(=O)[C@@H](NC(=O)NC(C)(C)C)C(C)(C)C)NC(C(=O)C(N)=O)CC1CCC1 LHHCSNFAOIFYRV-DOVBMPENSA-N 0.000 claims 6
125000004122 cyclic group Chemical group 0.000 claims 4
FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 claims 3
229910006080 SO2X Inorganic materials 0.000 claims 2
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 2
229940099990 ogen Drugs 0.000 claims 2
229940080818 propionamide Drugs 0.000 claims 2
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
208000027418 Wounds and injury Diseases 0.000 claims 1
125000002619 bicyclic group Chemical group 0.000 claims 1
125000000392 cycloalkenyl group Chemical group 0.000 claims 1
FKOGOYQRCDITFG-XJQHNOHDSA-N n-[(2r)-1-(3a-benzyl-3-oxo-2,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl)-1-oxo-3-phenylmethoxypropan-2-yl]-2-amino-2-methylpropanamide Chemical compound C([C@@H](NC(=O)C(C)(N)C)C(=O)N1CC2(CC=3C=CC=CC=3)C(=O)NN=C2CC1)OCC1=CC=CC=C1 FKOGOYQRCDITFG-XJQHNOHDSA-N 0.000 claims 1
208000020685 sleep-wake disease Diseases 0.000 claims 1
239000000543 intermediate Substances 0.000 abstract description 16
238000004519 manufacturing process Methods 0.000 abstract description 6
230000029663 wound healing Effects 0.000 abstract description 5
206010007559 Cardiac failure congestive Diseases 0.000 abstract 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 abstract description 3
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 abstract description 3
102100033367 Appetite-regulating hormone Human genes 0.000 abstract description 3
208000036119 Frailty Diseases 0.000 abstract description 3
206010003549 asthenia Diseases 0.000 abstract description 3
230000001925 catabolic effect Effects 0.000 abstract description 3
108010070965 hexarelin Proteins 0.000 abstract description 3
101710111255 Appetite-regulating hormone Proteins 0.000 abstract description 2
102000055006 Calcitonin Human genes 0.000 abstract description 2
108060001064 Calcitonin Proteins 0.000 abstract description 2
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 abstract description 2
229960004015 calcitonin Drugs 0.000 abstract description 2
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 abstract 2
230000002265 prevention Effects 0.000 abstract 1
239000000186 progesterone Substances 0.000 abstract 1
229960003387 progesterone Drugs 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 238
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 136
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 133
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 91
235000019439 ethyl acetate Nutrition 0.000 description 80
229940093499 ethyl acetate Drugs 0.000 description 78
229910000069 nitrogen hydride Inorganic materials 0.000 description 67
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 66
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 54
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 52
239000002253 acid Substances 0.000 description 50
239000000243 solution Substances 0.000 description 46
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
238000005160 1H NMR spectroscopy Methods 0.000 description 36
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
238000010992 reflux Methods 0.000 description 32
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
239000007787 solid Substances 0.000 description 30
239000012267 brine Substances 0.000 description 29
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 29
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 28
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
238000010898 silica gel chromatography Methods 0.000 description 26
238000010511 deprotection reaction Methods 0.000 description 23
230000036961 partial effect Effects 0.000 description 23
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 21
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
238000006243 chemical reaction Methods 0.000 description 21
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 17
238000010828 elution Methods 0.000 description 17
WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 17
COLOHWPRNRVWPI-UHFFFAOYSA-N 1,1,1-trifluoroethane Chemical compound [CH2]C(F)(F)F COLOHWPRNRVWPI-UHFFFAOYSA-N 0.000 description 16
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
239000002585 base Substances 0.000 description 16
239000003921 oil Substances 0.000 description 16
235000019198 oils Nutrition 0.000 description 16
239000002904 solvent Substances 0.000 description 16
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
150000001412 amines Chemical class 0.000 description 15
229910052943 magnesium sulfate Inorganic materials 0.000 description 15
235000019341 magnesium sulphate Nutrition 0.000 description 15
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
239000003795 chemical substances by application Substances 0.000 description 13
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
235000001014 amino acid Nutrition 0.000 description 12
150000001413 amino acids Chemical class 0.000 description 12
238000005859 coupling reaction Methods 0.000 description 12
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
229910000104 sodium hydride Inorganic materials 0.000 description 12
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 11
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
230000008878 coupling Effects 0.000 description 11
238000010168 coupling process Methods 0.000 description 11
230000000694 effects Effects 0.000 description 11
239000011541 reaction mixture Substances 0.000 description 11
239000012312 sodium hydride Substances 0.000 description 11
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
239000000284 extract Substances 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
239000000047 product Substances 0.000 description 9
125000006239 protecting group Chemical group 0.000 description 9
230000004936 stimulating effect Effects 0.000 description 9
238000012360 testing method Methods 0.000 description 8
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 7
239000011734 sodium Substances 0.000 description 7
229910052708 sodium Inorganic materials 0.000 description 7
239000007832 Na2SO4 Substances 0.000 description 6
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
150000001350 alkyl halides Chemical class 0.000 description 6
238000003556 assay Methods 0.000 description 6
150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
239000003054 catalyst Substances 0.000 description 6
210000004027 cell Anatomy 0.000 description 6
239000003814 drug Substances 0.000 description 6
239000012442 inert solvent Substances 0.000 description 6
239000004533 oil dispersion Substances 0.000 description 6
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 6
229910000027 potassium carbonate Inorganic materials 0.000 description 6
229940093956 potassium carbonate Drugs 0.000 description 6
235000011181 potassium carbonates Nutrition 0.000 description 6
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
150000003141 primary amines Chemical class 0.000 description 6
235000017557 sodium bicarbonate Nutrition 0.000 description 6
229960001407 sodium bicarbonate Drugs 0.000 description 6
229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
229910052938 sodium sulfate Inorganic materials 0.000 description 6
235000011152 sodium sulphate Nutrition 0.000 description 6
238000003756 stirring Methods 0.000 description 6
241000283690 Bos taurus Species 0.000 description 5
241000282465 Canis Species 0.000 description 5
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
238000005481 NMR spectroscopy Methods 0.000 description 5
230000029936 alkylation Effects 0.000 description 5
238000005804 alkylation reaction Methods 0.000 description 5
150000004663 bisphosphonates Chemical class 0.000 description 5
210000000988 bone and bone Anatomy 0.000 description 5
239000002552 dosage form Substances 0.000 description 5
238000005227 gel permeation chromatography Methods 0.000 description 5
238000002347 injection Methods 0.000 description 5
239000007924 injection Substances 0.000 description 5
HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 5
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 5
235000018102 proteins Nutrition 0.000 description 5
239000003586 protic polar solvent Substances 0.000 description 5
230000002829 reductive effect Effects 0.000 description 5
239000000377 silicon dioxide Substances 0.000 description 5
239000000126 substance Substances 0.000 description 5
210000001519 tissue Anatomy 0.000 description 5
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
241000282412 Homo Species 0.000 description 4
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
102100022831 Somatoliberin Human genes 0.000 description 4
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
239000008280 blood Substances 0.000 description 4
210000004369 blood Anatomy 0.000 description 4
230000003197 catalytic effect Effects 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
229940079593 drug Drugs 0.000 description 4
150000002081 enamines Chemical class 0.000 description 4
102000015694 estrogen receptors Human genes 0.000 description 4
108010038795 estrogen receptors Proteins 0.000 description 4
238000001727 in vivo Methods 0.000 description 4
GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium;hydroxide;hydrate Chemical compound [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 4
239000002609 medium Substances 0.000 description 4
229910052763 palladium Inorganic materials 0.000 description 4
239000002245 particle Substances 0.000 description 4
230000001817 pituitary effect Effects 0.000 description 4
230000008569 process Effects 0.000 description 4
102000004196 processed proteins & peptides Human genes 0.000 description 4
108090000765 processed proteins & peptides Proteins 0.000 description 4
230000003578 releasing effect Effects 0.000 description 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
229960001866 silicon dioxide Drugs 0.000 description 4
239000000725 suspension Substances 0.000 description 4
FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 4
FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 3
YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 3
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 3
241000282693 Cercopithecidae Species 0.000 description 3
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
108010016626 Dipeptides Proteins 0.000 description 3
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 3
206010028980 Neoplasm Diseases 0.000 description 3
108090000445 Parathyroid hormone Proteins 0.000 description 3
239000002202 Polyethylene glycol Substances 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
241000700159 Rattus Species 0.000 description 3
101000868151 Rattus norvegicus Somatotropin Proteins 0.000 description 3
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
238000007792 addition Methods 0.000 description 3
239000003263 anabolic agent Substances 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
230000037396 body weight Effects 0.000 description 3
201000011510 cancer Diseases 0.000 description 3
239000003638 chemical reducing agent Substances 0.000 description 3
239000012043 crude product Substances 0.000 description 3
238000002474 experimental method Methods 0.000 description 3
238000001914 filtration Methods 0.000 description 3
239000000499 gel Substances 0.000 description 3
150000004820 halides Chemical class 0.000 description 3
125000005843 halogen group Chemical group 0.000 description 3
230000007062 hydrolysis Effects 0.000 description 3
238000006460 hydrolysis reaction Methods 0.000 description 3
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
239000003701 inert diluent Substances 0.000 description 3
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
238000001819 mass spectrum Methods 0.000 description 3
230000004060 metabolic process Effects 0.000 description 3
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 3
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 3
239000006187 pill Substances 0.000 description 3
229910052697 platinum Inorganic materials 0.000 description 3
229920001223 polyethylene glycol Polymers 0.000 description 3
239000000843 powder Substances 0.000 description 3
239000001632 sodium acetate Substances 0.000 description 3
229960004249 sodium acetate Drugs 0.000 description 3
235000017281 sodium acetate Nutrition 0.000 description 3
208000011580 syndromic disease Diseases 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
239000003826 tablet Substances 0.000 description 3
238000004809 thin layer chromatography Methods 0.000 description 3
230000009466 transformation Effects 0.000 description 3
FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
RUROFEVDCUGKHD-UHFFFAOYSA-N 3-bromoprop-1-enylbenzene Chemical compound BrCC=CC1=CC=CC=C1 RUROFEVDCUGKHD-UHFFFAOYSA-N 0.000 description 2
DODQJNMQWMSYGS-QPLCGJKRSA-N 4-[(z)-1-[4-[2-(dimethylamino)ethoxy]phenyl]-1-phenylbut-1-en-2-yl]phenol Chemical compound C=1C=C(O)C=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 DODQJNMQWMSYGS-QPLCGJKRSA-N 0.000 description 2
FUSNOPLQVRUIIM-UHFFFAOYSA-N 4-amino-2-(4,4-dimethyl-2-oxoimidazolidin-1-yl)-n-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide Chemical compound O=C1NC(C)(C)CN1C(N=C1N)=NC=C1C(=O)NC1=CC=CC(C(F)(F)F)=C1 FUSNOPLQVRUIIM-UHFFFAOYSA-N 0.000 description 2
QJNLUNBGDFUULX-UHFFFAOYSA-N 4-n,4-n'-dimethyl-3h-pyridine-4,4-diamine Chemical compound CNC1(NC)CC=NC=C1 QJNLUNBGDFUULX-UHFFFAOYSA-N 0.000 description 2
208000030507 AIDS Diseases 0.000 description 2
102000009027 Albumins Human genes 0.000 description 2
108010088751 Albumins Proteins 0.000 description 2
241000282472 Canis lupus familiaris Species 0.000 description 2
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
QDHHCQZDFGDHMP-UHFFFAOYSA-N Chloramine Chemical compound ClN QDHHCQZDFGDHMP-UHFFFAOYSA-N 0.000 description 2
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
206010053759 Growth retardation Diseases 0.000 description 2
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
102100036893 Parathyroid hormone Human genes 0.000 description 2
NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
241001494479 Pecora Species 0.000 description 2
108091005804 Peptidases Proteins 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
239000004365 Protease Substances 0.000 description 2
208000020221 Short stature Diseases 0.000 description 2
102000005157 Somatostatin Human genes 0.000 description 2
108010056088 Somatostatin Proteins 0.000 description 2
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
101800004623 Thyrotropin-releasing hormone Proteins 0.000 description 2
102400000336 Thyrotropin-releasing hormone Human genes 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 2
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
230000009471 action Effects 0.000 description 2
239000002671 adjuvant Substances 0.000 description 2
125000005206 alkoxycarbonyloxymethyl group Chemical group 0.000 description 2
229940124325 anabolic agent Drugs 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
230000008901 benefit Effects 0.000 description 2
MSJHOJKVMMEMNX-UHFFFAOYSA-N benzylhydrazine;hydron;dichloride Chemical compound Cl.Cl.NNCC1=CC=CC=C1 MSJHOJKVMMEMNX-UHFFFAOYSA-N 0.000 description 2
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
239000002775 capsule Substances 0.000 description 2
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
238000005119 centrifugation Methods 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
230000001684 chronic effect Effects 0.000 description 2
239000012230 colorless oil Substances 0.000 description 2
238000002648 combination therapy Methods 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
230000003247 decreasing effect Effects 0.000 description 2
235000014113 dietary fatty acids Nutrition 0.000 description 2
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
208000035475 disorder Diseases 0.000 description 2
239000006185 dispersion Substances 0.000 description 2
238000004090 dissolution Methods 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
238000009547 dual-energy X-ray absorptiometry Methods 0.000 description 2
230000001804 emulsifying effect Effects 0.000 description 2
125000004494 ethyl ester group Chemical group 0.000 description 2
239000000194 fatty acid Substances 0.000 description 2
229930195729 fatty acid Natural products 0.000 description 2
150000004665 fatty acids Chemical class 0.000 description 2
238000003818 flash chromatography Methods 0.000 description 2
239000006260 foam Substances 0.000 description 2
239000008103 glucose Substances 0.000 description 2
235000001727 glucose Nutrition 0.000 description 2
239000001963 growth medium Substances 0.000 description 2
231100000001 growth retardation Toxicity 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
239000012493 hydrazine sulfate Substances 0.000 description 2
229910000377 hydrazine sulfate Inorganic materials 0.000 description 2
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
239000012948 isocyanate Substances 0.000 description 2
150000002513 isocyanates Chemical class 0.000 description 2
150000002576 ketones Chemical class 0.000 description 2
239000010410 layer Substances 0.000 description 2
229910052744 lithium Inorganic materials 0.000 description 2
238000004949 mass spectrometry Methods 0.000 description 2
239000002808 molecular sieve Substances 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
230000003647 oxidation Effects 0.000 description 2
238000007254 oxidation reaction Methods 0.000 description 2
PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 2
125000001151 peptidyl group Chemical group 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
229910000073 phosphorus hydride Inorganic materials 0.000 description 2
230000004962 physiological condition Effects 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
238000000746 purification Methods 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
150000003235 pyrrolidines Chemical class 0.000 description 2
239000000700 radioactive tracer Substances 0.000 description 2
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
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 description 2
229960000553 somatostatin Drugs 0.000 description 2
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
229940124597 therapeutic agent Drugs 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
238000001665 trituration Methods 0.000 description 2
210000003462 vein Anatomy 0.000 description 2
IDGQXGPQOGUGIX-SECBINFHSA-N (2r)-2-amino-3-phenylmethoxypropanoic acid Chemical compound OC(=O)[C@H](N)COCC1=CC=CC=C1 IDGQXGPQOGUGIX-SECBINFHSA-N 0.000 description 1
FHOAKXBXYSJBGX-RXMQYKEDSA-N (2r)-3-hydroxy-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](CO)C(O)=O FHOAKXBXYSJBGX-RXMQYKEDSA-N 0.000 description 1
HRNLPPBUBKMZMT-SSSXJSFTSA-N (2s)-6-amino-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-[[(2r)-2-aminopropanoyl]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](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](C)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(=O)[C@H](N)C)C(=O)N[C@@H](CCCCN)C(N)=O)C1=CC=CC=C1 HRNLPPBUBKMZMT-SSSXJSFTSA-N 0.000 description 1
STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 description 1
KNKOUDKOHSNMEL-UHFFFAOYSA-N (7-oxo-5,6-dihydro-4h-1-benzothiophen-4-yl)urea Chemical compound NC(=O)NC1CCC(=O)C2=C1C=CS2 KNKOUDKOHSNMEL-UHFFFAOYSA-N 0.000 description 1
125000002861 (C1-C4) alkanoyl group Chemical group 0.000 description 1
YFWHNAWEOZTIPI-DIPNUNPCSA-N 1,2-dioctadecanoyl-sn-glycerol-3-phosphate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCCCCCC YFWHNAWEOZTIPI-DIPNUNPCSA-N 0.000 description 1
OHVLMTFVQDZYHP-UHFFFAOYSA-N 1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-2-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound N1N=NC=2CN(CCC=21)C(CN1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)=O OHVLMTFVQDZYHP-UHFFFAOYSA-N 0.000 description 1
125000005846 1-(alkanoyloxy)ethyl group Chemical group 0.000 description 1
BLRHMMGNCXNXJL-UHFFFAOYSA-N 1-methylindole Chemical compound C1=CC=C2N(C)C=CC2=C1 BLRHMMGNCXNXJL-UHFFFAOYSA-N 0.000 description 1
ABBVAMUCDQETDO-UHFFFAOYSA-N 1-o-tert-butyl 3-o-ethyl 4-oxopiperidine-1,3-dicarboxylate Chemical compound CCOC(=O)C1CN(C(=O)OC(C)(C)C)CCC1=O ABBVAMUCDQETDO-UHFFFAOYSA-N 0.000 description 1
HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
OVSKIKFHRZPJSS-UHFFFAOYSA-N 2,4-D Chemical compound OC(=O)COC1=CC=C(Cl)C=C1Cl OVSKIKFHRZPJSS-UHFFFAOYSA-N 0.000 description 1
125000003870 2-(1-piperidinyl)ethoxy group Chemical group [*]OC([H])([H])C([H])([H])N1C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
NJWIMFZLESWFIM-UHFFFAOYSA-N 2-(chloromethyl)pyridine Chemical compound ClCC1=CC=CC=N1 NJWIMFZLESWFIM-UHFFFAOYSA-N 0.000 description 1
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
SNDPXSYFESPGGJ-UHFFFAOYSA-N 2-aminopentanoic acid Chemical compound CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
LGCYVLDNGBSOOW-UHFFFAOYSA-N 2H-benzotriazol-4-ol 1-hydroxybenzotriazole Chemical compound OC1=CC=CC2=C1N=NN2.C1=CC=C2N(O)N=NC2=C1 LGCYVLDNGBSOOW-UHFFFAOYSA-N 0.000 description 1
MTJGVAJYTOXFJH-UHFFFAOYSA-N 3-aminonaphthalene-1,5-disulfonic acid Chemical compound C1=CC=C(S(O)(=O)=O)C2=CC(N)=CC(S(O)(=O)=O)=C21 MTJGVAJYTOXFJH-UHFFFAOYSA-N 0.000 description 1
RRRCPCOJPQLWEP-UHFFFAOYSA-N 3-hydroxytriazolo[4,5-b]pyridine Chemical compound C1=CN=C2N(O)N=NC2=C1.C1=CN=C2N(O)N=NC2=C1 RRRCPCOJPQLWEP-UHFFFAOYSA-N 0.000 description 1
NKBCECULIDNNNY-MRXNPFEDSA-N 3-o-tert-butyl 1-o-methyl (2r)-2-amino-2-(phenylmethoxymethyl)propanedioate Chemical compound CC(C)(C)OC(=O)[C@](N)(C(=O)OC)COCC1=CC=CC=C1 NKBCECULIDNNNY-MRXNPFEDSA-N 0.000 description 1
WVTNKCOAFNRABI-UHFFFAOYSA-N 4-oxopiperidin-1-ium-3-carboxylate Chemical class OC(=O)C1CNCCC1=O WVTNKCOAFNRABI-UHFFFAOYSA-N 0.000 description 1
CLPAHLNMHOOBCY-UHFFFAOYSA-N 4-oxopiperidine-1,3-dicarboxylic acid Chemical compound OC(=O)C1CN(C(O)=O)CCC1=O CLPAHLNMHOOBCY-UHFFFAOYSA-N 0.000 description 1
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
DEXFNLNNUZKHNO-UHFFFAOYSA-N 6-[3-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperidin-1-yl]-3-oxopropyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1CCN(CC1)C(CCC1=CC2=C(NC(O2)=O)C=C1)=O DEXFNLNNUZKHNO-UHFFFAOYSA-N 0.000 description 1
UFKFOPFCKFMKTH-UHFFFAOYSA-N 6-oxo-1-phenylcyclohexane-1,3-dicarboxylic acid Chemical compound C1C(C(=O)O)CCC(=O)C1(C(O)=O)C1=CC=CC=C1 UFKFOPFCKFMKTH-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
206010002027 Amyotrophy Diseases 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
125000006847 BOC protecting group Chemical group 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
101100001686 Burkholderia cepacia andR gene Proteins 0.000 description 1
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
241000283707 Capra Species 0.000 description 1
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
238000006969 Curtius rearrangement reaction Methods 0.000 description 1
XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
150000008574 D-amino acids Chemical class 0.000 description 1
229930182827 D-tryptophan Natural products 0.000 description 1
QIVBCDIJIAJPQS-SECBINFHSA-N D-tryptophane Chemical compound C1=CC=C2C(C[C@@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-SECBINFHSA-N 0.000 description 1
208000016192 Demyelinating disease Diseases 0.000 description 1
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
101100440789 Dictyostelium discoideum cxfA gene Proteins 0.000 description 1
XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 1
206010013883 Dwarfism Diseases 0.000 description 1
241000283086 Equidae Species 0.000 description 1
IYXGSMUGOJNHAZ-UHFFFAOYSA-N Ethyl malonate Chemical compound CCOC(=O)CC(=O)OCC IYXGSMUGOJNHAZ-UHFFFAOYSA-N 0.000 description 1
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 1
208000001362 Fetal Growth Retardation Diseases 0.000 description 1
206010070531 Foetal growth restriction Diseases 0.000 description 1
241000287828 Gallus gallus Species 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
229930182566 Gentamicin Natural products 0.000 description 1
102000051325 Glucagon Human genes 0.000 description 1
108060003199 Glucagon Proteins 0.000 description 1
208000015752 Growth delay due to insulin-like growth factor type 1 deficiency Diseases 0.000 description 1
101710119601 Growth hormone-releasing peptides Proteins 0.000 description 1
HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
102000002265 Human Growth Hormone Human genes 0.000 description 1
108010000521 Human Growth Hormone Proteins 0.000 description 1
239000000854 Human Growth Hormone Substances 0.000 description 1
206010062767 Hypophysitis Diseases 0.000 description 1
108090001061 Insulin Proteins 0.000 description 1
102000004877 Insulin Human genes 0.000 description 1
108700038030 Insulin-Like Growth Factor I Deficiency Proteins 0.000 description 1
239000005909 Kieselgur Substances 0.000 description 1
WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 1
WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
150000008575 L-amino acids Chemical class 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
208000004155 Malabsorption Syndromes Diseases 0.000 description 1
238000006683 Mannich reaction Methods 0.000 description 1
208000029725 Metabolic bone disease Diseases 0.000 description 1
CMFDKVQQVCBZTI-DDAUYOFQSA-N N-[(2R)-1-(3a-benzyl-2-ethyl-3-oxo-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-5-yl)-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-2-amino-2-methylpropanamide Chemical compound O=C1N(CC)N=C2CCN(C(=O)[C@@H](CC=3C4=CC=CC=C4NC=3)NC(=O)C(C)(C)N)CC21CC1=CC=CC=C1 CMFDKVQQVCBZTI-DDAUYOFQSA-N 0.000 description 1
208000012902 Nervous system disease Diseases 0.000 description 1
208000000713 Nesidioblastosis Diseases 0.000 description 1
208000025966 Neurological disease Diseases 0.000 description 1
101100258328 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) crc-2 gene Proteins 0.000 description 1
206010029748 Noonan syndrome Diseases 0.000 description 1
UQONAEXHTGDOIH-AWEZNQCLSA-N O=C(N1CC[C@@H](C1)N1CCCC1=O)C1=CC2=C(NC3(CC3)CCO2)N=C1 Chemical compound O=C(N1CC[C@@H](C1)N1CCCC1=O)C1=CC2=C(NC3(CC3)CCO2)N=C1 UQONAEXHTGDOIH-AWEZNQCLSA-N 0.000 description 1
235000019502 Orange oil Nutrition 0.000 description 1
102000003982 Parathyroid hormone Human genes 0.000 description 1
229910002666 PdCl2 Inorganic materials 0.000 description 1
102000035195 Peptidases Human genes 0.000 description 1
241000286209 Phasianidae Species 0.000 description 1
PIJVFDBKTWXHHD-UHFFFAOYSA-N Physostigmine Natural products C12=CC(OC(=O)NC)=CC=C2N(C)C2C1(C)CCN2C PIJVFDBKTWXHHD-UHFFFAOYSA-N 0.000 description 1
240000007320 Pinus strobus Species 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
201000010769 Prader-Willi syndrome Diseases 0.000 description 1
RVOLLAQWKVFTGE-UHFFFAOYSA-N Pyridostigmine Chemical compound CN(C)C(=O)OC1=CC=C[N+](C)=C1 RVOLLAQWKVFTGE-UHFFFAOYSA-N 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
241000700157 Rattus norvegicus Species 0.000 description 1
102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
IIDJRNMFWXDHID-UHFFFAOYSA-N Risedronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CC1=CC=CN=C1 IIDJRNMFWXDHID-UHFFFAOYSA-N 0.000 description 1
208000034189 Sclerosis Diseases 0.000 description 1
206010072610 Skeletal dysplasia Diseases 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
102000013275 Somatomedins Human genes 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
208000007107 Stomach Ulcer Diseases 0.000 description 1
208000006011 Stroke Diseases 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
241000282887 Suidae Species 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
101000783611 Takifugu rubripes 5-hydroxytryptamine receptor 1D Proteins 0.000 description 1
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
DKJJVAGXPKPDRL-UHFFFAOYSA-N Tiludronic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)SC1=CC=C(Cl)C=C1 DKJJVAGXPKPDRL-UHFFFAOYSA-N 0.000 description 1
241000863032 Trieres Species 0.000 description 1
OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
GXBMIBRIOWHPDT-UHFFFAOYSA-N Vasopressin Natural products N1C(=O)C(CC=2C=C(O)C=CC=2)NC(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C1CC1=CC=CC=C1 GXBMIBRIOWHPDT-UHFFFAOYSA-N 0.000 description 1
108010004977 Vasopressins Proteins 0.000 description 1
102000002852 Vasopressins Human genes 0.000 description 1
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
150000001241 acetals Chemical class 0.000 description 1
KQNKJJBFUFKYFX-UHFFFAOYSA-N acetic acid;trihydrate Chemical compound O.O.O.CC(O)=O KQNKJJBFUFKYFX-UHFFFAOYSA-N 0.000 description 1
238000005903 acid hydrolysis reaction Methods 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
239000013543 active substance Substances 0.000 description 1
238000011360 adjunctive therapy Methods 0.000 description 1
238000009098 adjuvant therapy Methods 0.000 description 1
239000000048 adrenergic agonist Substances 0.000 description 1
229940116024 aftera Drugs 0.000 description 1
150000001336 alkenes Chemical class 0.000 description 1
125000005194 alkoxycarbonyloxy group Chemical group 0.000 description 1
125000003282 alkyl amino group Chemical group 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
125000002947 alkylene group Chemical group 0.000 description 1
BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
125000000746 allylic group Chemical group 0.000 description 1
125000005336 allyloxy group Chemical group 0.000 description 1
FPQFYIAXQDXNOR-QDKLYSGJSA-N alpha-Zearalenol Chemical compound O=C1O[C@@H](C)CCC[C@H](O)CCC\C=C\C2=CC(O)=CC(O)=C21 FPQFYIAXQDXNOR-QDKLYSGJSA-N 0.000 description 1
125000000266 alpha-aminoacyl group Chemical group 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
239000000908 ammonium hydroxide Substances 0.000 description 1
230000001195 anabolic effect Effects 0.000 description 1
229940070021 anabolic steroids Drugs 0.000 description 1
230000003444 anaesthetic effect Effects 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
230000000123 anti-resoprtive effect Effects 0.000 description 1
230000005875 antibody response Effects 0.000 description 1
239000000427 antigen Substances 0.000 description 1
102000036639 antigens Human genes 0.000 description 1
108091007433 antigens Proteins 0.000 description 1
239000000010 aprotic solvent Substances 0.000 description 1
238000009360 aquaculture Methods 0.000 description 1
244000144974 aquaculture Species 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 description 1
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
229940125388 beta agonist Drugs 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
230000003115 biocidal effect Effects 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
230000037182 bone density Effects 0.000 description 1
230000008416 bone turnover Effects 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
125000001589 carboacyl group Chemical group 0.000 description 1
230000025938 carbohydrate utilization Effects 0.000 description 1
235000014633 carbohydrates Nutrition 0.000 description 1
150000001720 carbohydrates Chemical class 0.000 description 1
150000007942 carboxylates Chemical class 0.000 description 1
210000000845 cartilage Anatomy 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
238000000451 chemical ionisation Methods 0.000 description 1
235000013330 chicken meat Nutrition 0.000 description 1
ACSIXWWBWUQEHA-UHFFFAOYSA-N clodronic acid Chemical compound OP(O)(=O)C(Cl)(Cl)P(O)(O)=O ACSIXWWBWUQEHA-UHFFFAOYSA-N 0.000 description 1
229960002286 clodronic acid Drugs 0.000 description 1
229910052681 coesite Inorganic materials 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
229940125878 compound 36 Drugs 0.000 description 1
229940125898 compound 5 Drugs 0.000 description 1
238000001816 cooling Methods 0.000 description 1
239000002285 corn oil Substances 0.000 description 1
235000005687 corn oil Nutrition 0.000 description 1
239000007822 coupling agent Substances 0.000 description 1
239000007819 coupling partner Substances 0.000 description 1
101150061265 cox6 gene Proteins 0.000 description 1
229910052906 cristobalite Inorganic materials 0.000 description 1
PYRZPBDTPRQYKG-UHFFFAOYSA-N cyclopentene-1-carboxylic acid Chemical compound OC(=O)C1=CCCC1 PYRZPBDTPRQYKG-UHFFFAOYSA-N 0.000 description 1
235000013365 dairy product Nutrition 0.000 description 1
230000007547 defect Effects 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
230000018109 developmental process Effects 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000037213 diet Effects 0.000 description 1
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
150000002009 diols Chemical class 0.000 description 1
HWMTUNCVVYPZHZ-UHFFFAOYSA-N diphenylmercury Chemical compound C=1C=CC=CC=1[Hg]C1=CC=CC=C1 HWMTUNCVVYPZHZ-UHFFFAOYSA-N 0.000 description 1
JFGHPLSPUGOSLV-UHFFFAOYSA-L disodium;[3-(dimethylamino)-1-hydroxy-1-[hydroxy(oxido)phosphoryl]propyl]-hydroxyphosphinate Chemical compound [Na+].[Na+].CN(C)CCC(O)(P(O)(O)=O)P([O-])([O-])=O JFGHPLSPUGOSLV-UHFFFAOYSA-L 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
VHJLVAABSRFDPM-ZXZARUISSA-N dithioerythritol Chemical compound SC[C@H](O)[C@H](O)CS VHJLVAABSRFDPM-ZXZARUISSA-N 0.000 description 1
VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
208000000718 duodenal ulcer Diseases 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
239000003797 essential amino acid Substances 0.000 description 1
235000020776 essential amino acid Nutrition 0.000 description 1
239000000328 estrogen antagonist Substances 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
RTYXWLMQWSFXNI-UHFFFAOYSA-N ethyl 4-oxopiperidin-1-ium-3-carboxylate;chloride Chemical compound Cl.CCOC(=O)C1CNCCC1=O RTYXWLMQWSFXNI-UHFFFAOYSA-N 0.000 description 1
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
PHTXVQQRWJXYPP-UHFFFAOYSA-N ethyltrifluoromethylaminoindane Chemical compound C1=C(C(F)(F)F)C=C2CC(NCC)CC2=C1 PHTXVQQRWJXYPP-UHFFFAOYSA-N 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 1
208000030941 fetal growth restriction Diseases 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000013305 food Nutrition 0.000 description 1
239000012458 free base Substances 0.000 description 1
235000021588 free fatty acids Nutrition 0.000 description 1
ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
125000005643 gamma-butyrolacton-4-yl group Chemical group 0.000 description 1
230000002496 gastric effect Effects 0.000 description 1
238000011902 gastrointestinal surgery Methods 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
210000004907 gland Anatomy 0.000 description 1
MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
229960004666 glucagon Drugs 0.000 description 1
239000003862 glucocorticoid Substances 0.000 description 1
125000003147 glycosyl group Chemical group 0.000 description 1
239000008187 granular material Substances 0.000 description 1
108010085742 growth hormone-releasing peptide-2 Proteins 0.000 description 1
230000035876 healing Effects 0.000 description 1
150000002373 hemiacetals Chemical class 0.000 description 1
229960002897 heparin Drugs 0.000 description 1
229920000669 heparin Polymers 0.000 description 1
125000006038 hexenyl group Chemical group 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
150000002429 hydrazines Chemical class 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
238000007327 hydrogenolysis reaction Methods 0.000 description 1
210000003016 hypothalamus Anatomy 0.000 description 1
150000002466 imines Chemical class 0.000 description 1
210000000987 immune system Anatomy 0.000 description 1
230000006872 improvement Effects 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
LWRDQHOZTAOILO-UHFFFAOYSA-N incadronic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)NC1CCCCCC1 LWRDQHOZTAOILO-UHFFFAOYSA-N 0.000 description 1
229950006971 incadronic acid Drugs 0.000 description 1
238000011534 incubation Methods 0.000 description 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical compound C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
229940125396 insulin Drugs 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
230000026045 iodination Effects 0.000 description 1
238000006192 iodination reaction Methods 0.000 description 1
239000011630 iodine Substances 0.000 description 1
MGFYSGNNHQQTJW-UHFFFAOYSA-N iodonium Chemical compound [IH2+] MGFYSGNNHQQTJW-UHFFFAOYSA-N 0.000 description 1
238000010849 ion bombardment Methods 0.000 description 1
150000002500 ions Chemical group 0.000 description 1
230000001678 irradiating effect Effects 0.000 description 1
125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
239000008101 lactose Substances 0.000 description 1
CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 1
ACKFDYCQCBEDNU-UHFFFAOYSA-J lead(2+);tetraacetate Chemical compound [Pb+2].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O ACKFDYCQCBEDNU-UHFFFAOYSA-J 0.000 description 1
239000007788 liquid Substances 0.000 description 1
244000144972 livestock Species 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
239000000463 material Substances 0.000 description 1
239000011159 matrix material Substances 0.000 description 1
238000005259 measurement Methods 0.000 description 1
230000005541 medical transmission Effects 0.000 description 1
230000004066 metabolic change Effects 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 1
PCLKHOKTUJSLDD-SNVBAGLBSA-N methyl (2r)-2-amino-3-phenylmethoxypropanoate Chemical compound COC(=O)[C@H](N)COCC1=CC=CC=C1 PCLKHOKTUJSLDD-SNVBAGLBSA-N 0.000 description 1
QXLOVPXUZAOKBL-CQSZACIVSA-N methyl (2r)-3-(1h-indol-3-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound C1=CC=C2C(C[C@H](C(=O)OC)NC(=O)OC(C)(C)C)=CNC2=C1 QXLOVPXUZAOKBL-CQSZACIVSA-N 0.000 description 1
YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
RIJWDPRXCXJDPK-UHFFFAOYSA-N methyl 3-cyclopropyl-3-oxopropanoate Chemical compound COC(=O)CC(=O)C1CC1 RIJWDPRXCXJDPK-UHFFFAOYSA-N 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
235000013336 milk Nutrition 0.000 description 1
239000008267 milk Substances 0.000 description 1
210000004080 milk Anatomy 0.000 description 1
PJUIMOJAAPLTRJ-UHFFFAOYSA-N monothioglycerol Chemical compound OCC(O)CS PJUIMOJAAPLTRJ-UHFFFAOYSA-N 0.000 description 1
201000006417 multiple sclerosis Diseases 0.000 description 1
210000004165 myocardium Anatomy 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
239000007922 nasal spray Substances 0.000 description 1
229940097496 nasal spray Drugs 0.000 description 1
201000001119 neuropathy Diseases 0.000 description 1
230000007823 neuropathy Effects 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
235000020925 non fasting Nutrition 0.000 description 1
239000012457 nonaqueous media Substances 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
235000016709 nutrition Nutrition 0.000 description 1
230000035764 nutrition Effects 0.000 description 1
235000003170 nutritional factors Nutrition 0.000 description 1
229960000988 nystatin Drugs 0.000 description 1
VQOXZBDYSJBXMA-NQTDYLQESA-N nystatin A1 Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/CC/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 VQOXZBDYSJBXMA-NQTDYLQESA-N 0.000 description 1
JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
230000011164 ossification Effects 0.000 description 1
210000000963 osteoblast Anatomy 0.000 description 1
229940094443 oxytocics prostaglandins Drugs 0.000 description 1
238000005949 ozonolysis reaction Methods 0.000 description 1
NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 description 1
229940046231 pamidronate Drugs 0.000 description 1
239000000199 parathyroid hormone Substances 0.000 description 1
229960001319 parathyroid hormone Drugs 0.000 description 1
239000008188 pellet Substances 0.000 description 1
WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
229960001412 pentobarbital Drugs 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
238000005897 peptide coupling reaction Methods 0.000 description 1
239000002304 perfume Substances 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
208000033808 peripheral neuropathy Diseases 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 description 1
DHRLEVQXOMLTIM-UHFFFAOYSA-N phosphoric acid;trioxomolybdenum Chemical compound O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.OP(O)(O)=O DHRLEVQXOMLTIM-UHFFFAOYSA-N 0.000 description 1
PIJVFDBKTWXHHD-HIFRSBDPSA-N physostigmine Chemical compound C12=CC(OC(=O)NC)=CC=C2N(C)[C@@H]2[C@@]1(C)CCN2C PIJVFDBKTWXHHD-HIFRSBDPSA-N 0.000 description 1
229960001697 physostigmine Drugs 0.000 description 1
210000003635 pituitary gland Anatomy 0.000 description 1
239000011148 porous material Substances 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
229960000208 pralmorelin Drugs 0.000 description 1
239000002243 precursor Substances 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
150000003180 prostaglandins Chemical class 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
238000001243 protein synthesis Methods 0.000 description 1
XNSAINXGIQZQOO-SRVKXCTJSA-N protirelin Chemical compound NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H]1NC(=O)CC1)CC1=CN=CN1 XNSAINXGIQZQOO-SRVKXCTJSA-N 0.000 description 1
230000010490 psychological well-being Effects 0.000 description 1
230000000541 pulsatile effect Effects 0.000 description 1
229960002290 pyridostigmine Drugs 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
238000003127 radioimmunoassay Methods 0.000 description 1
238000001525 receptor binding assay Methods 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
238000009256 replacement therapy Methods 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
238000012552 review Methods 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
229940089617 risedronate Drugs 0.000 description 1
238000007127 saponification reaction Methods 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
229940076279 serotonin Drugs 0.000 description 1
235000012239 silicon dioxide Nutrition 0.000 description 1
210000002027 skeletal muscle Anatomy 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
210000001875 somatotroph Anatomy 0.000 description 1
238000013223 sprague-dawley female rat Methods 0.000 description 1
238000010186 staining Methods 0.000 description 1
238000012289 standard assay Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000007858 starting material Substances 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
229910052682 stishovite Inorganic materials 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
229950007447 sulbenox Drugs 0.000 description 1
235000011149 sulphuric acid Nutrition 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
230000002195 synergetic effect Effects 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
229940037128 systemic glucocorticoids Drugs 0.000 description 1
WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
150000003536 tetrazoles Chemical class 0.000 description 1
229960000278 theophylline Drugs 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
150000003556 thioamides Chemical class 0.000 description 1
229940035024 thioglycerol Drugs 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
230000014616 translation Effects 0.000 description 1
229910052905 tridymite Inorganic materials 0.000 description 1
PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
229960000281 trometamol Drugs 0.000 description 1
238000002255 vaccination Methods 0.000 description 1
239000004474 valine Substances 0.000 description 1
229960003726 vasopressin Drugs 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
235000019786 weight gain Nutrition 0.000 description 1
230000004584 weight gain Effects 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
210000002268 wool Anatomy 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1
229960002300 zeranol Drugs 0.000 description 1
125000005853 β-dimethylaminoethyl group Chemical group 0.000 description 1

Classifications

- 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
- 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
- C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Biophysics (AREA)
Molecular Biology (AREA)
Physical Education & Sports Medicine (AREA)
Genetics & Genomics (AREA)
Biochemistry (AREA)
Cardiology (AREA)
Orthopedic Medicine & Surgery (AREA)
Heart & Thoracic Surgery (AREA)
Rheumatology (AREA)
Crystallography & Structural Chemistry (AREA)
Neurology (AREA)
Endocrinology (AREA)
Diabetes (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Peptides Or Proteins (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Steroid Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Cooling Or The Like Of Electrical Apparatus (AREA)

OA9800090A 1995-12-28 1998-06-19 Growth-hormone secretagogues. OA10702A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US946995P	1995-12-28	1995-12-28

Publications (1)

Publication Number	Publication Date
OA10702A true OA10702A (en)	2001-05-07

Family

ID=21737850

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA9800090A OA10702A (en)	1995-12-28	1998-06-19	Growth-hormone secretagogues.

Country Status (43)

Country	Link
US (7)	US6110932A (sr)
EP (1)	EP0869968B1 (sr)
JP (2)	JP3511382B2 (sr)
KR (1)	KR100320167B1 (sr)
CN (1)	CN1113895C (sr)
AP (2)	AP756A (sr)
AR (2)	AR004367A1 (sr)
AT (1)	ATE361314T1 (sr)
AU (1)	AU716934B2 (sr)
BG (1)	BG64055B1 (sr)
BR (1)	BR9612465B1 (sr)
CA (1)	CA2241725C (sr)
CO (1)	CO4480108A1 (sr)
CZ (1)	CZ293423B6 (sr)
DE (1)	DE69637063T2 (sr)
DK (1)	DK0869968T3 (sr)
EG (1)	EG24195A (sr)
ES (1)	ES2285715T3 (sr)
GT (1)	GT199600100A (sr)
HN (1)	HN1996000085A (sr)
HR (1)	HRP960618B1 (sr)
HU (1)	HUP9901246A3 (sr)
IL (4)	IL138911A (sr)
IS (1)	IS4758A (sr)
MA (1)	MA26415A1 (sr)
MX (1)	MX9805157A (sr)
MY (1)	MY135727A (sr)
NO (1)	NO325135B1 (sr)
NZ (1)	NZ322172A (sr)
OA (1)	OA10702A (sr)
PE (1)	PE30398A1 (sr)
PL (1)	PL186916B1 (sr)
PT (1)	PT869968E (sr)
RS (1)	RS49926B (sr)
SA (1)	SA97170581B1 (sr)
SI (1)	SI0869968T1 (sr)
SK (1)	SK285678B6 (sr)
TN (1)	TNSN96172A1 (sr)
TR (1)	TR199801233T2 (sr)
TW (1)	TW432073B (sr)
UA (1)	UA66754C2 (sr)
WO (1)	WO1997024369A1 (sr)
ZA (1)	ZA9610858B (sr)

Families Citing this family (146)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
TW432073B (en) *	1995-12-28	2001-05-01	Pfizer	Pyrazolopyridine compounds
HN1996000101A (es)	1996-02-28	1997-06-26	Inc Pfizer	Terapia combinada para la osteoporosis
AP2003002729A0 (en)	1997-04-15	2003-06-30	Csir	Pharmaceutical compositions having appetite suppressant activity
GB2324726A (en) *	1997-05-01	1998-11-04	Merck & Co Inc	Combination Therapy for the Treatment of Osteoporosis
DE69837264T2 (de) *	1997-06-25	2008-01-31	Pfizer Inc.	Dipeptidverbindungen, die Wachstumshormon-Sekretagoga sind
UA53716C2 (uk)	1997-06-25	2003-02-17	Пфайзер Продактс Інк.	Тартратна сіль заміщеного дипептиду, спосіб її одержання, проміжні сполуки та спосіб їх одержання, фармацевтична композиція (варіанти), спосіб підвищення рівнів ендогенного гормону росту та спосіб лікування або профілактики захворювань (варіанти)
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)
US6329342B1 (en)	1997-08-19	2001-12-11	Eli Lilly And Company	Treatment of congestive heart failure with growth hormone secretagogues
ZA987383B (en) *	1997-08-19	2000-02-17	Lilly Co Eli	Treatment of congestive heart failure with growth hormone secretagogues.
US6893877B2 (en)	1998-01-12	2005-05-17	Massachusetts Institute Of Technology	Methods for screening substances in a microwell array
KR20010034198A (ko)	1998-01-16	2001-04-25	한센 핀 베네드	성장 호르몬 방출성을 가지는 화합물
US6657063B1 (en) *	1998-04-30	2003-12-02	Pfizer Inc.	Combinations of β3 agonists and growth hormone secretagogues
CA2334012C (en) *	1998-06-03	2006-05-02	Pfizer Products Inc.	2-aminopyridines containing fused ring substituents as nitric oxide synthase inhibitors
HUP0102395A2 (hu) *	1998-06-16	2001-11-28	Pfizer Products Inc.	Izom- és csontrendszeri gyengeség kezelésére alkalmas szelektív ösztrogén receptor modulátorok és növekedési hormon szekretagógok (GHS) kombinációját tartalmazó gyógyszerkészítmények
PA8475901A1 (es) *	1998-06-16	2000-05-24	Pfizer Prod Inc	Terapia de combinacion para la fragilidad musculoesqueletica
PA8471201A1 (es) *	1998-06-16	2000-09-29	Pfizer Prod Inc	Combinaciones terapeuticas que comprenden un modulador del receptor de estrogenos selectivo y hormona paratiroidea
US6639076B1 (en)	1998-08-18	2003-10-28	Eli Lilly And Company	Growth hormone secretagogues
US6358951B1 (en) *	1998-08-21	2002-03-19	Pfizer Inc.	Growth hormone secretagogues
CA2341649A1 (en) *	1998-09-02	2000-03-09	Merck & Co., Inc.	Enhancement of return to independent living status with a growth hormone secretagogue
ES2187195T3 (es)	1998-09-11	2003-05-16	Gerhard Dr Schmidmaier	Implantes biologicamente activos.
US6337332B1 (en)	1998-09-17	2002-01-08	Pfizer Inc.	Neuropeptide Y receptor antagonists
US6380184B1 (en)	1998-10-28	2002-04-30	Bristol-Myers Squibb Co.	Benzoazepines and analogs thereof useful as growth hormone secretagogues
US6194578B1 (en) *	1998-11-20	2001-02-27	Pfizer Inc.	Dipeptide derivatives
SI1004583T1 (en) *	1998-11-23	2004-12-31	Pfizer Products Inc.	Process and hydantoin intermediates for the synthesis of growth hormone secretagogues
US6297380B1 (en)	1998-11-23	2001-10-02	Pfizer Inc.	Process and intermediates for growth hormone secretagogues
EP1158996A4 (en)	1999-02-18	2005-01-12	Kaken Pharma Co Ltd	NEW AMIDE SECRETAGOGUES OF GROWTH HORMONE DERIVATIVES
US6828331B1 (en)	1999-02-19	2004-12-07	Eli Lilly And Company	Growth hormone secretagogues
US6541634B2 (en)	1999-02-26	2003-04-01	Pfizer Inc.	Process for preparing growth hormone secretagogues
US6525203B1 (en)	1999-03-12	2003-02-25	Bristol-Myers Squibb Company	Heterocyclic aromatic compounds useful as growth hormone secretagogues
US6518292B1 (en)	1999-03-12	2003-02-11	Bristol-Myers Squibb Co.	Heterocyclic aromatic compounds usefuls as growth hormone secretagogues
ATE309358T1 (de) *	1999-07-26	2005-11-15	Baylor College Medicine	Superaktive, wachstumshormone freisetzende hormonanaloge vom schwein
GB2355657B (en)	1999-10-27	2004-07-28	Phytopharm Plc	Inhibitors Of Gastric Acid Secretion
EP1113007A1 (en) *	1999-12-24	2001-07-04	Pfizer Inc.	Tetrahydroisoquinoline compounds as estrogen agonists/antagonists
ATE304373T1 (de) *	1999-12-28	2005-09-15	Kaken Pharma Co Ltd	Nervenschutzmittel
CA2400644C (en) *	2000-02-18	2009-07-14	Board Of Trustees Of The Leland Stanford Junior University	Apparatus and methods for parallel processing of micro-volume liquid reactions
US20020151040A1 (en)	2000-02-18	2002-10-17	Matthew O' Keefe	Apparatus and methods for parallel processing of microvolume liquid reactions
EP1132388A3 (en)	2000-03-09	2004-03-03	Pfizer Products Inc.	Hexahydropyrazolo[4,3-c]pyridine metabolites
EP1149583A3 (en) *	2000-04-13	2001-11-14	Pfizer Products Inc.	Combinations of corticotropin releasing factor antagonists and growth hormone secretagogues
CA2408486A1 (en)	2000-05-11	2001-11-15	Bristol-Myers Squibb Company	Tetrahydroisoquinoline analogs useful as growth hormone secretagogues
DOP2001000154A (es) *	2000-05-25	2002-05-15	Pfizer Prod Inc	Combinación de secretagogos de hormona del crecimiento y antidepresivos
CA2410597A1 (en)	2000-05-30	2001-12-06	Merck & Co., Inc.	Melanocortin receptor agonists
DE60140285D1 (de) *	2000-05-31	2009-12-10	Pfizer Prod 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
IL143942A0 (en) *	2000-06-29	2002-04-21	Pfizer Prod Inc	Use of growth hormone secretagogues for treatment of physical performance decline
EP1181933A3 (en) *	2000-06-29	2002-04-10	Pfizer Products Inc.	Use of growth hormone secretagogues for stimulating or increasing appetite
GB2363985B (en)	2000-06-30	2004-09-29	Phytopharm Plc	Extracts,compounds & pharmaceutical compositions having anti-diabetic activity and their use
IL144468A0 (en) *	2000-07-27	2002-05-23	Pfizer Prod Inc	Use of growth hormone secretagogues for improvement of functional health status
IL145106A0 (en) *	2000-08-30	2002-06-30	Pfizer Prod Inc	Intermittent administration of a geowth hormone secretagogue
MXPA03001771A (es)	2000-08-30	2003-06-04	Pfizer Prod Inc	Formulaciones de liberacion sostenida para secretagogos de hormona del crecimiento.
IL145540A0 (en) *	2000-09-28	2002-06-30	Pfizer Prod Inc	Use of growth hormone secretagogues in conjunction with physical exercise
EP1330306A2 (en) *	2000-10-10	2003-07-30	BioTrove, Inc.	Apparatus for assay, synthesis and storage, and methods of manufacture, use, and manipulation thereof
US20100261159A1 (en)	2000-10-10	2010-10-14	Robert Hess	Apparatus for assay, synthesis and storage, and methods of manufacture, use, and manipulation thereof
CA2372450A1 (en) *	2001-05-10	2001-09-19	Pharmaceutical Partners Of Canada Inc.	Liquid injectable formulation of disodium pamidronate
US7125840B2 (en)	2001-10-09	2006-10-24	Eli Lilly And Company	Substituted dipeptides as growth hormone secretagogues
WO2003041641A2 (en)	2001-11-09	2003-05-22	Bristol-Myers Squibb Company	Tetrahydroisoquinoline analogs as modulators of chemokine receptor activity
US20030199514A1 (en) *	2002-03-27	2003-10-23	Fryburg David A.	Methods for improving efficacy of treatment with growth hormone secretagogues
EP1497316B1 (en)	2002-04-09	2006-07-05	Eli Lilly And Company	Growth hormone secretagogues
US7105526B2 (en)	2002-06-28	2006-09-12	Banyu Pharmaceuticals Co., Ltd.	Benzimidazole derivatives
US8277753B2 (en)	2002-08-23	2012-10-02	Life Technologies Corporation	Microfluidic transfer pin
NZ539218A (en) *	2002-09-18	2008-03-28	Univ Montreal Ct Hospitalier Chum	Synthetic GHRH analogues of 29 amino acids or more
US20060094108A1 (en) *	2002-12-20	2006-05-04	Karl Yoder	Thermal cycler for microfluidic array assays
AU2003302264A1 (en) *	2002-12-20	2004-09-09	Biotrove, Inc.	Assay apparatus and method using microfluidic arrays
US7772188B2 (en)	2003-01-28	2010-08-10	Ironwood Pharmaceuticals, Inc.	Methods and compositions for the treatment of gastrointestinal disorders
WO2004108120A1 (en) *	2003-06-11	2004-12-16	Pfizer Products Inc.	Use of growth hormone secretagogues for treatment of fibromyalgia
US7476653B2 (en)	2003-06-18	2009-01-13	Tranzyme Pharma, Inc.	Macrocyclic modulators of the ghrelin receptor
WO2005027913A1 (en) *	2003-09-19	2005-03-31	Pfizer Products Inc.	Pharmaceutical compositions and methods comprising combinations of 2-alkylidene-19-nor-vitamin d derivatives and a growth hormone secretagogue
WO2005028438A1 (ja)	2003-09-22	2005-03-31	Banyu Pharmaceutical Co., Ltd.	新規ピペリジン誘導体
US7129561B2 (en) *	2003-11-19	2006-10-31	International Business Machines Corporation	Tri-metal and dual-metal stacked inductors
AU2005222618A1 (en)	2004-03-12	2005-09-29	Biotrove, Inc.	Nanoliter array loading
EP1734963A4 (en)	2004-04-02	2008-06-18	Merck & Co Inc	METHOD FOR TREATING PEOPLE WITH METABOLIC AND ANTHROPOMETRIC DISORDER
EP1789409A4 (en) *	2004-04-02	2010-09-08	Elixir Pharmaceuticals Inc	SULPHONAMIDES AND ITS USES
WO2005097174A2 (en) *	2004-04-07	2005-10-20	Gastrotech Pharma A/S	Uses of a combination of ghrelin and somatotropin for the treatment of cachexia
RU2007107349A (ru)	2004-07-28	2008-09-10	Глэксо Груп Лимитед (GB)	Пиперазиновые производные, применение для лечения желудочно-кишечных расстройств
US12070731B2 (en)	2004-08-04	2024-08-27	Life Technologies Corporation	Methods and systems for aligning dispensing arrays with microfluidic sample arrays
US20060105453A1 (en) *	2004-09-09	2006-05-18	Brenan Colin J	Coating process for microfluidic sample arrays
WO2006020930A2 (en) *	2004-08-12	2006-02-23	Sapphire Therapeutics, Inc.	Method of stimulating the motility of the gastrointestinal system using growth hormone secretagogues
EP1781311A4 (en)	2004-08-18	2010-02-17	Elixir Pharmaceuticals Inc	WACHSTUMSHORMONSEKRETAGOGE
NZ562766A (en)	2005-05-30	2011-03-31	Banyu Pharma Co Ltd	Piperidine derivatives as histamine-H3 receptor antagonists
EP1916239A4 (en)	2005-08-10	2009-10-21	Banyu Pharma Co Ltd	PYRIDOLVERBINDUNG
AU2006282260A1 (en)	2005-08-24	2007-03-01	Msd K.K.	Phenylpyridone derivative
US20090264426A1 (en)	2005-09-07	2009-10-22	Shunji Sakuraba	Bicyclic aromatic substituted pyridone derivative
US8293900B2 (en)	2005-09-29	2012-10-23	Merck Sharp & Dohme Corp	Acylated spiropiperidine derivatives as melanocortin-4 receptor modulators
US20080255084A1 (en)	2005-10-21	2008-10-16	Randy Lee Webb	Combination of Organic Compounds
EP1944301A4 (en)	2005-10-27	2012-01-04	Msd Kk	NEW BENZOXATHIIN DERIVATIVES
CA2629018C (en)	2005-11-10	2013-12-31	Banyu Pharmaceutical Co., Ltd.	Aza-substituted spiro derivative
BRPI0618824A2 (pt) *	2005-11-21	2011-09-13	Univ Miyazaki	agente terapêutico acelerador de recuperação dérmica contendo grelina e derivados desta ou substáncias que atuam sobre ghs-r1a como ingrediente ativo
US8273702B2 (en) *	2006-02-17	2012-09-25	Wake Forest University Health Sciences	Wound healing compositions containing keratin biomaterials
CU23558A1 (es)	2006-02-28	2010-07-20	Ct Ingenieria Genetica Biotech	Compuestos análogos a los secretagogos peptidicos de la hormona de crecimiento
CU23592A1 (es) *	2006-02-28	2010-11-11	Ct Ingenieria Genetica Biotech	Método para prevenir y eliminar las fibrosis y otras formas de depósito patológico en los tejidos aplicando el péptido secretagogo ghrp-6
US20100227806A1 (en)	2006-03-10	2010-09-09	Tulipano Giovanni	Use Of A Ghrelin Agonist To Improve Catabolic Effects Of Glucocorticoid Treatment
MX2009002492A (es) *	2006-09-08	2009-08-28	Bayer Schering Pharma Ag	Agentes que comprenden compuestos marcados con 18f y metodos relacionados.
EP2698157B1 (en)	2006-09-22	2015-05-20	Merck Sharp & Dohme Corp.	Method of treatment using fatty acid synthesis inhibitors
WO2008038692A1 (en)	2006-09-28	2008-04-03	Banyu Pharmaceutical Co., Ltd.	Diaryl ketimine derivative
WO2008040441A2 (en) *	2006-10-02	2008-04-10	Bayer Schering Pharma Aktiengesellschaft	Silicon derivatives for pet imaging
US20080114055A1 (en) *	2006-11-10	2008-05-15	Zoltan Laboratories Llc	Thioxanthone Compounds to Reverse Weight Loss
EP2644618B1 (en)	2007-02-09	2016-08-17	Ocera Therapeutics, Inc.	tether intermediates for the synthesis of macrocyclic ghrelin receptor modulators
BRPI0721424A2 (pt) *	2007-03-01	2014-03-25	Bayer Schering Pharma Ag	Métodos de radiofluoração
JP2010520913A (ja)	2007-03-12	2010-06-17	サズセアーペーエス	ルイボスの抗糖尿病性抽出物
EP2002835A1 (en)	2007-06-04	2008-12-17	GenKyo Tex	Pyrazolo pyridine derivatives as NADPH oxidase inhibitors
US8106086B2 (en)	2007-04-02	2012-01-31	Msd K.K.	Indoledione derivative
MX354786B (es)	2007-06-04	2018-03-21	Synergy Pharmaceuticals Inc	Agonistas de guanilato ciclasa utiles para el tratamiento de trastornos gastrointestinales, inflamacion, cancer y otros trastornos.
US8969514B2 (en)	2007-06-04	2015-03-03	Synergy Pharmaceuticals, Inc.	Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases
EP2168602A4 (en) *	2007-06-12	2014-10-29	Inst Pharm & Toxicology Amms	LINEAR, PEGYLATED, SITE-SPECIFIC SALMON CALCITONIN DERIVATIVES
EP2264026A4 (en)	2008-03-06	2012-03-28	Msd Kk	ALKYLAMINOPYRIDINDERIVATE
JPWO2009119726A1 (ja)	2008-03-28	2011-07-28	Ｍｓｄ株式会社	メラニン凝集ホルモン受容体拮抗作用を有するジアリールメチルアミド誘導体
CA2726917C (en)	2008-06-04	2018-06-26	Synergy Pharmaceuticals Inc.	Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders
US20110071129A1 (en)	2008-06-19	2011-03-24	Makoto Ando	Spirodiamine-diaryl ketoxime derivative
EP2321341B1 (en)	2008-07-16	2017-02-22	Synergy Pharmaceuticals Inc.	Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders
WO2010013595A1 (ja)	2008-07-30	2010-02-04	萬有製薬株式会社	５員－５員又は５員－６員縮環シクロアルキルアミン誘導体
EP2166009A1 (en)	2008-09-23	2010-03-24	Genkyo Tex Sa	Pyrazolo pyridine derivatives as nadph oxidase inhibitors
EP2166010A1 (en)	2008-09-23	2010-03-24	Genkyo Tex Sa	Pyrazolo pyridine derivatives as NADPH oxidase inhibitors
EP2165707A1 (en)	2008-09-23	2010-03-24	Genkyo Tex Sa	Pyrazolo pyridine derivatives as NADPH oxidase inhibitors
US8410284B2 (en)	2008-10-22	2013-04-02	Merck Sharp & Dohme Corp	Cyclic benzimidazole derivatives useful as anti-diabetic agents
MX2011004551A (es)	2008-10-30	2011-05-25	Merck Sharp & Dohme	Antagonistas del receptor de orexina de isonicotinamida.
CA2741672A1 (en)	2008-10-31	2010-05-06	Merck Sharp & Dohme Corp.	Novel cyclic benzimidazole derivatives useful anti-diabetic agents
EP2305679A1 (en)	2009-09-28	2011-04-06	GenKyoTex SA	Pyrazoline dione derivatives as nadph oxidase inhibitors
EP2361911A1 (en) *	2010-02-18	2011-08-31	GenKyoTex SA	Pyrazolo piperidine derivatives as NADPH oxidase inhibitors
EP2361912A1 (en)	2010-02-18	2011-08-31	GenKyoTex SA	Pyrazolo piperidine derivatives as NADPH oxidase inhibitors
AU2011218830B2 (en)	2010-02-25	2014-07-24	Merck Sharp & Dohme Corp.	Novel cyclic benzimidazole derivatives useful anti-diabetic agents
ES2615731T3 (es) *	2010-02-26	2017-06-08	Raqualia Pharma Inc.	Agonista del receptor de ghrelina para el tratamiento de caquexia
US9616097B2 (en)	2010-09-15	2017-04-11	Synergy Pharmaceuticals, Inc.	Formulations of guanylate cyclase C agonists and methods of use
CA2826649C (en)	2011-02-25	2016-07-26	Merck Sharp & Dohme Corp.	Novel cyclic azabenzimidazole derivatives useful as anti-diabetic agents
JP6113144B2 (ja) *	2011-04-21	2017-04-12	セラテクノロジーズ・インコーポレーテッド	成長ホルモン放出因子（ｇｒｆ）類似体およびその使用
AR088352A1 (es)	2011-10-19	2014-05-28	Merck Sharp & Dohme	Antagonistas del receptor de 2-piridiloxi-4-nitrilo orexina
HK1203394A1 (en) *	2012-05-25	2015-10-30	Raqualia Pharma Inc	Ghrelin receptor agonists for the treatment of achlorhydria
RU2015106909A (ru)	2012-08-02	2016-09-27	Мерк Шарп И Доум Корп.	Антидиабетические трициклические соединения
EP2906041A4 (en)	2012-09-27	2016-10-26	Aratana Therapeutics Inc	COMPOSITIONS AND METHODS FOR USE IN A CAPACITY CONNECTOR
CA2889499C (en)	2012-10-24	2019-09-10	Daiichi Sankyo Company, Limited	Growth hormone secretagogue receptor agonists for treating amyotrophic lateral sclerosis
BR112015019836A2 (pt)	2013-02-22	2017-07-18	Merck Sharp & Dohme	composto, composição farmacêutica, e, uso de um composto
JP2016514671A (ja)	2013-03-15	2016-05-23	シナジーファーマシューティカルズインコーポレイテッド	グアニル酸シクラーゼのアゴニストおよびその使用
WO2014151200A2 (en)	2013-03-15	2014-09-25	Synergy Pharmaceuticals Inc.	Compositions useful for the treatment of gastrointestinal disorders
BR112015029586B1 (pt) *	2013-05-28	2022-05-03	Raqualia Pharma Inc	Formas polimorfas
CN105764916B (zh)	2013-06-05	2021-05-18	博士医疗爱尔兰有限公司	鸟苷酸环化酶c的超纯激动剂、制备和使用所述激动剂的方法
KR102051433B1 (ko) *	2013-08-27	2020-01-08	(주)네오팜	근육 분화 촉진 및 근육 강화용 조성물 및 외용제
US9119832B2 (en)	2014-02-05	2015-09-01	The Regents Of The University Of California	Methods of treating mild brain injury
ES2707124T3 (es) *	2014-08-05	2019-04-02	Raqualia Pharma Inc	Derivados de serina como agonistas del receptor de grelina
MX389591B (es)	2014-08-29	2025-03-20	Tes Pharma S R L	INHIBIDORES DE ACIDO A-AMINO-ß-CARBOXIMUCONICO SEMIALDEHIDO DESCARBOXILASA
TW201625613A (zh) *	2014-10-31	2016-07-16	拉夸里亞創藥股份有限公司	作為生長激素釋放肽受體激動劑之四氫吡唑並吡啶衍生物
WO2017075535A1 (en)	2015-10-28	2017-05-04	Oxeia Biopharmaceuticals, Inc.	Methods of treating neurodegenerative conditions
MX2019004321A (es)	2016-10-14	2019-06-12	Tes Pharma S R L	Inhibidores de la acido alfa-amino-beta-carboximuconico semialdehido descarboxilasa.
EP3479843A1 (en)	2017-11-01	2019-05-08	GenKyoTex Suisse SA	Use of nox inhibitors for treatment of cancer
CN118496217A (zh)	2018-11-20	2024-08-16	Tes制药有限责任公司	α-氨基-β-羧基己二烯二酸半醛去羧酶的抑制剂
CN109320515A (zh) *	2018-11-22	2019-02-12	常州大学	一种Capromorelin手性中间体的不对称合成方法
EP3924058B1 (en)	2019-02-13	2026-01-07	Merck Sharp & Dohme LLC	5-alkyl pyrrolidine orexin receptor agonists
WO2024217441A1 (zh) *	2023-04-21	2024-10-24	长春金赛药业有限责任公司	GHSR 1a激动剂、药物组合物及其制备方法和应用
CN119285632A (zh) *	2024-10-09	2025-01-10	威海中腾医药科技有限公司	一种基于酵母醇脱氢酶催化氧化的卡普瑞林中间体的制备方法

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DK139625B (da) *	1971-05-11	1979-03-19	Sandoz Ag	Analogifremgangsmåde til fremstilling af cycloalkan(c)pyridazin- eller pyrido(4,3-c)pyridazinderivater eller syreadditionssalte deraf.
DE2221808C2 (de) *	1972-05-04	1985-06-20	Sandoz-Patent-GmbH, 7850 Lörrach	Hydrazinopyridazin-Derivate, deren Säureadditionssalze, Verfahren zu deren Herstellung und Heilmittel
IL107836A (en) *	1992-12-11	1998-01-04	Merck & Co Inc	Spiro piperidines and homologues, their preparation and pharmaceutical preparations containing them
JP3670690B2 (ja) *	1993-10-04	2005-07-13	トーアエイヨー株式会社	３−ピリダジノン誘導体、その製造法およびそれを含有する循環器官用剤
FI961681L (fi) *	1993-10-19	1996-06-12	Merck & Co Inc	Bisfosfonaattien ja kasvuhormoonin eritystä lisäävien aineiden yhdistelmä
WO1995013069A1 (en) *	1993-11-09	1995-05-18	Merck & Co., Inc.	Piperidines, pyrrolidines and hexahydro-1h-azepines promote release of growth hormone
US5610134A (en) *	1994-04-15	1997-03-11	Genentech, Inc.	Treatment of congestive heart failure
US5935924A (en) *	1994-04-15	1999-08-10	Genentech, Inc.	Treatment of congestive heart failure
US5767118A (en) *	1994-10-26	1998-06-16	Merck & Co., Inc.	4-Heterocyclic peperidines promote release of growth hormone
US5798337A (en) *	1994-11-16	1998-08-25	Genentech, Inc.	Low molecular weight peptidomimetic growth hormone secretagogues
AU705744B2 (en) *	1995-01-27	1999-06-03	Sapphire Therapeutics, Inc.	Compounds with growth hormone releasing properties
WO1996024580A1 (en) *	1995-02-09	1996-08-15	Novo Nordisk A/S	Compounds with growth hormone releasing properties
AU4534696A (en) *	1995-02-09	1996-08-27	Novo Nordisk A/S	Compounds with growth hormone releasing properties
EP0761220A1 (en) *	1995-08-21	1997-03-12	Eli Lilly And Company	2-Acylaminopropanamides as growth hormone secretagogues
AU6724496A (en) *	1995-08-21	1997-03-12	Eli Lilly And Company	2-acylaminopropanamines as growth hormone secretagogues
TW432073B (en)	1995-12-28	2001-05-01	Pfizer	Pyrazolopyridine compounds
US6020358A (en) *	1998-10-30	2000-02-01	Celgene Corporation	Substituted phenethylsulfones and method of reducing TNFα levels

1996
- 1996-11-13 TW TW085113857A patent/TW432073B/zh not_active IP Right Cessation
- 1996-11-14 AP APAP/P/1996/000881A patent/AP756A/en active
- 1996-12-04 DE DE69637063T patent/DE69637063T2/de not_active Expired - Lifetime
- 1996-12-04 PT PT96938434T patent/PT869968E/pt unknown
- 1996-12-04 JP JP52412497A patent/JP3511382B2/ja not_active Expired - Lifetime
- 1996-12-04 AT AT96938434T patent/ATE361314T1/de not_active IP Right Cessation
- 1996-12-04 CN CN96199388A patent/CN1113895C/zh not_active Expired - Lifetime
- 1996-12-04 ES ES96938434T patent/ES2285715T3/es not_active Expired - Lifetime
- 1996-12-04 PL PL96327634A patent/PL186916B1/pl not_active IP Right Cessation
- 1996-12-04 SI SI9630755T patent/SI0869968T1/sl unknown
- 1996-12-04 CZ CZ19981995A patent/CZ293423B6/cs not_active IP Right Cessation
- 1996-12-04 HU HU9901246A patent/HUP9901246A3/hu unknown
- 1996-12-04 NZ NZ322172A patent/NZ322172A/xx unknown
- 1996-12-04 IL IL138911A patent/IL138911A/en not_active IP Right Cessation
- 1996-12-04 TR TR1998/01233T patent/TR199801233T2/xx unknown
- 1996-12-04 IL IL13891096A patent/IL138910A0/xx unknown
- 1996-12-04 IL IL12444996A patent/IL124449A/en not_active IP Right Cessation
- 1996-12-04 BR BRPI9612465-2A patent/BR9612465B1/pt not_active IP Right Cessation
- 1996-12-04 IL IL13890996A patent/IL138909A0/xx unknown
- 1996-12-04 WO PCT/IB1996/001353 patent/WO1997024369A1/en not_active Ceased
- 1996-12-04 AU AU75850/96A patent/AU716934B2/en not_active Ceased
- 1996-12-04 EP EP96938434A patent/EP0869968B1/en not_active Expired - Lifetime
- 1996-12-04 CA CA002241725A patent/CA2241725C/en not_active Expired - Lifetime
- 1996-12-04 DK DK96938434T patent/DK0869968T3/da active
- 1996-12-04 SK SK874-98A patent/SK285678B6/sk not_active IP Right Cessation
- 1996-12-04 UA UA98063368A patent/UA66754C2/xx unknown
- 1996-12-04 KR KR10-1998-0704973A patent/KR100320167B1/ko not_active Expired - Lifetime
- 1996-12-06 HN HN1996000085A patent/HN1996000085A/es unknown
- 1996-12-09 AR ARP960105571A patent/AR004367A1/es active IP Right Grant
- 1996-12-19 GT GT199600100A patent/GT199600100A/es unknown
- 1996-12-20 CO CO96066996A patent/CO4480108A1/es unknown
- 1996-12-23 ZA ZA9610858A patent/ZA9610858B/xx unknown
- 1996-12-24 TN TNTNSN96172A patent/TNSN96172A1/fr unknown
- 1996-12-24 MA MA24438A patent/MA26415A1/fr unknown
- 1996-12-24 EG EG117796A patent/EG24195A/xx active
- 1996-12-26 MY MYPI96005499A patent/MY135727A/en unknown
- 1996-12-26 RS YUP-702/96A patent/RS49926B/sr unknown
- 1996-12-27 HR HR960618A patent/HRP960618B1/xx not_active IP Right Cessation
- 1996-12-27 PE PE1996000961A patent/PE30398A1/es not_active Application Discontinuation
1997
- 1997-01-27 SA SA97170581A patent/SA97170581B1/ar unknown
1998
- 1998-05-26 IS IS4758A patent/IS4758A/is unknown
- 1998-06-11 BG BG102533A patent/BG64055B1/bg unknown
- 1998-06-19 OA OA9800090A patent/OA10702A/en unknown
- 1998-06-24 MX MX9805157A patent/MX9805157A/es active IP Right Grant
- 1998-06-26 NO NO19982991A patent/NO325135B1/no not_active IP Right Cessation
1999
- 1999-03-01 US US09/258,956 patent/US6110932A/en not_active Expired - Lifetime
- 1999-03-01 US US09/259,691 patent/US6107306A/en not_active Expired - Lifetime
- 1999-03-01 US US09/259,776 patent/US6124264A/en not_active Expired - Lifetime
- 1999-05-27 AP APAP/P/1999/001555A patent/AP860A/en active
- 1999-12-22 US US09/470,668 patent/US6278000B1/en not_active Expired - Lifetime
2000
- 2000-06-13 US US09/593,582 patent/US6306875B1/en not_active Expired - Lifetime
- 2000-06-13 US US09/593,581 patent/US6313140B1/en not_active Expired - Lifetime
- 2000-12-11 US US09/734,274 patent/US6482825B2/en not_active Expired - Lifetime
- 2000-12-20 JP JP2000386997A patent/JP2001213800A/ja active Pending
2006
- 2006-03-03 AR ARP060100824A patent/AR052506A2/es active IP Right Grant

Also Published As

Publication number	Publication date
HUP9901246A2 (hu)	1999-08-30
IS4758A (is)	1998-05-26
HUP9901246A3 (en)	1999-11-29
CN1113895C (zh)	2003-07-09
ATE361314T1 (de)	2007-05-15
JP3511382B2 (ja)	2004-03-29
AR004367A1 (es)	1998-11-04
RS49926B (sr)	2008-09-29
CN1206422A (zh)	1999-01-27
IL138911A (en)	2007-07-24
PL186916B1 (pl)	2004-03-31
AP9901555A0 (en)	1999-06-30
BG102533A (en)	1999-09-30
JPH11501945A (ja)	1999-02-16
AU716934B2 (en)	2000-03-09
IL138909A0 (en)	2001-11-25
US6313140B1 (en)	2001-11-06
PT869968E (pt)	2007-07-11
US6482825B2 (en)	2002-11-19
TR199801233T2 (xx)	1998-10-21
CZ293423B6 (cs)	2004-04-14
HN1996000085A (es)	1997-06-18
NZ322172A (en)	2000-08-25
US6107306A (en)	2000-08-22
AU7585096A (en)	1997-07-28
DK0869968T3 (da)	2007-09-10
UA66754C2 (en)	2004-06-15
TNSN96172A1 (fr)	2005-03-15
DE69637063D1 (de)	2007-06-14
BR9612465B1 (pt)	2010-08-10
KR19990076846A (ko)	1999-10-25
SA97170581B1 (ar)	2006-03-15
MA26415A1 (fr)	2004-12-20
CZ199598A3 (cs)	1999-05-12
EG24195A (en)	2008-10-14
US6306875B1 (en)	2001-10-23
MY135727A (en)	2008-06-30
KR100320167B1 (ko)	2003-11-14
IL138910A0 (en)	2001-11-25
EP0869968B1 (en)	2007-05-02
NO982991D0 (no)	1998-06-26
US6278000B1 (en)	2001-08-21
CO4480108A1 (es)	1997-07-09
SI0869968T1 (sl)	2007-08-31
SK87498A3 (en)	1999-08-06
WO1997024369A1 (en)	1997-07-10
AP860A (en)	1999-08-06
PE30398A1 (es)	1998-07-21
MX9805157A (es)	1998-10-31
CA2241725A1 (en)	1997-07-10
NO982991L (no)	1998-08-26
SK285678B6 (sk)	2007-06-07
BR9612465A (pt)	1999-07-13
JP2001213800A (ja)	2001-08-07
HRP960618A2 (en)	1998-04-30
ZA9610858B (en)	1998-06-23
IL138911A0 (en)	2001-11-25
TW432073B (en)	2001-05-01
EP0869968A1 (en)	1998-10-14
HRP960618B1 (en)	2007-12-31
IL124449A (en)	2004-06-01
GT199600100A (es)	1998-06-12
YU70296A (en)	1999-11-22
BG64055B1 (bg)	2003-11-28
US6124264A (en)	2000-09-26
CA2241725C (en)	2002-06-18
NO325135B1 (no)	2008-02-04
AP756A (en)	1999-08-06
PL327634A1 (en)	1998-12-21
AR052506A2 (es)	2007-03-21
US20020049196A1 (en)	2002-04-25
IL124449A0 (en)	1998-12-06
US6110932A (en)	2000-08-29
DE69637063T2 (de)	2008-02-07
AP9600881A0 (en)	1997-01-31
ES2285715T3 (es)	2007-11-16

Publication	Publication Date	Title
OA10702A (en)	2001-05-07	Growth-hormone secretagogues.
US6525047B2 (en)	2003-02-25	Dipeptide derivatives
OA11242A (en)	2003-07-23	Treatment of insulin resistance with growth hormone secretagogues
EP1002802B1 (en)	2004-12-08	Dipeptide derivatives as growth hormone secretagogues