IL156465A

IL156465A - Scrotagogens of growth hormone for use in the treatment of sleep disorders

Scrotagogens of growth hormone for use in the treatment of sleep disorders

Info

Publication number: IL156465A
Authority: IL; Israel
Prior art keywords: alkyl; oxo; optionally substituted; alkylene; phenyl
Prior art date: 1997-06-25

Application number

IL15646598A

Other languages

English (en)

Hebrew (he)

Other versions

IL156465A0 (en

Original Assignee

Pfizer Prod Inc

Priority date

1997-06-25

Filing date

1998-06-05

Publication date

2004-07-25

1998-06-05 Application filed by Pfizer Prod Inc filed Critical Pfizer Prod Inc

2004-01-04 Publication of IL156465A0 publication Critical patent/IL156465A0/xx

2004-07-25 Publication of IL156465A publication Critical patent/IL156465A/en

Links

208000019116 sleep disease Diseases 0.000 title claims description 4
238000011282 treatment Methods 0.000 title description 40
239000003324 growth hormone secretagogue Substances 0.000 title description 4
239000000203 mixture Substances 0.000 claims abstract description 256
150000001875 compounds Chemical class 0.000 claims abstract description 176
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 112
125000000217 alkyl group Chemical group 0.000 claims abstract description 102
229920006395 saturated elastomer Polymers 0.000 claims abstract description 93
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 72
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 61
-1 1H-tetrazol-5-yl Chemical group 0.000 claims abstract description 58
239000001257 hydrogen Substances 0.000 claims abstract description 57
229910052760 oxygen Inorganic materials 0.000 claims abstract description 46
229910052717 sulfur Chemical group 0.000 claims abstract description 41
150000003839 salts Chemical class 0.000 claims abstract description 36
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 34
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 34
239000001301 oxygen Substances 0.000 claims abstract description 34
239000011593 sulfur Chemical group 0.000 claims abstract description 34
125000005842 heteroatom Chemical group 0.000 claims abstract description 30
229910052799 carbon Inorganic materials 0.000 claims abstract description 28
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 27
239000000651 prodrug Substances 0.000 claims abstract description 24
229940002612 prodrug Drugs 0.000 claims abstract description 24
150000001721 carbon Chemical group 0.000 claims abstract description 23
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 21
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 20
229910052736 halogen Inorganic materials 0.000 claims abstract description 18
150000002367 halogens Chemical class 0.000 claims abstract description 18
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 17
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 16
125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 16
125000001424 substituent group Chemical group 0.000 claims abstract description 15
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 14
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 14
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 10
125000001153 fluoro group Chemical group F* 0.000 claims abstract description 8
125000006709 (C5-C7) cycloalkenyl group Chemical group 0.000 claims abstract description 6
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 5
125000002947 alkylene group Chemical group 0.000 claims abstract description 4
125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims abstract description 3
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract 5
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract 4
229940047889 isobutyramide Drugs 0.000 claims description 58
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 26
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 19
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
241000124008 Mammalia Species 0.000 claims description 14
150000002431 hydrogen Chemical class 0.000 claims description 14
238000002360 preparation method Methods 0.000 claims description 14
125000003545 alkoxy group Chemical group 0.000 claims description 13
239000003814 drug Substances 0.000 claims description 12
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 10
101710142969 Somatoliberin Proteins 0.000 claims description 9
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
229910052740 iodine Inorganic materials 0.000 claims description 9
125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims description 8
239000000095 Growth Hormone-Releasing Hormone Substances 0.000 claims description 6
125000004429 atom Chemical group 0.000 claims description 6
125000002883 imidazolyl group Chemical group 0.000 claims description 6
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 6
125000000335 thiazolyl group Chemical group 0.000 claims description 6
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
125000005907 alkyl ester group Chemical group 0.000 claims description 5
125000004423 acyloxy group Chemical group 0.000 claims description 4
229910052794 bromium Inorganic materials 0.000 claims description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
229910052731 fluorine Inorganic materials 0.000 claims description 4
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
125000001544 thienyl group Chemical group 0.000 claims description 4
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 3
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
125000002541 furyl group Chemical group 0.000 claims description 3
125000005059 halophenyl group Chemical group 0.000 claims description 3
125000003831 tetrazolyl group Chemical group 0.000 claims description 3
MPHQKNPPPRRISM-UHFFFAOYSA-N 2-amino-2-methyl-n-[1-[2-methyl-3-oxo-3a-(pyridin-2-ylmethyl)-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl]-1-oxo-3-phenylmethoxypropan-2-yl]propanamide Chemical compound O=C1N(C)N=C2CCN(C(=O)C(COCC=3C=CC=CC=3)NC(=O)C(C)(C)N)CC21CC1=CC=CC=N1 MPHQKNPPPRRISM-UHFFFAOYSA-N 0.000 claims description 2
FJRPCTQTURPDCD-UHFFFAOYSA-N 2-amino-n-[3-[(4-chlorothiophen-2-yl)methoxy]-1-oxo-1-[3-oxo-3a-(pyridin-2-ylmethyl)-2-(2,2,2-trifluoroethyl)-5,7-dihydro-4h-pyrazolo[3,4-c]pyridin-6-yl]propan-2-yl]-2-methylpropanamide Chemical compound C1CC(C(N(CC(F)(F)F)N=2)=O)(CC=3N=CC=CC=3)C=2CN1C(=O)C(NC(=O)C(C)(N)C)COCC1=CC(Cl)=CS1 FJRPCTQTURPDCD-UHFFFAOYSA-N 0.000 claims description 2
150000007942 carboxylates Chemical class 0.000 claims description 2
FKOGOYQRCDITFG-UHFFFAOYSA-N n-[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 C1CC2=NNC(=O)C2(CC=2C=CC=CC=2)CN1C(=O)C(NC(=O)C(C)(N)C)COCC1=CC=CC=C1 FKOGOYQRCDITFG-UHFFFAOYSA-N 0.000 claims description 2
QUAJHCSLZMRTTM-UHFFFAOYSA-N 2-amino-n-[3-[(2,4-difluorophenyl)methoxy]-1-oxo-1-[3-oxo-3a-(pyridin-2-ylmethyl)-2-(2,2,2-trifluoroethyl)-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl]propan-2-yl]-2-methylpropanamide Chemical compound C1CC2=NN(CC(F)(F)F)C(=O)C2(CC=2N=CC=CC=2)CN1C(=O)C(NC(=O)C(C)(N)C)COCC1=CC=C(F)C=C1F QUAJHCSLZMRTTM-UHFFFAOYSA-N 0.000 claims 1
102000038461 Growth Hormone-Releasing Hormone Human genes 0.000 claims 1
125000004453 alkoxycarbonyl group Chemical group 0.000 claims 1
125000000392 cycloalkenyl group Chemical group 0.000 claims 1
UBEBVVBBTDUZKB-UHFFFAOYSA-N n-[1-(3a-benzyl-2-ethyl-3-oxo-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl)-1-oxo-3-phenylmethoxypropan-2-yl]-2-amino-2-methylpropanamide Chemical compound O=C1N(CC)N=C2CCN(C(=O)C(COCC=3C=CC=CC=3)NC(=O)C(C)(C)N)CC21CC1=CC=CC=C1 UBEBVVBBTDUZKB-UHFFFAOYSA-N 0.000 claims 1
CMFDKVQQVCBZTI-UHFFFAOYSA-N n-[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(CC=3C4=CC=CC=C4NC=3)NC(=O)C(C)(C)N)CC21CC1=CC=CC=C1 CMFDKVQQVCBZTI-UHFFFAOYSA-N 0.000 claims 1
KVLLHLWBPNCVNR-UHFFFAOYSA-N n-[1-(3a-benzyl-2-methyl-3-oxo-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl)-1-oxo-3-phenylmethoxypropan-2-yl]-2-amino-2-methylpropanamide Chemical compound O=C1N(C)N=C2CCN(C(=O)C(COCC=3C=CC=CC=3)NC(=O)C(C)(C)N)CC21CC1=CC=CC=C1 KVLLHLWBPNCVNR-UHFFFAOYSA-N 0.000 claims 1
RHQTZSQNBZVDGW-UHFFFAOYSA-N n-[1-(3a-benzyl-2-methyl-3-oxo-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl)-1-oxo-5-phenylpentan-2-yl]-2-amino-2-methylpropanamide Chemical compound O=C1N(C)N=C2CCN(C(=O)C(CCCC=3C=CC=CC=3)NC(=O)C(C)(C)N)CC21CC1=CC=CC=C1 RHQTZSQNBZVDGW-UHFFFAOYSA-N 0.000 claims 1
GWDQWGUUUGDHLC-UHFFFAOYSA-N n-[1-[3a-[(4-fluorophenyl)methyl]-2-methyl-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(C)N=C2CCN(C(=O)C(CC=3C4=CC=CC=C4NC=3)NC(=O)C(C)(C)N)CC21CC1=CC=C(F)C=C1 GWDQWGUUUGDHLC-UHFFFAOYSA-N 0.000 claims 1
125000000008 (C1-C10) alkyl group Chemical group 0.000 abstract description 2
125000004209 (C1-C8) alkyl group Chemical group 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 327
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 155
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 138
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 131
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 118
235000019439 ethyl acetate Nutrition 0.000 description 110
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 106
239000000243 solution Substances 0.000 description 85
238000000034 method Methods 0.000 description 80
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 78
102000018997 Growth Hormone Human genes 0.000 description 73
239000000122 growth hormone Substances 0.000 description 73
108010051696 Growth Hormone Proteins 0.000 description 72
229910000069 nitrogen hydride Inorganic materials 0.000 description 68
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 58
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 58
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 57
239000007787 solid Substances 0.000 description 56
229910001868 water Inorganic materials 0.000 description 51
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 49
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 39
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 38
238000010898 silica gel chromatography Methods 0.000 description 38
239000000047 product Substances 0.000 description 37
238000010992 reflux Methods 0.000 description 37
239000012267 brine Substances 0.000 description 34
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 34
239000011541 reaction mixture Substances 0.000 description 31
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
239000002253 acid Substances 0.000 description 27
238000006243 chemical reaction Methods 0.000 description 27
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 26
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 25
238000010511 deprotection reaction Methods 0.000 description 24
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 23
230000036961 partial effect Effects 0.000 description 23
239000002904 solvent Substances 0.000 description 22
241000700159 Rattus Species 0.000 description 20
238000005160 1H NMR spectroscopy Methods 0.000 description 19
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 19
239000002585 base Substances 0.000 description 19
239000003921 oil Substances 0.000 description 19
235000019198 oils Nutrition 0.000 description 19
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 18
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 18
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
150000001412 amines Chemical class 0.000 description 17
239000000543 intermediate Substances 0.000 description 17
238000005859 coupling reaction Methods 0.000 description 15
229910052943 magnesium sulfate Inorganic materials 0.000 description 15
229910000104 sodium hydride Inorganic materials 0.000 description 15
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 14
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 14
230000008878 coupling Effects 0.000 description 14
238000010168 coupling process Methods 0.000 description 14
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
239000012312 sodium hydride Substances 0.000 description 14
238000012360 testing method Methods 0.000 description 14
102100033367 Appetite-regulating hormone Human genes 0.000 description 13
102000004877 Insulin Human genes 0.000 description 13
108090001061 Insulin Proteins 0.000 description 13
210000004369 blood Anatomy 0.000 description 13
239000008280 blood Substances 0.000 description 13
238000010828 elution Methods 0.000 description 13
239000000284 extract Substances 0.000 description 13
229940125396 insulin Drugs 0.000 description 13
230000008569 process Effects 0.000 description 13
125000006239 protecting group Chemical group 0.000 description 13
229910000030 sodium bicarbonate Inorganic materials 0.000 description 13
150000002148 esters Chemical class 0.000 description 12
239000012442 inert solvent Substances 0.000 description 12
210000002966 serum Anatomy 0.000 description 12
COLOHWPRNRVWPI-UHFFFAOYSA-N 1,1,1-trifluoroethane Chemical compound [CH2]C(F)(F)F COLOHWPRNRVWPI-UHFFFAOYSA-N 0.000 description 11
239000003795 chemical substances by application Substances 0.000 description 11
230000000694 effects Effects 0.000 description 11
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 10
101710119601 Growth hormone-releasing peptides Proteins 0.000 description 10
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 10
239000008103 glucose Substances 0.000 description 10
230000028327 secretion Effects 0.000 description 10
235000017557 sodium bicarbonate Nutrition 0.000 description 10
208000001072 type 2 diabetes mellitus Diseases 0.000 description 10
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 9
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 9
150000001413 amino acids Chemical class 0.000 description 9
239000003054 catalyst Substances 0.000 description 9
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 9
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
241000282465 Canis Species 0.000 description 8
206010022489 Insulin Resistance Diseases 0.000 description 8
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 8
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
102100022831 Somatoliberin Human genes 0.000 description 8
238000001914 filtration Methods 0.000 description 8
230000001817 pituitary effect Effects 0.000 description 8
235000017281 sodium acetate Nutrition 0.000 description 8
238000003756 stirring Methods 0.000 description 8
238000005481 NMR spectroscopy Methods 0.000 description 7
208000008589 Obesity Diseases 0.000 description 7
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 7
239000000384 adrenergic alpha-2 receptor agonist Substances 0.000 description 7
150000001350 alkyl halides Chemical class 0.000 description 7
238000003556 assay Methods 0.000 description 7
230000037396 body weight Effects 0.000 description 7
150000001732 carboxylic acid derivatives Chemical group 0.000 description 7
210000004027 cell Anatomy 0.000 description 7
FEWJPZIEWOKRBE-LWMBPPNESA-N levotartaric acid Chemical compound OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 description 7
HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 7
235000020824 obesity Nutrition 0.000 description 7
229910000027 potassium carbonate Inorganic materials 0.000 description 7
239000001632 sodium acetate Substances 0.000 description 7
238000003786 synthesis reaction Methods 0.000 description 7
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 7
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