SK4182003A3 - Substituted dipeptides as growth hormone secretagogues - Google Patents

Substituted dipeptides as growth hormone secretagogues Download PDF

Info

Publication number: SK4182003A3
Authority: SK; Slovakia
Prior art keywords: alkyl; aryl; amino; azaspiro; ylmethyl
Prior art date: 2000-10-13

Application number

SK418-2003A

Other languages

English (en)

Slovak (sk)

Inventor

Jeffrey Alan Dodge

Britta Evers

Louis Nickolaus Jungheim

Brian Stephen Muehl

Gerd Ruehter

Kenneth Jeff Thrasher

Original Assignee

Lilly Co Eli

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.)

2000-10-13

Filing date

2001-10-09

Publication date

2004-01-08

2001-10-09 Application filed by Lilly Co Eli filed Critical Lilly Co Eli

2004-01-08 Publication of SK4182003A3 publication Critical patent/SK4182003A3/sk

Links

239000003324 growth hormone secretagogue Substances 0.000 title claims description 12
108010016626 Dipeptides Proteins 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 325
238000000034 method Methods 0.000 claims abstract description 208
239000000122 growth hormone Substances 0.000 claims abstract description 36
102000018997 Growth Hormone Human genes 0.000 claims abstract description 35
108010051696 Growth Hormone Proteins 0.000 claims abstract description 35
230000008569 process Effects 0.000 claims abstract description 8
-1 C 1 -C 6 alkylaryl Chemical group 0.000 claims description 834
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 594
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 99
229910052739 hydrogen Inorganic materials 0.000 claims description 86
239000001257 hydrogen Substances 0.000 claims description 85
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 63
125000003118 aryl group Chemical group 0.000 claims description 59
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 56
150000003839 salts Chemical class 0.000 claims description 42
125000004093 cyano group Chemical group *C#N 0.000 claims description 39
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 36
229910052799 carbon Inorganic materials 0.000 claims description 32
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 30
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 28
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 24
229910052736 halogen Inorganic materials 0.000 claims description 22
150000002367 halogens Chemical class 0.000 claims description 22
125000006239 protecting group Chemical group 0.000 claims description 22
238000002360 preparation method Methods 0.000 claims description 21
125000000217 alkyl group Chemical group 0.000 claims description 20
239000003814 drug Substances 0.000 claims description 19
125000001041 indolyl group Chemical group 0.000 claims description 19
125000003107 substituted aryl group Chemical group 0.000 claims description 19
UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 18
125000005843 halogen group Chemical group 0.000 claims description 17
239000002253 acid Substances 0.000 claims description 16
125000004432 carbon atom Chemical group C* 0.000 claims description 16
101100240516 Caenorhabditis elegans nhr-10 gene Proteins 0.000 claims description 15
150000001408 amides Chemical class 0.000 claims description 15
RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 14
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 13
125000001424 substituent group Chemical group 0.000 claims description 13
125000002837 carbocyclic group Chemical group 0.000 claims description 12
239000003795 chemical substances by application Substances 0.000 claims description 12
125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 12
GMKYVKWGXBQAMB-UHFFFAOYSA-N n-[[3-(4-chlorophenyl)-2,2-dioxo-2$l^{6}-thia-1-azaspiro[4.5]dec-3-en-4-yl]methyl]ethanamine Chemical compound O=S1(=O)NC2(CCCCC2)C(CNCC)=C1C1=CC=C(Cl)C=C1 GMKYVKWGXBQAMB-UHFFFAOYSA-N 0.000 claims description 12
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 12
239000012453 solvate Substances 0.000 claims description 12
125000000392 cycloalkenyl group Chemical group 0.000 claims description 11
UWRNOZDQLDBVKY-UHFFFAOYSA-N n-[[3-(2-bromophenyl)-2,2-dioxo-2$l^{6}-thia-1-azaspiro[4.5]dec-3-en-4-yl]methyl]ethanamine Chemical compound O=S1(=O)NC2(CCCCC2)C(CNCC)=C1C1=CC=CC=C1Br UWRNOZDQLDBVKY-UHFFFAOYSA-N 0.000 claims description 11
YWAVZUWLSRORPG-UHFFFAOYSA-N 2-[(2-amino-2-methylpropanoyl)amino]-5-phenylpentanoic acid Chemical compound CC(C)(N)C(=O)NC(C(O)=O)CCCC1=CC=CC=C1 YWAVZUWLSRORPG-UHFFFAOYSA-N 0.000 claims description 10
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 10
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 10
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
125000001544 thienyl group Chemical group 0.000 claims description 10
125000004429 atom Chemical group 0.000 claims description 9
238000010168 coupling process Methods 0.000 claims description 9
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 9
238000004519 manufacturing process Methods 0.000 claims description 9
125000001624 naphthyl group Chemical group 0.000 claims description 9
230000008878 coupling Effects 0.000 claims description 8
238000005859 coupling reaction Methods 0.000 claims description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
125000002877 alkyl aryl group Chemical group 0.000 claims description 7
125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 7
230000000694 effects Effects 0.000 claims description 7
DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 claims description 7
241001465754 Metazoa Species 0.000 claims description 6
125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 6
238000010511 deprotection reaction Methods 0.000 claims description 6
239000008194 pharmaceutical composition Substances 0.000 claims description 6
NTYQZLYVUKIFLI-UHFFFAOYSA-N 1-[3-(4-chlorophenyl)-2,2-dioxo-2$l^{6}-thia-1-azaspiro[4.5]dec-3-en-4-yl]-n-methylmethanamine Chemical compound O=S1(=O)NC2(CCCCC2)C(CNC)=C1C1=CC=C(Cl)C=C1 NTYQZLYVUKIFLI-UHFFFAOYSA-N 0.000 claims description 5
239000000969 carrier Substances 0.000 claims description 5
239000003085 diluting agent Substances 0.000 claims description 5
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
JLLYLQLDYORLBB-UHFFFAOYSA-N 5-bromo-n-methylthiophene-2-sulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(Br)S1 JLLYLQLDYORLBB-UHFFFAOYSA-N 0.000 claims description 4
208000006386 Bone Resorption Diseases 0.000 claims description 4
OKJSKLOXFXGOCG-UHFFFAOYSA-N (2,2-dioxo-3-phenyl-2lambda6-thia-1-azaspiro[4.5]dec-3-en-4-yl)methanamine Chemical compound C1CCC2(CC1)C(=C(S(=O)(=O)N2)C3=CC=CC=C3)CN OKJSKLOXFXGOCG-UHFFFAOYSA-N 0.000 claims description 3
125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 3
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 3
125000000753 cycloalkyl group Chemical group 0.000 claims description 3
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
IDVXTUKJAJQHQG-UHFFFAOYSA-N n-[[1-methyl-3-(4-nitrophenyl)-2,2-dioxo-2$l^{6}-thia-1-azaspiro[4.5]dec-3-en-4-yl]methyl]ethanamine Chemical compound O=S1(=O)N(C)C2(CCCCC2)C(CNCC)=C1C1=CC=C([N+]([O-])=O)C=C1 IDVXTUKJAJQHQG-UHFFFAOYSA-N 0.000 claims description 3
125000002971 oxazolyl group Chemical group 0.000 claims description 3
125000004076 pyridyl group Chemical group 0.000 claims description 3
125000000335 thiazolyl group Chemical group 0.000 claims description 3
125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 2
239000000825 pharmaceutical preparation Substances 0.000 claims description 2
230000004962 physiological condition Effects 0.000 claims description 2
150000002431 hydrogen Chemical class 0.000 claims 59
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 5
125000000896 monocarboxylic acid group Chemical group 0.000 claims 5
125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 2
HGQGOTDKOQQFOU-UHFFFAOYSA-N n-[[3-(4-bromophenyl)-2,2-dioxo-2$l^{6}-thia-1-azaspiro[4.5]dec-3-en-4-yl]methyl]ethanamine Chemical compound O=S1(=O)NC2(CCCCC2)C(CNCC)=C1C1=CC=C(Br)C=C1 HGQGOTDKOQQFOU-UHFFFAOYSA-N 0.000 claims 2
102100033367 Appetite-regulating hormone Human genes 0.000 claims 1
101710111255 Appetite-regulating hormone Proteins 0.000 claims 1
GKFCLVIXLZIPSB-UHFFFAOYSA-N n-[(1-methyl-2,2-dioxo-3-phenyl-2$l^{6}-thia-1-azaspiro[4.5]dec-3-en-4-yl)methyl]ethanamine Chemical compound O=S1(=O)N(C)C2(CCCCC2)C(CNCC)=C1C1=CC=CC=C1 GKFCLVIXLZIPSB-UHFFFAOYSA-N 0.000 claims 1
AEPDNJKNJBBNGP-UHFFFAOYSA-N n-[[5-(4-chlorophenyl)-3,3-dimethyl-1,1-dioxo-2h-1,2-thiazol-4-yl]methyl]ethanamine Chemical compound O=S1(=O)NC(C)(C)C(CNCC)=C1C1=CC=C(Cl)C=C1 AEPDNJKNJBBNGP-UHFFFAOYSA-N 0.000 claims 1
230000001575 pathological effect Effects 0.000 claims 1
238000003786 synthesis reaction Methods 0.000 abstract description 12
230000015572 biosynthetic process Effects 0.000 abstract description 10
239000000543 intermediate Substances 0.000 abstract description 8
241000124008 Mammalia Species 0.000 abstract description 5
125000001309 chloro group Chemical group Cl* 0.000 description 199
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 123
239000000203 mixture Substances 0.000 description 98
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 76
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 60
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 59
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 52
239000000047 product Substances 0.000 description 50
239000000460 chlorine Substances 0.000 description 49
239000000243 solution Substances 0.000 description 49
239000007787 solid Substances 0.000 description 48
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical class O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 43
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 42
238000002844 melting Methods 0.000 description 42
230000008018 melting Effects 0.000 description 42
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 37
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 36
GDKOYYDQISQOMH-UHFFFAOYSA-N 1-ethynylcyclohexan-1-amine Chemical compound C#CC1(N)CCCCC1 GDKOYYDQISQOMH-UHFFFAOYSA-N 0.000 description 34
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 33
239000011734 sodium Substances 0.000 description 31
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 28
125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 27
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 26
238000005160 1H NMR spectroscopy Methods 0.000 description 25
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 25
125000004287 oxazol-2-yl group Chemical group [H]C1=C([H])N=C(*)O1 0.000 description 25
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 24
239000004480 active ingredient Substances 0.000 description 24
238000004458 analytical method Methods 0.000 description 24
102100022831 Somatoliberin Human genes 0.000 description 22
101710142969 Somatoliberin Proteins 0.000 description 22
239000000095 Growth Hormone-Releasing Hormone Substances 0.000 description 21
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 19
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 18
150000002500 ions Chemical class 0.000 description 18
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 17
238000000354 decomposition reaction Methods 0.000 description 17
239000012044 organic layer Substances 0.000 description 17
239000000377 silicon dioxide Substances 0.000 description 17
229910052938 sodium sulfate Inorganic materials 0.000 description 17
235000011152 sodium sulphate Nutrition 0.000 description 17
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 16
239000007921 spray Substances 0.000 description 16
239000011541 reaction mixture Substances 0.000 description 15
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 14
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 14
238000006243 chemical reaction Methods 0.000 description 14
229940079593 drug Drugs 0.000 description 13
238000003756 stirring Methods 0.000 description 13
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 12
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
229920006395 saturated elastomer Polymers 0.000 description 12
239000012267 brine Substances 0.000 description 11
238000009472 formulation Methods 0.000 description 11
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 10
229920002472 Starch Polymers 0.000 description 10
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 10
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 10
108090000765 processed proteins & peptides Proteins 0.000 description 10
239000008107 starch Substances 0.000 description 10
235000019698 starch Nutrition 0.000 description 10
239000003826 tablet Substances 0.000 description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 9
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
150000001721 carbon Chemical group 0.000 description 9
239000003480 eluent Substances 0.000 description 9
239000000284 extract Substances 0.000 description 9
229910000104 sodium hydride Inorganic materials 0.000 description 9
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 8
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 8
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 8
150000002148 esters Chemical class 0.000 description 8
238000000605 extraction Methods 0.000 description 8
239000000706 filtrate Substances 0.000 description 8
235000019359 magnesium stearate Nutrition 0.000 description 8
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 8
238000005481 NMR spectroscopy Methods 0.000 description 7
239000002775 capsule Substances 0.000 description 7
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 7
WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 7
230000028327 secretion Effects 0.000 description 7
239000000741 silica gel Substances 0.000 description 7
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239000002904 solvent Substances 0.000 description 7
239000007858 starting material Substances 0.000 description 7
PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 6
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 6
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
150000001412 amines Chemical group 0.000 description 6
125000003277 amino group Chemical group 0.000 description 6
239000002585 base Substances 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
238000001816 cooling Methods 0.000 description 6
239000007789 gas Substances 0.000 description 6
125000005842 heteroatom Chemical group 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
238000001953 recrystallisation Methods 0.000 description 6
125000004924 2-naphthylethyl group Chemical group C1=C(C=CC2=CC=CC=C12)CC* 0.000 description 5
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
150000001413 amino acids Chemical class 0.000 description 5
239000004615 ingredient Substances 0.000 description 5
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239000002674 ointment Substances 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
125000000962 organic group Chemical group 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
239000001301 oxygen Chemical group 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
KGCNHWXDPDPSBV-UHFFFAOYSA-N p-nitrobenzyl chloride Chemical compound [O-][N+](=O)C1=CC=C(CCl)C=C1 KGCNHWXDPDPSBV-UHFFFAOYSA-N 0.000 description 1
125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
230000004526 pharmaceutical effect Effects 0.000 description 1
239000012071 phase Substances 0.000 description 1
229960003531 phenolsulfonphthalein Drugs 0.000 description 1
DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical compound CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 1
229950009215 phenylbutanoic acid Drugs 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
125000005544 phthalimido group Chemical group 0.000 description 1
239000006187 pill Substances 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
230000017363 positive regulation of growth Effects 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011736 potassium bicarbonate Substances 0.000 description 1
235000015497 potassium bicarbonate Nutrition 0.000 description 1
229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
235000011181 potassium carbonates Nutrition 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
229960000208 pralmorelin Drugs 0.000 description 1
150000003141 primary amines Chemical group 0.000 description 1
KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical compound CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000005470 propylenyl group Chemical group 0.000 description 1
125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
238000000746 purification Methods 0.000 description 1
239000008213 purified water Substances 0.000 description 1
150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
150000003242 quaternary ammonium salts Chemical class 0.000 description 1
239000003488 releasing hormone Substances 0.000 description 1
239000003340 retarding agent Substances 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
238000012216 screening Methods 0.000 description 1
230000000580 secretagogue effect Effects 0.000 description 1
229940095743 selective estrogen receptor modulator Drugs 0.000 description 1
239000000333 selective estrogen receptor modulator Substances 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000002356 single layer Substances 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
238000007711 solidification Methods 0.000 description 1
230000008023 solidification Effects 0.000 description 1
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 1
229960000553 somatostatin Drugs 0.000 description 1
238000001179 sorption measurement Methods 0.000 description 1
241000894007 species Species 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000012058 sterile packaged powder Substances 0.000 description 1
239000006190 sub-lingual tablet Substances 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
229960004793 sucrose Drugs 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
150000003458 sulfonic acid derivatives Chemical class 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
230000002195 synergetic effect Effects 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
QFMOPRNLDIPINY-UHFFFAOYSA-N tert-butyl 3-(methylamino)propanoate Chemical compound CNCCC(=O)OC(C)(C)C QFMOPRNLDIPINY-UHFFFAOYSA-N 0.000 description 1
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
238000011287 therapeutic dose Methods 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
230000037317 transdermal delivery Effects 0.000 description 1
238000012546 transfer Methods 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
239000012588 trypsin Substances 0.000 description 1
238000000870 ultraviolet spectroscopy Methods 0.000 description 1
125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
229960003726 vasopressin Drugs 0.000 description 1
239000001993 wax Substances 0.000 description 1
238000005303 weighing Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
229940071104 xylenesulfonate Drugs 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/04—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems
- C07D275/06—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems with hetero atoms directly attached to the ring sulfur atom
- 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
- C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
- 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
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
- 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)
Veterinary Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Animal Behavior & Ethology (AREA)
Bioinformatics & Cheminformatics (AREA)
Public Health (AREA)
Engineering & Computer Science (AREA)
Genetics & Genomics (AREA)
Biophysics (AREA)
Biochemistry (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Diabetes (AREA)
Endocrinology (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Peptides Or Proteins (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

SK418-2003A 2000-10-13 2001-10-09 Substituted dipeptides as growth hormone secretagogues SK4182003A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US24045600P	2000-10-13	2000-10-13
PCT/US2001/027756 WO2002032888A1 (en)	2000-10-13	2001-10-09	Substituted dipeptides as growth hormone secretagogues

Publications (1)

Publication Number	Publication Date
SK4182003A3 true SK4182003A3 (en)	2004-01-08

Family

ID=22906598

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK418-2003A SK4182003A3 (en)	2000-10-13	2001-10-09	Substituted dipeptides as growth hormone secretagogues

Country Status (26)

Country	Link
EP (1)	EP1326851B1 (de)
JP (1)	JP2004511552A (de)
KR (1)	KR20030042014A (de)
CN (1)	CN1469871A (de)
AT (1)	ATE270280T1 (de)
AU (2)	AU1121902A (de)
BR (1)	BR0114630A (de)
CA (1)	CA2419388A1 (de)
CZ (1)	CZ20031029A3 (de)
DE (1)	DE60104141T2 (de)
DZ (1)	DZ3482A1 (de)
EA (1)	EA006102B1 (de)
EC (1)	ECSP034551A (de)
ES (1)	ES2223926T3 (de)
HR (1)	HRP20030288B1 (de)
HU (1)	HUP0301351A3 (de)
IL (1)	IL154809A0 (de)
MX (1)	MXPA03003217A (de)
NO (1)	NO20031687L (de)
NZ (1)	NZ524232A (de)
PL (1)	PL361675A1 (de)
PT (1)	PT1326851E (de)
SK (1)	SK4182003A3 (de)
TR (1)	TR200402046T4 (de)
WO (1)	WO2002032888A1 (de)
ZA (1)	ZA200301720B (de)

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JPWO2009154132A1 (ja)	2008-06-19	2011-12-01	Ｍｓｄ株式会社	スピロジアミン−ジアリールケトオキシム誘導体
CA2730603C (en)	2008-07-16	2019-09-24	Synergy Pharmaceuticals Inc.	Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders
JPWO2010013595A1 (ja)	2008-07-30	2012-01-12	Ｍｓｄ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
EP2348857B1 (de)	2008-10-22	2016-02-24	Merck Sharp & Dohme Corp.	Neue cyclische benzimidazolderivate als antidiabetika
EP2350010B1 (de)	2008-10-30	2014-03-26	Merck Sharp & Dohme Corp.	Isonikotinamide als orexinrezeptorantagonisten
JP5557845B2 (ja)	2008-10-31	2014-07-23	メルク・シャープ・アンド・ドーム・コーポレーション	糖尿病用剤として有用な新規環状ベンゾイミダゾール誘導体
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WO2014022528A1 (en)	2012-08-02	2014-02-06	Merck Sharp & Dohme Corp.	Antidiabetic tricyclic compounds
WO2014130608A1 (en)	2013-02-22	2014-08-28	Merck Sharp & Dohme Corp.	Antidiabetic bicyclic compounds
WO2014139388A1 (en)	2013-03-14	2014-09-18	Merck Sharp & Dohme Corp.	Novel indole derivatives useful as anti-diabetic agents
JP2016514670A (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	他の薬物と組み合わせたグアニル酸シクラーゼ受容体アゴニスト
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
EA201592263A1 (ru)	2013-06-05	2016-05-31	Синерджи Фармасьютикалз, Инк.	Ультрачистые агонисты гуанилатциклазы c, способ их получения и использования
WO2015051496A1 (en)	2013-10-08	2015-04-16	Merck Sharp & Dohme Corp.	Antidiabetic tricyclic compounds
EP3186242B1 (de)	2014-08-29	2021-10-06	Tes Pharma S.r.l.	Inhibitoren von alpha-amino-beta-carboxymuconsäure semialdehyd-decarboxylase
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2001
- 2001-10-09 HU HU0301351A patent/HUP0301351A3/hu unknown
- 2001-10-09 CN CNA018172822A patent/CN1469871A/zh active Pending
- 2001-10-09 EA EA200300462A patent/EA006102B1/ru not_active IP Right Cessation
- 2001-10-09 SK SK418-2003A patent/SK4182003A3/sk unknown
- 2001-10-09 MX MXPA03003217A patent/MXPA03003217A/es unknown
- 2001-10-09 CA CA002419388A patent/CA2419388A1/en not_active Abandoned
- 2001-10-09 IL IL15480901A patent/IL154809A0/xx unknown
- 2001-10-09 HR HR20030288A patent/HRP20030288B1/xx not_active IP Right Cessation
- 2001-10-09 TR TR2004/02046T patent/TR200402046T4/xx unknown
- 2001-10-09 PT PT01979233T patent/PT1326851E/pt unknown
- 2001-10-09 AT AT01979233T patent/ATE270280T1/de not_active IP Right Cessation
- 2001-10-09 WO PCT/US2001/027756 patent/WO2002032888A1/en not_active Ceased
- 2001-10-09 CZ CZ20031029A patent/CZ20031029A3/cs unknown
- 2001-10-09 ES ES01979233T patent/ES2223926T3/es not_active Expired - Lifetime
- 2001-10-09 NZ NZ524232A patent/NZ524232A/en unknown
- 2001-10-09 AU AU1121902A patent/AU1121902A/xx active Pending
- 2001-10-09 PL PL01361675A patent/PL361675A1/xx not_active Application Discontinuation
- 2001-10-09 DE DE60104141T patent/DE60104141T2/de not_active Expired - Lifetime
- 2001-10-09 EP EP01979233A patent/EP1326851B1/de not_active Expired - Lifetime
- 2001-10-09 KR KR10-2003-7005203A patent/KR20030042014A/ko not_active Withdrawn
- 2001-10-09 JP JP2002536270A patent/JP2004511552A/ja active Pending
- 2001-10-09 BR BR0114630-0A patent/BR0114630A/pt not_active IP Right Cessation
- 2001-10-09 DZ DZ013482A patent/DZ3482A1/fr active
- 2001-10-09 AU AU2002211219A patent/AU2002211219B2/en not_active Ceased
2003
- 2003-02-28 ZA ZA200301720A patent/ZA200301720B/en unknown
- 2003-04-10 EC EC2003004551A patent/ECSP034551A/es unknown
- 2003-04-11 NO NO20031687A patent/NO20031687L/no unknown

Also Published As

Publication number	Publication date
ZA200301720B (en)	2004-06-21
EA200300462A1 (ru)	2003-08-28
CA2419388A1 (en)	2002-04-25
HK1058194A1 (en)	2004-05-07
HRP20030288B1 (en)	2005-02-28
HUP0301351A3 (en)	2007-05-29
KR20030042014A (ko)	2003-05-27
MXPA03003217A (es)	2003-06-06
AU2002211219B2 (en)	2006-09-14
HRP20030288A2 (en)	2004-02-29
IL154809A0 (en)	2003-10-31
ES2223926T3 (es)	2005-03-01
NZ524232A (en)	2005-01-28
ATE270280T1 (de)	2004-07-15
TR200402046T4 (tr)	2004-10-21
WO2002032888A1 (en)	2002-04-25
EP1326851B1 (de)	2004-06-30
PL361675A1 (en)	2004-10-04
CN1469871A (zh)	2004-01-21
DE60104141D1 (de)	2004-08-05
DE60104141T2 (de)	2005-06-30
NO20031687L (no)	2003-05-08
EA006102B1 (ru)	2005-08-25
ECSP034551A (es)	2003-05-26
BR0114630A (pt)	2003-07-01
AU1121902A (en)	2002-04-29
PT1326851E (pt)	2004-11-30
JP2004511552A (ja)	2004-04-15
CZ20031029A3 (cs)	2003-09-17
EP1326851A1 (de)	2003-07-16
DZ3482A1 (fr)	2002-04-25
NO20031687D0 (no)	2003-04-11
HUP0301351A2 (hu)	2003-11-28

Legal Events

Date	Code	Title	Description
2012-04-03	FB9A	Suspension of patent application procedure

Publication	Publication Date	Title
EP1326851B1 (de)	2004-06-30	Substituierte dipeptide zur förderung der sekretion von wachstumshormon
AU2002211219A1 (en)	2002-07-04	Substituted dipeptides as growth hormone secretagogues
US6639076B1 (en)	2003-10-28	Growth hormone secretagogues
CA2302467A1 (en)	1999-02-25	Growth hormone secretagogues
WO1997006803A1 (en)	1997-02-27	2-acylaminopropanamides as growth hormone secretagogues
CA2300848A1 (en)	1999-02-25	Treatment of congestive heart failure with growth hormone secretagogues
US6329342B1 (en)	2001-12-11	Treatment of congestive heart failure with growth hormone secretagogues
EP1153034B1 (de)	2007-10-17	Sekretionsfordermittel fur wachtumshormon
EP1497317B1 (de)	2006-09-06	Dipeptidische wachstumshormonsekretionsförderern
US7125840B2 (en)	2006-10-24	Substituted dipeptides as growth hormone secretagogues
US6828331B1 (en)	2004-12-07	Growth hormone secretagogues
HK1058194B (en)	2005-04-22	Substituted dipeptides as growth hormone secretagogues
US20060167268A1 (en)	2006-07-27	Growth hormone secretagogues
CZ2000596A3 (cs)	2000-12-13	Sekretagogy růstového hormonu, způsob jejich přípravy a farmaceutický prostředek s jejich obsahem