CN1571796A - 黑皮素受体配体 - Google Patents
黑皮素受体配体 Download PDFInfo
- Publication number
- CN1571796A CN1571796A CNA01816384XA CN01816384A CN1571796A CN 1571796 A CN1571796 A CN 1571796A CN A01816384X A CNA01816384X A CN A01816384XA CN 01816384 A CN01816384 A CN 01816384A CN 1571796 A CN1571796 A CN 1571796A
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- Prior art keywords
- hydrogen
- alkyl
- group
- milliliters
- ring
- Prior art date
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- 239000003446 ligand Substances 0.000 title abstract description 9
- 108090000950 Melanocortin Receptors Proteins 0.000 title description 12
- 102000004378 Melanocortin Receptors Human genes 0.000 title description 11
- 150000001408 amides Chemical class 0.000 claims abstract description 125
- 150000003839 salts Chemical class 0.000 claims abstract description 27
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 16
- 201000010099 disease Diseases 0.000 claims abstract description 14
- 150000002148 esters Chemical class 0.000 claims abstract description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- 150000003949 imides Chemical class 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 203
- 125000000217 alkyl group Chemical group 0.000 claims description 160
- 239000001257 hydrogen Substances 0.000 claims description 138
- 229910052739 hydrogen Inorganic materials 0.000 claims description 138
- 229910052799 carbon Inorganic materials 0.000 claims description 85
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical class [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 72
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 72
- 125000003118 aryl group Chemical group 0.000 claims description 70
- 150000002431 hydrogen Chemical group 0.000 claims description 64
- -1 1H-indenyl Chemical group 0.000 claims description 61
- 150000001721 carbon Chemical group 0.000 claims description 49
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 47
- 125000001072 heteroaryl group Chemical group 0.000 claims description 45
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 41
- 125000003368 amide group Chemical group 0.000 claims description 40
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 37
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 36
- 125000004432 carbon atom Chemical group C* 0.000 claims description 35
- 229910052736 halogen Inorganic materials 0.000 claims description 32
- 150000002367 halogens Chemical class 0.000 claims description 32
- 125000003545 alkoxy group Chemical group 0.000 claims description 31
- 125000004429 atom Chemical group 0.000 claims description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
- 125000002252 acyl group Chemical group 0.000 claims description 26
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 23
- 239000011737 fluorine Chemical group 0.000 claims description 23
- 229910052731 fluorine Inorganic materials 0.000 claims description 23
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 22
- 125000003342 alkenyl group Chemical group 0.000 claims description 21
- 125000000304 alkynyl group Chemical group 0.000 claims description 21
- 125000000623 heterocyclic group Chemical group 0.000 claims description 21
- 125000004104 aryloxy group Chemical group 0.000 claims description 20
- 125000002837 carbocyclic group Chemical group 0.000 claims description 20
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 18
- 150000003573 thiols Chemical class 0.000 claims description 16
- 125000004423 acyloxy group Chemical group 0.000 claims description 15
- 239000000460 chlorine Substances 0.000 claims description 14
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 14
- 230000037396 body weight Effects 0.000 claims description 13
- 125000003282 alkyl amino group Chemical group 0.000 claims description 12
- 125000004414 alkyl thio group Chemical group 0.000 claims description 11
- 229910052801 chlorine Inorganic materials 0.000 claims description 11
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 10
- 208000008589 Obesity Diseases 0.000 claims description 10
- 235000020824 obesity Nutrition 0.000 claims description 9
- 241001465754 Metazoa Species 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 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 7
- 125000002619 bicyclic group Chemical group 0.000 claims description 7
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 6
- 125000002541 furyl group Chemical group 0.000 claims description 6
- 230000014509 gene expression Effects 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 5
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 5
- 102000001189 Cyclic Peptides Human genes 0.000 claims description 5
- 108010069514 Cyclic Peptides Proteins 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- 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 claims description 4
- 125000005110 aryl thio group Chemical group 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 230000036772 blood pressure Effects 0.000 claims description 3
- 239000008103 glucose Substances 0.000 claims description 3
- 230000007062 hydrolysis Effects 0.000 claims description 3
- 238000006460 hydrolysis reaction Methods 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 210000001672 ovary Anatomy 0.000 claims description 3
- 125000002971 oxazolyl group Chemical group 0.000 claims description 3
- 229930192474 thiophene Natural products 0.000 claims description 3
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 3
- 206010006895 Cachexia Diseases 0.000 claims description 2
- 206010009944 Colon cancer Diseases 0.000 claims description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 2
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 2
- 208000005189 Embolism Diseases 0.000 claims description 2
- 201000005569 Gout Diseases 0.000 claims description 2
- 206010020112 Hirsutism Diseases 0.000 claims description 2
- 206010020772 Hypertension Diseases 0.000 claims description 2
- 206010022489 Insulin Resistance Diseases 0.000 claims description 2
- 208000019255 Menstrual disease Diseases 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 claims description 2
- 208000030934 Restrictive pulmonary disease Diseases 0.000 claims description 2
- 208000001435 Thromboembolism Diseases 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- 210000003679 cervix uteri Anatomy 0.000 claims description 2
- 201000010989 colorectal carcinoma Diseases 0.000 claims description 2
- 208000029078 coronary artery disease Diseases 0.000 claims description 2
- 125000004122 cyclic group Chemical group 0.000 claims description 2
- 206010012601 diabetes mellitus Diseases 0.000 claims description 2
- 125000005265 dialkylamine group Chemical group 0.000 claims description 2
- 210000004696 endometrium Anatomy 0.000 claims description 2
- 210000000232 gallbladder Anatomy 0.000 claims description 2
- 208000020694 gallbladder disease Diseases 0.000 claims description 2
- 230000036512 infertility Effects 0.000 claims description 2
- 208000000509 infertility Diseases 0.000 claims description 2
- 231100000535 infertility Toxicity 0.000 claims description 2
- 210000005075 mammary gland Anatomy 0.000 claims description 2
- 201000008482 osteoarthritis Diseases 0.000 claims description 2
- 210000002307 prostate Anatomy 0.000 claims description 2
- 201000002859 sleep apnea Diseases 0.000 claims description 2
- 125000001425 triazolyl group Chemical group 0.000 claims description 2
- FGFBEHFJSQBISW-UHFFFAOYSA-N 1h-cyclopenta[b]pyridine Chemical compound C1=CNC2=CC=CC2=C1 FGFBEHFJSQBISW-UHFFFAOYSA-N 0.000 claims 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims 2
- 125000001041 indolyl group Chemical group 0.000 claims 2
- 125000005956 isoquinolyl group Chemical group 0.000 claims 2
- 125000005493 quinolyl group Chemical group 0.000 claims 2
- 125000003435 aroyl group Chemical group 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 104
- 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 abstract 1
- 150000004677 hydrates Chemical class 0.000 abstract 1
- 230000003287 optical effect Effects 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 235
- 239000000243 solution Substances 0.000 description 194
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 177
- 239000000203 mixture Substances 0.000 description 138
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 123
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 120
- 239000002904 solvent Substances 0.000 description 118
- 230000002829 reductive effect Effects 0.000 description 105
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 94
- 238000004128 high performance liquid chromatography Methods 0.000 description 81
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 78
- 238000002360 preparation method Methods 0.000 description 77
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 64
- 229940005605 valeric acid Drugs 0.000 description 64
- 108090000765 processed proteins & peptides Proteins 0.000 description 62
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 61
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 60
- 239000000370 acceptor Substances 0.000 description 59
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 57
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 56
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 52
- 235000019439 ethyl acetate Nutrition 0.000 description 49
- 239000012043 crude product Substances 0.000 description 47
- 239000000047 product Substances 0.000 description 47
- 238000001035 drying Methods 0.000 description 45
- 239000012071 phase Substances 0.000 description 43
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 42
- 239000002994 raw material Substances 0.000 description 38
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 36
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 34
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 34
- 238000006243 chemical reaction Methods 0.000 description 34
- 239000000725 suspension Substances 0.000 description 34
- 238000003756 stirring Methods 0.000 description 33
- 239000002253 acid Substances 0.000 description 32
- 238000005406 washing Methods 0.000 description 31
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 30
- 229940024606 amino acid Drugs 0.000 description 29
- 239000007864 aqueous solution Substances 0.000 description 29
- 238000002390 rotary evaporation Methods 0.000 description 29
- 229960001866 silicon dioxide Drugs 0.000 description 29
- 229910052763 palladium Inorganic materials 0.000 description 28
- 239000000741 silica gel Substances 0.000 description 28
- 229910002027 silica gel Inorganic materials 0.000 description 28
- 235000001014 amino acid Nutrition 0.000 description 27
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 27
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
- 238000010828 elution Methods 0.000 description 26
- 238000005984 hydrogenation reaction Methods 0.000 description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 25
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 25
- 150000001413 amino acids Chemical class 0.000 description 25
- 238000004587 chromatography analysis Methods 0.000 description 25
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
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- 238000013019 agitation Methods 0.000 description 21
- 238000010168 coupling process Methods 0.000 description 21
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 18
- 235000017550 sodium carbonate Nutrition 0.000 description 18
- 229910000029 sodium carbonate Inorganic materials 0.000 description 18
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 18
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- 239000000908 ammonium hydroxide Substances 0.000 description 17
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 17
- BXGTVNLGPMZLAZ-UHFFFAOYSA-N n'-ethylmethanediimine;hydrochloride Chemical class Cl.CCN=C=N BXGTVNLGPMZLAZ-UHFFFAOYSA-N 0.000 description 16
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- BQXUPNKLZNSUMC-YUQWMIPFSA-N CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 Chemical compound CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 BQXUPNKLZNSUMC-YUQWMIPFSA-N 0.000 description 12
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- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 11
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- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
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- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 8
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- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 7
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- 241000124008 Mammalia Species 0.000 description 7
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Classifications
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- 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
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
- C07K5/1008—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
-
- 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
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1016—Tetrapeptides with the first amino acid being neutral and aromatic or cycloaliphatic
-
- 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
- C07K5/10—Tetrapeptides
- C07K5/1024—Tetrapeptides with the first amino acid being heterocyclic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- Health & Medical Sciences (AREA)
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Diabetes (AREA)
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- Obesity (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Endocrinology (AREA)
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US23585800P | 2000-09-27 | 2000-09-27 | |
| US60/235,858 | 2000-09-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1571796A true CN1571796A (zh) | 2005-01-26 |
Family
ID=22887187
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA01816384XA Pending CN1571796A (zh) | 2000-09-27 | 2001-09-26 | 黑皮素受体配体 |
Country Status (19)
| Country | Link |
|---|---|
| EP (1) | EP1409540A2 (ko) |
| JP (1) | JP2004509974A (ko) |
| KR (1) | KR100519204B1 (ko) |
| CN (1) | CN1571796A (ko) |
| AR (1) | AR030806A1 (ko) |
| AU (2) | AU2001296313B2 (ko) |
| BR (1) | BR0114257A (ko) |
| CA (1) | CA2420045A1 (ko) |
| CZ (1) | CZ2003788A3 (ko) |
| HU (1) | HUP0303085A2 (ko) |
| IL (1) | IL154437A0 (ko) |
| MX (1) | MXPA03002691A (ko) |
| NO (1) | NO20031287L (ko) |
| NZ (1) | NZ524190A (ko) |
| PE (1) | PE20020447A1 (ko) |
| PL (1) | PL362003A1 (ko) |
| RU (1) | RU2246501C2 (ko) |
| WO (1) | WO2002026774A2 (ko) |
| ZA (1) | ZA200301561B (ko) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106966927A (zh) * | 2017-04-13 | 2017-07-21 | 菲立化学工程（上海）有限公司 | 一种抗艾滋病药物中间体重氮酮与氯酮的合成方法 |
Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7176279B2 (en) | 2000-06-28 | 2007-02-13 | Palatin Technologies, Inc. | Cyclic peptide compositions and methods for treatment of sexual dysfunction |
| US7226755B1 (en) | 2002-09-25 | 2007-06-05 | The Procter & Gamble Company | HPTPbeta as a target in treatment of angiogenesis mediated disorders |
| US7507568B2 (en) | 2002-09-25 | 2009-03-24 | The Proctor & Gamble Company | Three dimensional coordinates of HPTPbeta |
| CN1909930B (zh) | 2004-01-21 | 2015-12-16 | 诺和诺德医疗保健公司 | 转谷氨酰胺酶介导的肽的接合 |
| RU2309144C2 (ru) * | 2005-03-25 | 2007-10-27 | Общество С Ограниченной Ответственностью "Фарминтерпрайсез" | Фенилсодержащие n-ацильные производные аминов, способ их получения, фармацевтическая композиция и их применение в качестве противовоспалительных и анальгетических средств |
| US8247530B2 (en) | 2005-11-08 | 2012-08-21 | Palatin Technologies, Inc. | N-alkylated cyclic peptide melanocortin agonists |
| EP2371865B1 (en) | 2006-04-07 | 2017-07-12 | Aerpio Therapeutics, Inc. | Antibodies that bind human protein tyrosine phosphatase beta (HPTP-ß) and uses thereof |
| RU2303597C1 (ru) * | 2006-05-12 | 2007-07-27 | Иващенко Андрей Александрович | Фармацевтическая композиция, способы ее получения и применения |
| US7622593B2 (en) | 2006-06-27 | 2009-11-24 | The Procter & Gamble Company | Human protein tyrosine phosphatase inhibitors and methods of use |
| US8846685B2 (en) | 2006-06-27 | 2014-09-30 | Aerpio Therapeutics Inc. | Human protein tyrosine phosphatase inhibitors and methods of use |
| US7589212B2 (en) | 2006-06-27 | 2009-09-15 | Procter & Gamble Company | Human protein tyrosine phosphatase inhibitors and methods of use |
| US7795444B2 (en) | 2006-06-27 | 2010-09-14 | Warner Chilcott Company | Human protein tyrosine phosphatase inhibitors and methods of use |
| WO2008107362A2 (en) * | 2007-03-07 | 2008-09-12 | Novo Nordisk Health Care Ag | Stabiliser and inhibitors of factor vii |
| AU2009257631B2 (en) | 2008-06-09 | 2014-07-24 | Palatin Technologies, Inc. | Melanocortin receptor-specific peptides for treatment of sexual dysfunction |
| US9096555B2 (en) | 2009-01-12 | 2015-08-04 | Aerpio Therapeutics, Inc. | Methods for treating vascular leak syndrome |
| UY32690A (es) | 2009-06-08 | 2011-01-31 | Astrazeneca Ab | Péptidos específicos para receptores de melanocortina |
| KR101726893B1 (ko) | 2009-06-08 | 2017-04-13 | 팔라틴 테크놀로지스 인코포레이티드 | 멜라노코르틴 수용체-특이적 펩티드 |
| EP2440572B1 (en) | 2009-06-08 | 2017-04-05 | Palatin Technologies, Inc. | Lactam-bridged melanocortin receptor-specific peptides |
| RU2519123C2 (ru) | 2009-07-06 | 2014-06-10 | Аэрпио Терапьютикс Инк. | Соединения, композиции и способы предупреждения метастазов раковых клеток |
| US8883832B2 (en) | 2009-07-06 | 2014-11-11 | Aerpio Therapeutics Inc. | Compounds, compositions, and methods for preventing metastasis of cancer cells |
| CN102686601A (zh) * | 2009-11-16 | 2012-09-19 | 益普生制药股份有限公司 | 合成Ac-Arg-环(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2的方法 |
| MX2012005859A (es) | 2009-11-23 | 2012-12-17 | Palatin Technologies Inc | Peptidos lineales especificos del receptor de melanocortina-1. |
| WO2011063366A1 (en) | 2009-11-23 | 2011-05-26 | Palatin Technologies, Inc. | Melanocortin-1 receptor-specific cyclic peptides |
| US10340082B2 (en) | 2015-05-12 | 2019-07-02 | Capacitor Sciences Incorporated | Capacitor and method of production thereof |
| US10347423B2 (en) | 2014-05-12 | 2019-07-09 | Capacitor Sciences Incorporated | Solid multilayer structure as semiproduct for meta-capacitor |
| CA2947983C (en) | 2014-05-12 | 2022-10-25 | Capacitor Sciences Incorporated | Energy storage device and method of production thereof |
| SG11201703441YA (en) | 2014-11-04 | 2017-05-30 | Capacitor Sciences Inc | Energy storage devices and methods of production thereof |
| US9852846B2 (en) | 2015-02-26 | 2017-12-26 | Capacitor Sciences Incorporated | Self-healing capacitor and methods of production thereof |
| US9932358B2 (en) | 2015-05-21 | 2018-04-03 | Capacitor Science Incorporated | Energy storage molecular material, crystal dielectric layer and capacitor |
| US9941051B2 (en) | 2015-06-26 | 2018-04-10 | Capactor Sciences Incorporated | Coiled capacitor |
| US10026553B2 (en) | 2015-10-21 | 2018-07-17 | Capacitor Sciences Incorporated | Organic compound, crystal dielectric layer and capacitor |
| US10305295B2 (en) | 2016-02-12 | 2019-05-28 | Capacitor Sciences Incorporated | Energy storage cell, capacitive energy storage module, and capacitive energy storage system |
| US10153087B2 (en) | 2016-04-04 | 2018-12-11 | Capacitor Sciences Incorporated | Electro-polarizable compound and capacitor |
| US9978517B2 (en) | 2016-04-04 | 2018-05-22 | Capacitor Sciences Incorporated | Electro-polarizable compound and capacitor |
| US10395841B2 (en) | 2016-12-02 | 2019-08-27 | Capacitor Sciences Incorporated | Multilayered electrode and film energy storage device |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU7464998A (en) * | 1997-10-27 | 1999-05-17 | Trega Biosciences, Inc. | Melanocortin receptor ligands and methods of using same |
| HUP0202203A3 (en) * | 1999-03-29 | 2003-09-29 | Procter & Gamble | Melanocortin receptor ligands, pharmaceutical compositions comprising thereof and method for their preparation |
| US6579968B1 (en) * | 1999-06-29 | 2003-06-17 | Palatin Technologies, Inc. | Compositions and methods for treatment of sexual dysfunction |
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2001
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- 2001-09-26 WO PCT/US2001/030051 patent/WO2002026774A2/en active IP Right Grant
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- 2001-09-26 MX MXPA03002691A patent/MXPA03002691A/es unknown
- 2001-09-26 AU AU2001296313A patent/AU2001296313B2/en not_active Ceased
- 2001-09-26 PL PL36200301A patent/PL362003A1/xx not_active Application Discontinuation
- 2001-09-26 BR BR0114257-7A patent/BR0114257A/pt not_active IP Right Cessation
- 2001-09-26 HU HU0303085A patent/HUP0303085A2/hu unknown
- 2001-09-26 CA CA002420045A patent/CA2420045A1/en not_active Abandoned
- 2001-09-26 IL IL15443701A patent/IL154437A0/xx unknown
- 2001-09-26 RU RU2003112211/04A patent/RU2246501C2/ru not_active IP Right Cessation
- 2001-09-26 CN CNA01816384XA patent/CN1571796A/zh active Pending
- 2001-09-26 EP EP01977175A patent/EP1409540A2/en not_active Withdrawn
- 2001-09-26 NZ NZ524190A patent/NZ524190A/en unknown
- 2001-09-26 JP JP2002531157A patent/JP2004509974A/ja active Pending
- 2001-09-26 AU AU9631301A patent/AU9631301A/xx active Pending
- 2001-09-27 PE PE2001000965A patent/PE20020447A1/es not_active Application Discontinuation
- 2001-09-27 AR ARP010104557A patent/AR030806A1/es unknown
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2003
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- 2003-03-20 NO NO20031287A patent/NO20031287L/no not_active Application Discontinuation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106966927A (zh) * | 2017-04-13 | 2017-07-21 | 菲立化学工程（上海）有限公司 | 一种抗艾滋病药物中间体重氮酮与氯酮的合成方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| AU9631301A (en) | 2002-04-08 |
| RU2246501C2 (ru) | 2005-02-20 |
| NZ524190A (en) | 2004-09-24 |
| ZA200301561B (en) | 2004-03-10 |
| HUP0303085A2 (hu) | 2003-12-29 |
| JP2004509974A (ja) | 2004-04-02 |
| PL362003A1 (en) | 2004-10-18 |
| IL154437A0 (en) | 2003-09-17 |
| KR100519204B1 (ko) | 2005-10-06 |
| NO20031287D0 (no) | 2003-03-20 |
| PE20020447A1 (es) | 2002-07-02 |
| NO20031287L (no) | 2003-03-20 |
| CA2420045A1 (en) | 2002-04-04 |
| CZ2003788A3 (cs) | 2003-08-13 |
| MXPA03002691A (es) | 2003-06-06 |
| KR20030061814A (ko) | 2003-07-22 |
| WO2002026774A2 (en) | 2002-04-04 |
| AU2001296313B2 (en) | 2005-06-02 |
| EP1409540A2 (en) | 2004-04-21 |
| AR030806A1 (es) | 2003-09-03 |
| BR0114257A (pt) | 2003-07-01 |
| WO2002026774A3 (en) | 2003-03-27 |
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