NO322910B1 - 4-Pyridyl-N-acyl-L-fenylalaniner, anvendelse av disse som medikamenter, farmasoytiske preparater inneholdende slike forbindelser og fremgangsmate for fremstilling av disse. - Google Patents

4-Pyridyl-N-acyl-L-fenylalaniner, anvendelse av disse som medikamenter, farmasoytiske preparater inneholdende slike forbindelser og fremgangsmate for fremstilling av disse. Download PDF

Info

Publication number: NO322910B1
Authority: NO; Norway
Prior art keywords: alkyl; hydrogen; oxo; carbonyl; pyridinyl
Prior art date: 1999-12-06

Application number

NO20022650A

Other languages

English (en)

Norwegian (no)

Other versions

NO20022650D0 (no

NO20022650L (no

Inventor

Jefferson Wright Tilley

Achyutharao Sidduri

Gerald Lewis Kaplan

Original Assignee

Hoffmann La Roche

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.)

1999-12-06

Filing date

2002-06-05

Publication date

2006-12-18

2002-06-05 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

2002-06-05 Publication of NO20022650D0 publication Critical patent/NO20022650D0/no

2002-06-05 Publication of NO20022650L publication Critical patent/NO20022650L/no

2006-12-18 Publication of NO322910B1 publication Critical patent/NO322910B1/no

Links

150000001875 compounds Chemical class 0.000 title claims description 154
238000000034 method Methods 0.000 title claims description 33
239000003814 drug Substances 0.000 title claims description 10
239000000825 pharmaceutical preparation Substances 0.000 title claims description 8
238000002360 preparation method Methods 0.000 title description 64
229910052739 hydrogen Inorganic materials 0.000 claims description 133
239000001257 hydrogen Substances 0.000 claims description 132
-1 Q-C6alkylsulfinyl Chemical group 0.000 claims description 106
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 99
150000002431 hydrogen Chemical class 0.000 claims description 76
229910052736 halogen Inorganic materials 0.000 claims description 53
150000002367 halogens Chemical class 0.000 claims description 53
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 49
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 44
125000000217 alkyl group Chemical group 0.000 claims description 40
229960005190 phenylalanine Drugs 0.000 claims description 36
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
125000001624 naphthyl group Chemical group 0.000 claims description 26
239000000460 chlorine Substances 0.000 claims description 23
108010008212 Integrin alpha4beta1 Proteins 0.000 claims description 19
108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 claims description 19
102100023543 Vascular cell adhesion protein 1 Human genes 0.000 claims description 19
230000027455 binding Effects 0.000 claims description 17
125000004494 ethyl ester group Chemical group 0.000 claims description 17
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 16
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 13
229910052757 nitrogen Inorganic materials 0.000 claims description 13
UJSGTHFOHGFQMM-KRWDZBQOSA-N (2s)-2-[(2,6-dichlorobenzoyl)amino]-3-[4-[1,4-dimethyl-2-oxo-6-(trifluoromethyl)pyridin-3-yl]phenyl]propanoic acid Chemical compound C1=C(C(F)(F)F)N(C)C(=O)C(C=2C=CC(C[C@H](NC(=O)C=3C(=CC=CC=3Cl)Cl)C(O)=O)=CC=2)=C1C UJSGTHFOHGFQMM-KRWDZBQOSA-N 0.000 claims description 12
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 12
125000003545 alkoxy group Chemical group 0.000 claims description 12
208000006673 asthma Diseases 0.000 claims description 12
150000003839 salts Chemical class 0.000 claims description 11
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
229910052717 sulfur Inorganic materials 0.000 claims description 10
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 9
229910052801 chlorine Inorganic materials 0.000 claims description 9
125000004093 cyano group Chemical group *C#N 0.000 claims description 9
125000001072 heteroaryl group Chemical group 0.000 claims description 9
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
WVTAFEUTNNWYQO-SFHVURJKSA-N (2s)-2-[(2,6-dichlorobenzoyl)amino]-3-[4-(1,4-dimethyl-2-oxopyridin-3-yl)phenyl]propanoic acid Chemical compound C1=CN(C)C(=O)C(C=2C=CC(C[C@H](NC(=O)C=3C(=CC=CC=3Cl)Cl)C(O)=O)=CC=2)=C1C WVTAFEUTNNWYQO-SFHVURJKSA-N 0.000 claims description 8
SQKRZWKSHPTTCU-IBGZPJMESA-N (2s)-2-[(2-chloro-6-methylbenzoyl)amino]-3-[4-(1,4-dimethyl-2-oxopyridin-3-yl)phenyl]propanoic acid Chemical compound CC1=CC=CC(Cl)=C1C(=O)N[C@H](C(O)=O)CC1=CC=C(C=2C(N(C)C=CC=2C)=O)C=C1 SQKRZWKSHPTTCU-IBGZPJMESA-N 0.000 claims description 8
APVDSPBBKYMHQH-IBGZPJMESA-N (2s)-2-[(2-chloro-6-methylbenzoyl)amino]-3-[4-[1,6-dimethyl-2-oxo-4-(trifluoromethyl)pyridin-3-yl]phenyl]propanoic acid Chemical compound CC1=CC=CC(Cl)=C1C(=O)N[C@H](C(O)=O)CC1=CC=C(C=2C(N(C)C(C)=CC=2C(F)(F)F)=O)C=C1 APVDSPBBKYMHQH-IBGZPJMESA-N 0.000 claims description 8
125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 8
208000022559 Inflammatory bowel disease Diseases 0.000 claims description 8
IBAZQIKVHCLTHH-SFHVURJKSA-N N-(2,6-dichlorobenzoyl)-4-[1,6-dimethyl-2-oxo-4-(trifluoromethyl)-1,2-dihydropyridin-3-yl]-L-phenylalanine Chemical compound O=C1N(C)C(C)=CC(C(F)(F)F)=C1C(C=C1)=CC=C1C[C@@H](C(O)=O)NC(=O)C1=C(Cl)C=CC=C1Cl IBAZQIKVHCLTHH-SFHVURJKSA-N 0.000 claims description 8
LFMFPKKYRXFHHZ-UHFFFAOYSA-N R24 Chemical compound C1=C(Cl)C(C)=CC=C1NC1=NC(N)=C(C=CC=C2)C2=N1 LFMFPKKYRXFHHZ-UHFFFAOYSA-N 0.000 claims description 8
125000004432 carbon atom Chemical group C* 0.000 claims description 8
201000010099 disease Diseases 0.000 claims description 8
201000006417 multiple sclerosis Diseases 0.000 claims description 8
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
CGDRAVDJURFDMP-SFHVURJKSA-N (2s)-2-[(2-chloro-6-methylbenzoyl)amino]-3-[4-[1,4-dimethyl-2-oxo-6-(trifluoromethyl)pyridin-3-yl]phenyl]propanoic acid Chemical compound CC1=CC=CC(Cl)=C1C(=O)N[C@H](C(O)=O)CC1=CC=C(C=2C(N(C)C(=CC=2C)C(F)(F)F)=O)C=C1 CGDRAVDJURFDMP-SFHVURJKSA-N 0.000 claims description 7
229910052760 oxygen Inorganic materials 0.000 claims description 7
125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 6
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 6
238000004519 manufacturing process Methods 0.000 claims description 6
206010039073 rheumatoid arthritis Diseases 0.000 claims description 6
BWJPNBIUIHZRPA-FQEVSTJZSA-N (2s)-2-[(2-bromo-5-methoxybenzoyl)amino]-3-[4-(1-methyl-2-oxopyridin-3-yl)phenyl]propanoic acid Chemical compound COC1=CC=C(Br)C(C(=O)N[C@@H](CC=2C=CC(=CC=2)C=2C(N(C)C=CC=2)=O)C(O)=O)=C1 BWJPNBIUIHZRPA-FQEVSTJZSA-N 0.000 claims description 5
CBPNUSPLCWQDTD-NRFANRHFSA-N (2s)-3-[4-[1,6-dimethyl-2-oxo-4-(trifluoromethyl)pyridin-3-yl]phenyl]-2-[(2-ethyl-6-methylbenzoyl)amino]propanoic acid Chemical compound CCC1=CC=CC(C)=C1C(=O)N[C@H](C(O)=O)CC1=CC=C(C=2C(N(C)C(C)=CC=2C(F)(F)F)=O)C=C1 CBPNUSPLCWQDTD-NRFANRHFSA-N 0.000 claims description 5
QWKCHTVWYPJVFD-QFIPXVFZSA-N (2s)-3-[4-[1,6-dimethyl-2-oxo-4-(trifluoromethyl)pyridin-3-yl]phenyl]-2-[(2-methyl-6-propan-2-ylbenzoyl)amino]propanoic acid Chemical compound CC(C)C1=CC=CC(C)=C1C(=O)N[C@H](C(O)=O)CC1=CC=C(C=2C(N(C)C(C)=CC=2C(F)(F)F)=O)C=C1 QWKCHTVWYPJVFD-QFIPXVFZSA-N 0.000 claims description 5
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 5
229910052799 carbon Inorganic materials 0.000 claims description 5
125000005842 heteroatom Chemical group 0.000 claims description 5
RFEBDZANCVHDLP-UHFFFAOYSA-N 3-[(4-cyanophenyl)methylamino]-6-(trifluoromethyl)quinoxaline-2-carboxylic acid Chemical compound OC(=O)C1=NC2=CC=C(C(F)(F)F)C=C2N=C1NCC1=CC=C(C#N)C=C1 RFEBDZANCVHDLP-UHFFFAOYSA-N 0.000 claims description 4
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
125000004429 atom Chemical group 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
230000001404 mediated effect Effects 0.000 claims description 4
125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 claims description 4
125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 3
LCEHGBPILWMVQF-DEOSSOPVSA-N 2-(diethylamino)ethyl (2s)-2-[(2,6-dichlorobenzoyl)amino]-3-[4-[1,6-dimethyl-2-oxo-4-(trifluoromethyl)pyridin-3-yl]phenyl]propanoate Chemical compound C([C@@H](C(=O)OCCN(CC)CC)NC(=O)C=1C(=CC=CC=1Cl)Cl)C(C=C1)=CC=C1C1=C(C(F)(F)F)C=C(C)N(C)C1=O LCEHGBPILWMVQF-DEOSSOPVSA-N 0.000 claims description 3
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 3
BZUQBPXFWRLGCI-FQEVSTJZSA-N ethyl (2s)-2-[(2,6-dichlorobenzoyl)amino]-3-[4-[1,6-dimethyl-2-oxo-4-(trifluoromethyl)pyridin-3-yl]phenyl]propanoate Chemical compound C([C@@H](C(=O)OCC)NC(=O)C=1C(=CC=CC=1Cl)Cl)C(C=C1)=CC=C1C1=C(C(F)(F)F)C=C(C)N(C)C1=O BZUQBPXFWRLGCI-FQEVSTJZSA-N 0.000 claims description 3
PBIAFEAQIMQDNE-FQEVSTJZSA-N (2s)-3-[4-[1,6-dimethyl-2-oxo-4-(trifluoromethyl)pyridin-3-yl]phenyl]-2-[[1-(2-methoxyethyl)cyclopentanecarbonyl]amino]propanoic acid Chemical compound N([C@@H](CC=1C=CC(=CC=1)C=1C(N(C)C(C)=CC=1C(F)(F)F)=O)C(O)=O)C(=O)C1(CCOC)CCCC1 PBIAFEAQIMQDNE-FQEVSTJZSA-N 0.000 claims description 2
125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 2
KAJHDLSDJFIURS-XLDIYJRPSA-N 1-acetyloxyethyl (2s)-2-[(2,6-dichlorobenzoyl)amino]-3-[4-[1,6-dimethyl-2-oxo-4-(trifluoromethyl)pyridin-3-yl]phenyl]propanoate Chemical compound C([C@@H](C(=O)OC(OC(C)=O)C)NC(=O)C=1C(=CC=CC=1Cl)Cl)C(C=C1)=CC=C1C1=C(C(F)(F)F)C=C(C)N(C)C1=O KAJHDLSDJFIURS-XLDIYJRPSA-N 0.000 claims description 2
125000001589 carboacyl group Chemical group 0.000 claims 3
125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims 1
125000006727 (C1-C6) alkenyl group Chemical class 0.000 claims 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 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 189
239000000243 solution Substances 0.000 description 110
239000000203 mixture Substances 0.000 description 91
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 57
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 52
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 52
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 49
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 49
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 46
239000007787 solid Substances 0.000 description 44
238000001704 evaporation Methods 0.000 description 41
230000008020 evaporation Effects 0.000 description 41
239000011541 reaction mixture Substances 0.000 description 40
239000011734 sodium Substances 0.000 description 40
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 39
239000012267 brine Substances 0.000 description 38
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 38
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
239000000725 suspension Substances 0.000 description 35
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 34
238000001914 filtration Methods 0.000 description 34
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 31
239000002274 desiccant Substances 0.000 description 30
210000004027 cell Anatomy 0.000 description 29
238000006243 chemical reaction Methods 0.000 description 26
IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 22
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 22
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
239000000284 extract Substances 0.000 description 22
238000010898 silica gel chromatography Methods 0.000 description 21
239000002253 acid Substances 0.000 description 19
239000012043 crude product Substances 0.000 description 19
239000000741 silica gel Substances 0.000 description 18
229910002027 silica gel Inorganic materials 0.000 description 18
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 17
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 17
239000002904 solvent Substances 0.000 description 17
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
150000002500 ions Chemical class 0.000 description 15
239000000047 product Substances 0.000 description 15
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 14
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
239000000872 buffer Substances 0.000 description 14
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
229960000583 acetic acid Drugs 0.000 description 12
239000010410 layer Substances 0.000 description 12
239000003153 chemical reaction reagent Substances 0.000 description 11
229920006395 saturated elastomer Polymers 0.000 description 11
238000004809 thin layer chromatography Methods 0.000 description 11
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
125000003118 aryl group Chemical group 0.000 description 10
239000000706 filtrate Substances 0.000 description 10
238000007429 general method Methods 0.000 description 10
238000005259 measurement Methods 0.000 description 10
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 9
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
150000001299 aldehydes Chemical class 0.000 description 9
239000002585 base Substances 0.000 description 9
238000007796 conventional method Methods 0.000 description 9
238000010790 dilution Methods 0.000 description 9
239000012895 dilution Substances 0.000 description 9
125000006239 protecting group Chemical group 0.000 description 9
238000012360 testing method Methods 0.000 description 9
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 8
230000015572 biosynthetic process Effects 0.000 description 8
229910052794 bromium Inorganic materials 0.000 description 8
230000000694 effects Effects 0.000 description 8
239000007788 liquid Substances 0.000 description 8
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
229910000027 potassium carbonate Inorganic materials 0.000 description 8
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 8
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical class [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 7
239000007864 aqueous solution Substances 0.000 description 7
229910052786 argon Inorganic materials 0.000 description 7
239000012131 assay buffer Substances 0.000 description 7
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 7
229910002091 carbon monoxide Inorganic materials 0.000 description 7
239000003054 catalyst Substances 0.000 description 7
210000003979 eosinophil Anatomy 0.000 description 7
239000012535 impurity Substances 0.000 description 7
239000012442 inert solvent Substances 0.000 description 7
230000007935 neutral effect Effects 0.000 description 7
238000010992 reflux Methods 0.000 description 7
238000003786 synthesis reaction Methods 0.000 description 7
VNNBTSYVKBFTEF-IBGZPJMESA-N (2s)-2-[(2-chloro-6-methylbenzoyl)amino]-3-[4-(1-methyl-2-oxopyridin-3-yl)phenyl]propanoic acid Chemical compound CC1=CC=CC(Cl)=C1C(=O)N[C@H](C(O)=O)CC1=CC=C(C=2C(N(C)C=CC=2)=O)C=C1 VNNBTSYVKBFTEF-IBGZPJMESA-N 0.000 description 6
LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 6
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 6
LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 6
OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 6
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 6
239000006196 drop Substances 0.000 description 6
125000004185 ester group Chemical group 0.000 description 6
150000002148 esters Chemical class 0.000 description 6
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical group I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 6
238000011534 incubation Methods 0.000 description 6
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 6
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
210000004698 lymphocyte Anatomy 0.000 description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
229910052763 palladium Inorganic materials 0.000 description 6
238000004007 reversed phase HPLC Methods 0.000 description 6
102000016359 Fibronectins Human genes 0.000 description 5
108010067306 Fibronectins Proteins 0.000 description 5
150000001412 amines Chemical class 0.000 description 5
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
238000005859 coupling reaction Methods 0.000 description 5
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JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
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229910052703 rhodium Inorganic materials 0.000 description 1
239000010948 rhodium Substances 0.000 description 1
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
102220046159 rs587782693 Human genes 0.000 description 1
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238000013207 serial dilution Methods 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
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UKLNMMHNWFDKNT-UHFFFAOYSA-M sodium chlorite Chemical compound [Na+].[O-]Cl=O UKLNMMHNWFDKNT-UHFFFAOYSA-M 0.000 description 1
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QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
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239000011975 tartaric acid Substances 0.000 description 1
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125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
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RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
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REDSKZBUUUQMSK-UHFFFAOYSA-N tributyltin Chemical compound CCCC[Sn](CCCC)CCCC.CCCC[Sn](CCCC)CCCC REDSKZBUUUQMSK-UHFFFAOYSA-N 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
WTVXIBRMWGUIMI-UHFFFAOYSA-N trifluoro($l^{1}-oxidanylsulfonyl)methane Chemical group [O]S(=O)(=O)C(F)(F)F WTVXIBRMWGUIMI-UHFFFAOYSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
- 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
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/61—Halogen atoms or nitro radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Rheumatology (AREA)
Pulmonology (AREA)
Orthopedic Medicine & Surgery (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Immunology (AREA)
Pain & Pain Management (AREA)
Physical Education & Sports Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Pyridine Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Hydrogenated Pyridines (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

NO20022650A 1999-12-06 2002-06-05 4-Pyridyl-N-acyl-L-fenylalaniner, anvendelse av disse som medikamenter, farmasoytiske preparater inneholdende slike forbindelser og fremgangsmate for fremstilling av disse. NO322910B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US16909099P	1999-12-06	1999-12-06
PCT/EP2000/011979 WO2001042215A1 (en)	1999-12-06	2000-11-29	4-pyridinyl-n-acyl-l-phenylalanines

Publications (3)

Publication Number	Publication Date
NO20022650D0 NO20022650D0 (no)	2002-06-05
NO20022650L NO20022650L (no)	2002-06-05
NO322910B1 true NO322910B1 (no)	2006-12-18

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ID=22614226

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Application Number	Title	Priority Date	Filing Date
NO20022650A NO322910B1 (no)	1999-12-06	2002-06-05	4-Pyridyl-N-acyl-L-fenylalaniner, anvendelse av disse som medikamenter, farmasoytiske preparater inneholdende slike forbindelser og fremgangsmate for fremstilling av disse.

Country Status (34)

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EP (1)	EP1244625B1 (ar)
JP (2)	JP2003516392A (ar)
KR (1)	KR100492111B1 (ar)
CN (1)	CN1196682C (ar)
AR (1)	AR031083A1 (ar)
AT (1)	ATE297895T1 (ar)
AU (1)	AU779063B2 (ar)
BR (1)	BR0016172A (ar)
CA (1)	CA2392566A1 (ar)
CO (1)	CO5080771A1 (ar)
CZ (1)	CZ20022352A3 (ar)
DE (1)	DE60020883T2 (ar)
DK (1)	DK1244625T3 (ar)
ES (1)	ES2243335T3 (ar)
GC (1)	GC0000214A (ar)
HK (1)	HK1053470A1 (ar)
HR (1)	HRP20020467A2 (ar)
HU (1)	HUP0203735A3 (ar)
IL (2)	IL149622A0 (ar)
JO (1)	JO2281B1 (ar)
MA (1)	MA26849A1 (ar)
MX (1)	MXPA02005240A (ar)
MY (1)	MY128003A (ar)
NO (1)	NO322910B1 (ar)
NZ (1)	NZ518888A (ar)
PE (1)	PE20010960A1 (ar)
PL (1)	PL364814A1 (ar)
PT (1)	PT1244625E (ar)
RU (1)	RU2270193C2 (ar)
TW (1)	TWI276629B (ar)
UY (1)	UY26470A1 (ar)
WO (1)	WO2001042215A1 (ar)
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ZA (1)	ZA200203762B (ar)

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US6960597B2 (en)	2000-06-30	2005-11-01	Orth-Mcneil Pharmaceutical, Inc.	Aza-bridged-bicyclic amino acid derivatives as α4 integrin antagonists
IL154350A0 (en)	2000-08-18	2003-09-17	Ajinomoto Kk	New phenylalanine derivatives
AU2001290303A1 (en)	2000-09-29	2002-04-15	Ajinomoto Co., Inc.	Novel phenylalanine derivatives
AU2002354224A1 (en) *	2001-12-13	2003-07-09	Ajinomoto Co., Inc.	Novel phenylalanine derivative
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2000
- 2000-11-29 AU AU21639/01A patent/AU779063B2/en not_active Ceased
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Publication number	Publication date
MA26849A1 (fr)	2004-12-20
JP2008094842A (ja)	2008-04-24
AU779063B2 (en)	2005-01-06
ATE297895T1 (de)	2005-07-15
HK1053470A1 (en)	2003-10-24
EP1244625B1 (en)	2005-06-15
MXPA02005240A (es)	2002-11-07
ZA200203762B (en)	2004-01-28
NO20022650D0 (no)	2002-06-05
NZ518888A (en)	2004-02-27
KR100492111B1 (ko)	2005-06-01
GC0000214A (en)	2006-03-29
DE60020883T2 (de)	2006-03-23
MY128003A (en)	2007-01-31
IL149622A0 (en)	2002-11-10
AU2163901A (en)	2001-06-18
PL364814A1 (en)	2004-12-13
TWI276629B (en)	2007-03-21
AR031083A1 (es)	2003-09-10
PT1244625E (pt)	2005-09-30
CZ20022352A3 (cs)	2003-05-14
JO2281B1 (ar)	2005-09-12
WO2001042215A1 (en)	2001-06-14
CN1402709A (zh)	2003-03-12
CN1196682C (zh)	2005-04-13
NO20022650L (no)	2002-06-05
CO5080771A1 (es)	2001-09-25
IL149622A (en)	2006-12-10
BR0016172A (pt)	2002-08-20
ES2243335T3 (es)	2005-12-01
CA2392566A1 (en)	2001-06-14
DE60020883D1 (de)	2005-07-21
DK1244625T3 (da)	2005-10-10
HUP0203735A3 (en)	2005-03-29
EP1244625A1 (en)	2002-10-02
JP2003516392A (ja)	2003-05-13
HUP0203735A2 (hu)	2003-03-28
UY26470A1 (es)	2001-05-31
KR20020060256A (ko)	2002-07-16
YU40502A (sh)	2005-03-15
HRP20020467A2 (en)	2004-04-30
PE20010960A1 (es)	2001-09-22
RU2270193C2 (ru)	2006-02-20

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JP3824935B2 (ja)	2006-09-20	４−ピリミジニル−ｎ−アシル−ｌ−フェニルアラニン
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SK140994A3 (en)	1995-07-11	Imidazopyridazines, method of their production and pharmaceutical preparation on their base and method of their production
EP0595610A1 (en)	1994-05-04	Benzo-fused lactams
CZ2000597A3 (cs)	2000-07-12	N-Aroylfenylalaninové deriváty