HRP960141A2 - Pyrrolidinyl hydroxamic acid compounds and their production process - Google Patents

Pyrrolidinyl hydroxamic acid compounds and their production process Download PDF

Info

Publication number: HRP960141A2
Authority: HR; Croatia
Prior art keywords: hydroxy; compound; acetamide; hydroxypyrrolidin; formula
Prior art date: 1995-03-31

Application number

HRPCT/JP95/631A

Other languages

English (en)

Croatian (hr)

Inventor

Ito Fumitaka

Original Assignee

Pfizer

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

1995-03-31

Filing date

1996-03-26

Publication date

1997-10-31

1996-03-26 Application filed by Pfizer filed Critical Pfizer

1997-10-31 Publication of HRP960141A2 publication Critical patent/HRP960141A2/hr

Links

150000001875 compounds Chemical class 0.000 title claims description 128
-1 Pyrrolidinyl hydroxamic Chemical compound 0.000 title claims description 21
239000002253 acid Substances 0.000 title description 9
238000004519 manufacturing process Methods 0.000 title description 2
238000000034 method Methods 0.000 claims description 70
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 56
239000000203 mixture Substances 0.000 claims description 36
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 35
125000006239 protecting group Chemical group 0.000 claims description 23
239000001257 hydrogen Substances 0.000 claims description 22
229910052739 hydrogen Inorganic materials 0.000 claims description 22
150000003839 salts Chemical class 0.000 claims description 20
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 14
238000006243 chemical reaction Methods 0.000 claims description 14
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
241000124008 Mammalia Species 0.000 claims description 10
150000002431 hydrogen Chemical class 0.000 claims description 10
239000000730 antalgic agent Substances 0.000 claims description 9
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
125000003545 alkoxy group Chemical group 0.000 claims description 8
125000001424 substituent group Chemical group 0.000 claims description 8
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 6
125000001475 halogen functional group Chemical group 0.000 claims description 6
229940127240 opiate Drugs 0.000 claims description 6
208000004998 Abdominal Pain Diseases 0.000 claims description 5
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 5
239000012359 Methanesulfonyl chloride Substances 0.000 claims description 5
230000001270 agonistic effect Effects 0.000 claims description 5
230000003444 anaesthetic effect Effects 0.000 claims description 5
239000003795 chemical substances by application Substances 0.000 claims description 5
239000002934 diuretic Substances 0.000 claims description 5
230000001882 diuretic effect Effects 0.000 claims description 5
239000003193 general anesthetic agent Substances 0.000 claims description 5
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
102000048260 kappa Opioid Receptors Human genes 0.000 claims description 5
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 claims description 5
239000004090 neuroprotective agent Substances 0.000 claims description 5
108020001588 κ-opioid receptors Proteins 0.000 claims description 5
HOGIAGOSNJXVGR-LJQANCHMSA-N 2-(3,4-dichlorophenyl)-n-hydroxy-n-[(1s)-1-phenyl-2-pyrrolidin-1-ylethyl]acetamide Chemical group C([C@@H](N(O)C(=O)CC=1C=C(Cl)C(Cl)=CC=1)C=1C=CC=CC=1)N1CCCC1 HOGIAGOSNJXVGR-LJQANCHMSA-N 0.000 claims description 4
230000000202 analgesic effect Effects 0.000 claims description 4
239000002260 anti-inflammatory agent Substances 0.000 claims description 4
230000003110 anti-inflammatory effect Effects 0.000 claims description 4
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 4
208000028774 intestinal disease Diseases 0.000 claims description 4
GCJKQYAPGBMXGO-RBUKOAKNSA-N 2-(4-chlorophenyl)-n-hydroxy-n-[(1s)-2-[(3s)-3-hydroxypyrrolidin-1-yl]-1-phenylethyl]acetamide Chemical compound C1[C@@H](O)CCN1C[C@H](C=1C=CC=CC=1)N(O)C(=O)CC1=CC=C(Cl)C=C1 GCJKQYAPGBMXGO-RBUKOAKNSA-N 0.000 claims description 3
230000029936 alkylation Effects 0.000 claims description 3
238000005804 alkylation reaction Methods 0.000 claims description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
LTWLIAPKBJYWFN-GOSISDBHSA-N n-hydroxy-n-[(1s)-1-phenyl-2-pyrrolidin-1-ylethyl]-2-(2,3,6-trichlorophenyl)acetamide Chemical compound C([C@@H](N(O)C(=O)CC=1C(=C(Cl)C=CC=1Cl)Cl)C=1C=CC=CC=1)N1CCCC1 LTWLIAPKBJYWFN-GOSISDBHSA-N 0.000 claims description 3
ZJCHKZRCGMEKBN-JOCHJYFZSA-N n-hydroxy-n-[(1s)-1-phenyl-2-pyrrolidin-1-ylethyl]-2-(2,4,6-trimethylphenyl)acetamide Chemical compound CC1=CC(C)=CC(C)=C1CC(=O)N(O)[C@@H](C=1C=CC=CC=1)CN1CCCC1 ZJCHKZRCGMEKBN-JOCHJYFZSA-N 0.000 claims description 3
QTEPVPGNPIHYTL-LJQANCHMSA-N n-hydroxy-n-[(1s)-1-phenyl-2-pyrrolidin-1-ylethyl]-2-[4-(trifluoromethyl)phenyl]acetamide Chemical compound C([C@@H](N(O)C(=O)CC=1C=CC(=CC=1)C(F)(F)F)C=1C=CC=CC=1)N1CCCC1 QTEPVPGNPIHYTL-LJQANCHMSA-N 0.000 claims description 3
NJPBQRWPNXDMEA-KBXCAEBGSA-N n-hydroxy-n-[(1s)-2-[(3s)-3-hydroxypyrrolidin-1-yl]-1-phenylethyl]-2-(2,3,6-trichlorophenyl)acetamide Chemical compound C1[C@@H](O)CCN1C[C@H](C=1C=CC=CC=1)N(O)C(=O)CC1=C(Cl)C=CC(Cl)=C1Cl NJPBQRWPNXDMEA-KBXCAEBGSA-N 0.000 claims description 3
JRAKCMZRAZMQCS-RBUKOAKNSA-N n-hydroxy-n-[(1s)-2-[(3s)-3-hydroxypyrrolidin-1-yl]-1-phenylethyl]-2-[4-(trifluoromethyl)phenyl]acetamide Chemical compound C1[C@@H](O)CCN1C[C@H](C=1C=CC=CC=1)N(O)C(=O)CC1=CC=C(C(F)(F)F)C=C1 JRAKCMZRAZMQCS-RBUKOAKNSA-N 0.000 claims description 3
125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 3
YUZQPRVLDUFZKA-PKOBYXMFSA-N 2-(2,4-dichlorophenyl)-n-hydroxy-n-[(1s)-2-[(3s)-3-hydroxypyrrolidin-1-yl]-1-phenylethyl]acetamide Chemical compound C1[C@@H](O)CCN1C[C@H](C=1C=CC=CC=1)N(O)C(=O)CC1=CC=C(Cl)C=C1Cl YUZQPRVLDUFZKA-PKOBYXMFSA-N 0.000 claims description 2
OZAKEAQVNFXLLC-HNAYVOBHSA-N 2-(2,6-dichlorophenyl)-n-hydroxy-n-[(1s)-2-[(3s)-3-hydroxypyrrolidin-1-yl]-1-phenylethyl]acetamide Chemical compound C1[C@@H](O)CCN1C[C@H](C=1C=CC=CC=1)N(O)C(=O)CC1=C(Cl)C=CC=C1Cl OZAKEAQVNFXLLC-HNAYVOBHSA-N 0.000 claims description 2
LMPBXMBUTBQPJJ-QFBILLFUSA-N 2-(3,4-dichlorophenyl)-n-hydroxy-n-[(1s)-2-[(3s)-3-hydroxypyrrolidin-1-yl]-1-phenylethyl]acetamide Chemical compound C1[C@@H](O)CCN1C[C@H](C=1C=CC=CC=1)N(O)C(=O)CC1=CC=C(Cl)C(Cl)=C1 LMPBXMBUTBQPJJ-QFBILLFUSA-N 0.000 claims description 2
JFOKVTUCFJZORN-RBUKOAKNSA-N 2-(4-bromophenyl)-n-hydroxy-n-[(1s)-2-[(3s)-3-hydroxypyrrolidin-1-yl]-1-phenylethyl]acetamide Chemical compound C1[C@@H](O)CCN1C[C@H](C=1C=CC=CC=1)N(O)C(=O)CC1=CC=C(Br)C=C1 JFOKVTUCFJZORN-RBUKOAKNSA-N 0.000 claims description 2
125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 2
JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 2
125000005530 alkylenedioxy group Chemical group 0.000 claims description 2
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
239000004305 biphenyl Chemical group 0.000 claims description 2
235000010290 biphenyl Nutrition 0.000 claims description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 2
125000002541 furyl group Chemical group 0.000 claims description 2
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 2
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
125000001624 naphthyl group Chemical group 0.000 claims description 2
239000008194 pharmaceutical composition Substances 0.000 claims description 2
125000004076 pyridyl group Chemical group 0.000 claims description 2
125000001544 thienyl group Chemical group 0.000 claims description 2
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical class C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 claims 1
229940031098 ethanolamine Drugs 0.000 claims 1
HZAXFHJVJLSVMW-UHFFFAOYSA-N monoethanolamine hydrochloride Natural products NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims 1
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 142
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
238000005160 1H NMR spectroscopy Methods 0.000 description 71
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
238000002360 preparation method Methods 0.000 description 54
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 49
238000004458 analytical method Methods 0.000 description 46
239000003921 oil Substances 0.000 description 42
235000019198 oils Nutrition 0.000 description 42
239000007787 solid Substances 0.000 description 41
150000003840 hydrochlorides Chemical class 0.000 description 39
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 22
239000000243 solution Substances 0.000 description 22
JVWZVGMSJISZQR-PYNWJHIZSA-N (2r)-2-[(3s)-3-(oxan-2-yloxy)pyrrolidin-1-yl]-2-phenylethanol Chemical compound O([C@H]1CCN(C1)[C@@H](CO)C=1C=CC=CC=1)C1CCCCO1 JVWZVGMSJISZQR-PYNWJHIZSA-N 0.000 description 18
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 18
239000011541 reaction mixture Substances 0.000 description 18
239000002904 solvent Substances 0.000 description 16
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
150000001412 amines Chemical class 0.000 description 15
238000003756 stirring Methods 0.000 description 15
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
239000012267 brine Substances 0.000 description 13
238000004440 column chromatography Methods 0.000 description 13
239000002632 kappa opiate receptor agonist Substances 0.000 description 13
239000000741 silica gel Substances 0.000 description 13
229910002027 silica gel Inorganic materials 0.000 description 13
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
125000006237 oxymethylenoxy group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 12
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
238000001914 filtration Methods 0.000 description 11
CNONYXFNOHXTLC-KBPBESRZSA-N (2r)-2-[(3s)-3-(methoxymethoxy)pyrrolidin-1-yl]-2-phenylethanol Chemical compound C1[C@@H](OCOC)CCN1[C@@H](CO)C1=CC=CC=C1 CNONYXFNOHXTLC-KBPBESRZSA-N 0.000 description 10
239000000284 extract Substances 0.000 description 9
XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 9
229920006395 saturated elastomer Polymers 0.000 description 9
239000011734 sodium Substances 0.000 description 8
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
230000000694 effects Effects 0.000 description 7
239000000843 powder Substances 0.000 description 7
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 6
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 6
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
238000001704 evaporation Methods 0.000 description 6
230000008020 evaporation Effects 0.000 description 6
238000010561 standard procedure Methods 0.000 description 6
238000012360 testing method Methods 0.000 description 6
ZOUPGSMSNQLUNW-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(Cl)C(Cl)=C1 ZOUPGSMSNQLUNW-UHFFFAOYSA-N 0.000 description 5
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
239000007864 aqueous solution Substances 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
239000000543 intermediate Substances 0.000 description 5
239000000047 product Substances 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
239000000126 substance Substances 0.000 description 5
MWGPNRQVCPJJBW-LURJTMIESA-N (3s)-3-(methoxymethoxy)pyrrolidine Chemical compound COCO[C@H]1CCNC1 MWGPNRQVCPJJBW-LURJTMIESA-N 0.000 description 4
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 4
241000700159 Rattus Species 0.000 description 4
230000002378 acidificating effect Effects 0.000 description 4
229940035676 analgesics Drugs 0.000 description 4
239000012230 colorless oil Substances 0.000 description 4
239000003085 diluting agent Substances 0.000 description 4
BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
238000000746 purification Methods 0.000 description 4
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
JCZDMBKPCOKANB-VEDVMXKPSA-N (3r)-3-(oxan-2-yloxy)pyrrolidine Chemical compound C1NCC[C@H]1OC1OCCCC1 JCZDMBKPCOKANB-VEDVMXKPSA-N 0.000 description 3
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical class C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
238000005481 NMR spectroscopy Methods 0.000 description 3
102000003840 Opioid Receptors Human genes 0.000 description 3
108090000137 Opioid Receptors Proteins 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
239000003480 eluent Substances 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
239000007789 gas Substances 0.000 description 3
238000004128 high performance liquid chromatography Methods 0.000 description 3
SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 3
NLXXVSKHVGDQAT-UHFFFAOYSA-N o-(oxan-2-yl)hydroxylamine Chemical compound NOC1CCCCO1 NLXXVSKHVGDQAT-UHFFFAOYSA-N 0.000 description 3
230000003287 optical effect Effects 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
239000000018 receptor agonist Substances 0.000 description 3
229940044601 receptor agonist Drugs 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
WPVZJYFBUIBTRC-SECBINFHSA-N (1s)-1-(3-methylphenyl)ethane-1,2-diol Chemical compound CC1=CC=CC([C@H](O)CO)=C1 WPVZJYFBUIBTRC-SECBINFHSA-N 0.000 description 2
CYRLHHDBZGNKEA-SNVBAGLBSA-N (1s)-1-[3-(methoxymethoxy)phenyl]ethane-1,2-diol Chemical compound COCOC1=CC=CC([C@H](O)CO)=C1 CYRLHHDBZGNKEA-SNVBAGLBSA-N 0.000 description 2
UZCBDOLPPICICR-YNPPLXCJSA-N (1s)-2-[(3r)-3-(oxan-2-yloxy)pyrrolidin-1-yl]-1-phenylethanol Chemical compound O([C@@H]1CCN(C1)C[C@@H](O)C=1C=CC=CC=1)C1CCCCO1 UZCBDOLPPICICR-YNPPLXCJSA-N 0.000 description 2
RCPWHIUMQKNAHD-LSDHHAIUSA-N (1s)-2-[(3s)-3-(methoxymethoxy)pyrrolidin-1-yl]-1-(3-methylphenyl)ethanol Chemical compound C1[C@@H](OCOC)CCN1C[C@@H](O)C1=CC=CC(C)=C1 RCPWHIUMQKNAHD-LSDHHAIUSA-N 0.000 description 2
CDLHNMKWIQZIOI-LSDHHAIUSA-N (1s)-2-[(3s)-3-(methoxymethoxy)pyrrolidin-1-yl]-1-(4-methylphenyl)ethanol Chemical compound C1[C@@H](OCOC)CCN1C[C@@H](O)C1=CC=C(C)C=C1 CDLHNMKWIQZIOI-LSDHHAIUSA-N 0.000 description 2
IWWIUDASVBIUQU-PYNWJHIZSA-N (2r)-2-(4-fluorophenyl)-2-[(3s)-3-(oxan-2-yloxy)pyrrolidin-1-yl]ethanol Chemical compound O([C@H]1CCN(C1)[C@@H](CO)C=1C=CC(F)=CC=1)C1CCCCO1 IWWIUDASVBIUQU-PYNWJHIZSA-N 0.000 description 2
RTZBSBZVOWQBQX-GJZGRUSLSA-N (2r)-2-[(3s)-3-(methoxymethoxy)pyrrolidin-1-yl]-2-(3-methylphenyl)ethanol Chemical compound C1[C@@H](OCOC)CCN1[C@@H](CO)C1=CC=CC(C)=C1 RTZBSBZVOWQBQX-GJZGRUSLSA-N 0.000 description 2
JHAQDLQRDPXVQL-GJZGRUSLSA-N (2r)-2-[(3s)-3-(methoxymethoxy)pyrrolidin-1-yl]-2-(4-methylphenyl)ethanol Chemical compound C1[C@@H](OCOC)CCN1[C@@H](CO)C1=CC=C(C)C=C1 JHAQDLQRDPXVQL-GJZGRUSLSA-N 0.000 description 2
SRQPEYLZIUEVIA-QMMMGPOBSA-N (2r)-2-amino-2-(4-fluorophenyl)ethanol Chemical compound OC[C@H](N)C1=CC=C(F)C=C1 SRQPEYLZIUEVIA-QMMMGPOBSA-N 0.000 description 2
QAWJAMQTRGCJMH-SECBINFHSA-N (2s)-2-(4-methylphenyl)oxirane Chemical compound C1=CC(C)=CC=C1[C@@H]1OC1 QAWJAMQTRGCJMH-SECBINFHSA-N 0.000 description 2
GLZXZTWPGUEGPE-AAFJCEBUSA-N (3r)-1-benzyl-3-(oxan-2-yloxy)pyrrolidine Chemical compound O([C@@H]1CCN(C1)CC=1C=CC=CC=1)C1CCCCO1 GLZXZTWPGUEGPE-AAFJCEBUSA-N 0.000 description 2
HPZJMUBDEAMBFI-WTNAPCKOSA-N (D-Ala(2)-mephe(4)-gly-ol(5))enkephalin Chemical compound C([C@H](N)C(=O)N[C@H](C)C(=O)NCC(=O)N(C)[C@@H](CC=1C=CC=CC=1)C(=O)NCCO)C1=CC=C(O)C=C1 HPZJMUBDEAMBFI-WTNAPCKOSA-N 0.000 description 2
IJXJGQCXFSSHNL-QMMMGPOBSA-N (R)-(-)-2-Phenylglycinol Chemical compound OC[C@H](N)C1=CC=CC=C1 IJXJGQCXFSSHNL-QMMMGPOBSA-N 0.000 description 2
AWMVMTVKBNGEAK-QMMMGPOBSA-N (R)-styrene oxide Chemical compound C1O[C@@H]1C1=CC=CC=C1 AWMVMTVKBNGEAK-QMMMGPOBSA-N 0.000 description 2
YCAKYFIYUHHCKW-UHFFFAOYSA-N 2-(3,4-difluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(F)C(F)=C1 YCAKYFIYUHHCKW-UHFFFAOYSA-N 0.000 description 2
YHVGRPXIEKFDRC-IENPIDJESA-N 2-[(2s)-1,4-diiodobutan-2-yl]oxyoxane Chemical compound ICC[C@@H](CI)OC1CCCCO1 YHVGRPXIEKFDRC-IENPIDJESA-N 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
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 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
108700022183 Ala(2)-MePhe(4)-Gly(5)- Enkephalin Proteins 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
108700022182 D-Penicillamine (2,5)- Enkephalin Proteins 0.000 description 2
MCMMCRYPQBNCPH-WMIMKTLMSA-N DPDPE Chemical compound C([C@H](N)C(=O)N[C@@H]1C(C)(C)SSC([C@@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)CNC1=O)C(O)=O)(C)C)C1=CC=C(O)C=C1 MCMMCRYPQBNCPH-WMIMKTLMSA-N 0.000 description 2
BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
GNEUNRFKCMUKPB-MRXNPFEDSA-N [(2s)-2-hydroxy-2-(3-methylphenyl)ethyl] 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC[C@@H](O)C1=CC=CC(C)=C1 GNEUNRFKCMUKPB-MRXNPFEDSA-N 0.000 description 2
ULEKQBRCHWEQHX-MRXNPFEDSA-N [(2s)-2-hydroxy-2-(4-methylphenyl)ethyl] 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1[C@H](O)COS(=O)(=O)C1=CC=C(C)C=C1 ULEKQBRCHWEQHX-MRXNPFEDSA-N 0.000 description 2
GQTZSUDZKNVOFX-QGZVFWFLSA-N [(2s)-2-hydroxy-2-[3-(methoxymethoxy)phenyl]ethyl] 4-methylbenzenesulfonate Chemical compound COCOC1=CC=CC([C@H](O)COS(=O)(=O)C=2C=CC(C)=CC=2)=C1 GQTZSUDZKNVOFX-QGZVFWFLSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
238000005917 acylation reaction Methods 0.000 description 2
239000000556 agonist Substances 0.000 description 2
150000001447 alkali salts Chemical class 0.000 description 2
235000011114 ammonium hydroxide Nutrition 0.000 description 2
239000007900 aqueous suspension Substances 0.000 description 2
239000012298 atmosphere Substances 0.000 description 2
TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
150000007514 bases Chemical class 0.000 description 2
239000002131 composite material Substances 0.000 description 2
239000006071 cream Substances 0.000 description 2
PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
201000010099 disease Diseases 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
239000003814 drug Substances 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
238000001035 drying Methods 0.000 description 2
239000000945 filler Substances 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
WUAXWQRULBZETB-UHFFFAOYSA-N homoveratric acid Chemical compound COC1=CC=C(CC(O)=O)C=C1OC WUAXWQRULBZETB-UHFFFAOYSA-N 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
235000015110 jellies Nutrition 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
238000002844 melting Methods 0.000 description 2
229920000609 methyl cellulose Polymers 0.000 description 2
239000001923 methylcellulose Substances 0.000 description 2
235000010981 methylcellulose Nutrition 0.000 description 2
229960005181 morphine Drugs 0.000 description 2
102000051367 mu Opioid Receptors Human genes 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
229910052763 palladium Inorganic materials 0.000 description 2
NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 2
235000015320 potassium carbonate Nutrition 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
238000011160 research Methods 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
239000008107 starch Substances 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
239000003826 tablet Substances 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
108020001612 μ-opioid receptors Proteins 0.000 description 2
PSZIWKRIFPTGTA-QINBWVTOSA-N (1s)-n-(oxan-2-yloxy)-2-[(3s)-3-(oxan-2-yloxy)pyrrolidin-1-yl]-1-phenylethanamine Chemical compound N([C@H](CN1C[C@H](CC1)OC1OCCCC1)C=1C=CC=CC=1)OC1CCCCO1 PSZIWKRIFPTGTA-QINBWVTOSA-N 0.000 description 1
JVWZVGMSJISZQR-GARXDOFDSA-N (2r)-2-[(3r)-3-(oxan-2-yloxy)pyrrolidin-1-yl]-2-phenylethanol Chemical compound O([C@@H]1CCN(C1)[C@@H](CO)C=1C=CC=CC=1)C1CCCCO1 JVWZVGMSJISZQR-GARXDOFDSA-N 0.000 description 1
JKFYKCYQEWQPTM-SSDOTTSWSA-N (2r)-2-amino-2-(4-fluorophenyl)acetic acid Chemical compound OC(=O)[C@H](N)C1=CC=C(F)C=C1 JKFYKCYQEWQPTM-SSDOTTSWSA-N 0.000 description 1
YQDISZZVFYLYOG-LBPRGKRZSA-N (2r)-2-phenyl-2-pyrrolidin-1-ylethanol Chemical compound N1([C@@H](CO)C=2C=CC=CC=2)CCCC1 YQDISZZVFYLYOG-LBPRGKRZSA-N 0.000 description 1
CNONYXFNOHXTLC-UONOGXRCSA-N (2s)-2-[(3s)-3-(methoxymethoxy)pyrrolidin-1-yl]-2-phenylethanol Chemical compound C1[C@@H](OCOC)CCN1[C@H](CO)C1=CC=CC=C1 CNONYXFNOHXTLC-UONOGXRCSA-N 0.000 description 1
YQMXOIAIYXXXEE-LLVKDONJSA-N (3r)-1-benzylpyrrolidin-3-ol Chemical compound C1[C@H](O)CCN1CC1=CC=CC=C1 YQMXOIAIYXXXEE-LLVKDONJSA-N 0.000 description 1
YBADLXQNJCMBKR-UHFFFAOYSA-N (4-nitrophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C([N+]([O-])=O)C=C1 YBADLXQNJCMBKR-UHFFFAOYSA-N 0.000 description 1
ODIGIKRIUKFKHP-UHFFFAOYSA-N (n-propan-2-yloxycarbonylanilino) acetate Chemical compound CC(C)OC(=O)N(OC(C)=O)C1=CC=CC=C1 ODIGIKRIUKFKHP-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
ZWXDAANEJMSCEX-UHFFFAOYSA-N 1-(3-anilinophenyl)ethanone Chemical compound CC(=O)C1=CC=CC(NC=2C=CC=CC=2)=C1 ZWXDAANEJMSCEX-UHFFFAOYSA-N 0.000 description 1
KTZVZZJJVJQZHV-UHFFFAOYSA-N 1-chloro-4-ethenylbenzene Chemical compound ClC1=CC=C(C=C)C=C1 KTZVZZJJVJQZHV-UHFFFAOYSA-N 0.000 description 1
YYRGFWRHEKGYOX-UHFFFAOYSA-N 1-ethenyl-3-(methoxymethoxy)benzene Chemical compound COCOC1=CC=CC(C=C)=C1 YYRGFWRHEKGYOX-UHFFFAOYSA-N 0.000 description 1
JZHGRUMIRATHIU-UHFFFAOYSA-N 1-ethenyl-3-methylbenzene Chemical compound CC1=CC=CC(C=C)=C1 JZHGRUMIRATHIU-UHFFFAOYSA-N 0.000 description 1
CEWDRCQPGANDRS-UHFFFAOYSA-N 1-ethenyl-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(C=C)C=C1 CEWDRCQPGANDRS-UHFFFAOYSA-N 0.000 description 1
UAJRSHJHFRVGMG-UHFFFAOYSA-N 1-ethenyl-4-methoxybenzene Chemical compound COC1=CC=C(C=C)C=C1 UAJRSHJHFRVGMG-UHFFFAOYSA-N 0.000 description 1
BDBQCIYBXGSWKU-ZWKOTPCHSA-N 2-(1,3-benzodioxol-5-yl)-n-hydroxy-n-[(1s)-2-[(3s)-3-hydroxypyrrolidin-1-yl]-1-phenylethyl]acetamide Chemical compound C1[C@@H](O)CCN1C[C@H](C=1C=CC=CC=1)N(O)C(=O)CC1=CC=C(OCO2)C2=C1 BDBQCIYBXGSWKU-ZWKOTPCHSA-N 0.000 description 1
ODVLMCWNGKLROU-UHFFFAOYSA-N 2-(1,3-benzodioxol-5-yl)acetic acid Chemical compound OC(=O)CC1=CC=C2OCOC2=C1 ODVLMCWNGKLROU-UHFFFAOYSA-N 0.000 description 1
HXHPBZWJEJCRJH-HXUWFJFHSA-N 2-(1-benzofuran-4-yl)-n-hydroxy-n-[(1s)-1-phenyl-2-pyrrolidin-1-ylethyl]acetamide Chemical compound C([C@@H](N(O)C(=O)CC=1C=2C=COC=2C=CC=1)C=1C=CC=CC=1)N1CCCC1 HXHPBZWJEJCRJH-HXUWFJFHSA-N 0.000 description 1
IFOMXIGWQFOYLA-UHFFFAOYSA-N 2-(1-benzothiophen-4-yl)acetic acid Chemical compound OC(=O)CC1=CC=CC2=C1C=CS2 IFOMXIGWQFOYLA-UHFFFAOYSA-N 0.000 description 1
RSAGOGCETZHNDA-UHFFFAOYSA-N 2-(2,3,5-trichlorophenyl)acetic acid Chemical compound OC(=O)CC1=CC(Cl)=CC(Cl)=C1Cl RSAGOGCETZHNDA-UHFFFAOYSA-N 0.000 description 1
YWMXEUIQZOQESD-UHFFFAOYSA-N 2-(2,3-dichlorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Cl)=C1Cl YWMXEUIQZOQESD-UHFFFAOYSA-N 0.000 description 1
XOVZSZLZMZBHHV-UHFFFAOYSA-N 2-(2,4,6-trichlorophenyl)acetic acid Chemical compound OC(=O)CC1=C(Cl)C=C(Cl)C=C1Cl XOVZSZLZMZBHHV-UHFFFAOYSA-N 0.000 description 1
CQWMQAKKAHTCSC-UHFFFAOYSA-N 2-(2,4,6-trimethylphenyl)acetic acid Chemical compound CC1=CC(C)=C(CC(O)=O)C(C)=C1 CQWMQAKKAHTCSC-UHFFFAOYSA-N 0.000 description 1
GXMWLJKTGBZMBH-UHFFFAOYSA-N 2-(2,4-dichlorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(Cl)C=C1Cl GXMWLJKTGBZMBH-UHFFFAOYSA-N 0.000 description 1
GWTUGCOXTFFBMM-UHFFFAOYSA-N 2-(2,5-dichlorophenyl)acetic acid Chemical compound OC(=O)CC1=CC(Cl)=CC=C1Cl GWTUGCOXTFFBMM-UHFFFAOYSA-N 0.000 description 1
SFAILOOQFZNOAU-UHFFFAOYSA-N 2-(2,6-dichlorophenyl)acetic acid Chemical compound OC(=O)CC1=C(Cl)C=CC=C1Cl SFAILOOQFZNOAU-UHFFFAOYSA-N 0.000 description 1
MVVCJIVSQDJOOR-VKLKMBQZSA-N 2-(2-aminophenyl)-n-[(1s)-2-[(3s)-3-hydroxypyrrolidin-1-yl]-1-phenylethyl]-n-methylacetamide;hydrochloride Chemical compound Cl.C([C@@H](N(C)C(=O)CC=1C(=CC=CC=1)N)C=1C=CC=CC=1)N1CC[C@H](O)C1 MVVCJIVSQDJOOR-VKLKMBQZSA-N 0.000 description 1
IUJAAIZKRJJZGQ-UHFFFAOYSA-N 2-(2-chlorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC=C1Cl IUJAAIZKRJJZGQ-UHFFFAOYSA-N 0.000 description 1
MBKVNMMQARELRC-IVIAQFCDSA-N 2-(3,4-dichlorophenyl)-n-(oxan-2-yloxy)-n-[(1s)-2-[(3r)-3-(oxan-2-yloxy)pyrrolidin-1-yl]-1-phenylethyl]acetamide Chemical compound C1=C(Cl)C(Cl)=CC=C1CC(=O)N([C@H](CN1C[C@@H](CC1)OC1OCCCC1)C=1C=CC=CC=1)OC1OCCCC1 MBKVNMMQARELRC-IVIAQFCDSA-N 0.000 description 1
MBKVNMMQARELRC-PBGWYDOXSA-N 2-(3,4-dichlorophenyl)-n-(oxan-2-yloxy)-n-[(1s)-2-[(3s)-3-(oxan-2-yloxy)pyrrolidin-1-yl]-1-phenylethyl]acetamide Chemical compound C1=C(Cl)C(Cl)=CC=C1CC(=O)N([C@H](CN1C[C@H](CC1)OC1OCCCC1)C=1C=CC=CC=1)OC1OCCCC1 MBKVNMMQARELRC-PBGWYDOXSA-N 0.000 description 1
VKYFYAIEINGWKF-NKJJMXICSA-N 2-(3,4-dichlorophenyl)-n-[(1s)-1-[3-(methoxymethoxy)phenyl]-2-[(3s)-3-(oxan-2-yloxy)pyrrolidin-1-yl]ethyl]-n-(oxan-2-yloxy)acetamide Chemical compound COCOC1=CC=CC([C@@H](CN2C[C@H](CC2)OC2OCCCC2)N(OC2OCCCC2)C(=O)CC=2C=C(Cl)C(Cl)=CC=2)=C1 VKYFYAIEINGWKF-NKJJMXICSA-N 0.000 description 1
IXGFNBMRTNSCMU-YRVHRZEMSA-N 2-(3,4-dichlorophenyl)-n-[(1s)-2-[(3s)-3-(methoxymethoxy)pyrrolidin-1-yl]-1-(3-methylphenyl)ethyl]-n-(oxan-2-yloxy)acetamide Chemical compound C1[C@@H](OCOC)CCN1C[C@H](C=1C=C(C)C=CC=1)N(C(=O)CC=1C=C(Cl)C(Cl)=CC=1)OC1OCCCC1 IXGFNBMRTNSCMU-YRVHRZEMSA-N 0.000 description 1
ZRSAIKFSTCYXEN-QFBILLFUSA-N 2-(3,4-dichlorophenyl)-n-hydroxy-n-[(1s)-1-(3-hydroxyphenyl)-2-[(3s)-3-hydroxypyrrolidin-1-yl]ethyl]acetamide Chemical compound C1[C@@H](O)CCN1C[C@H](C=1C=C(O)C=CC=1)N(O)C(=O)CC1=CC=C(Cl)C(Cl)=C1 ZRSAIKFSTCYXEN-QFBILLFUSA-N 0.000 description 1
SYOCFRBECAEHNW-FXAWDEMLSA-N 2-(3,4-dichlorophenyl)-n-hydroxy-n-[(1s)-2-[(3s)-3-hydroxypyrrolidin-1-yl]-1-(3-methylphenyl)ethyl]acetamide Chemical compound CC1=CC=CC([C@@H](CN2C[C@@H](O)CC2)N(O)C(=O)CC=2C=C(Cl)C(Cl)=CC=2)=C1 SYOCFRBECAEHNW-FXAWDEMLSA-N 0.000 description 1
QERPKZIGXQVZIR-OXJNMPFZSA-N 2-(3,4-dichlorophenyl)-n-hydroxy-n-[(1s)-2-[(3s)-3-hydroxypyrrolidin-1-yl]-1-(4-methoxyphenyl)ethyl]acetamide Chemical compound C1=CC(OC)=CC=C1[C@H](N(O)C(=O)CC=1C=C(Cl)C(Cl)=CC=1)CN1C[C@@H](O)CC1 QERPKZIGXQVZIR-OXJNMPFZSA-N 0.000 description 1
CAAUQUQEIGLESA-FXAWDEMLSA-N 2-(3,4-dichlorophenyl)-n-hydroxy-n-[(1s)-2-[(3s)-3-hydroxypyrrolidin-1-yl]-1-(4-methylphenyl)ethyl]acetamide Chemical compound C1=CC(C)=CC=C1[C@H](N(O)C(=O)CC=1C=C(Cl)C(Cl)=CC=1)CN1C[C@@H](O)CC1 CAAUQUQEIGLESA-FXAWDEMLSA-N 0.000 description 1
NRTYIIDOIZSAPY-QFBILLFUSA-N 2-(3,4-dichlorophenyl)-n-hydroxy-n-[(1s)-2-[(3s)-3-hydroxypyrrolidin-1-yl]-1-[4-(trifluoromethyl)phenyl]ethyl]acetamide Chemical compound C1[C@@H](O)CCN1C[C@H](C=1C=CC(=CC=1)C(F)(F)F)N(O)C(=O)CC1=CC=C(Cl)C(Cl)=C1 NRTYIIDOIZSAPY-QFBILLFUSA-N 0.000 description 1
VGGWJCXTMMXNLF-HXUWFJFHSA-N 2-(3,4-dichlorophenyl)-n-methoxy-n-[(1s)-1-phenyl-2-pyrrolidin-1-ylethyl]acetamide Chemical compound C([C@@H](N(OC)C(=O)CC=1C=C(Cl)C(Cl)=CC=1)C=1C=CC=CC=1)N1CCCC1 VGGWJCXTMMXNLF-HXUWFJFHSA-N 0.000 description 1
UCBXSHMDLGBSTO-AREMUKBSSA-N 2-(3,4-dichlorophenyl)-n-phenylmethoxy-n-[(1s)-1-phenyl-2-pyrrolidin-1-ylethyl]acetamide Chemical compound C1=C(Cl)C(Cl)=CC=C1CC(=O)N([C@H](CN1CCCC1)C=1C=CC=CC=1)OCC1=CC=CC=C1 UCBXSHMDLGBSTO-AREMUKBSSA-N 0.000 description 1
OTTPBKINJOYJGW-UHFFFAOYSA-N 2-(3,4-dimethylphenyl)acetic acid Chemical compound CC1=CC=C(CC(O)=O)C=C1C OTTPBKINJOYJGW-UHFFFAOYSA-N 0.000 description 1
RERINLRFXYGZEE-UHFFFAOYSA-N 2-(3,5-dichlorophenyl)acetic acid Chemical compound OC(=O)CC1=CC(Cl)=CC(Cl)=C1 RERINLRFXYGZEE-UHFFFAOYSA-N 0.000 description 1
HOVCTAYHEWGIRY-RBUKOAKNSA-N 2-(3-chlorophenyl)-n-hydroxy-n-[(1s)-2-[(3s)-3-hydroxypyrrolidin-1-yl]-1-phenylethyl]acetamide Chemical compound C1[C@@H](O)CCN1C[C@H](C=1C=CC=CC=1)N(O)C(=O)CC1=CC=CC(Cl)=C1 HOVCTAYHEWGIRY-RBUKOAKNSA-N 0.000 description 1
WFPMUFXQDKMVCO-UHFFFAOYSA-N 2-(3-chlorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Cl)=C1 WFPMUFXQDKMVCO-UHFFFAOYSA-N 0.000 description 1
MGKPFALCNDRSQD-UHFFFAOYSA-N 2-(4-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(F)C=C1 MGKPFALCNDRSQD-UHFFFAOYSA-N 0.000 description 1
DRNNZMMOBSRGPG-UHFFFAOYSA-N 2-(5-oxo-7,8-dihydro-6h-naphthalen-2-yl)acetic acid Chemical compound O=C1CCCC2=CC(CC(=O)O)=CC=C21 DRNNZMMOBSRGPG-UHFFFAOYSA-N 0.000 description 1
BLXXCCIBGGBDHI-UHFFFAOYSA-N 2-[3-(trifluoromethyl)phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(C(F)(F)F)=C1 BLXXCCIBGGBDHI-UHFFFAOYSA-N 0.000 description 1
HNORVZDAANCHAY-UHFFFAOYSA-N 2-[4-(trifluoromethyl)phenyl]acetic acid Chemical compound OC(=O)CC1=CC=C(C(F)(F)F)C=C1 HNORVZDAANCHAY-UHFFFAOYSA-N 0.000 description 1
PBGKTSKYUHBZQM-UHFFFAOYSA-N 2-cyclopenta[b]pyran-2-ylacetic acid Chemical compound O1C(CC(=O)O)=CC=C2C=CC=C21 PBGKTSKYUHBZQM-UHFFFAOYSA-N 0.000 description 1
ARXKVVRQIIOZGF-BYPYZUCNSA-N 2-deoxyerythritol Chemical compound OCC[C@H](O)CO ARXKVVRQIIOZGF-BYPYZUCNSA-N 0.000 description 1
YNGIFMKMDRDNBQ-UHFFFAOYSA-N 3-ethenylphenol Chemical compound OC1=CC=CC(C=C)=C1 YNGIFMKMDRDNBQ-UHFFFAOYSA-N 0.000 description 1
QOWSWEBLNVACCL-UHFFFAOYSA-N 4-Bromophenyl acetate Chemical compound OC(=O)CC1=CC=C(Br)C=C1 QOWSWEBLNVACCL-UHFFFAOYSA-N 0.000 description 1
JLBJTVDPSNHSKJ-UHFFFAOYSA-N 4-Methylstyrene Chemical compound CC1=CC=C(C=C)C=C1 JLBJTVDPSNHSKJ-UHFFFAOYSA-N 0.000 description 1
CDPKJZJVTHSESZ-UHFFFAOYSA-N 4-chlorophenylacetic acid Chemical compound OC(=O)CC1=CC=C(Cl)C=C1 CDPKJZJVTHSESZ-UHFFFAOYSA-N 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
241000700199 Cavia porcellus Species 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
DSLZVSRJTYRBFB-LLEIAEIESA-N D-glucaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O DSLZVSRJTYRBFB-LLEIAEIESA-N 0.000 description 1
RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
206010012335 Dependence Diseases 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
108010092674 Enkephalins Proteins 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
230000005526 G1 to G0 transition Effects 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
235000019487 Hazelnut oil Nutrition 0.000 description 1
239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
URLZCHNOLZSCCA-VABKMULXSA-N Leu-enkephalin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 URLZCHNOLZSCCA-VABKMULXSA-N 0.000 description 1
240000007472 Leucaena leucocephala Species 0.000 description 1
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
239000002841 Lewis acid Substances 0.000 description 1
240000005265 Lupinus mutabilis Species 0.000 description 1
235000008755 Lupinus mutabilis Nutrition 0.000 description 1
240000003183 Manihot esculenta Species 0.000 description 1
235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
108010093625 Opioid Peptides Proteins 0.000 description 1
102000001490 Opioid Peptides Human genes 0.000 description 1
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
208000004550 Postoperative Pain Diseases 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
FCLZCOCSZQNREK-UHFFFAOYSA-N Pyrrolidine, hydrochloride Chemical compound Cl.C1CCNC1 FCLZCOCSZQNREK-UHFFFAOYSA-N 0.000 description 1
241001474728 Satyrodes eurydice Species 0.000 description 1
235000019095 Sechium edule Nutrition 0.000 description 1
244000000231 Sesamum indicum Species 0.000 description 1
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
244000061456 Solanum tuberosum Species 0.000 description 1
235000002595 Solanum tuberosum Nutrition 0.000 description 1
AWMVMTVKBNGEAK-UHFFFAOYSA-N Styrene oxide Chemical class C1OC1C1=CC=CC=C1 AWMVMTVKBNGEAK-UHFFFAOYSA-N 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
240000008042 Zea mays Species 0.000 description 1
235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
235000002017 Zea mays subsp mays Nutrition 0.000 description 1
230000003187 abdominal effect Effects 0.000 description 1
238000000862 absorption spectrum Methods 0.000 description 1
229960001171 acetohydroxamic acid Drugs 0.000 description 1
239000003377 acid catalyst Substances 0.000 description 1
238000005903 acid hydrolysis reaction Methods 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
230000010933 acylation Effects 0.000 description 1
125000005042 acyloxymethyl group Chemical group 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
150000001350 alkyl halides Chemical class 0.000 description 1
230000002152 alkylating effect Effects 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
239000000908 ammonium hydroxide Substances 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
230000027455 binding Effects 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
QRZAKQDHEVVFRX-UHFFFAOYSA-N biphenyl-4-ylacetic acid Chemical compound C1=CC(CC(=O)O)=CC=C1C1=CC=CC=C1 QRZAKQDHEVVFRX-UHFFFAOYSA-N 0.000 description 1
230000037396 body weight Effects 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
229910000019 calcium carbonate Inorganic materials 0.000 description 1
235000010216 calcium carbonate Nutrition 0.000 description 1
MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
239000002775 capsule Substances 0.000 description 1
150000001718 carbodiimides Chemical class 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
239000000969 carrier Substances 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
QZXCCPZJCKEPSA-UHFFFAOYSA-N chlorfenac Chemical compound OC(=O)CC1=C(Cl)C=CC(Cl)=C1Cl QZXCCPZJCKEPSA-UHFFFAOYSA-N 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
GGRHYQCXXYLUTL-UHFFFAOYSA-N chloromethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCCl GGRHYQCXXYLUTL-UHFFFAOYSA-N 0.000 description 1
239000003086 colorant Substances 0.000 description 1
235000009508 confectionery Nutrition 0.000 description 1
238000001816 cooling Methods 0.000 description 1
235000005822 corn Nutrition 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
230000006735 deficit Effects 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
238000001514 detection method Methods 0.000 description 1
150000005690 diesters Chemical class 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
NKDDWNXOKDWJAK-UHFFFAOYSA-N dimethoxymethane Chemical compound COCOC NKDDWNXOKDWJAK-UHFFFAOYSA-N 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
229910000397 disodium phosphate Inorganic materials 0.000 description 1
235000019800 disodium phosphate Nutrition 0.000 description 1
238000002224 dissection Methods 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000000975 dye Substances 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
210000002683 foot Anatomy 0.000 description 1
239000000499 gel Substances 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
229940050410 gluconate Drugs 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
238000005469 granulation Methods 0.000 description 1
230000003179 granulation Effects 0.000 description 1
150000008282 halocarbons Chemical class 0.000 description 1
239000010468 hazelnut oil Substances 0.000 description 1
210000000548 hind-foot Anatomy 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
230000004968 inflammatory condition Effects 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
239000008101 lactose Substances 0.000 description 1
150000007517 lewis acids Chemical class 0.000 description 1
239000003446 ligand Substances 0.000 description 1
239000007788 liquid Substances 0.000 description 1
239000006210 lotion Substances 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
230000008018 melting Effects 0.000 description 1
238000003328 mesylation reaction Methods 0.000 description 1
238000005667 methoxymethylation reaction Methods 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
KXDOGABXVPLQQJ-QFBILLFUSA-N n-[(1s)-1-(4-chlorophenyl)-2-[(3s)-3-hydroxypyrrolidin-1-yl]ethyl]-2-(3,4-dichlorophenyl)-n-hydroxyacetamide Chemical compound C1[C@@H](O)CCN1C[C@H](C=1C=CC(Cl)=CC=1)N(O)C(=O)CC1=CC=C(Cl)C(Cl)=C1 KXDOGABXVPLQQJ-QFBILLFUSA-N 0.000 description 1
FMYWCTPWTIDWSP-HSZRJFAPSA-N n-hydroxy-2-naphthalen-1-yl-n-[(1s)-1-phenyl-2-pyrrolidin-1-ylethyl]acetamide Chemical compound C([C@@H](N(O)C(=O)CC=1C2=CC=CC=C2C=CC=1)C=1C=CC=CC=1)N1CCCC1 FMYWCTPWTIDWSP-HSZRJFAPSA-N 0.000 description 1
SXZXLQLYGSCLON-GOSISDBHSA-N n-hydroxy-n-[(1s)-1-phenyl-2-pyrrolidin-1-ylethyl]-2-pyridin-4-ylacetamide Chemical compound C([C@@H](N(O)C(=O)CC=1C=CN=CC=1)C=1C=CC=CC=1)N1CCCC1 SXZXLQLYGSCLON-GOSISDBHSA-N 0.000 description 1
JYQORVIEZYYOOQ-RBUKOAKNSA-N n-hydroxy-n-[(1s)-2-[(3s)-3-hydroxypyrrolidin-1-yl]-1-phenylethyl]-2-(3-nitrophenyl)acetamide Chemical compound C1[C@@H](O)CCN1C[C@H](C=1C=CC=CC=1)N(O)C(=O)CC1=CC=CC([N+]([O-])=O)=C1 JYQORVIEZYYOOQ-RBUKOAKNSA-N 0.000 description 1
STUUHGNXENPYPH-RBUKOAKNSA-N n-hydroxy-n-[(1s)-2-[(3s)-3-hydroxypyrrolidin-1-yl]-1-phenylethyl]-2-(4-nitrophenyl)acetamide Chemical compound C1[C@@H](O)CCN1C[C@H](C=1C=CC=CC=1)N(O)C(=O)CC1=CC=C([N+]([O-])=O)C=C1 STUUHGNXENPYPH-RBUKOAKNSA-N 0.000 description 1
QLYRBFOGSZYOQI-RBBKRZOGSA-N n-hydroxy-n-[(1s)-2-[(3s)-3-hydroxypyrrolidin-1-yl]-1-phenylethyl]-2-(5-oxo-7,8-dihydro-6h-naphthalen-2-yl)acetamide Chemical compound C1[C@@H](O)CCN1C[C@H](C=1C=CC=CC=1)N(O)C(=O)CC1=CC=C(C(=O)CCC2)C2=C1 QLYRBFOGSZYOQI-RBBKRZOGSA-N 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
XYEOALKITRFCJJ-UHFFFAOYSA-N o-benzylhydroxylamine Chemical compound NOCC1=CC=CC=C1 XYEOALKITRFCJJ-UHFFFAOYSA-N 0.000 description 1
HYDZPXNVHXJHBG-UHFFFAOYSA-N o-benzylhydroxylamine;hydron;chloride Chemical compound Cl.NOCC1=CC=CC=C1 HYDZPXNVHXJHBG-UHFFFAOYSA-N 0.000 description 1
239000002674 ointment Substances 0.000 description 1
239000003399 opiate peptide Substances 0.000 description 1
239000008203 oral pharmaceutical composition Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical class C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000006072 paste Substances 0.000 description 1
235000010603 pastilles Nutrition 0.000 description 1
210000000578 peripheral nerve Anatomy 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
239000003444 phase transfer catalyst Substances 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000002243 precursor Substances 0.000 description 1
239000000651 prodrug Substances 0.000 description 1
229940002612 prodrug Drugs 0.000 description 1
ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
230000006340 racemization Effects 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
238000010992 reflux Methods 0.000 description 1
238000010825 rotarod performance test Methods 0.000 description 1
230000001624 sedative effect Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
150000004760 silicates Chemical class 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
235000011083 sodium citrates Nutrition 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
235000019345 sodium thiosulphate Nutrition 0.000 description 1
241000894007 species Species 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000007921 spray 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
239000005720 sucrose Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
238000001665 trituration Methods 0.000 description 1

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
- C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- 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
- A61P23/00—Anaesthetics
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
- C07D207/12—Oxygen or sulfur atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/13—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Pain & Pain Management (AREA)
Diabetes (AREA)
Hematology (AREA)
Hospice & Palliative Care (AREA)
Psychiatry (AREA)
Rheumatology (AREA)
Anesthesiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Furan Compounds (AREA)
Pyrrole Compounds (AREA)

HRPCT/JP95/631A 1995-03-31 1996-03-26 Pyrrolidinyl hydroxamic acid compounds and their production process HRP960141A2 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
JP9500631		1995-03-31

Publications (1)

Publication Number	Publication Date
HRP960141A2 true HRP960141A2 (en)	1997-10-31

Family

ID=14125824

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HRPCT/JP95/631A HRP960141A2 (en)	1995-03-31	1996-03-26	Pyrrolidinyl hydroxamic acid compounds and their production process

Country Status (35)

Country	Link
US (2)	US5952369A (pt)
EP (1)	EP0817772B1 (pt)
JP (1)	JP3035356B2 (pt)
KR (1)	KR100258657B1 (pt)
AP (1)	AP625A (pt)
AR (1)	AR002729A1 (pt)
AT (1)	ATE231840T1 (pt)
AU (1)	AU693336B2 (pt)
BG (1)	BG62611B1 (pt)
BR (1)	BR9607750A (pt)
CA (1)	CA2213815C (pt)
CZ (1)	CZ306497A3 (pt)
DE (1)	DE69626009T2 (pt)
DK (1)	DK0817772T3 (pt)
ES (1)	ES2188743T3 (pt)
HR (1)	HRP960141A2 (pt)
HU (1)	HUP9900767A3 (pt)
IL (2)	IL117440A0 (pt)
IS (1)	IS4547A (pt)
LV (1)	LV11971B (pt)
MA (1)	MA23832A1 (pt)
NO (1)	NO974513D0 (pt)
NZ (1)	NZ304113A (pt)
OA (1)	OA10518A (pt)
PE (1)	PE43397A1 (pt)
PL (1)	PL322652A1 (pt)
RU (1)	RU2144917C1 (pt)
SI (1)	SI9620039A (pt)
SK (1)	SK129897A3 (pt)
TN (1)	TNSN96045A1 (pt)
TR (1)	TR199701082T1 (pt)
TW (1)	TW408111B (pt)
WO (1)	WO1996030339A1 (pt)
YU (1)	YU18696A (pt)
ZA (1)	ZA962476B (pt)

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
MX9701042A (es) *	1996-02-07	1998-05-31	Pfizer	Compuestos del acido hidroxamico.
TNSN97092A1 (ar)	1996-09-18	1999-12-31	Agouron Pharma	مثبطات انزيم بروتيني فلزي وتركيبات صيدلانية تحتوي على تلك المثبتطات واستخدامها الصيدلاني وطرق ومركبات وسيطة مفيدة لتحضير التركيبات المذكورة.
ATE235903T1 (de) *	1996-12-02	2003-04-15	Kyorin Seiyaku Kk	Neue derivate von n-substituierten pyrrolidin derivaten und deren herstellungsverfahren
JP2000507970A (ja) *	1997-01-10	2000-06-27	メルクエンドカンパニーインコーポレーテッド	キラルメディエータの効率的な合成
IL130429A0 (en) *	1998-08-24	2000-06-01	Pfizer Prod Inc	Process for preparing pyrrolidinyl hydroxamic acid compounds
KR100295740B1 (ko) *	1998-09-17	2001-11-05	박영구	N-치환된-하이드록시고리화알킬아민유도체의제조방법
US6444829B1 (en) *	2000-07-19	2002-09-03	Hoffmann-La Roche Inc.	Pyrrolidine compounds
CA2445874A1 (en)	2001-04-30	2002-11-07	Fumitaka Ito	Process for preparing hydroxypyrrolidinyl ethylamine compounds useful as kappa agonists
US7091357B2 (en) *	2001-12-26	2006-08-15	University Of Kentucky Research Foundation	Chain-modified pyridino-N substituted nicotine compounds for use in the treatment of CNS pathologies
AU2003269399A1 (en) *	2002-11-01	2004-05-25	Pfizer Products Inc.	Process for the preparation of pyrrolidinyl ethylamine compounds via a copper-mediated aryl amination
GB0821010D0 (en) *	2008-11-17	2008-12-24	Univ Warwick	Plant development control composition
WO2012155199A1 (en)	2011-05-16	2012-11-22	Bionomics Limited	Amine derivatives as potassium channel blockers
MX355142B (es) *	2012-03-05	2018-04-05	Dr Reddys Laboratories Ltd	Acetamidas heterociclicas sustituidas como agonistas del receptor opioide kappa (kor).
GB201210395D0 (en) *	2012-06-11	2012-07-25	Syngenta Participations Ag	Crop enhancement compositions

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3268539A (en) *	1963-05-20	1966-08-23	Universal Oil Prod Co	Tertiary-aminoalkyl derivatives of diaryl substituted acetohydroxamic acid esters

1996
- 1996-03-11 IL IL11744096A patent/IL117440A0/xx unknown
- 1996-03-14 AP APAP/P/1996/000791A patent/AP625A/en active
- 1996-03-15 TW TW085103136A patent/TW408111B/zh active
- 1996-03-25 MA MA24191A patent/MA23832A1/fr unknown
- 1996-03-25 PE PE1996000208A patent/PE43397A1/es not_active Application Discontinuation
- 1996-03-26 HR HRPCT/JP95/631A patent/HRP960141A2/hr not_active Application Discontinuation
- 1996-03-27 YU YU18696A patent/YU18696A/sh unknown
- 1996-03-28 SI SI9620039A patent/SI9620039A/sl not_active IP Right Cessation
- 1996-03-28 DK DK96907686T patent/DK0817772T3/da active
- 1996-03-28 ES ES96907686T patent/ES2188743T3/es not_active Expired - Lifetime
- 1996-03-28 JP JP08529174A patent/JP3035356B2/ja not_active Expired - Fee Related
- 1996-03-28 ZA ZA9602476A patent/ZA962476B/xx unknown
- 1996-03-28 HU HU9900767A patent/HUP9900767A3/hu unknown
- 1996-03-28 TR TR97/01082T patent/TR199701082T1/xx unknown
- 1996-03-28 AT AT96907686T patent/ATE231840T1/de not_active IP Right Cessation
- 1996-03-28 SK SK1298-97A patent/SK129897A3/sk unknown
- 1996-03-28 US US08/913,823 patent/US5952369A/en not_active Expired - Fee Related
- 1996-03-28 WO PCT/JP1996/000820 patent/WO1996030339A1/en active IP Right Grant
- 1996-03-28 CZ CZ973064A patent/CZ306497A3/cs unknown
- 1996-03-28 PL PL96322652A patent/PL322652A1/xx unknown
- 1996-03-28 AU AU51211/96A patent/AU693336B2/en not_active Ceased
- 1996-03-28 RU RU97117590A patent/RU2144917C1/ru active
- 1996-03-28 EP EP96907686A patent/EP0817772B1/en not_active Expired - Lifetime
- 1996-03-28 CA CA002213815A patent/CA2213815C/en not_active Expired - Fee Related
- 1996-03-28 NZ NZ304113A patent/NZ304113A/xx unknown
- 1996-03-28 KR KR1019970706880A patent/KR100258657B1/ko not_active IP Right Cessation
- 1996-03-28 DE DE69626009T patent/DE69626009T2/de not_active Expired - Fee Related
- 1996-03-28 BR BR9607750A patent/BR9607750A/pt active Search and Examination
- 1996-03-29 TN TNTNSN96045A patent/TNSN96045A1/fr unknown
- 1996-03-29 AR ARP960101993A patent/AR002729A1/es unknown
1997
- 1997-08-19 IS IS4547A patent/IS4547A/is unknown
- 1997-09-17 BG BG101896A patent/BG62611B1/bg unknown
- 1997-09-29 NO NO974513A patent/NO974513D0/no not_active Application Discontinuation
- 1997-09-30 OA OA70091A patent/OA10518A/en unknown
- 1997-10-21 LV LVP-97-203A patent/LV11971B/en unknown
1999
- 1999-04-15 IL IL12947999A patent/IL129479A0/xx unknown
- 1999-04-29 US US09/302,097 patent/US6110947A/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
AP625A (en)	1997-12-24
HUP9900767A3 (en)	2001-01-29
BG62611B1 (bg)	2000-03-31
NO974513L (no)	1997-09-29
SI9620039A (sl)	1998-08-31
CZ306497A3 (cs)	1998-07-15
ES2188743T3 (es)	2003-07-01
LV11971B (en)	1998-06-20
SK129897A3 (en)	1998-11-04
PL322652A1 (en)	1998-02-16
MA23832A1 (fr)	1996-10-01
OA10518A (en)	2002-04-22
EP0817772A1 (en)	1998-01-14
WO1996030339A1 (en)	1996-10-03
DE69626009T2 (de)	2003-08-14
IL117440A0 (en)	1996-07-23
IL129479A0 (en)	2000-02-29
TR199701082T1 (xx)	1998-02-21
KR100258657B1 (ko)	2000-07-01
NO974513D0 (no)	1997-09-29
NZ304113A (en)	1999-01-28
AR002729A1 (es)	1998-04-29
KR19980703476A (ko)	1998-11-05
HUP9900767A2 (hu)	1999-07-28
ZA962476B (en)	1997-09-29
CA2213815A1 (en)	1996-10-03
TNSN96045A1 (fr)	2005-03-15
DE69626009D1 (de)	2003-03-06
JP3035356B2 (ja)	2000-04-24
LV11971A (lv)	1998-02-20
PE43397A1 (es)	1997-10-13
AP9600791A0 (en)	1996-04-30
DK0817772T3 (da)	2003-05-19
MX9707454A (es)	1998-07-31
TW408111B (en)	2000-10-11
BG101896A (en)	1999-01-29
AU693336B2 (en)	1998-06-25
AU5121196A (en)	1996-10-16
US5952369A (en)	1999-09-14
BR9607750A (pt)	1998-06-30
US6110947A (en)	2000-08-29
JPH11501048A (ja)	1999-01-26
YU18696A (sh)	1999-06-15
EP0817772B1 (en)	2003-01-29
IS4547A (is)	1997-08-19
ATE231840T1 (de)	2003-02-15
CA2213815C (en)	2001-12-18
RU2144917C1 (ru)	2000-01-27

Legal Events

Date	Code	Title
1997-10-31	A1OB	Publication of a patent application
1998-04-29	AIPI	Request for the grant of a patent on the basis of a substantive examination of a patent application
2004-04-21	ODBC	Application rejected

Publication	Publication Date	Title
JP6392888B2 (ja)	2018-09-19	ヒストン脱アセチル化酵素６阻害剤としての新規化合物およびこれを含む薬剤学的組成物
AU693336B2 (en)	1998-06-25	Pyrrolidinyl hydroxamic acid compounds and their production process
EP1254895A1 (en)	2002-11-06	Nitrogenous cyclic compounds and pharmaceutical compositions containing the same
AU5714096A (en)	1996-11-21	Substituted oximes, hydrazones and olefins as neurokinin antagonists
KR100523184B1 (ko)	2005-10-24	아제티딘 및 피롤리딘의 유도체
AU2004309280A1 (en)	2005-07-14	Benzene compounds disubstituted with cyclic groups at the 1- and 2-positions
WO1995030675A1 (en)	1995-11-16	Biphenylcarboxamides useful as 5-ht1d antagonists
NO171060B (no)	1992-10-12	Analogifremgangsmaate for fremstilling av terapeutisk aktive n-cykloalkylalkyl-benzylaminer
AU2003220215A1 (en)	2003-09-29	Nk1 antagonists
WO1998031677A1 (fr)	1998-07-23	Nouvelles amines aromatiques derivees d'amines cycliques utiles comme medicaments
JP2935899B2 (ja)	1999-08-16	▲下ｋ▼レセプターアゴニストとしてのｎ−（２−（ピロリジニル−１）−１−フェニルエチル）アセトアミド
EP1870396B1 (en)	2012-10-31	Benzyloxypropylamine derivative
EP0782989A1 (en)	1997-07-09	Indole derivatives
EP0789021B1 (en)	2000-10-11	Hydroxamic acid compounds as opioid kappa receptor agonists
US20040034070A1 (en)	2004-02-19	Propanolaminotetralines, preparation thereof and compositions containing same
MXPA97007454A (en)	1998-11-09	Hydroxamic pirrolidinil acid compounds and their product procedure
JP2012107006A (ja)	2012-06-07	Ｎ−置換−環状アミノ誘導体の製造方法