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
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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
- C07D213/24—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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- 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
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- 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
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- 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
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- 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
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- 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
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- Y02P20/00—Technologies relating to chemical industry
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General Chemical & Material Sciences (AREA)
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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)
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Plural Heterocyclic Compounds (AREA)
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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 (fr)
EP (1)	EP0817772B1 (fr)
JP (1)	JP3035356B2 (fr)
KR (1)	KR100258657B1 (fr)
AP (1)	AP625A (fr)
AR (1)	AR002729A1 (fr)
AT (1)	ATE231840T1 (fr)
AU (1)	AU693336B2 (fr)
BG (1)	BG62611B1 (fr)
BR (1)	BR9607750A (fr)
CA (1)	CA2213815C (fr)
CZ (1)	CZ306497A3 (fr)
DE (1)	DE69626009T2 (fr)
DK (1)	DK0817772T3 (fr)
ES (1)	ES2188743T3 (fr)
HR (1)	HRP960141A2 (fr)
HU (1)	HUP9900767A3 (fr)
IL (2)	IL117440A0 (fr)
IS (1)	IS4547A (fr)
LV (1)	LV11971B (fr)
MA (1)	MA23832A1 (fr)
NO (1)	NO974513D0 (fr)
NZ (1)	NZ304113A (fr)
OA (1)	OA10518A (fr)
PE (1)	PE43397A1 (fr)
PL (1)	PL322652A1 (fr)
RU (1)	RU2144917C1 (fr)
SI (1)	SI9620039A (fr)
SK (1)	SK129897A3 (fr)
TN (1)	TNSN96045A1 (fr)
TR (1)	TR199701082T1 (fr)
TW (1)	TW408111B (fr)
WO (1)	WO1996030339A1 (fr)
YU (1)	YU18696A (fr)
ZA (1)	ZA962476B (fr)

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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.
JP4167302B2 (ja) *	1996-12-02	2008-10-15	杏林製薬株式会社	新規ｎ―置換ピロリジン誘導体及びその製造法
EP0973737A4 (fr) *	1997-01-10	2000-04-26	Merck & Co Inc	Synthese efficace d'un mediateur chiral
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 (fr)	2001-04-30	2002-11-07	Fumitaka Ito	Procede de preparation de composes d'ethylamine d'hydroxypyrrolidinyle utilises comme agonistes de kappa
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
GB0202873D0 (en) *	2002-02-07	2002-03-27	Novartis Ag	Organic compounds
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
RS20050760A (sr) *	2003-04-14	2008-04-04	Warner-Lambert Company Llc.,	Postupak za izradu fenilamida 5-(4- fluorofenil)-1-(2-((2r, 4r)-4-hidroksi- 6-okso-tetrahidro-piran-2-il)etil)-2- izopropil-4-fenil-1h-pirol-3- karboksilne kiseline
UA89035C2 (ru) *	2003-12-03	2009-12-25	Лео Фарма А/С	Эфиры гидроксамовых кислот и их фармацевтическое применение
GB0821010D0 (en)	2008-11-17	2008-12-24	Univ Warwick	Plant development control composition
US9493451B2 (en)	2011-05-16	2016-11-15	Bionomics Limited	Amine derivatives as potassium channel blockers
AU2013230425B2 (en)	2012-03-05	2017-05-25	Dr.Reddy's Laboratories Ltd.	Substituted heterocyclic acetamides as kappa opioid receptor (kor) agonists
GB201210395D0 (en) *	2012-06-11	2012-07-25	Syngenta Participations Ag	Crop enhancement compositions

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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 PL PL96322652A patent/PL322652A1/xx unknown
- 1996-03-28 AT AT96907686T patent/ATE231840T1/de not_active IP Right Cessation
- 1996-03-28 CA CA002213815A patent/CA2213815C/fr not_active Expired - Fee Related
- 1996-03-28 KR KR1019970706880A patent/KR100258657B1/ko not_active Expired - Fee Related
- 1996-03-28 SK SK1298-97A patent/SK129897A3/sk unknown
- 1996-03-28 RU RU97117590A patent/RU2144917C1/ru active
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- 1996-03-28 JP JP08529174A patent/JP3035356B2/ja not_active Expired - Fee Related
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- 1996-03-28 DK DK96907686T patent/DK0817772T3/da active
- 1996-03-28 HU HU9900767A patent/HUP9900767A3/hu unknown
- 1996-03-28 EP EP96907686A patent/EP0817772B1/fr not_active Expired - Lifetime
- 1996-03-28 SI SI9620039A patent/SI9620039A/sl not_active IP Right Cessation
- 1996-03-28 TR TR97/01082T patent/TR199701082T1/xx unknown
- 1996-03-28 AU AU51211/96A patent/AU693336B2/en not_active Ceased
- 1996-03-28 BR BR9607750A patent/BR9607750A/pt active Search and Examination
- 1996-03-28 CZ CZ973064A patent/CZ306497A3/cs unknown
- 1996-03-28 WO PCT/JP1996/000820 patent/WO1996030339A1/fr not_active Ceased
- 1996-03-29 AR ARP960101993A patent/AR002729A1/es unknown
- 1996-03-29 TN TNTNSN96045A patent/TNSN96045A1/fr 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
KR100258657B1 (ko)	2000-07-01
HUP9900767A3 (en)	2001-01-29
PE43397A1 (es)	1997-10-13
DE69626009T2 (de)	2003-08-14
WO1996030339A1 (fr)	1996-10-03
DE69626009D1 (de)	2003-03-06
MX9707454A (es)	1998-07-31
KR19980703476A (ko)	1998-11-05
BG62611B1 (bg)	2000-03-31
CA2213815C (fr)	2001-12-18
AU5121196A (en)	1996-10-16
BG101896A (en)	1999-01-29
TNSN96045A1 (fr)	2005-03-15
US5952369A (en)	1999-09-14
US6110947A (en)	2000-08-29
OA10518A (en)	2002-04-22
HUP9900767A2 (hu)	1999-07-28
JPH11501048A (ja)	1999-01-26
CZ306497A3 (cs)	1998-07-15
TW408111B (en)	2000-10-11
AP9600791A0 (en)	1996-04-30
LV11971A (lv)	1998-02-20
BR9607750A (pt)	1998-06-30
TR199701082T1 (xx)	1998-02-21
LV11971B (en)	1998-06-20
ZA962476B (en)	1997-09-29
MA23832A1 (fr)	1996-10-01
YU18696A (sh)	1999-06-15
ES2188743T3 (es)	2003-07-01
JP3035356B2 (ja)	2000-04-24
PL322652A1 (en)	1998-02-16
SK129897A3 (en)	1998-11-04
SI9620039A (sl)	1998-08-31
NO974513L (no)	1997-09-29
AU693336B2 (en)	1998-06-25
EP0817772B1 (fr)	2003-01-29
AP625A (en)	1997-12-24
IS4547A (is)	1997-08-19
RU2144917C1 (ru)	2000-01-27
CA2213815A1 (fr)	1996-10-03
IL129479A0 (en)	2000-02-29
DK0817772T3 (da)	2003-05-19
IL117440A0 (en)	1996-07-23
NO974513D0 (no)	1997-09-29
NZ304113A (en)	1999-01-28
ATE231840T1 (de)	2003-02-15
AR002729A1 (es)	1998-04-29
EP0817772A1 (fr)	1998-01-14

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
AU693336B2 (en)	1998-06-25	Pyrrolidinyl hydroxamic acid compounds and their production process
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
EP1254895A1 (fr)	2002-11-06	Composes azotes cycliques et compositions pharmaceutiques les contenant
DE69411949T2 (de)	1999-01-14	Dihydrobenzofuranyl-biphenyl-carboxamide mit 5ht1d-antagonistischer wirkung
DE69417427T2 (de)	1999-11-25	Indol- und indolin-derivate als 5ht1d rezeptor antagonisten
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
AU2003220215A1 (en)	2003-09-29	Nk1 antagonists
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RS8504A (sr)	2007-02-05	Novi cikloheksil sulfoni
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
DE69411589T2 (de)	1999-01-07	Indol, indolin und chinolin derivate mit einer 5ht1d antagonistischen wirkung
Liu et al.	2017	Divergent syntheses of L-733, 060 and CP-122721 from functionalized pieridinones made by one-pot tandem cyclization
EP0789021B1 (fr)	2000-10-11	Dérivés d'acide hydroxamique et leur utilisation comme agonistes du récepteur opioid kappa
EP1870396B1 (fr)	2012-10-31	Derive de la benzyloxypropylamine
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