ZA200504050B - Pyrrolidine and thiazolidine compounds, a process for their preparation and pharmaceutical compositions containing them - Google Patents

Pyrrolidine and thiazolidine compounds, a process for their preparation and pharmaceutical compositions containing them Download PDF

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Publication number: ZA200504050B
Authority: ZA; South Africa
Prior art keywords: formula; compound; group; acetyl; pyrrolidinecarbonitrile
Prior art date: 2004-05-19

Application number

ZA200504050A

Other languages

English (en)

Inventor

Guillaume De Nanteuil

Alain Benoist

Murielle Combettes

Elizabeth Harley

Original Assignee

Servier Lab

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.)

2004-05-19

Filing date

2005-05-19

Publication date

2006-07-26

2005-05-19 Application filed by Servier Lab filed Critical Servier Lab

2006-07-26 Publication of ZA200504050B publication Critical patent/ZA200504050B/en

Links

238000000034 method Methods 0.000 title claims description 55
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 title description 9
238000002360 preparation method Methods 0.000 title description 7
239000008194 pharmaceutical composition Substances 0.000 title description 4
150000003548 thiazolidines Chemical class 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims description 118
229910052799 carbon Inorganic materials 0.000 claims description 35
150000003839 salts Chemical class 0.000 claims description 27
239000002253 acid Substances 0.000 claims description 22
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 20
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
125000003003 spiro group Chemical group 0.000 claims description 10
125000003277 amino group Chemical group 0.000 claims description 6
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
125000004429 atom Chemical group 0.000 claims description 4
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
125000004093 cyano group Chemical group *C#N 0.000 claims description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
150000001721 carbon Chemical group 0.000 claims description 2
229910052760 oxygen Inorganic materials 0.000 claims description 2
125000004430 oxygen atom Chemical group O* 0.000 claims description 2
125000005843 halogen group Chemical group 0.000 claims 2
230000015572 biosynthetic process Effects 0.000 claims 1
238000003786 synthesis reaction Methods 0.000 claims 1
239000000047 product Substances 0.000 description 78
229910052739 hydrogen Inorganic materials 0.000 description 30
238000004452 microanalysis Methods 0.000 description 30
229910052757 nitrogen Inorganic materials 0.000 description 30
KVFDZFBHBWTVID-UHFFFAOYSA-N cyclohexanecarbaldehyde Chemical compound O=CC1CCCCC1 KVFDZFBHBWTVID-UHFFFAOYSA-N 0.000 description 20
239000000243 solution Substances 0.000 description 20
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
YCWRPKBYQZOLCD-LURJTMIESA-N (2s)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrile Chemical compound ClCC(=O)N1CCC[C@H]1C#N YCWRPKBYQZOLCD-LURJTMIESA-N 0.000 description 14
239000011541 reaction mixture Substances 0.000 description 14
-1 amide compounds Chemical class 0.000 description 13
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 11
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 8
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
CXLGNJCMPWUZKM-UHFFFAOYSA-N oxane-4-carbaldehyde Chemical compound O=CC1CCOCC1 CXLGNJCMPWUZKM-UHFFFAOYSA-N 0.000 description 7
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
FUSUHKVFWTUUBE-UHFFFAOYSA-N buten-2-one Chemical compound CC(=O)C=C FUSUHKVFWTUUBE-UHFFFAOYSA-N 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
QIRVGKYPAOQVNP-UHFFFAOYSA-N methylidenecyclobutane Chemical compound C=C1CCC1 QIRVGKYPAOQVNP-UHFFFAOYSA-N 0.000 description 6
239000000203 mixture Substances 0.000 description 6
239000003921 oil Substances 0.000 description 6
235000019198 oils Nutrition 0.000 description 6
102000016622 Dipeptidyl Peptidase 4 Human genes 0.000 description 5
101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 5
239000008346 aqueous phase Substances 0.000 description 5
238000004949 mass spectrometry Methods 0.000 description 5
239000012074 organic phase Substances 0.000 description 5
239000000843 powder Substances 0.000 description 5
238000003756 stirring Methods 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
208000035475 disorder Diseases 0.000 description 4
239000003112 inhibitor Substances 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
229910052717 sulfur Inorganic materials 0.000 description 4
239000000725 suspension Substances 0.000 description 4
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
238000011282 treatment Methods 0.000 description 4
TYMLOMAKGOJONV-UHFFFAOYSA-N 4-nitroaniline Chemical compound NC1=CC=C([N+]([O-])=O)C=C1 TYMLOMAKGOJONV-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
108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 description 3
102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 3
DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 3
101800000224 Glucagon-like peptide 1 Proteins 0.000 description 3
208000002705 Glucose Intolerance Diseases 0.000 description 3
206010018429 Glucose tolerance impaired Diseases 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
102100040918 Pro-glucagon Human genes 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
239000007983 Tris buffer Substances 0.000 description 3
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
229960000583 acetic acid Drugs 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
230000000694 effects Effects 0.000 description 3
201000001421 hyperglycemia Diseases 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
210000003734 kidney Anatomy 0.000 description 3
238000002844 melting Methods 0.000 description 3
230000008018 melting Effects 0.000 description 3
238000010992 reflux Methods 0.000 description 3
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
208000001072 type 2 diabetes mellitus Diseases 0.000 description 3
229910052725 zinc Inorganic materials 0.000 description 3
239000011701 zinc Substances 0.000 description 3
WPMZIZVPJORINX-RXMQYKEDSA-N (4r)-3-(2-chloroacetyl)-1,3-thiazolidine-4-carbonitrile Chemical compound ClCC(=O)N1CSC[C@H]1C#N WPMZIZVPJORINX-RXMQYKEDSA-N 0.000 description 2
IMADNQJYACUCLA-XFULWGLBSA-N (4r)-3-[2-(spiro[5.5]undecan-3-ylamino)acetyl]-1,3-thiazolidine-4-carbonitrile;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N1([C@@H](CSC1)C#N)C(=O)CNC(CC1)CCC21CCCCC2 IMADNQJYACUCLA-XFULWGLBSA-N 0.000 description 2
MKNUBLDIUFQXPI-UHFFFAOYSA-N 1,1-dioxothiane-4-carbaldehyde Chemical compound O=CC1CCS(=O)(=O)CC1 MKNUBLDIUFQXPI-UHFFFAOYSA-N 0.000 description 2
ZPKCBDBPTCYRLX-UHFFFAOYSA-N 3-azaspiro[5.5]undecan-9-one Chemical compound C1CC(=O)CCC11CCNCC1 ZPKCBDBPTCYRLX-UHFFFAOYSA-N 0.000 description 2
NSELYKZLLNWRED-UHFFFAOYSA-N 4-methylideneoxane Chemical compound C=C1CCOCC1 NSELYKZLLNWRED-UHFFFAOYSA-N 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
208000008589 Obesity Diseases 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
229910021529 ammonia Inorganic materials 0.000 description 2
239000001099 ammonium carbonate Substances 0.000 description 2
235000012501 ammonium carbonate Nutrition 0.000 description 2
AYJRCSIUFZENHW-UHFFFAOYSA-L barium carbonate Chemical compound [Ba+2].[O-]C([O-])=O AYJRCSIUFZENHW-UHFFFAOYSA-L 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
239000000872 buffer Substances 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
230000003197 catalytic effect Effects 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
VELDYOPRLMJFIK-UHFFFAOYSA-N cyclopentanecarbaldehyde Chemical compound O=CC1CCCC1 VELDYOPRLMJFIK-UHFFFAOYSA-N 0.000 description 2
238000010511 deprotection reaction Methods 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
229910052731 fluorine Inorganic materials 0.000 description 2
239000011737 fluorine Substances 0.000 description 2
229910052736 halogen Inorganic materials 0.000 description 2
150000002367 halogens Chemical class 0.000 description 2
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
VXWPONVCMVLXBW-UHFFFAOYSA-M magnesium;carbanide;iodide Chemical compound [CH3-].[Mg+2].[I-] VXWPONVCMVLXBW-UHFFFAOYSA-M 0.000 description 2
238000005259 measurement Methods 0.000 description 2
239000012528 membrane Substances 0.000 description 2
YULMNMJFAZWLLN-UHFFFAOYSA-N methylenecyclohexane Chemical compound C=C1CCCCC1 YULMNMJFAZWLLN-UHFFFAOYSA-N 0.000 description 2
WPHGSKGZRAQSGP-UHFFFAOYSA-N methylenecyclohexane Natural products C1CCCC2CC21 WPHGSKGZRAQSGP-UHFFFAOYSA-N 0.000 description 2
NFJPEKRRHIYYES-UHFFFAOYSA-N methylidenecyclopentane Chemical compound C=C1CCCC1 NFJPEKRRHIYYES-UHFFFAOYSA-N 0.000 description 2
235000020824 obesity Nutrition 0.000 description 2
239000008188 pellet Substances 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
239000000377 silicon dioxide Substances 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
229910000104 sodium hydride Inorganic materials 0.000 description 2
239000007787 solid Substances 0.000 description 2
BAERJJQGHJOXHR-UHFFFAOYSA-N spiro[5.5]undecan-3-amine Chemical compound C1CC(N)CCC11CCCCC1 BAERJJQGHJOXHR-UHFFFAOYSA-N 0.000 description 2
239000001117 sulphuric acid Substances 0.000 description 2
235000011149 sulphuric acid Nutrition 0.000 description 2
239000003826 tablet Substances 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
210000001519 tissue Anatomy 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
PVFOMCVHYWHZJE-UHFFFAOYSA-N trichloroacetyl chloride Chemical compound ClC(=O)C(Cl)(Cl)Cl PVFOMCVHYWHZJE-UHFFFAOYSA-N 0.000 description 2
YCWRPKBYQZOLCD-ZCFIWIBFSA-N (2r)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrile Chemical compound ClCC(=O)N1CCC[C@@H]1C#N YCWRPKBYQZOLCD-ZCFIWIBFSA-N 0.000 description 1
LSBPCBRYNZTOJB-OAHLLOKOSA-N (2r)-1-[2-[[9-(hydroxymethyl)-3-oxaspiro[5.5]undecan-9-yl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound C1CC(CO)(NCC(=O)N2[C@H](CCC2)C#N)CCC21CCOCC2 LSBPCBRYNZTOJB-OAHLLOKOSA-N 0.000 description 1
PBXJEAYKZGZMIE-YFKPBYRVSA-N (2s)-1-(2-chloroacetyl)-4,4-difluoropyrrolidine-2-carbonitrile Chemical compound FC1(F)C[C@@H](C#N)N(C(=O)CCl)C1 PBXJEAYKZGZMIE-YFKPBYRVSA-N 0.000 description 1
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FYFOCMSXVYVCJK-RSAXXLAASA-N (2s)-1-[2-(3-oxaspiro[5.5]undecan-9-ylamino)acetyl]pyrrolidine-2-carbonitrile;hydrochloride Chemical compound Cl.N1([C@@H](CCC1)C#N)C(=O)CNC(CC1)CCC21CCOCC2 FYFOCMSXVYVCJK-RSAXXLAASA-N 0.000 description 1
CHPOCTZFAMXYHG-RSAXXLAASA-N (2s)-1-[2-(3-thiaspiro[5.5]undecan-9-ylamino)acetyl]pyrrolidine-2-carbonitrile;hydrochloride Chemical compound Cl.N1([C@@H](CCC1)C#N)C(=O)CNC(CC1)CCC21CCSCC2 CHPOCTZFAMXYHG-RSAXXLAASA-N 0.000 description 1
GGGKJCLFIIBKHM-ZDUSSCGKSA-N (2s)-1-[2-(spiro[2.5]octan-6-ylamino)acetyl]pyrrolidine-2-carbonitrile Chemical compound N1([C@@H](CCC1)C#N)C(=O)CNC(CC1)CCC21CC2 GGGKJCLFIIBKHM-ZDUSSCGKSA-N 0.000 description 1
ODSJUFDNYAJLKO-YDALLXLXSA-N (2s)-1-[2-(spiro[3.3]heptan-2-ylamino)acetyl]pyrrolidine-2-carbonitrile;hydrochloride Chemical compound Cl.N1([C@@H](CCC1)C#N)C(=O)CNC(C1)CC21CCC2 ODSJUFDNYAJLKO-YDALLXLXSA-N 0.000 description 1
YSEZFMLSRZGYSW-UQKRIMTDSA-N (2s)-1-[2-(spiro[3.5]nonan-2-ylamino)acetyl]pyrrolidine-2-carbonitrile;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N1([C@@H](CCC1)C#N)C(=O)CNC(C1)CC21CCCCC2 YSEZFMLSRZGYSW-UQKRIMTDSA-N 0.000 description 1
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Classifications

- 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
- A—HUMAN NECESSITIES
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- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- 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
- 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
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/08—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D277/12—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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
- 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
- C07D295/16—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 acylated on ring nitrogen atoms
- C07D295/18—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 acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

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Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Diabetes (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Engineering & Computer Science (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Hematology (AREA)
Obesity (AREA)
Child & Adolescent Psychology (AREA)
Emergency Medicine (AREA)
Endocrinology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Thiazole And Isothizaole Compounds (AREA)
Pyrrole Compounds (AREA)
Pyrane Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

ZA200504050A 2004-05-19 2005-05-19 Pyrrolidine and thiazolidine compounds, a process for their preparation and pharmaceutical compositions containing them ZA200504050B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
FR0405454A FR2870538B1 (fr)	2004-05-19	2004-05-19	Nouveaux derives de pyrrolidines et de thiazolidines, leur procede de preparation et les compositions pharmaceutiques qui les contiennent

Publications (1)

Publication Number	Publication Date
ZA200504050B true ZA200504050B (en)	2006-07-26

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ID=34942306

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ZA200504050A ZA200504050B (en)	2004-05-19	2005-05-19	Pyrrolidine and thiazolidine compounds, a process for their preparation and pharmaceutical compositions containing them

Country Status (29)

Country	Link
US (1)	US7439263B2 (pt)
EP (1)	EP1598350B1 (pt)
JP (1)	JP4335171B2 (pt)
KR (1)	KR100747967B1 (pt)
CN (1)	CN100381438C (pt)
AR (1)	AR049278A1 (pt)
AT (1)	ATE366731T1 (pt)
AU (1)	AU2005202180B2 (pt)
BR (1)	BRPI0501769A (pt)
CA (1)	CA2506491C (pt)
CY (1)	CY1106878T1 (pt)
DE (1)	DE602005001576T2 (pt)
DK (1)	DK1598350T3 (pt)
EA (1)	EA009292B1 (pt)
ES (1)	ES2290864T3 (pt)
FR (1)	FR2870538B1 (pt)
GE (1)	GEP20074103B (pt)
HK (1)	HK1086259A1 (pt)
HR (1)	HRP20070376T3 (pt)
MX (1)	MXPA05005256A (pt)
MY (1)	MY139481A (pt)
NO (1)	NO330294B1 (pt)
NZ (1)	NZ540108A (pt)
PL (1)	PL1598350T3 (pt)
PT (1)	PT1598350E (pt)
RS (1)	RS50526B (pt)
SG (1)	SG117551A1 (pt)
SI (1)	SI1598350T1 (pt)
ZA (1)	ZA200504050B (pt)

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US8338450B2 (en) *	2007-09-21	2012-12-25	Lupin Limited	Compounds as dipeptidyl peptidase IV (DPP IV) inhibitors
BRPI0822143A2 (pt) *	2008-01-23	2019-09-24	Jiangsu Hansoh Pharmaceutical Cio Ltd	derivados de dicicloaza-alcano, processos de preparação e usos médicos dos mesmos
GB2483614B (en)	2009-06-18	2014-12-03	Lupin Ltd	2-Amino-2- [8-(dimethyl carbamoyl)- 8-aza- bicyclo [3.2.1] oct-3-yl]-exo- ethanoyl derivatives as potent dpp-iv inhibitors
US8440710B2 (en) *	2009-10-15	2013-05-14	Hoffmann-La Roche Inc.	HSL inhibitors useful in the treatment of diabetes
WO2014000629A1 (zh)	2012-06-25	2014-01-03	广东东阳光药业有限公司	六氢并环戊二烯衍生物、其制备方法及其在医药上的应用
KR102449196B1 (ko)	2016-01-15	2022-09-29	삼성전자주식회사	비휘발성 메모리 장치 및 비휘발성 메모리 장치의 프로그램 방법

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JPH0618957B2 (ja) *	1988-01-26	1994-03-16	日本合成化学工業株式会社	成形物の製造方法
CA2046801C (en) *	1990-08-07	2002-02-26	Peter D. Davis	Substituted pyrroles
DE4222459C2 (de) *	1992-07-08	1995-09-14	Sigma Tau Ind Farmaceuti	3,9-disubstituierte-Spiro[5.5]undecane, ein Verfahren zu deren Herstellung und pharmazeutische Zusammensetzungen, die diese enthalten
ES2167371T3 (es) *	1993-07-02	2002-05-16	Bayer Ag	Derivados de 1h-3-aril-pirrolidin-2,4-diona espirociclicos substituidos.
TW492957B (en) *	1996-11-07	2002-07-01	Novartis Ag	N-substituted 2-cyanopyrrolidnes
US6110949A (en) *	1999-06-24	2000-08-29	Novartis Ag	N-(substituted glycyl)-4-cyanothiazolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV
TW583185B (en) *	2000-06-13	2004-04-11	Novartis Ag	N-(substituted glycyl)-2-cyanopyrrolidines and pharmaceutical composition for inhibiting dipeptidyl peptidase-IV (DPP-IV) or for the prevention or treatment of diseases or conditions associated with elevated levels of DPP-IV comprising the same
ES2311534T3 (es) *	2000-08-10	2009-02-16	Mitsubishi Tanabe Pharma Corporation	Derivados de prolina y su uso como farmacos.
DE60122555T2 (de) *	2000-09-25	2007-07-12	Toray Industries, Inc.	Spiroverbindungen und diese als wirkstoff enthaltende adhäsionsmolekülinhibitoren
FR2824825B1 (fr) *	2001-05-15	2005-05-06	Servier Lab	Nouveaux derives d'alpha-amino-acides, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
AU2002360732A1 (en) *	2001-12-26	2003-07-24	Guilford Pharmaceuticals	Change inhibitors of dipeptidyl peptidase iv
HUP0200849A2 (hu) *	2002-03-06	2004-08-30	Sanofi-Synthelabo	N-aminoacetil-2-ciano-pirrolidin-származékok, e vegyületeket tartalmazó gyógyszerkészítmények és eljárás előállításukra
RU2004132719A (ru) *	2002-04-08	2005-08-27	Торрент Фармасьютикалз Лтд. (In)	Тиазолидин-4-карбонитрилы и их аналоги, применение указанных соединений в качестве ингибиторов дипептидилпептидаз
TW200404796A (en) *	2002-08-19	2004-04-01	Ono Pharmaceutical Co	Nitrogen-containing compound
US7262207B2 (en) *	2002-09-19	2007-08-28	Abbott Laboratories	Pharmaceutical compositions as inhibitors of dipeptidyl peptidase-IV (DPP-IV)
DE60310991T2 (de) *	2002-11-07	2007-10-18	Merck & Co, Inc.	Phenylalaninderivate als hemmer der dipeptidyl peptidase zur behandlung oder prävention von diabetes

2004
- 2004-05-19 FR FR0405454A patent/FR2870538B1/fr not_active Expired - Fee Related
2005
- 2005-05-04 SG SG200502766A patent/SG117551A1/en unknown
- 2005-05-05 CA CA002506491A patent/CA2506491C/fr not_active Expired - Fee Related
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- 2005-05-18 AR ARP050102045A patent/AR049278A1/es unknown
- 2005-05-18 RS RSP-2007/0392A patent/RS50526B/sr unknown
- 2005-05-18 SI SI200530030T patent/SI1598350T1/sl unknown
- 2005-05-18 PL PL05291066T patent/PL1598350T3/pl unknown
- 2005-05-18 GE GEAP20058802A patent/GEP20074103B/en unknown
- 2005-05-18 AT AT05291066T patent/ATE366731T1/de active
- 2005-05-18 PT PT05291066T patent/PT1598350E/pt unknown
- 2005-05-18 DK DK05291066T patent/DK1598350T3/da active
- 2005-05-18 EP EP05291066A patent/EP1598350B1/fr active Active
- 2005-05-18 NZ NZ540108A patent/NZ540108A/en unknown
- 2005-05-18 DE DE602005001576T patent/DE602005001576T2/de active Active
- 2005-05-18 KR KR1020050041742A patent/KR100747967B1/ko not_active IP Right Cessation
- 2005-05-18 MY MYPI20052248A patent/MY139481A/en unknown
- 2005-05-18 US US11/131,510 patent/US7439263B2/en not_active Expired - Fee Related
- 2005-05-19 JP JP2005146186A patent/JP4335171B2/ja not_active Expired - Fee Related
- 2005-05-19 CN CNB200510087845XA patent/CN100381438C/zh not_active Expired - Fee Related
- 2005-05-19 BR BR0501769-6A patent/BRPI0501769A/pt not_active IP Right Cessation
- 2005-05-19 AU AU2005202180A patent/AU2005202180B2/en not_active Ceased
- 2005-05-19 ZA ZA200504050A patent/ZA200504050B/en unknown
- 2005-05-19 NO NO20052414A patent/NO330294B1/no not_active IP Right Cessation
2006
- 2006-05-29 HK HK06106186A patent/HK1086259A1/xx not_active IP Right Cessation
2007
- 2007-09-03 HR HR20070376T patent/HRP20070376T3/xx unknown
- 2007-09-19 CY CY20071101205T patent/CY1106878T1/el unknown

Also Published As

Publication number	Publication date
RS50526B (sr)	2010-05-07
BRPI0501769A (pt)	2006-01-10
NO330294B1 (no)	2011-03-21
FR2870538B1 (fr)	2006-07-14
ES2290864T3 (es)	2008-02-16
CN1721417A (zh)	2006-01-18
JP4335171B2 (ja)	2009-09-30
PL1598350T3 (pl)	2007-10-31
KR100747967B1 (ko)	2007-08-08
ATE366731T1 (de)	2007-08-15
DE602005001576D1 (de)	2007-08-23
FR2870538A1 (fr)	2005-11-25
DK1598350T3 (da)	2007-11-12
MY139481A (en)	2009-10-30
EP1598350B1 (fr)	2007-07-11
KR20060048007A (ko)	2006-05-18
SG117551A1 (en)	2005-12-29
CA2506491C (fr)	2009-09-01
CN100381438C (zh)	2008-04-16
HRP20070376T3 (en)	2007-12-31
NO20052414L (no)	2005-11-21
EA009292B1 (ru)	2007-12-28
US7439263B2 (en)	2008-10-21
EP1598350A1 (fr)	2005-11-23
CY1106878T1 (el)	2012-09-26
NO20052414D0 (no)	2005-05-19
DE602005001576T2 (de)	2008-04-17
GEP20074103B (en)	2007-05-10
AU2005202180A1 (en)	2005-12-08
US20050261501A1 (en)	2005-11-24
AR049278A1 (es)	2006-07-12
CA2506491A1 (fr)	2005-11-19
JP2005350456A (ja)	2005-12-22
AU2005202180B2 (en)	2010-10-28
SI1598350T1 (sl)	2007-10-31
PT1598350E (pt)	2007-10-04
EA200500683A1 (ru)	2005-12-29
MXPA05005256A (es)	2005-11-24
HK1086259A1 (en)	2006-09-15
NZ540108A (en)	2006-04-28

Publication	Publication Date	Title
US10039746B2 (en)	2018-08-07	1-aryl-3-azabicyclo[3.1.0]hexanes: preparation and use to treat neuropsychiatric disorders
US20070004791A1 (en)	2007-01-04	3,6-disubstituted azabicyclo {3.1.0} hexane derivatives useful as muscarnic receptor antagonists
US20100160302A1 (en)	2010-06-24	Novel dipeptidyl peptidase iv inhibitors and processes for their preparation and pharmaceutical compositions containing them
ZA200504050B (en)	2006-07-26	Pyrrolidine and thiazolidine compounds, a process for their preparation and pharmaceutical compositions containing them
EP0093805B1 (en)	1987-05-13	Octahydro-2-(omega-mercaptoalkanoyl)3-oxo-1h-isoindole-1-carboxylic acids and esters
US7560479B2 (en)	2009-07-14	3,6-Disubstituted azabicyclo hexane derivatives as muscarinic receptor antagonists
GB2037285A (en)	1980-07-09	Derivatives of 4,5-dihydro-1h-pyrrole-2-carboxylic acids and 1,4,5,6-tetrahydropyridine-2-carboxylic acids
EP0745079A1 (en)	1996-12-04	Phenylpyrrole derivatives and their use as dopamine d3 antagonists
EP0711278A1 (en)	1996-05-15	2-(2-hydroxyphenyl)-5-(n-phenylmethyl-aminomethyl)-pyrroles as antipsychotic agents
WO2001093867A1 (fr)	2001-12-13	Derives de 4,5-dihydro-thiazol-2-ylamine et leur utilisation comme inhibiteurs de no synthase
SK285989B6 (sk)	2008-01-07	Cyklické alfa-amino-gama-hydroxyamidy, spôsob ichprípravy a farmaceutické prostriedky, ktoré ich obsahujú
FR2832152A1 (fr)	2003-05-16	Utilisation de derives de 2-amino-thiazoline comme inhibiteurs de no-synthase inductible