ZA200203256B - Novel cyclopropanes as CGRP antagonists, medicaments containing said compounds and method for the production thereof. - Google Patents

Novel cyclopropanes as CGRP antagonists, medicaments containing said compounds and method for the production thereof. Download PDF

Info

Publication number: ZA200203256B
Authority: ZA; South Africa
Prior art keywords: groups; amino; group; carbonyl; general formula
Prior art date: 1999-10-29

Application number

ZA200203256A

Other languages

English (en)

Inventor

Wolfgang Eberlein

Wolfhard Engel

Klaus Rudolf

Henri Doods

Gerhard Hallermayer

Eckhart Bauer

Original Assignee

Boehringer Ingelheim Pharma

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

1999-10-29

Filing date

2002-04-24

Publication date

2003-04-10

2002-04-24 Application filed by Boehringer Ingelheim Pharma filed Critical Boehringer Ingelheim Pharma

2003-04-10 Publication of ZA200203256B publication Critical patent/ZA200203256B/en

Links

150000001875 compounds Chemical class 0.000 title claims description 64
238000000034 method Methods 0.000 title claims description 20
150000001942 cyclopropanes Chemical class 0.000 title claims description 5
238000004519 manufacturing process Methods 0.000 title claims description 5
229940127597 CGRP antagonist Drugs 0.000 title description 3
239000003814 drug Substances 0.000 title description 2
-1 biphenylyl Chemical group 0.000 claims description 138
239000000203 mixture Substances 0.000 claims description 37
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 31
125000000623 heterocyclic group Chemical group 0.000 claims description 30
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 29
150000003839 salts Chemical class 0.000 claims description 29
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 28
125000000217 alkyl group Chemical group 0.000 claims description 28
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
229910052757 nitrogen Inorganic materials 0.000 claims description 26
125000004433 nitrogen atom Chemical group N* 0.000 claims description 24
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 19
125000003545 alkoxy group Chemical group 0.000 claims description 19
229910052799 carbon Inorganic materials 0.000 claims description 18
239000000460 chlorine Substances 0.000 claims description 18
229910052801 chlorine Inorganic materials 0.000 claims description 18
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
125000001246 bromo group Chemical group Br* 0.000 claims description 17
125000001424 substituent group Chemical group 0.000 claims description 17
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 16
229910052731 fluorine Inorganic materials 0.000 claims description 16
239000011737 fluorine Substances 0.000 claims description 16
125000004432 carbon atom Chemical group C* 0.000 claims description 15
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 14
229910021529 ammonia Inorganic materials 0.000 claims description 14
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 13
125000004076 pyridyl group Chemical group 0.000 claims description 13
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 12
125000001153 fluoro group Chemical group F* 0.000 claims description 12
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 11
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 11
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 10
125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 10
125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 10
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
239000002253 acid Substances 0.000 claims description 8
125000001589 carboacyl group Chemical group 0.000 claims description 8
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125000000842 isoxazolyl group Chemical group 0.000 claims description 8
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 8
125000004430 oxygen atom Chemical group O* 0.000 claims description 8
230000008569 process Effects 0.000 claims description 8
125000003226 pyrazolyl group Chemical group 0.000 claims description 8
125000000168 pyrrolyl group Chemical group 0.000 claims description 8
239000000126 substance Substances 0.000 claims description 8
125000001544 thienyl group Chemical group 0.000 claims description 8
239000008194 pharmaceutical composition Substances 0.000 claims description 7
108090000765 processed proteins & peptides Proteins 0.000 claims description 7
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 7
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 6
125000005085 alkoxycarbonylalkoxy group Chemical group 0.000 claims description 6
125000002947 alkylene group Chemical group 0.000 claims description 6
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
125000005605 benzo group Chemical group 0.000 claims description 6
125000002837 carbocyclic group Chemical group 0.000 claims description 6
150000001721 carbon Chemical group 0.000 claims description 6
125000004181 carboxyalkyl group Chemical group 0.000 claims description 6
125000004122 cyclic group Chemical group 0.000 claims description 6
125000002541 furyl group Chemical group 0.000 claims description 6
125000002883 imidazolyl group Chemical group 0.000 claims description 6
229910052760 oxygen Inorganic materials 0.000 claims description 6
239000001301 oxygen Substances 0.000 claims description 6
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 6
238000007127 saponification reaction Methods 0.000 claims description 6
238000006467 substitution reaction Methods 0.000 claims description 6
150000007513 acids Chemical class 0.000 claims description 5
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 5
150000007522 mineralic acids Chemical class 0.000 claims description 5
229920006395 saturated elastomer Polymers 0.000 claims description 5
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 claims description 4
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 4
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 4
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 4
125000004949 alkyl amino carbonyl amino group Chemical group 0.000 claims description 4
150000001412 amines Chemical class 0.000 claims description 4
125000003277 amino group Chemical group 0.000 claims description 4
125000006598 aminocarbonylamino group Chemical group 0.000 claims description 4
125000003118 aryl group Chemical group 0.000 claims description 4
125000000753 cycloalkyl group Chemical group 0.000 claims description 4
125000005842 heteroatom Chemical group 0.000 claims description 4
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 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 claims description 4
150000007524 organic acids Chemical class 0.000 claims description 4
125000006239 protecting group Chemical group 0.000 claims description 4
SEEPANYCNGTZFQ-UHFFFAOYSA-N sulfadiazine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NC1=NC=CC=N1 SEEPANYCNGTZFQ-UHFFFAOYSA-N 0.000 claims description 4
125000000335 thiazolyl group Chemical group 0.000 claims description 4
JYOGPDQDXPDNHR-QZTJIDSGSA-N 3-[1-[(1r,2r)-2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]piperidin-4-yl]-5-(3-chlorophenyl)-1h-imidazol-2-one Chemical compound C1=C(Br)C(N)=C(Br)C=C1C(=O)[C@H]1[C@H](C(=O)N2CCC(CC2)N2C(NC(=C2)C=2C=C(Cl)C=CC=2)=O)C1 JYOGPDQDXPDNHR-QZTJIDSGSA-N 0.000 claims description 3
206010047141 Vasodilatation Diseases 0.000 claims description 3
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 3
125000004744 butyloxycarbonyl group Chemical group 0.000 claims description 3
150000001733 carboxylic acid esters Chemical class 0.000 claims description 3
239000003085 diluting agent Substances 0.000 claims description 3
201000010099 disease Diseases 0.000 claims description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
208000027866 inflammatory disease Diseases 0.000 claims description 3
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 3
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 3
208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 3
230000024883 vasodilation Effects 0.000 claims description 3
OXHNLMTVIGZXSG-UHFFFAOYSA-N 1-Methylpyrrole Chemical compound CN1C=CC=C1 OXHNLMTVIGZXSG-UHFFFAOYSA-N 0.000 claims description 2
OVEBHCCJIWQLFX-SKLUMECTSA-N 1-[1-[(1r,2r)-2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]piperidin-4-yl]-5-phenyl-1,2,4-triazolidin-3-one Chemical compound C1=C(Br)C(N)=C(Br)C=C1C(=O)[C@H]1[C@H](C(=O)N2CCC(CC2)N2C(NC(=O)N2)C=2C=CC=CC=2)C1 OVEBHCCJIWQLFX-SKLUMECTSA-N 0.000 claims description 2
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
125000000586 2-(4-morpholinyl)ethoxy group Chemical group [H]C([H])(O*)C([H])([H])N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 2
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
NUBNSKOIGYPWDD-QZTJIDSGSA-N 3-[1-[(1r,2r)-2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]piperidin-4-yl]-5-(3-hydroxyphenyl)-1h-imidazol-2-one Chemical compound C1=C(Br)C(N)=C(Br)C=C1C(=O)[C@H]1[C@H](C(=O)N2CCC(CC2)N2C(NC(=C2)C=2C=C(O)C=CC=2)=O)C1 NUBNSKOIGYPWDD-QZTJIDSGSA-N 0.000 claims description 2
HGPRJNNGQCPFDR-RTBURBONSA-N 3-[1-[(1r,2r)-2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]piperidin-4-yl]-5-(3-methoxyphenyl)-1h-imidazol-2-one Chemical compound COC1=CC=CC(C=2NC(=O)N(C3CCN(CC3)C(=O)[C@H]3[C@@H](C3)C(=O)C=3C=C(Br)C(N)=C(Br)C=3)C=2)=C1 HGPRJNNGQCPFDR-RTBURBONSA-N 0.000 claims description 2
RLJLQNLYLWGOES-QZTJIDSGSA-N 3-[1-[(1r,2r)-2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]piperidin-4-yl]-5-phenyl-1h-imidazol-2-one Chemical compound C1=C(Br)C(N)=C(Br)C=C1C(=O)[C@H]1[C@H](C(=O)N2CCC(CC2)N2C(NC(=C2)C=2C=CC=CC=2)=O)C1 RLJLQNLYLWGOES-QZTJIDSGSA-N 0.000 claims description 2
UTATXYLZLKRHCP-WOJBJXKFSA-N 3-[1-[(1r,2r)-2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]piperidin-4-yl]-6-(1,3-dioxolan-2-ylmethoxy)-1,4-dihydroquinazolin-2-one Chemical compound C1=C(Br)C(N)=C(Br)C=C1C(=O)[C@H]1[C@H](C(=O)N2CCC(CC2)N2C(NC3=CC=C(OCC4OCCO4)C=C3C2)=O)C1 UTATXYLZLKRHCP-WOJBJXKFSA-N 0.000 claims description 2
FVBTUAQLPAVBGJ-FGZHOGPDSA-N 3-[1-[(1r,2r)-2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]piperidin-4-yl]-6-[3-(dimethylamino)propoxy]-1,4-dihydroquinazolin-2-one Chemical compound O=C([C@@H]1C[C@H]1C(=O)N1CCC(CC1)N1C(=O)NC2=CC=C(C=C2C1)OCCCN(C)C)C1=CC(Br)=C(N)C(Br)=C1 FVBTUAQLPAVBGJ-FGZHOGPDSA-N 0.000 claims description 2
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
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ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 2
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208000006673 asthma Diseases 0.000 claims description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
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230000017531 blood circulation Effects 0.000 claims description 2
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
125000004093 cyano group Chemical group *C#N 0.000 claims description 2
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231100000869 headache Toxicity 0.000 claims description 2
125000001072 heteroaryl group Chemical group 0.000 claims description 2
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125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 claims description 2
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
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229960005181 morphine Drugs 0.000 claims description 2
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
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238000011321 prophylaxis Methods 0.000 claims description 2
208000017520 skin disease Diseases 0.000 claims description 2
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239000000969 carrier Substances 0.000 claims 2
WRIOMYHORIZPQI-QZTJIDSGSA-N 2-[[3-[1-[(1r,2r)-2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]piperidin-4-yl]-2-oxo-1,4-dihydroquinazolin-6-yl]oxy]acetic acid Chemical compound C1=C(Br)C(N)=C(Br)C=C1C(=O)[C@H]1[C@H](C(=O)N2CCC(CC2)N2C(NC3=CC=C(OCC(O)=O)C=C3C2)=O)C1 WRIOMYHORIZPQI-QZTJIDSGSA-N 0.000 claims 1
KUKIMOYIGBFOHW-IAGOWNOFSA-N 3-[1-[(1r,2r)-2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]piperidin-4-yl]-1,4-dihydroquinazolin-2-one Chemical compound C1=C(Br)C(N)=C(Br)C=C1C(=O)[C@H]1[C@H](C(=O)N2CCC(CC2)N2C(NC3=CC=CC=C3C2)=O)C1 KUKIMOYIGBFOHW-IAGOWNOFSA-N 0.000 claims 1
125000001624 naphthyl group Chemical group 0.000 claims 1
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QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
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VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
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RPNNPZHFJPXFQS-UHFFFAOYSA-N methane;rhodium Chemical compound C.[Rh] RPNNPZHFJPXFQS-UHFFFAOYSA-N 0.000 description 1
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XRKQMIFKHDXFNQ-UHFFFAOYSA-N n-cyclohexyl-n-ethylcyclohexanamine Chemical compound C1CCCCC1N(CC)C1CCCCC1 XRKQMIFKHDXFNQ-UHFFFAOYSA-N 0.000 description 1
VWPOSFSPZNDTMJ-UCWKZMIHSA-N nadolol Chemical compound C1[C@@H](O)[C@@H](O)CC2=C1C=CC=C2OCC(O)CNC(C)(C)C VWPOSFSPZNDTMJ-UCWKZMIHSA-N 0.000 description 1
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IPLJNQFXJUCRNH-UHFFFAOYSA-L nickel(2+);dibromide Chemical compound [Ni+2].[Br-].[Br-] IPLJNQFXJUCRNH-UHFFFAOYSA-L 0.000 description 1
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239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
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BSCHIACBONPEOB-UHFFFAOYSA-N oxolane;hydrate Chemical compound O.C1CCOC1 BSCHIACBONPEOB-UHFFFAOYSA-N 0.000 description 1
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229910052763 palladium Inorganic materials 0.000 description 1
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LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
239000008188 pellet Substances 0.000 description 1
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125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
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235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
230000008092 positive effect Effects 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
235000011056 potassium acetate Nutrition 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000002243 precursor Substances 0.000 description 1
230000003449 preventive effect Effects 0.000 description 1
229960003910 promethazine Drugs 0.000 description 1
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229960004063 propylene glycol Drugs 0.000 description 1
235000013772 propylene glycol Nutrition 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
230000005855 radiation Effects 0.000 description 1
238000000163 radioactive labelling Methods 0.000 description 1
230000009257 reactivity Effects 0.000 description 1
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TXHZXHICDBAVJW-UHFFFAOYSA-N rizatriptan Chemical compound C=1[C]2C(CCN(C)C)=CN=C2C=CC=1CN1C=NC=N1 TXHZXHICDBAVJW-UHFFFAOYSA-N 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
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235000009518 sodium iodide Nutrition 0.000 description 1
AEQFSUDEHCCHBT-UHFFFAOYSA-M sodium valproate Chemical compound [Na+].CCCC(C([O-])=O)CCC AEQFSUDEHCCHBT-UHFFFAOYSA-M 0.000 description 1
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RVLBWBWZOLQRMM-UHFFFAOYSA-N tert-butyl 4-(6-bromo-2-oxo-1,4-dihydroquinazolin-3-yl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1N1C(=O)NC2=CC=C(Br)C=C2C1 RVLBWBWZOLQRMM-UHFFFAOYSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
238000010257 thawing Methods 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
238000011282 treatment Methods 0.000 description 1
IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 description 1
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BPLKQGGAXWRFOE-UHFFFAOYSA-M trimethylsulfoxonium iodide Chemical compound [I-].C[S+](C)(C)=O BPLKQGGAXWRFOE-UHFFFAOYSA-M 0.000 description 1
238000005533 tritiation Methods 0.000 description 1
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150000003751 zinc Chemical class 0.000 description 1
WEKISHNHYNINFX-UHFFFAOYSA-N zinc;iodomethane Chemical compound [Zn+2].I[CH2-].I[CH2-] WEKISHNHYNINFX-UHFFFAOYSA-N 0.000 description 1
ULSDMUVEXKOYBU-ZDUSSCGKSA-N zolmitriptan Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1C[C@H]1COC(=O)N1 ULSDMUVEXKOYBU-ZDUSSCGKSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P11/02—Nasal agents, e.g. decongestants
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P39/02—Antidotes
- 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
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Pulmonology (AREA)
Diabetes (AREA)
Endocrinology (AREA)
Pain & Pain Management (AREA)
Cardiology (AREA)
Dermatology (AREA)
Otolaryngology (AREA)
Emergency Medicine (AREA)
Hematology (AREA)
Obesity (AREA)
Immunology (AREA)
Rheumatology (AREA)
Toxicology (AREA)
Heart & Thoracic Surgery (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Pyridine Compounds (AREA)

ZA200203256A 1999-10-29 2002-04-24 Novel cyclopropanes as CGRP antagonists, medicaments containing said compounds and method for the production thereof. ZA200203256B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DE19952147A DE19952147A1 (de)	1999-10-29	1999-10-29	Neue Cyclopropane, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung

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ZA200203256B true ZA200203256B (en)	2003-04-10

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ZA200203256A ZA200203256B (en)	1999-10-29	2002-04-24	Novel cyclopropanes as CGRP antagonists, medicaments containing said compounds and method for the production thereof.

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US (2)	US20030139417A1 (xx)
EP (1)	EP1228059B1 (xx)
JP (1)	JP3869721B2 (xx)
KR (1)	KR20020047290A (xx)
CN (1)	CN1177844C (xx)
AT (1)	ATE301117T1 (xx)
AU (1)	AU781856B2 (xx)
BG (1)	BG106638A (xx)
BR (1)	BR0015147A (xx)
CA (1)	CA2387134C (xx)
CZ (1)	CZ20021812A3 (xx)
DE (2)	DE19952147A1 (xx)
EA (1)	EA005137B1 (xx)
EE (1)	EE200200220A (xx)
HK (1)	HK1051858A1 (xx)
HR (1)	HRP20020373A2 (xx)
HU (1)	HUP0203496A3 (xx)
IL (1)	IL148975A0 (xx)
MX (1)	MXPA02004119A (xx)
NO (1)	NO20021799L (xx)
NZ (1)	NZ518698A (xx)
PL (1)	PL354715A1 (xx)
SK (1)	SK7282002A3 (xx)
TR (1)	TR200201168T2 (xx)
WO (1)	WO2001032648A1 (xx)
YU (1)	YU30902A (xx)
ZA (1)	ZA200203256B (xx)

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US7220862B2 (en)	2002-06-05	2007-05-22	Bristol-Myers Squibb Company	Calcitonin gene related peptide receptor antagonists
PL374017A1 (en) *	2002-06-05	2005-09-19	Bristol-Myers Squibb Company	Calcitonin gene related peptide receptor antagonists
AR046787A1 (es)	2003-12-05	2005-12-21	Bristol Myers Squibb Co	Agentes antimigrana heterociclicos
CA2549330A1 (en)	2003-12-05	2005-07-21	Bristol-Myers Squibb Company	Calcitonin gene related peptide receptor antagonists
TW200533398A (en)	2004-03-29	2005-10-16	Bristol Myers Squibb Co	Novel therapeutic agents for the treatment of migraine
ATE537153T1 (de) *	2004-09-09	2011-12-15	Merck Sharp & Dohme	Arylspirolactamverbindungen als antagonisten des cgrp-rezeptors
US7384931B2 (en)	2004-11-03	2008-06-10	Bristol-Myers Squibb Company	Constrained compounds as CGRP-receptor antagonists
US7384930B2 (en)	2004-11-03	2008-06-10	Bristol-Myers Squibb Company	Constrained compounds as CGRP-receptor antagonists
US7449586B2 (en)	2004-12-03	2008-11-11	Bristol-Myers Squibb Company	Processes for the preparation of CGRP-receptor antagonists and intermediates thereof
US7834007B2 (en)	2005-08-25	2010-11-16	Bristol-Myers Squibb Company	CGRP antagonists
JP2009515972A (ja) *	2005-11-18	2009-04-16	メルクエンドカムパニーインコーポレーテッド	スピロラクタムアリールｃｇｒｐ受容体アンタゴニスト
WO2009034029A2 (de) *	2007-09-07	2009-03-19	Boehringer Ingelheim International Gmbh	1-substituierte 4 -heterocyclylpiperidine als cgrp antagonisten
EP2065381A1 (de)	2007-10-18	2009-06-03	Boehringer Ingelheim Pharma GmbH & Co. KG	CGRP Antagonisten
CN101827845A (zh)	2007-10-18	2010-09-08	贝林格尔.英格海姆国际有限公司	Cgrp拮抗剂
CA2705405A1 (en)	2007-11-22	2009-05-28	Boehringer Ingelheim International Gmbh	New compounds
US9315449B2 (en)	2008-05-15	2016-04-19	Duke University	Substituted pyrazoles as heat shock transcription factor activators
UA105182C2 (ru)	2008-07-03	2014-04-25	Ньюрексон, Інк.	Бензоксазины, бензотиазины и родственные соединения, которые имеют ингибирующую nos активность
BR112014024693A2 (pt) *	2012-04-05	2017-07-11	Chdi Foundation Inc	composto de fórmula / ou um sal farmaceuticamente aceitável ou pró-fármaco do mesmo; composto; composição farmacêutica; método de tratamento de uma afecção ou distúrbio mediado por atividade de quinurenina 3-mono-oxigenase em um indivíduo que necessita de tal tratamento
WO2015047982A2 (en)	2013-09-26	2015-04-02	Chdi Foundation, Inc.	Kynurenine-3-monooxygenase inhibitors, pharmaceutical compositions, and methods of use thereof
WO2015047978A1 (en)	2013-09-26	2015-04-02	Chdi Foundation, Inc.	Kynurenine-3-monooxygenase inhibitors, pharmaceutical compositions, and methods of use thereof
JP2019040859A (ja) *	2017-08-22	2019-03-14	株式会社エンプラス	発光装置、面光源装置および光束制御部材
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1999
- 1999-10-29 DE DE19952147A patent/DE19952147A1/de not_active Withdrawn
2000
- 2000-10-21 EA EA200200447A patent/EA005137B1/ru not_active IP Right Cessation
- 2000-10-21 CA CA002387134A patent/CA2387134C/en not_active Expired - Fee Related
- 2000-10-21 IL IL14897500A patent/IL148975A0/xx unknown
- 2000-10-21 CZ CZ20021812A patent/CZ20021812A3/cs unknown
- 2000-10-21 EE EEP200200220A patent/EE200200220A/xx unknown
- 2000-10-21 BR BR0015147-5A patent/BR0015147A/pt not_active Expired - Fee Related
- 2000-10-21 HU HU0203496A patent/HUP0203496A3/hu unknown
- 2000-10-21 WO PCT/EP2000/010391 patent/WO2001032648A1/de not_active Application Discontinuation
- 2000-10-21 KR KR1020027005386A patent/KR20020047290A/ko not_active Application Discontinuation
- 2000-10-21 NZ NZ518698A patent/NZ518698A/xx unknown
- 2000-10-21 EP EP00969529A patent/EP1228059B1/de not_active Expired - Lifetime
- 2000-10-21 MX MXPA02004119A patent/MXPA02004119A/es unknown
- 2000-10-21 DE DE50010886T patent/DE50010886D1/de not_active Expired - Fee Related
- 2000-10-21 YU YU30902A patent/YU30902A/sh unknown
- 2000-10-21 CN CNB008151490A patent/CN1177844C/zh not_active Expired - Fee Related
- 2000-10-21 PL PL00354715A patent/PL354715A1/xx not_active Application Discontinuation
- 2000-10-21 AT AT00969529T patent/ATE301117T1/de not_active IP Right Cessation
- 2000-10-21 SK SK728-2002A patent/SK7282002A3/sk unknown
- 2000-10-21 AU AU79213/00A patent/AU781856B2/en not_active Ceased
- 2000-10-21 TR TR2002/01168T patent/TR200201168T2/xx unknown
- 2000-10-21 JP JP2001534799A patent/JP3869721B2/ja not_active Expired - Fee Related
2002
- 2002-04-12 US US10/121,872 patent/US20030139417A1/en not_active Abandoned
- 2002-04-17 NO NO20021799A patent/NO20021799L/no not_active Application Discontinuation
- 2002-04-23 BG BG106638A patent/BG106638A/bg active Pending
- 2002-04-24 ZA ZA200203256A patent/ZA200203256B/en unknown
- 2002-04-26 HR HR20020373A patent/HRP20020373A2/hr not_active Application Discontinuation
2003
- 2003-06-11 HK HK03104096A patent/HK1051858A1/xx not_active IP Right Cessation
2005
- 2005-06-27 US US11/169,078 patent/US7407963B2/en not_active Expired - Lifetime

Also Published As

Publication number	Publication date
EE200200220A (et)	2003-06-16
CA2387134A1 (en)	2001-05-10
MXPA02004119A (es)	2003-10-06
US20030139417A1 (en)	2003-07-24
NO20021799D0 (no)	2002-04-17
KR20020047290A (ko)	2002-06-21
TR200201168T2 (tr)	2002-08-21
AU7921300A (en)	2001-05-14
CA2387134C (en)	2008-07-08
WO2001032648A1 (de)	2001-05-10
CN1177844C (zh)	2004-12-01
CN1387526A (zh)	2002-12-25
ATE301117T1 (de)	2005-08-15
BG106638A (bg)	2003-01-31
EA200200447A1 (ru)	2002-10-31
DE19952147A1 (de)	2001-05-03
NZ518698A (en)	2004-12-24
EP1228059B1 (de)	2005-08-03
HK1051858A1 (en)	2003-08-22
BR0015147A (pt)	2002-07-16
US7407963B2 (en)	2008-08-05
IL148975A0 (en)	2002-11-10
HRP20020373A2 (en)	2003-10-31
EP1228059A1 (de)	2002-08-07
EA005137B1 (ru)	2004-12-30
HUP0203496A2 (hu)	2003-02-28
PL354715A1 (en)	2004-02-09
NO20021799L (no)	2002-04-17
AU781856B2 (en)	2005-06-16
CZ20021812A3 (cs)	2002-08-14
JP3869721B2 (ja)	2007-01-17
HUP0203496A3 (en)	2004-01-28
JP2003513087A (ja)	2003-04-08
DE50010886D1 (de)	2005-09-08
YU30902A (sh)	2005-07-19
US20050267137A1 (en)	2005-12-01
SK7282002A3 (en)	2002-11-06

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JP4210322B2 (ja)	2009-01-14	Ｃｇｒｐアンタゴニストとして使用される２−オキソ−１，２，４，５−テトラヒドロ−１，３−ベンゾジアゼピン−３−イル−ピペリジン