JP2002519324A - ＣＯＸ−２阻害剤およびｉＮＯＳ阻害剤を含んでなる薬学的組合わせ - Google Patents
ＣＯＸ−２阻害剤およびｉＮＯＳ阻害剤を含んでなる薬学的組合わせInfo
- Publication number
- JP2002519324A JP2002519324A JP2000556785A JP2000556785A JP2002519324A JP 2002519324 A JP2002519324 A JP 2002519324A JP 2000556785 A JP2000556785 A JP 2000556785A JP 2000556785 A JP2000556785 A JP 2000556785A JP 2002519324 A JP2002519324 A JP 2002519324A
- Authority
- JP
- Japan
- Prior art keywords
- quinazoline
- piperidine
- amine
- spiro
- fluorospiro
- Prior art date
- Legal status (The legal status 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 status listed.)
- Pending
Links
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 title claims abstract description 23
- 229940111134 coxibs Drugs 0.000 title claims description 22
- 239000003112 inhibitor Substances 0.000 title abstract description 25
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 title description 34
- 101710089543 Nitric oxide synthase, inducible Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 14
- 238000011282 treatment Methods 0.000 claims abstract description 12
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 11
- -1 nitro, hydroxymethyl Chemical group 0.000 claims description 76
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 30
- 125000000217 alkyl group Chemical group 0.000 claims description 28
- 229910052739 hydrogen Inorganic materials 0.000 claims description 24
- 239000001257 hydrogen Substances 0.000 claims description 24
- 125000003118 aryl group Chemical group 0.000 claims description 21
- 229910052760 oxygen Inorganic materials 0.000 claims description 20
- 229910052717 sulfur Inorganic materials 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- 150000002367 halogens Chemical class 0.000 claims description 19
- 229910052757 nitrogen Inorganic materials 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 14
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 9
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 6
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 241000282414 Homo sapiens Species 0.000 claims description 5
- 239000002671 adjuvant Substances 0.000 claims description 5
- 229960000590 celecoxib Drugs 0.000 claims description 5
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 125000003386 piperidinyl group Chemical group 0.000 claims description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 2
- CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 claims description 2
- ZRVUJXDFFKFLMG-UHFFFAOYSA-N Meloxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=NC=C(C)S1 ZRVUJXDFFKFLMG-UHFFFAOYSA-N 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000004965 chloroalkyl group Chemical group 0.000 claims description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 229950005722 flosulide Drugs 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 2
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 2
- 229960001929 meloxicam Drugs 0.000 claims description 2
- CXJONBHNIJFARE-UHFFFAOYSA-N n-[6-(2,4-difluorophenoxy)-1-oxo-2,3-dihydroinden-5-yl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=2CCC(=O)C=2C=C1OC1=CC=C(F)C=C1F CXJONBHNIJFARE-UHFFFAOYSA-N 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- MIMJSJSRRDZIPW-UHFFFAOYSA-N tilmacoxib Chemical compound C=1C=C(S(N)(=O)=O)C(F)=CC=1C=1OC(C)=NC=1C1CCCCC1 MIMJSJSRRDZIPW-UHFFFAOYSA-N 0.000 claims description 2
- 125000003003 spiro group Chemical group 0.000 claims 17
- 229910052698 phosphorus Inorganic materials 0.000 claims 11
- 239000011574 phosphorus Substances 0.000 claims 11
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims 7
- RUZOQNAMPCLLFI-UHFFFAOYSA-N 5-fluorospiro[1h-quinazoline-2,4'-piperidine]-4-amine Chemical compound N1C2=CC=CC(F)=C2C(N)=NC21CCNCC2 RUZOQNAMPCLLFI-UHFFFAOYSA-N 0.000 claims 6
- YSIFOLULMFTZKL-UHFFFAOYSA-N spiro[1h-quinazoline-2,4'-piperidine]-4-amine Chemical compound N1C2=CC=CC=C2C(N)=NC21CCNCC2 YSIFOLULMFTZKL-UHFFFAOYSA-N 0.000 claims 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims 2
- 150000001412 amines Chemical class 0.000 claims 2
- 150000007942 carboxylates Chemical class 0.000 claims 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 claims 2
- AKWKXFUXQQNUGE-UHFFFAOYSA-N (3-amino-4-chlorophenyl)-(4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)methanone Chemical compound N1C2=CC=CC=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=C(Cl)C(N)=C1 AKWKXFUXQQNUGE-UHFFFAOYSA-N 0.000 claims 1
- GIVFIZXMEZDGBR-UHFFFAOYSA-N (3-aminophenyl)-(4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)methanone Chemical compound N1C2=CC=CC=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=CC(N)=C1 GIVFIZXMEZDGBR-UHFFFAOYSA-N 0.000 claims 1
- KOCBGBJUDZNSJE-UHFFFAOYSA-N (4-amino-5,7-difluorospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-thiophen-2-ylmethanone Chemical compound N1C2=CC(F)=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=CS1 KOCBGBJUDZNSJE-UHFFFAOYSA-N 0.000 claims 1
- UVYGCLROCNKXPQ-UHFFFAOYSA-N (4-amino-5,8-difluorospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(4-chlorophenyl)methanone Chemical compound N1C2=C(F)C=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=C(Cl)C=C1 UVYGCLROCNKXPQ-UHFFFAOYSA-N 0.000 claims 1
- RSWKKGGFYGUXKX-UHFFFAOYSA-N (4-amino-5,8-difluorospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-thiophen-2-ylmethanone Chemical compound N1C2=C(F)C=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=CS1 RSWKKGGFYGUXKX-UHFFFAOYSA-N 0.000 claims 1
- DNFWRSPJYBBOPI-UHFFFAOYSA-N (4-amino-5-fluorospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(1,2-thiazol-4-yl)methanone Chemical compound N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C=1C=NSC=1 DNFWRSPJYBBOPI-UHFFFAOYSA-N 0.000 claims 1
- XIWOHKSOWPQQKR-UHFFFAOYSA-N (4-amino-5-fluorospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(1,3-benzodioxol-5-yl)methanone Chemical compound N1C2=CC=CC(F)=C2C(N)=NC11CCN(C(=O)C=2C=C3OCOC3=CC=2)CC1 XIWOHKSOWPQQKR-UHFFFAOYSA-N 0.000 claims 1
- VIMLGTXWXHFWLU-UHFFFAOYSA-N (4-amino-5-fluorospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(3,4-dichlorophenyl)methanone Chemical compound N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=C(Cl)C(Cl)=C1 VIMLGTXWXHFWLU-UHFFFAOYSA-N 0.000 claims 1
- HKGKHOSURFYMEX-UHFFFAOYSA-N (4-amino-5-fluorospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(4-bromophenyl)methanone Chemical compound N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=C(Br)C=C1 HKGKHOSURFYMEX-UHFFFAOYSA-N 0.000 claims 1
- LPHXOGYMVXBMGV-UHFFFAOYSA-N (4-amino-5-fluorospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(4-bromothiophen-2-yl)methanone Chemical compound N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC(Br)=CS1 LPHXOGYMVXBMGV-UHFFFAOYSA-N 0.000 claims 1
- WQDRNIPMIVSODU-UHFFFAOYSA-N (4-amino-5-fluorospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(4-butylphenyl)methanone Chemical compound C1=CC(CCCC)=CC=C1C(=O)N1CCC2(N=C(N)C3=C(F)C=CC=C3N2)CC1 WQDRNIPMIVSODU-UHFFFAOYSA-N 0.000 claims 1
- OMUVOAMSPIQCOR-UHFFFAOYSA-N (4-amino-5-fluorospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(4-chloro-3-iodophenyl)methanone Chemical compound N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=C(Cl)C(I)=C1 OMUVOAMSPIQCOR-UHFFFAOYSA-N 0.000 claims 1
- QVSKLCBLEFIJIU-UHFFFAOYSA-N (4-amino-5-fluorospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(4-chlorophenyl)methanone Chemical compound N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=C(Cl)C=C1 QVSKLCBLEFIJIU-UHFFFAOYSA-N 0.000 claims 1
- QHHPFGJIVBDRLM-UHFFFAOYSA-N (4-amino-5-fluorospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(4-ethylphenyl)methanone Chemical compound C1=CC(CC)=CC=C1C(=O)N1CCC2(N=C(N)C3=C(F)C=CC=C3N2)CC1 QHHPFGJIVBDRLM-UHFFFAOYSA-N 0.000 claims 1
- HYADBWLWDQEHQC-UHFFFAOYSA-N (4-amino-5-fluorospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(4-ethynylphenyl)methanone Chemical compound N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=C(C#C)C=C1 HYADBWLWDQEHQC-UHFFFAOYSA-N 0.000 claims 1
- ZTPZBIJLCSPGQL-UHFFFAOYSA-N (4-amino-5-fluorospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(5-bromothiophen-2-yl)methanone Chemical compound N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=C(Br)S1 ZTPZBIJLCSPGQL-UHFFFAOYSA-N 0.000 claims 1
- UVOWHTMQZPDFMX-UHFFFAOYSA-N (4-amino-5-fluorospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(5-bromothiophen-3-yl)methanone Chemical compound N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CSC(Br)=C1 UVOWHTMQZPDFMX-UHFFFAOYSA-N 0.000 claims 1
- PSSXHJXRSQJUCU-UHFFFAOYSA-N (4-amino-5-fluorospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(5-ethylthiophen-2-yl)methanone Chemical compound S1C(CC)=CC=C1C(=O)N1CCC2(N=C(N)C3=C(F)C=CC=C3N2)CC1 PSSXHJXRSQJUCU-UHFFFAOYSA-N 0.000 claims 1
- IZTDKOVHEGYKPL-UHFFFAOYSA-N (4-amino-5-fluorospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(6-chloropyridin-3-yl)methanone Chemical compound N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=C(Cl)N=C1 IZTDKOVHEGYKPL-UHFFFAOYSA-N 0.000 claims 1
- WFHLOVTZLHSUJR-UHFFFAOYSA-N (4-amino-5-fluorospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-[4-(1,3-thiazol-2-yl)phenyl]methanone Chemical compound N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C(C=C1)=CC=C1C1=NC=CS1 WFHLOVTZLHSUJR-UHFFFAOYSA-N 0.000 claims 1
- ABHMXNAQNFTILP-UHFFFAOYSA-N (4-amino-5-fluorospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-imidazol-1-ylmethanone Chemical compound N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)N1C=CN=C1 ABHMXNAQNFTILP-UHFFFAOYSA-N 0.000 claims 1
- YOGMHFXUEGAVGP-UHFFFAOYSA-N (4-amino-5-hydroxyspiro[1H-quinazoline-2,4'-piperidine]-1'-yl)-(4-bromophenyl)methanone Chemical compound BrC1=CC=C(C(=O)N2CCC3(CC2)NC2=CC=CC(=C2C(=N3)N)O)C=C1 YOGMHFXUEGAVGP-UHFFFAOYSA-N 0.000 claims 1
- HUGDORSEMMDVLL-UHFFFAOYSA-N (4-aminophenyl)-(4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)methanone Chemical compound N1C2=CC=CC=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=C(N)C=C1 HUGDORSEMMDVLL-UHFFFAOYSA-N 0.000 claims 1
- YSLVFEKXFLRWJB-UHFFFAOYSA-N (4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(2-methylphenyl)methanone Chemical compound CC1=CC=CC=C1C(=O)N1CCC2(N=C(N)C3=CC=CC=C3N2)CC1 YSLVFEKXFLRWJB-UHFFFAOYSA-N 0.000 claims 1
- YTFXUYQLAYFSDK-UHFFFAOYSA-N (4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(2-nitrophenyl)methanone Chemical compound N1C2=CC=CC=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=CC=C1[N+]([O-])=O YTFXUYQLAYFSDK-UHFFFAOYSA-N 0.000 claims 1
- PQURLOMPBCHPGL-UHFFFAOYSA-N (4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(3-fluoro-4-methylphenyl)methanone Chemical compound C1=C(F)C(C)=CC=C1C(=O)N1CCC2(N=C(N)C3=CC=CC=C3N2)CC1 PQURLOMPBCHPGL-UHFFFAOYSA-N 0.000 claims 1
- ATCGMXBENMJJLF-UHFFFAOYSA-N (4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(3-methylphenyl)methanone Chemical compound CC1=CC=CC(C(=O)N2CCC3(CC2)N=C(N)C2=CC=CC=C2N3)=C1 ATCGMXBENMJJLF-UHFFFAOYSA-N 0.000 claims 1
- CCBWQNZCZLKXGW-UHFFFAOYSA-N (4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(3-nitrophenyl)methanone Chemical compound N1C2=CC=CC=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=CC([N+]([O-])=O)=C1 CCBWQNZCZLKXGW-UHFFFAOYSA-N 0.000 claims 1
- VNWSZDTZAXJWTA-UHFFFAOYSA-N (4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(4-bromophenyl)methanone Chemical compound N1C2=CC=CC=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=C(Br)C=C1 VNWSZDTZAXJWTA-UHFFFAOYSA-N 0.000 claims 1
- RSHKJRVJSVODHV-UHFFFAOYSA-N (4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(4-chlorophenyl)methanone Chemical compound N1C2=CC=CC=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=C(Cl)C=C1 RSHKJRVJSVODHV-UHFFFAOYSA-N 0.000 claims 1
- ZHMUHIIKTOAYBJ-UHFFFAOYSA-N (4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(4-ethylphenyl)methanone Chemical compound C1=CC(CC)=CC=C1C(=O)N1CCC2(N=C(N)C3=CC=CC=C3N2)CC1 ZHMUHIIKTOAYBJ-UHFFFAOYSA-N 0.000 claims 1
- ZYTYCDYFRYWVRC-UHFFFAOYSA-N (4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(4-fluorophenyl)methanone Chemical compound N1C2=CC=CC=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=C(F)C=C1 ZYTYCDYFRYWVRC-UHFFFAOYSA-N 0.000 claims 1
- UBAXEWSWJWAHFE-UHFFFAOYSA-N (4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(4-iodophenyl)methanone Chemical compound N1C2=CC=CC=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=C(I)C=C1 UBAXEWSWJWAHFE-UHFFFAOYSA-N 0.000 claims 1
- OHNSXMZWFQQTCM-UHFFFAOYSA-N (4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(4-methoxyphenyl)methanone Chemical compound C1=CC(OC)=CC=C1C(=O)N1CCC2(N=C(N)C3=CC=CC=C3N2)CC1 OHNSXMZWFQQTCM-UHFFFAOYSA-N 0.000 claims 1
- WVIIEGBETUCHMM-UHFFFAOYSA-N (4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(4-methylphenyl)methanone Chemical compound C1=CC(C)=CC=C1C(=O)N1CCC2(N=C(N)C3=CC=CC=C3N2)CC1 WVIIEGBETUCHMM-UHFFFAOYSA-N 0.000 claims 1
- PDOBPTCTJCNTFG-UHFFFAOYSA-N (4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(4-methylsulfonylphenyl)methanone Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C(=O)N1CCC2(N=C(N)C3=CC=CC=C3N2)CC1 PDOBPTCTJCNTFG-UHFFFAOYSA-N 0.000 claims 1
- NJTHXCSIFDORLB-UHFFFAOYSA-N (4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(4-nitrophenyl)methanone Chemical compound N1C2=CC=CC=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=C([N+]([O-])=O)C=C1 NJTHXCSIFDORLB-UHFFFAOYSA-N 0.000 claims 1
- STMUJZVGRUGXPP-UHFFFAOYSA-N (4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(4-phenylmethoxyphenyl)methanone Chemical compound N1C2=CC=CC=C2C(N)=NC1(CC1)CCN1C(=O)C(C=C1)=CC=C1OCC1=CC=CC=C1 STMUJZVGRUGXPP-UHFFFAOYSA-N 0.000 claims 1
- BKEHWSDXDOKAKY-UHFFFAOYSA-N (4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(4-pyrrol-1-ylphenyl)methanone Chemical compound N1C2=CC=CC=C2C(N)=NC1(CC1)CCN1C(=O)C(C=C1)=CC=C1N1C=CC=C1 BKEHWSDXDOKAKY-UHFFFAOYSA-N 0.000 claims 1
- OPTLWKIMIHXNQP-UHFFFAOYSA-N (4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(5-chlorothiophen-2-yl)methanone Chemical compound N1C2=CC=CC=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=C(Cl)S1 OPTLWKIMIHXNQP-UHFFFAOYSA-N 0.000 claims 1
- CDTAQGVWXTWJSL-UHFFFAOYSA-N (4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(furan-2-yl)methanone Chemical compound N1C2=CC=CC=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=CO1 CDTAQGVWXTWJSL-UHFFFAOYSA-N 0.000 claims 1
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- 230000000144 pharmacologic effect Effects 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- 201000006292 polyarteritis nodosa Diseases 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
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- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
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- 239000008117 stearic acid Substances 0.000 description 1
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Classifications
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Rheumatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Communicable Diseases (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Immunology (AREA)
- Oncology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9802333-6 | 1998-06-29 | ||
| SE9802333A SE9802333D0 (sv) | 1998-06-29 | 1998-06-29 | Novel combination |
| PCT/SE1999/001144 WO2000000200A1 (en) | 1998-06-29 | 1999-06-23 | A PHARMACEUTICAL COMBINATION COMPRISING A COX-2 INHIBITOR AND A iNOS INHIBITOR |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2002519324A true JP2002519324A (ja) | 2002-07-02 |
Family
ID=20411898
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000556785A Pending JP2002519324A (ja) | 1998-06-29 | 1999-06-23 | ＣＯＸ−２阻害剤およびｉＮＯＳ阻害剤を含んでなる薬学的組合わせ |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US6248745B1 (OSRAM) |
| EP (1) | EP1100505A1 (OSRAM) |
| JP (1) | JP2002519324A (OSRAM) |
| KR (1) | KR20010053252A (OSRAM) |
| CN (1) | CN1313769A (OSRAM) |
| AU (1) | AU4944799A (OSRAM) |
| BR (1) | BR9911666A (OSRAM) |
| CA (1) | CA2334515A1 (OSRAM) |
| CZ (1) | CZ20004896A3 (OSRAM) |
| EE (1) | EE200000766A (OSRAM) |
| ID (1) | ID27394A (OSRAM) |
| IL (1) | IL140022A0 (OSRAM) |
| IN (1) | IN2000MU00721A (OSRAM) |
| IS (1) | IS5794A (OSRAM) |
| MX (1) | MXPA00012162A (OSRAM) |
| NO (1) | NO20006559L (OSRAM) |
| PL (1) | PL345028A1 (OSRAM) |
| SE (1) | SE9802333D0 (OSRAM) |
| SK (1) | SK18482000A3 (OSRAM) |
| TR (1) | TR200003808T2 (OSRAM) |
| WO (1) | WO2000000200A1 (OSRAM) |
| ZA (1) | ZA200007076B (OSRAM) |
Families Citing this family (75)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL203262B1 (pl) * | 1999-12-08 | 2009-09-30 | Pharmacia Corp | Substancja lecznicza celekoksyb, jej zastosowanie i sposób jej wytwarzania, kompozyt celekoksyb-inhibitor krystalizacji i sposób jego wytwarzania, kompozycja farmaceutyczna i sposób jej wytwarzania |
| RU2002119574A (ru) * | 1999-12-23 | 2004-01-10 | Нитромед, Инк. (Us) | Нитрозированные и нитрозилированные ингибиторы циклооксигеназы-2, композиции на их основе и способы их применения |
| EP1406609B1 (en) * | 2000-12-21 | 2006-09-06 | Nitromed, Inc. | Substituted aryl compounds as novel cyclooxygenase-2 selective inhibitors, compositions and methods of use |
| US7012098B2 (en) * | 2001-03-23 | 2006-03-14 | Pharmacia Corporation | Inhibitors of inducible nitric oxide synthase for chemoprevention and treatment of cancers |
| EP1469846A2 (en) * | 2002-01-07 | 2004-10-27 | Pharmacia Corporation | Treatment of pain, inflammation, and inflammation-related disorders with a combination of a cyclooxygenase-2 selective inhibitor and aspirin |
| AU2003248642A1 (en) | 2002-06-11 | 2003-12-22 | Nitromed, Inc. | Nitrosated and/or nitrosylated cyclooxygenase-2 selective inhibitors, compositions and methods of use |
| US20040077691A1 (en) * | 2002-06-21 | 2004-04-22 | Medinox, Inc. | Hydroxamate derivatives of non-steroidal anti-inflammatory drugs |
| US7163958B2 (en) | 2002-07-03 | 2007-01-16 | Nitromed Inc. | Nitrosated nonsteroidal antiinflammatory compounds, compositions and methods of use |
| JP2005538110A (ja) * | 2002-07-29 | 2005-12-15 | ニトロメッド インコーポレーティッド | シクロオキシゲナーゼ−２選択的阻害剤、組成物、および使用方法 |
| WO2004019986A1 (en) * | 2002-08-29 | 2004-03-11 | Schering Aktiengesellschaft | Methods of treating acute respiratory distress syndrome |
| EP1534305B9 (en) | 2003-05-07 | 2007-03-07 | Osteologix A/S | Treating cartilage / bone conditions with water-soluble strontium salts |
| KR101052122B1 (ko) | 2005-10-25 | 2011-07-26 | 시오노기세야쿠 가부시키가이샤 | 아미노디히드로티아진 유도체 |
| JP2007275193A (ja) * | 2006-04-04 | 2007-10-25 | Fujifilm Corp | 光プローブおよび光断層画像化装置 |
| EP2083579B1 (en) | 2006-10-25 | 2014-02-12 | Huawei Technologies Co., Ltd. | Processing location update request method, network entity, congestion control method and apparatus |
| JP2010516679A (ja) * | 2007-01-19 | 2010-05-20 | マリンクロット インコーポレイテッド | 診断用および治療用シクロオキシゲナーゼ−２結合リガンド |
| EP2147914B1 (en) | 2007-04-24 | 2014-06-04 | Shionogi&Co., Ltd. | Aminodihydrothiazine derivatives substituted with cyclic groups |
| EP2151435A4 (en) | 2007-04-24 | 2011-09-14 | Shionogi & Co | PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OF ALZHEIMER'S DISEASE |
| CA2716628A1 (en) * | 2008-03-24 | 2009-10-01 | Carolus Therapeutics, Inc. | Methods and compositions for treating atherosclerosis and related conditions |
| MX2010013256A (es) | 2008-06-13 | 2010-12-21 | Shionogi & Co | Derivado heterociclico que contiene azufre que tiene actividad inhibitoria de beta-secretasa. |
| JPWO2010047372A1 (ja) | 2008-10-22 | 2012-03-22 | 塩野義製薬株式会社 | Ｂａｃｅ１阻害活性を有する２−アミノピリミジン−４−オンおよび２−アミノピリジン誘導体 |
| US8453441B2 (en) | 2008-11-06 | 2013-06-04 | Purdue Research Foundation | System and method for pump-controlled cylinder cushioning |
| MY145791A (en) * | 2009-05-25 | 2012-04-30 | Liang Woon San | A method for producing a nutraceutical composition and the nutraceutical produced by the method |
| JPWO2011071135A1 (ja) | 2009-12-11 | 2013-04-22 | 塩野義製薬株式会社 | オキサジン誘導体 |
| JPWO2011077726A1 (ja) * | 2009-12-24 | 2013-05-02 | 塩野義製薬株式会社 | ４−アミノ−１，３−チアジンまたはオキサジン誘導体 |
| MY157206A (en) | 2010-01-13 | 2016-05-13 | Basf Se | Novel mannanase variants |
| WO2011110932A1 (en) | 2010-03-12 | 2011-09-15 | Council Of Scientific & Industrial Research | Process for the production of violacein and its derivative deoxyviolacein containing bioactive pigment from chromobacterium sp. (mtcc 5522) |
| DE102010030500A1 (de) | 2010-06-24 | 2011-12-29 | Heliatek Gmbh | Verdampfbares organisch halbleitendes Material und dessen Verwendung in einem optoelektronischen Bauelement |
| EP2634188A4 (en) | 2010-10-29 | 2014-05-07 | Shionogi & Co | FUSIONED AMINODIHYDROPYRIMIDINE DERIVATIVE |
| CA2816285A1 (en) | 2010-10-29 | 2012-05-03 | Shionogi & Co., Ltd. | Naphthyridine derivative |
| DE102011018604A1 (de) | 2011-04-25 | 2014-02-13 | Michael Friebe | Medikamenteninfusor für die Anwendung in stark magnetischen Umgebungen |
| TW201247635A (en) | 2011-04-26 | 2012-12-01 | Shionogi & Co | Oxazine derivatives and a pharmaceutical composition for inhibiting BAC1 containing them |
| EP2713937A1 (de) | 2011-06-01 | 2014-04-09 | Josef Schweiger | Verbundkrone/verbundbrücke und verfahren zu deren herstellung |
| BR112014008152A2 (pt) | 2011-10-07 | 2017-04-18 | Lonza Ag | método para produção de uma proteina de interesse cultivando uma linhagem celular eucariótica recombinante compreendendo uma construção de expressão compreendendo um promotor regulável e uma molécula de ácido nucleico que codifica uma poi sob o controle transcricional de tal promotor |
| DE102012201426A1 (de) | 2012-02-01 | 2013-08-01 | Leibniz-Institut Für Polymerforschung Dresden E.V. | Verfahren zum verbinden von kunststoffen und verfahren zum lösen einer verbindung im kunststoffverbund und kunststoffverbund |
| DE102012007141A1 (de) | 2012-04-10 | 2013-10-10 | Bernhard Spindler | Jalousierbarer Rollladenpanzer |
| DE102012106428A1 (de) | 2012-07-17 | 2014-01-23 | Reha Technology GmbH | Vorrichtung zur therapeutischen Behandlung, System zur gerätegestützten Lokomotionstherapie und Verfahren zur Steuerung der Vorrichtung |
| DE112013003956T5 (de) | 2012-08-08 | 2015-06-03 | Luis Ramiro Medina Terrazas | Kompostierung von festen und flüssigen Abfällen und biologisch abbaubaren Schlämmen unter Verwendung von Würmerhumus (Eisenia fostida und ähnlichen Spezies) und Mischungen von Würmerhumus und Magen Material mit einem hohen Mikroorganismen-Anteil |
| DE102012214452B4 (de) | 2012-08-14 | 2019-08-01 | Henkel Ag & Co. Kgaa | Vorrichtung zum Auftragen einer fadenförmigen Masse |
| DE102012016116A1 (de) | 2012-08-15 | 2014-02-20 | Josip Fellner | 360° Bag ln Box Spendersystem |
| DE102012214554A1 (de) | 2012-08-16 | 2014-02-20 | Robert Bosch Gmbh | Verfahren zur Überführung von Batterien in einen entladenen Zustand, Batteriemanagementsystem, Inverter, System zur Erzeugung einer Wechselspannung, Ladestromquelle und Kraftfahrzeug |
| DE102012108153A1 (de) | 2012-09-03 | 2014-03-06 | Ludwig-Maximilians-Universität München | Rohling und Verfahren zur Herstellung einer Dentalrestauration durch substraktive Bearbeitung |
| JP2016501827A (ja) | 2012-10-24 | 2016-01-21 | 塩野義製薬株式会社 | Ｂａｃｅ１阻害作用を有するジヒドロオキサジンまたはオキサゼピン誘導体 |
| DE102012112186A1 (de) | 2012-12-12 | 2014-06-26 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Materialverbund, Verfahren zu dessen Herstellung, daraus hergestelltes System und Anwendung desselben |
| EP2956041A2 (de) | 2013-02-15 | 2015-12-23 | Jochen Mertens | Mixer mit massnahmen zur reduzierung des eintrages von luftsauerstoff in den mixer-inhalt |
| DE102013101713B4 (de) | 2013-02-21 | 2020-10-01 | Heliatek Gmbh | Photoaktives, organisches Material für optoelektronische Bauelemente |
| DE102013101712B4 (de) | 2013-02-21 | 2020-05-28 | Heliatek Gmbh | Photoaktives organisches Material für optoelektronische Bauelemente |
| DE102013102366A1 (de) | 2013-03-10 | 2014-09-11 | Informium Ag | Vorrichtungen zur Herstellung und zum Auslesen eines Identifikationsmerkmals mit integriertem Kopierschutz |
| DE102013102364A1 (de) | 2013-03-10 | 2014-09-11 | Informium Ag | Verfahren zur Herstellung eines Identifikationsmerkmals mit integriertem Kopierschutz |
| DE102013102365A1 (de) | 2013-03-10 | 2014-09-11 | Informium Ag | Identifikationsmerkmal mit integriertem Kopierschutz |
| DE102013004288A1 (de) | 2013-03-13 | 2014-09-18 | Matthias Lietzau | Fahrzeug Verbindungsfolie |
| DE202013002767U1 (de) | 2013-03-22 | 2013-05-28 | Lorenz-Montagesysteme Gmbh | Ausgleichende Seitverbindung von Solarmodulen |
| DE102013005741B3 (de) | 2013-04-05 | 2014-05-22 | IOT - Innovative Oberflächentechnologien GmbH | Vorrichtung zur Inertisierung bei UV-Bestrahlung in offenen Durchlaufanlagen |
| EP2792394B1 (de) | 2013-04-16 | 2016-07-27 | Jörg Beutler | Interaktive Geschwindigkeitssteuerung |
| DE102013104501A1 (de) | 2013-05-02 | 2014-11-06 | B. Braun Avitum Ag | Vorrichtung zur extrakorporalen Blutbehandlung |
| DE102013008359A1 (de) | 2013-05-16 | 2014-11-20 | Sew-Eurodrive Gmbh & Co Kg | Energiespeicher, der aus in Reihe geschalten Energiespeicherzellen aufgebaut ist, und Schaltungsanordnung zur passiven Symmetrierung einer Reihenschaltung von Kondensatoren |
| DE102013008919B4 (de) | 2013-05-24 | 2017-12-07 | Magdeburger Windkraftanlagen GmbH | Rotorsystem für die Energiewandlung von kinetischer Energie in Fluiden und Massenströmen |
| DE202013006258U1 (de) | 2013-07-11 | 2013-10-11 | IMM Ingenieurbüro GmbH | Vorrichtung zum Erzeugen von heizbaren Flächen mit homogener Wärmeverteilung |
| DE102013110693B4 (de) | 2013-09-27 | 2024-04-25 | Heliatek Gmbh | Photoaktives, organisches Material für optoelektronische Bauelemente |
| EP2873807A1 (de) | 2013-11-18 | 2015-05-20 | Siemens Aktiengesellschaft | Abdeckplatte, Laufschaufel, Radscheibe, Bolzen und Gasturbine |
| WO2015075040A1 (de) | 2013-11-19 | 2015-05-28 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Verfahren zum verbinden von silikongummi mit einem substrat |
| EP2902692B1 (de) | 2013-12-06 | 2017-10-25 | MAGNA STEYR Engineering AG & Co KG | Bauteil eines Tanksystems |
| DE202014100570U1 (de) | 2014-02-10 | 2014-03-10 | Schlaadt Plastics Gmbh | Klappsystem zur Verbindung von Partikelschaumbauteilen mittels eines gegen Verlust gesicherten Steckelements |
| DE102014004280A1 (de) | 2014-03-26 | 2015-10-01 | Florian M. König | Impulssignal-Erzeugungsvorrichtung für Zwecke der autonomen Batterieaufladung oder 120-/230-Volt-Lampenversorgung |
| DE202014003299U1 (de) | 2014-04-14 | 2014-08-25 | Antje Koss | Stollenschuh mit Wechselstollensystem |
| DE202014004532U1 (de) | 2014-05-28 | 2014-08-05 | Hans-Dieter Cornelius | Hygienevorlage |
| DE102015214641B4 (de) | 2014-11-10 | 2024-10-24 | Hermann Roth | Zusammensetzung mit Säure und Isochinolinalkaloid |
| DE102014017938A1 (de) | 2014-12-05 | 2016-06-09 | Florian M. König | Trichter-turbinenartige Vorrichtung mit elektromagnetischer Rotationssteuerung von Flüssigkeits-Mischvorgängen |
| DE102015000003A1 (de) | 2015-01-02 | 2016-07-07 | Solukon Ingenieure GbR (vertretungsberechtigte Gesellschafter: Andreas Hartmann, 86391 Stadtbergen und Dominik Schmid, 86165 Augsburg) | Baubehälter für Produktionsanlagen zur Herstellung von Bauteilen in Schichtbauverfahren |
| DE102015008129A1 (de) | 2015-01-22 | 2016-07-28 | Liebherr-Hausgeräte Lienz Gmbh | Verfahren zur Bestimmung der Dämmeigenschaft einer Wandung eines wärmeisolierten Behältnisses |
| DE102015000887A1 (de) | 2015-01-23 | 2016-07-28 | Arnulf Deinzer | Zahnreinigungsgerät mit ausfahrbaren Borsten |
| DE102015015877A1 (de) | 2015-12-09 | 2017-06-14 | Bayerisches Zentrum für angewandte Energieforschung, e.V. (ZAE Bayern) | Optisch schaltendes Element |
| DE102016006696A1 (de) | 2016-05-27 | 2017-11-30 | Christoph Jaeger | Flugautosystem |
| DE202016004226U1 (de) | 2016-07-06 | 2016-11-11 | Helmut Senkel | Schienensystem mit verfahrbaren Verbrauchern |
| CN106279585A (zh) * | 2016-08-26 | 2017-01-04 | 宁波圣达精工智能科技有限公司 | 一种阻燃智能密集书架的制备方法 |
| CN108832306B (zh) * | 2018-06-13 | 2023-11-03 | 中国科学院国家天文台 | 一种fast反射面中心孔柔性封堵结构 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CZ119398A3 (cs) | 1995-10-17 | 1998-09-16 | Astra Aktiebolag | Farmaceuticky účinné sloučeniny na bázi chinazolinu |
-
1998
- 1998-06-29 SE SE9802333A patent/SE9802333D0/xx unknown
-
1999
- 1999-06-23 TR TR2000/03808T patent/TR200003808T2/xx unknown
- 1999-06-23 ID IDW20002691A patent/ID27394A/id unknown
- 1999-06-23 EP EP99933384A patent/EP1100505A1/en not_active Withdrawn
- 1999-06-23 BR BR9911666-9A patent/BR9911666A/pt not_active Application Discontinuation
- 1999-06-23 KR KR1020007014933A patent/KR20010053252A/ko not_active Withdrawn
- 1999-06-23 JP JP2000556785A patent/JP2002519324A/ja active Pending
- 1999-06-23 WO PCT/SE1999/001144 patent/WO2000000200A1/en not_active Ceased
- 1999-06-23 PL PL99345028A patent/PL345028A1/xx not_active Application Discontinuation
- 1999-06-23 EE EEP200000766A patent/EE200000766A/xx unknown
- 1999-06-23 US US09/380,379 patent/US6248745B1/en not_active Expired - Fee Related
- 1999-06-23 MX MXPA00012162 patent/MXPA00012162A/es unknown
- 1999-06-23 CN CN99810007A patent/CN1313769A/zh active Pending
- 1999-06-23 IL IL14002299A patent/IL140022A0/xx unknown
- 1999-06-23 CZ CZ20004896A patent/CZ20004896A3/cs unknown
- 1999-06-23 CA CA002334515A patent/CA2334515A1/en not_active Abandoned
- 1999-06-23 SK SK1848-2000A patent/SK18482000A3/sk unknown
- 1999-06-23 AU AU49447/99A patent/AU4944799A/en not_active Abandoned
-
2000
- 2000-08-01 IN IN721MU2000 patent/IN2000MU00721A/en unknown
- 2000-11-30 ZA ZA200007076A patent/ZA200007076B/en unknown
- 2000-12-21 NO NO20006559A patent/NO20006559L/no not_active Application Discontinuation
- 2000-12-27 IS IS5794A patent/IS5794A/is unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IL140022A0 (en) | 2002-02-10 |
| EE200000766A (et) | 2002-06-17 |
| SE9802333D0 (sv) | 1998-06-29 |
| NO20006559D0 (no) | 2000-12-21 |
| CZ20004896A3 (en) | 2001-06-13 |
| ZA200007076B (en) | 2002-02-28 |
| PL345028A1 (en) | 2001-11-19 |
| US6248745B1 (en) | 2001-06-19 |
| EP1100505A1 (en) | 2001-05-23 |
| SK18482000A3 (sk) | 2001-07-10 |
| TR200003808T2 (tr) | 2001-06-21 |
| IN2000MU00721A (OSRAM) | 2005-03-18 |
| WO2000000200A1 (en) | 2000-01-06 |
| KR20010053252A (ko) | 2001-06-25 |
| CA2334515A1 (en) | 2000-01-06 |
| IS5794A (is) | 2000-12-27 |
| NO20006559L (no) | 2001-02-28 |
| CN1313769A (zh) | 2001-09-19 |
| ID27394A (id) | 2001-04-05 |
| BR9911666A (pt) | 2001-03-20 |
| MXPA00012162A (es) | 2001-05-01 |
| AU4944799A (en) | 2000-01-17 |
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