UA73513C2 - 8-PHENYL-6,9 ûDIHYDRO- [1,2,4] TRIAZOLO [3,4-I] PURIN û5-ON DERIVATIVES, A METHOD FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION BASED THEREON - Google Patents

8-PHENYL-6,9 ûDIHYDRO- [1,2,4] TRIAZOLO [3,4-I] PURIN û5-ON DERIVATIVES, A METHOD FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION BASED THEREON Download PDF

Info

Publication number: UA73513C2
Authority: UA; Ukraine
Prior art keywords: dihydro; preparation; group; sulfonyl; propyl
Prior art date: 1999-07-27

Application number

UA2002010660A

Other languages

English (en)

Ukrainian (uk)

Original Assignee

Almirall Prodespharma S A

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.)

1999-07-27

Filing date

2000-07-24

Publication date

2005-08-15

2000-07-24 Application filed by Almirall Prodespharma S A filed Critical Almirall Prodespharma S A

2005-08-15 Publication of UA73513C2 publication Critical patent/UA73513C2/uk

Links

238000000034 method Methods 0.000 title claims description 167
239000008194 pharmaceutical composition Substances 0.000 title claims description 6
238000002360 preparation method Methods 0.000 title description 217
150000003839 salts Chemical class 0.000 claims abstract description 17
150000001875 compounds Chemical class 0.000 claims description 211
-1 monoalkylamino Chemical group 0.000 claims description 126
239000000203 mixture Substances 0.000 claims description 51
125000000217 alkyl group Chemical group 0.000 claims description 41
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 27
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
238000006243 chemical reaction Methods 0.000 claims description 22
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
125000003545 alkoxy group Chemical group 0.000 claims description 19
125000005843 halogen group Chemical group 0.000 claims description 19
229910052739 hydrogen Inorganic materials 0.000 claims description 19
239000001257 hydrogen Substances 0.000 claims description 19
125000000753 cycloalkyl group Chemical group 0.000 claims description 14
229910052757 nitrogen Inorganic materials 0.000 claims description 14
125000004193 piperazinyl group Chemical group 0.000 claims description 14
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 13
229910052760 oxygen Inorganic materials 0.000 claims description 13
239000002904 solvent Substances 0.000 claims description 13
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
150000001412 amines Chemical class 0.000 claims description 12
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
125000004076 pyridyl group Chemical group 0.000 claims description 12
125000002757 morpholinyl group Chemical group 0.000 claims description 11
239000004480 active ingredient Substances 0.000 claims description 10
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
125000003342 alkenyl group Chemical group 0.000 claims description 8
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
239000001301 oxygen Chemical group 0.000 claims description 8
125000005530 alkylenedioxy group Chemical group 0.000 claims description 7
125000000304 alkynyl group Chemical group 0.000 claims description 7
125000005842 heteroatom Chemical group 0.000 claims description 7
150000002431 hydrogen Chemical class 0.000 claims description 7
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
150000007530 organic bases Chemical class 0.000 claims description 7
125000005936 piperidyl group Chemical group 0.000 claims description 7
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
229910052717 sulfur Inorganic materials 0.000 claims description 7
239000011593 sulfur Substances 0.000 claims description 7
125000001425 triazolyl group Chemical group 0.000 claims description 7
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 claims description 6
125000004414 alkyl thio group Chemical group 0.000 claims description 6
125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 6
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
125000004432 carbon atom Chemical group C* 0.000 claims description 6
XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 claims description 6
125000004093 cyano group Chemical group *C#N 0.000 claims description 6
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims description 6
HOXPMFBXNMYFSM-UHFFFAOYSA-N 7h-purin-2-ylhydrazine Chemical class NNC1=NC=C2NC=NC2=N1 HOXPMFBXNMYFSM-UHFFFAOYSA-N 0.000 claims description 5
125000002947 alkylene group Chemical group 0.000 claims description 5
125000002393 azetidinyl group Chemical group 0.000 claims description 5
229910052736 halogen Inorganic materials 0.000 claims description 5
125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 5
125000003831 tetrazolyl group Chemical group 0.000 claims description 5
208000019553 vascular disease Diseases 0.000 claims description 5
206010007559 Cardiac failure congestive Diseases 0.000 claims description 4
208000010228 Erectile Dysfunction Diseases 0.000 claims description 4
206010057671 Female sexual dysfunction Diseases 0.000 claims description 4
208000010412 Glaucoma Diseases 0.000 claims description 4
206010019280 Heart failures Diseases 0.000 claims description 4
206010020772 Hypertension Diseases 0.000 claims description 4
208000006011 Stroke Diseases 0.000 claims description 4
208000006673 asthma Diseases 0.000 claims description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
208000035475 disorder Diseases 0.000 claims description 4
230000000694 effects Effects 0.000 claims description 4
150000002367 halogens Chemical class 0.000 claims description 4
ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 4
201000001881 impotence Diseases 0.000 claims description 4
239000000546 pharmaceutical excipient Substances 0.000 claims description 4
239000003880 polar aprotic solvent Substances 0.000 claims description 4
QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 claims description 3
125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 3
206010002383 Angina Pectoris Diseases 0.000 claims description 3
201000001320 Atherosclerosis Diseases 0.000 claims description 3
201000001068 Prinzmetal angina Diseases 0.000 claims description 3
208000001647 Renal Insufficiency Diseases 0.000 claims description 3
206010039085 Rhinitis allergic Diseases 0.000 claims description 3
208000007718 Stable Angina Diseases 0.000 claims description 3
208000007814 Unstable Angina Diseases 0.000 claims description 3
239000002253 acid Substances 0.000 claims description 3
125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 3
201000009961 allergic asthma Diseases 0.000 claims description 3
201000010105 allergic rhinitis Diseases 0.000 claims description 3
210000004204 blood vessel Anatomy 0.000 claims description 3
206010006451 bronchitis Diseases 0.000 claims description 3
208000023819 chronic asthma Diseases 0.000 claims description 3
230000008991 intestinal motility Effects 0.000 claims description 3
201000006370 kidney failure Diseases 0.000 claims description 3
208000002815 pulmonary hypertension Diseases 0.000 claims description 3
125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 3
125000003373 pyrazinyl group Chemical group 0.000 claims description 3
208000015891 sexual disease Diseases 0.000 claims description 3
OFQXVHPYWBHEMD-UHFFFAOYSA-N 1-phenyl-3,7-dihydropurine-2,6-dione Chemical compound O=C1NC=2N=CNC=2C(=O)N1C1=CC=CC=C1 OFQXVHPYWBHEMD-UHFFFAOYSA-N 0.000 claims description 2
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 2
RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 claims description 2
125000004442 acylamino group Chemical group 0.000 claims description 2
230000015572 biosynthetic process Effects 0.000 claims description 2
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
230000005764 inhibitory process Effects 0.000 claims description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
125000005188 oxoalkyl group Chemical group 0.000 claims description 2
125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 claims description 2
125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 2
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 2
125000004663 dialkyl amino group Chemical group 0.000 claims 11
230000003993 interaction Effects 0.000 claims 3
241001465754 Metazoa Species 0.000 claims 2
208000009325 Variant Angina Pectoris Diseases 0.000 claims 2
230000002093 peripheral effect Effects 0.000 claims 2
101100287724 Caenorhabditis elegans shk-1 gene Proteins 0.000 claims 1
241001024304 Mino Species 0.000 claims 1
241001122767 Theaceae Species 0.000 claims 1
150000001735 carboxylic acids Chemical class 0.000 claims 1
239000003814 drug Substances 0.000 claims 1
125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 claims 1
125000003226 pyrazolyl group Chemical group 0.000 claims 1
238000012876 topography Methods 0.000 claims 1
239000007787 solid Substances 0.000 description 165
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 18
239000000243 solution Substances 0.000 description 18
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
150000001732 carboxylic acid derivatives Chemical class 0.000 description 15
PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 14
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 14
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 14
235000002639 sodium chloride Nutrition 0.000 description 13
WFCSWCVEJLETKA-UHFFFAOYSA-N 2-piperazin-1-ylethanol Chemical compound OCCN1CCNCC1 WFCSWCVEJLETKA-UHFFFAOYSA-N 0.000 description 10
238000010992 reflux Methods 0.000 description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
125000004544 purin-8-yl group Chemical group N1=CN=C2N=C(NC2=C1)* 0.000 description 9
125000001424 substituent group Chemical group 0.000 description 9
KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 8
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 8
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
XCAYUNJSPOEITF-UHFFFAOYSA-N n-[(3-methoxyphenyl)methyl]-1-phenylmethanamine Chemical compound COC1=CC=CC(CNCC=2C=CC=CC=2)=C1 XCAYUNJSPOEITF-UHFFFAOYSA-N 0.000 description 8
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 7
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
235000019253 formic acid Nutrition 0.000 description 7
239000002244 precipitate Substances 0.000 description 7
239000000725 suspension Substances 0.000 description 7
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 6
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
238000009835 boiling Methods 0.000 description 6
238000001914 filtration Methods 0.000 description 6
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 6
238000002347 injection Methods 0.000 description 6
239000007924 injection Substances 0.000 description 6
RWIVICVCHVMHMU-UHFFFAOYSA-N n-aminoethylmorpholine Chemical compound NCCN1CCOCC1 RWIVICVCHVMHMU-UHFFFAOYSA-N 0.000 description 6
ACCCXSZCOGNLFL-UHFFFAOYSA-N 8-phenyl-3,7-dihydropurine-2,6-dione Chemical class N1C=2C(=O)NC(=O)NC=2N=C1C1=CC=CC=C1 ACCCXSZCOGNLFL-UHFFFAOYSA-N 0.000 description 5
125000003118 aryl group Chemical group 0.000 description 5
239000003153 chemical reaction reagent Substances 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
239000003826 tablet Substances 0.000 description 5
WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 description 4
OBWROQGNIMBKKV-UHFFFAOYSA-N 5,6-diamino-1-butylpyrimidine-2,4-dione Chemical compound CCCCN1C(N)=C(N)C(=O)NC1=O OBWROQGNIMBKKV-UHFFFAOYSA-N 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
239000002585 base Substances 0.000 description 4
239000012299 nitrogen atmosphere Substances 0.000 description 4
239000003921 oil Substances 0.000 description 4
239000003960 organic solvent Substances 0.000 description 4
CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
239000012258 stirred mixture Substances 0.000 description 4
FXHRAKUEZPSMLJ-UHFFFAOYSA-N 1-methyl-1,4-diazepane Chemical compound CN1CCCNCC1 FXHRAKUEZPSMLJ-UHFFFAOYSA-N 0.000 description 3
MDKAAWDKKBFSTK-UHFFFAOYSA-N 2-ethoxybenzoyl chloride Chemical compound CCOC1=CC=CC=C1C(Cl)=O MDKAAWDKKBFSTK-UHFFFAOYSA-N 0.000 description 3
CJNRGSHEMCMUOE-UHFFFAOYSA-N 2-piperidin-1-ylethanamine Chemical compound NCCN1CCCCC1 CJNRGSHEMCMUOE-UHFFFAOYSA-N 0.000 description 3
NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 3
108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
150000001408 amides Chemical class 0.000 description 3
229910021529 ammonia Inorganic materials 0.000 description 3
CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 3
239000012267 brine Substances 0.000 description 3
239000002775 capsule Substances 0.000 description 3
238000001816 cooling Methods 0.000 description 3
AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 3
MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 3
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 3
239000003085 diluting agent Substances 0.000 description 3
229960004979 fampridine Drugs 0.000 description 3
239000007788 liquid Substances 0.000 description 3
230000014759 maintenance of location Effects 0.000 description 3
HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
229940124530 sulfonamide Drugs 0.000 description 3
238000004809 thin layer chromatography Methods 0.000 description 3
125000004568 thiomorpholinyl group Chemical group 0.000 description 3
150000003852 triazoles Chemical class 0.000 description 3
KISVATOISQDZJU-UHFFFAOYSA-N (1-benzhydrylazetidin-3-yl)methanamine Chemical compound C1C(CN)CN1C(C=1C=CC=CC=1)C1=CC=CC=C1 KISVATOISQDZJU-UHFFFAOYSA-N 0.000 description 2
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
NKBWMBRPILTCRD-UHFFFAOYSA-N 2-Methylheptanoic acid Chemical compound CCCCCC(C)C(O)=O NKBWMBRPILTCRD-UHFFFAOYSA-N 0.000 description 2
BDPARNTXGNJTCC-UHFFFAOYSA-N 2-butoxybenzoyl chloride Chemical compound CCCCOC1=CC=CC=C1C(Cl)=O BDPARNTXGNJTCC-UHFFFAOYSA-N 0.000 description 2
STSAIUCZKQGPNG-UHFFFAOYSA-N 2-piperazin-1-ylpropan-1-ol Chemical compound OCC(C)N1CCNCC1 STSAIUCZKQGPNG-UHFFFAOYSA-N 0.000 description 2
NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 2
HEXZSEOAILCDMD-UHFFFAOYSA-N 5,6-diamino-1-ethylpyrimidine-2,4-dione Chemical compound CCN1C(N)=C(N)C(=O)NC1=O HEXZSEOAILCDMD-UHFFFAOYSA-N 0.000 description 2
YOMSKQSCRYRZDC-UHFFFAOYSA-N 5,6-diamino-1-propylpyrimidine-2,4-dione Chemical compound CCCN1C(N)=C(N)C(=O)NC1=O YOMSKQSCRYRZDC-UHFFFAOYSA-N 0.000 description 2
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
102000004190 Enzymes Human genes 0.000 description 2
108090000790 Enzymes Proteins 0.000 description 2
NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 2
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
HUMHYXGDUOGHTG-HEZXSMHISA-N alpha-D-GalpNAc-(1->3)-[alpha-L-Fucp-(1->2)]-D-Galp Chemical compound O[C@H]1[C@H](O)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](O[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](O)[C@@H](CO)OC1O HUMHYXGDUOGHTG-HEZXSMHISA-N 0.000 description 2
150000008064 anhydrides Chemical class 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
125000003710 aryl alkyl group Chemical group 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
229940075614 colloidal silicon dioxide Drugs 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
239000012043 crude product Substances 0.000 description 2
125000004122 cyclic group Chemical group 0.000 description 2
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
235000013355 food flavoring agent Nutrition 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
125000002632 imidazolidinyl group Chemical group 0.000 description 2
125000002883 imidazolyl group Chemical group 0.000 description 2
125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
208000002551 irritable bowel syndrome Diseases 0.000 description 2
125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 2
CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 2
239000012280 lithium aluminium hydride Substances 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
238000002844 melting Methods 0.000 description 2
230000008018 melting Effects 0.000 description 2
BVOCPVIXARZNQN-UHFFFAOYSA-N nipecotamide Chemical compound NC(=O)C1CCCNC1 BVOCPVIXARZNQN-UHFFFAOYSA-N 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
238000000746 purification Methods 0.000 description 2
125000002755 pyrazolinyl group Chemical group 0.000 description 2
125000000168 pyrrolyl group Chemical group 0.000 description 2
150000003456 sulfonamides Chemical class 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
125000001544 thienyl group Chemical group 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
229910052727 yttrium Inorganic materials 0.000 description 2
VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
WHJANSWOSODZBT-UHFFFAOYSA-N (1-methyl-4-phenylpiperidin-4-yl)methanamine Chemical compound C1CN(C)CCC1(CN)C1=CC=CC=C1 WHJANSWOSODZBT-UHFFFAOYSA-N 0.000 description 1
HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 description 1
NSMWYRLQHIXVAP-OLQVQODUSA-N (2r,5s)-2,5-dimethylpiperazine Chemical compound C[C@H]1CN[C@H](C)CN1 NSMWYRLQHIXVAP-OLQVQODUSA-N 0.000 description 1
IFNWESYYDINUHV-OLQVQODUSA-N (2s,6r)-2,6-dimethylpiperazine Chemical compound C[C@H]1CNC[C@@H](C)N1 IFNWESYYDINUHV-OLQVQODUSA-N 0.000 description 1
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 1
MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
NDQXKKFRNOPRDW-UHFFFAOYSA-N 1,1,1-triethoxyethane Chemical compound CCOC(C)(OCC)OCC NDQXKKFRNOPRDW-UHFFFAOYSA-N 0.000 description 1
JAFMOTJMRSZOJE-UHFFFAOYSA-N 1,1,1-trimethoxybutane Chemical compound CCCC(OC)(OC)OC JAFMOTJMRSZOJE-UHFFFAOYSA-N 0.000 description 1
BMEMBBFDTYHTLH-UHFFFAOYSA-N 1-(2-methoxyethyl)piperazine Chemical compound COCCN1CCNCC1 BMEMBBFDTYHTLH-UHFFFAOYSA-N 0.000 description 1
OCKKCUWOBXCPOU-UHFFFAOYSA-N 1-(aminomethyl)-n,n-diethylcycloheptan-1-amine Chemical compound CCN(CC)C1(CN)CCCCCC1 OCKKCUWOBXCPOU-UHFFFAOYSA-N 0.000 description 1
FNFZQQDMUXFKDE-UHFFFAOYSA-N 1-(aminomethyl)-n,n-diethylcyclohexan-1-amine Chemical compound CCN(CC)C1(CN)CCCCC1 FNFZQQDMUXFKDE-UHFFFAOYSA-N 0.000 description 1
ZVHHFWKWIVLISO-UHFFFAOYSA-N 1-(azetidin-3-yl)-n,n-dimethylmethanamine;dihydrochloride Chemical compound Cl.Cl.CN(C)CC1CNC1 ZVHHFWKWIVLISO-UHFFFAOYSA-N 0.000 description 1
IXMOEAHDRKNAAG-UHFFFAOYSA-N 1-benzhydrylazetidine-3-carbonitrile Chemical compound C1C(C#N)CN1C(C=1C=CC=CC=1)C1=CC=CC=C1 IXMOEAHDRKNAAG-UHFFFAOYSA-N 0.000 description 1
125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 description 1
ZWAQJGHGPPDZSF-UHFFFAOYSA-N 1-prop-2-enylpiperazine Chemical compound C=CCN1CCNCC1 ZWAQJGHGPPDZSF-UHFFFAOYSA-N 0.000 description 1
QLEIDMAURCRVCX-UHFFFAOYSA-N 1-propylpiperazine Chemical compound CCCN1CCNCC1 QLEIDMAURCRVCX-UHFFFAOYSA-N 0.000 description 1
GCUOLJOTJRUDIZ-UHFFFAOYSA-N 2-(2-bromoethoxy)oxane Chemical compound BrCCOC1CCCCO1 GCUOLJOTJRUDIZ-UHFFFAOYSA-N 0.000 description 1
HNJWKRMESUMDQE-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-n-methylethanamine Chemical compound CNCCC1=CC=C(OC)C(OC)=C1 HNJWKRMESUMDQE-UHFFFAOYSA-N 0.000 description 1
WWXXMJJYXAXHMX-UHFFFAOYSA-N 2-(azetidin-3-ylmethylamino)ethanol Chemical compound OCCNCC1CNC1 WWXXMJJYXAXHMX-UHFFFAOYSA-N 0.000 description 1
BCLSJHWBDUYDTR-UHFFFAOYSA-N 2-(propylamino)ethanol Chemical compound CCCNCCO BCLSJHWBDUYDTR-UHFFFAOYSA-N 0.000 description 1
FWIISKJEWSUYKX-UHFFFAOYSA-N 2-[1-(aminomethyl)cycloheptyl]ethanamine Chemical compound NCCC1(CN)CCCCCC1 FWIISKJEWSUYKX-UHFFFAOYSA-N 0.000 description 1
GGKYFXJCWHPRGI-UHFFFAOYSA-N 2-[1-(aminomethyl)cyclohexyl]ethanamine Chemical compound NCCC1(CN)CCCCC1 GGKYFXJCWHPRGI-UHFFFAOYSA-N 0.000 description 1
XXSPGBOGLXKMDU-UHFFFAOYSA-N 2-bromo-2-methylpropanoic acid Chemical compound CC(C)(Br)C(O)=O XXSPGBOGLXKMDU-UHFFFAOYSA-N 0.000 description 1
DXOHZOPKNFZZAD-UHFFFAOYSA-N 2-ethylpiperazine Chemical compound CCC1CNCCN1 DXOHZOPKNFZZAD-UHFFFAOYSA-N 0.000 description 1
PZCAATRCZPVQPA-UHFFFAOYSA-N 2-methyl-2-piperazin-1-ylpropan-1-ol Chemical compound OCC(C)(C)N1CCNCC1 PZCAATRCZPVQPA-UHFFFAOYSA-N 0.000 description 1
JBYQUIIFLIBKFJ-UHFFFAOYSA-N 2-morpholin-3-ylethanamine Chemical compound NCCC1COCCN1 JBYQUIIFLIBKFJ-UHFFFAOYSA-N 0.000 description 1
VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 description 1
LWEOFVINMVZGAS-UHFFFAOYSA-N 3-piperazin-1-ylpropan-1-ol Chemical compound OCCCN1CCNCC1 LWEOFVINMVZGAS-UHFFFAOYSA-N 0.000 description 1
ZSDLHCLPOBIBSD-UHFFFAOYSA-N 4-(1-ethoxy-2-methyl-1-oxopropan-2-yl)piperazine-1-carboxylic acid Chemical compound CCOC(=O)C(C)(C)N1CCN(C(O)=O)CC1 ZSDLHCLPOBIBSD-UHFFFAOYSA-N 0.000 description 1
CZWOMYKDIAASBD-UHFFFAOYSA-N 4-(1-hydroxy-2-methylpropan-2-yl)piperazine-1-carboxylic acid Chemical compound OCC(C)(C)N1CCN(C(O)=O)CC1 CZWOMYKDIAASBD-UHFFFAOYSA-N 0.000 description 1
DPBWFNDFMCCGGJ-UHFFFAOYSA-N 4-Piperidine carboxamide Chemical compound NC(=O)C1CCNCC1 DPBWFNDFMCCGGJ-UHFFFAOYSA-N 0.000 description 1
QISOBCMNUJQOJU-UHFFFAOYSA-N 4-bromo-1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1NN=CC=1Br QISOBCMNUJQOJU-UHFFFAOYSA-N 0.000 description 1
AKJYGXFLPNNPAZ-UHFFFAOYSA-N 5,6-diamino-1-(2-methoxyethyl)pyrimidine-2,4-dione Chemical compound COCCN1C(N)=C(N)C(=O)NC1=O AKJYGXFLPNNPAZ-UHFFFAOYSA-N 0.000 description 1
CGFXGMANBNXKER-UHFFFAOYSA-N 5,6-diamino-1-(2-methylpropyl)pyrimidine-2,4-dione Chemical compound CC(C)CN1C(N)=C(N)C(=O)NC1=O CGFXGMANBNXKER-UHFFFAOYSA-N 0.000 description 1
OVVBFVIULMDOEE-UHFFFAOYSA-N 5,6-diamino-1-pentylpyrimidine-2,4-dione Chemical compound CCCCCN1C(N)=C(N)C(=O)NC1=O OVVBFVIULMDOEE-UHFFFAOYSA-N 0.000 description 1
KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
125000003341 7 membered heterocyclic group Chemical group 0.000 description 1
YNKZGYXJJXMVMD-UHFFFAOYSA-N 8-(2-ethoxyphenyl)-3-ethyl-6-hydrazinyl-7h-purin-2-one Chemical compound CCOC1=CC=CC=C1C(N1)=NC2=C1C(NN)=NC(=O)N2CC YNKZGYXJJXMVMD-UHFFFAOYSA-N 0.000 description 1
CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
XUUAFGZYDFOQJH-UHFFFAOYSA-N 8-(5-piperazin-1-ylsulfonyl-2-propoxyphenyl)-3-propyl-7h-purine-2,6-dione Chemical compound C1=C(C=2NC=3C(=O)NC(=O)N(CCC)C=3N=2)C(OCCC)=CC=C1S(=O)(=O)N1CCNCC1 XUUAFGZYDFOQJH-UHFFFAOYSA-N 0.000 description 1
101800000055 Adipokinetic hormone 1 Proteins 0.000 description 1
244000005894 Albizia lebbeck Species 0.000 description 1
WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 1
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
206010002388 Angina unstable Diseases 0.000 description 1
OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
240000005220 Bischofia javanica Species 0.000 description 1
235000010893 Bischofia javanica Nutrition 0.000 description 1
101100314454 Caenorhabditis elegans tra-1 gene Proteins 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
241000543381 Cliftonia monophylla Species 0.000 description 1
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 1
NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
241000408495 Iton Species 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
102100026933 Myelin-associated neurite-outgrowth inhibitor Human genes 0.000 description 1
AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
241001387976 Pera Species 0.000 description 1
208000018262 Peripheral vascular disease Diseases 0.000 description 1
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
208000003782 Raynaud disease Diseases 0.000 description 1
208000012322 Raynaud phenomenon Diseases 0.000 description 1
229940124639 Selective inhibitor Drugs 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
239000005864 Sulphur Chemical group 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
102000011016 Type 5 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 description 1
108010037581 Type 5 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 description 1
LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
235000011114 ammonium hydroxide Nutrition 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
230000003496 anti-amnesic effect Effects 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
125000003435 aroyl group Chemical group 0.000 description 1
238000003491 array Methods 0.000 description 1
KFRAKQXWWCKHKF-UHFFFAOYSA-N azanium;dichloromethane;ethanol;hydroxide Chemical compound [NH4+].[OH-].CCO.ClCCl KFRAKQXWWCKHKF-UHFFFAOYSA-N 0.000 description 1
RPIWUWHVJYNNJL-UHFFFAOYSA-N benzyl 4-(1-ethoxy-2-methyl-1-oxopropan-2-yl)piperazine-1-carboxylate Chemical compound C1CN(C(C)(C)C(=O)OCC)CCN1C(=O)OCC1=CC=CC=C1 RPIWUWHVJYNNJL-UHFFFAOYSA-N 0.000 description 1
CBQGRQMUIXZBTJ-UHFFFAOYSA-N benzyl 4-(1-hydroxy-2-methylpropan-2-yl)piperazine-1-carboxylate Chemical compound C1CN(C(C)(CO)C)CCN1C(=O)OCC1=CC=CC=C1 CBQGRQMUIXZBTJ-UHFFFAOYSA-N 0.000 description 1
229940124630 bronchodilator Drugs 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
239000003086 colorant Substances 0.000 description 1
238000004040 coloring Methods 0.000 description 1
238000010411 cooking Methods 0.000 description 1
229910052802 copper Inorganic materials 0.000 description 1
239000010949 copper Substances 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
239000006071 cream Substances 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
239000007950 delayed release tablet Substances 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
230000001882 diuretic effect Effects 0.000 description 1
CYESCLHCWJKRKM-UHFFFAOYSA-N diuron-desdimethyl Chemical compound NC(=O)NC1=CC=C(Cl)C(Cl)=C1 CYESCLHCWJKRKM-UHFFFAOYSA-N 0.000 description 1
238000011067 equilibration Methods 0.000 description 1
MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
239000012530 fluid Substances 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
239000010931 gold Substances 0.000 description 1
229910052737 gold Inorganic materials 0.000 description 1
229940029575 guanosine Drugs 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
150000002430 hydrocarbons Chemical group 0.000 description 1
239000005457 ice water Substances 0.000 description 1
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
201000004332 intermediate coronary syndrome Diseases 0.000 description 1
238000004255 ion exchange chromatography Methods 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
125000005956 isoquinolyl group Chemical group 0.000 description 1
229960001375 lactose Drugs 0.000 description 1
239000008101 lactose Substances 0.000 description 1
229960001021 lactose monohydrate Drugs 0.000 description 1
239000006166 lysate Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
STEPQTYSZVCJPV-UHFFFAOYSA-N metazachlor Chemical compound CC1=CC=CC(C)=C1N(C(=O)CCl)CN1N=CC=C1 STEPQTYSZVCJPV-UHFFFAOYSA-N 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
YCNHOXDFQLCQEU-UHFFFAOYSA-N n,1-dimethylazetidin-3-amine Chemical compound CNC1CN(C)C1 YCNHOXDFQLCQEU-UHFFFAOYSA-N 0.000 description 1
IRQWCOFOSMREBQ-UHFFFAOYSA-N n,n-dimethylazetidin-3-amine Chemical compound CN(C)C1CNC1 IRQWCOFOSMREBQ-UHFFFAOYSA-N 0.000 description 1
125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
239000012071 phase Substances 0.000 description 1
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
RFIOZSIHFNEKFF-UHFFFAOYSA-N piperazine-1-carboxylic acid Chemical compound OC(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-N 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000000047 product Substances 0.000 description 1
JKANAVGODYYCQF-UHFFFAOYSA-N prop-2-yn-1-amine Chemical compound NCC#C JKANAVGODYYCQF-UHFFFAOYSA-N 0.000 description 1
125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
125000005493 quinolyl group Chemical group 0.000 description 1
125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
229940058287 salicylic acid derivative anticestodals Drugs 0.000 description 1
150000003872 salicylic acid derivatives Chemical class 0.000 description 1
238000000926 separation method Methods 0.000 description 1
XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
229940045902 sodium stearyl fumarate Drugs 0.000 description 1
238000001694 spray drying Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
238000003756 stirring Methods 0.000 description 1
239000006190 sub-lingual tablet Substances 0.000 description 1
125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000000758 substrate Substances 0.000 description 1
239000001384 succinic acid Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
229940055764 triaz Drugs 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/14—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- 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
- A61P11/06—Antiasthmatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/18—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/22—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one sulfur atom

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
General Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Chemical & Material Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pulmonology (AREA)
Ophthalmology & Optometry (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Urology & Nephrology (AREA)
Reproductive Health (AREA)
Endocrinology (AREA)
Gynecology & Obstetrics (AREA)
Immunology (AREA)
Vascular Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

UA2002010660A 1999-07-27 2000-07-24 8-PHENYL-6,9 ûDIHYDRO- [1,2,4] TRIAZOLO [3,4-I] PURIN û5-ON DERIVATIVES, A METHOD FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION BASED THEREON UA73513C2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
ES009901694A ES2166270B1 (es)	1999-07-27	1999-07-27	Derivados de 8-fenil-6,9-dihidro-(1,2,4,)triazolo(3,4-i)purin-5-ona.
PCT/EP2000/007062 WO2001007441A1 (en)	1999-07-27	2000-07-24	8-PHENYL-6,9-DIHYDRO-[1,2,4]TRIAZOLO[3,4-i]PURIN-5-ONE DERIVATIVES

Publications (1)

Publication Number	Publication Date
UA73513C2 true UA73513C2 (en)	2005-08-15

Family

ID=8309393

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
UA2002010660A UA73513C2 (en)	1999-07-27	2000-07-24	8-PHENYL-6,9 ûDIHYDRO- [1,2,4] TRIAZOLO [3,4-I] PURIN û5-ON DERIVATIVES, A METHOD FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION BASED THEREON

Country Status (34)

Country	Link
US (1)	US7034016B2 (de)
EP (1)	EP1198464B1 (de)
JP (1)	JP2003505461A (de)
KR (1)	KR20020022786A (de)
CN (1)	CN1198825C (de)
AR (1)	AR024969A1 (de)
AT (1)	ATE251625T1 (de)
AU (1)	AU777571B2 (de)
BG (1)	BG106346A (de)
BR (1)	BR0012764A (de)
CA (1)	CA2380181A1 (de)
CO (1)	CO5190717A1 (de)
CZ (1)	CZ2002311A3 (de)
DE (1)	DE60005838T2 (de)
DK (1)	DK1198464T3 (de)
EE (1)	EE200200046A (de)
ES (2)	ES2166270B1 (de)
HK (1)	HK1044332B (de)
HU (1)	HUP0202103A3 (de)
IL (1)	IL147770A0 (de)
MY (1)	MY129590A (de)
NO (1)	NO20020391L (de)
NZ (1)	NZ516780A (de)
PE (1)	PE20010401A1 (de)
PL (1)	PL353827A1 (de)
PT (1)	PT1198464E (de)
RU (1)	RU2258705C2 (de)
SK (1)	SK1352002A3 (de)
TR (1)	TR200200785T2 (de)
TW (1)	TW568912B (de)
UA (1)	UA73513C2 (de)
UY (1)	UY26258A1 (de)
WO (1)	WO2001007441A1 (de)
ZA (1)	ZA200200561B (de)

Families Citing this family (36)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN1127506C (zh) *	2001-06-29	2003-11-12	刘宝顺	一种治疗阳痿的新化合物
US7407955B2 (en)	2002-08-21	2008-08-05	Boehringer Ingelheim Pharma Gmbh & Co., Kg	8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions
SE0300917D0 (sv)	2003-03-31	2003-03-31	St Jude Medical	Multi-chamber pacing system
JP2007501866A (ja) *	2003-06-13	2007-02-01	マイクロバイアインコーポレイテッド	胃腸疾患の治療のための方法および組成物
US7501426B2 (en)	2004-02-18	2009-03-10	Boehringer Ingelheim International Gmbh	8-[3-amino-piperidin-1-yl]-xanthines, their preparation and their use as pharmaceutical compositions
AU2005243192A1 (en) *	2004-04-29	2005-11-24	Merck & Co., Inc.	Azetidine glycine transporter inhibitors
DE102004054054A1 (de)	2004-11-05	2006-05-11	Boehringer Ingelheim Pharma Gmbh & Co. Kg	Verfahren zur Herstellung chiraler 8-(3-Amino-piperidin-1-yl)-xanthine
JP2008520679A (ja) *	2004-11-18	2008-06-19	シェーリングコーポレイション	うっ血性心不全の処置のためにｐｄｅｖインヒビターを使用する方法
DE102005035891A1 (de)	2005-07-30	2007-02-08	Boehringer Ingelheim Pharma Gmbh & Co. Kg	8-(3-Amino-piperidin-1-yl)-xanthine, deren Herstellung und deren Verwendung als Arzneimittel
EP2540725A1 (de)	2006-05-04	2013-01-02	Boehringer Ingelheim International GmbH	Polymorphe von 1-((4-Methyl-chinazolin-2-yl)methyl)-3-methyl-7-(2-butin-1-yl)-8-(3-(R)-amino-piperidin-1-yl)xanthin
PE20080251A1 (es)	2006-05-04	2008-04-25	Boehringer Ingelheim Int	Usos de inhibidores de dpp iv
EP1852108A1 (de)	2006-05-04	2007-11-07	Boehringer Ingelheim Pharma GmbH & Co.KG	Zusammensetzungen von DPP-IV-Inhibitoren
PE20091730A1 (es)	2008-04-03	2009-12-10	Boehringer Ingelheim Int	Formulaciones que comprenden un inhibidor de dpp4
BRPI0916997A2 (pt)	2008-08-06	2020-12-15	Boehringer Ingelheim International Gmbh	Inibidor de dpp-4 e seu uso
UY32030A (es)	2008-08-06	2010-03-26	Boehringer Ingelheim Int	"tratamiento para diabetes en pacientes inapropiados para terapia con metformina"
CN102149407A (zh)	2008-09-10	2011-08-10	贝林格尔.英格海姆国际有限公司	治疗糖尿病和相关病症的组合疗法
US20200155558A1 (en)	2018-11-20	2020-05-21	Boehringer Ingelheim International Gmbh	Treatment for diabetes in patients with insufficient glycemic control despite therapy with an oral antidiabetic drug
CN102256976A (zh)	2008-12-23	2011-11-23	贝林格尔.英格海姆国际有限公司	有机化合物的盐形式
AR074990A1 (es)	2009-01-07	2011-03-02	Boehringer Ingelheim Int	Tratamiento de diabetes en pacientes con un control glucemico inadecuado a pesar de la terapia con metformina
KR20240090632A (ko)	2009-11-27	2024-06-21	베링거 인겔하임 인터내셔날 게엠베하	리나글립틴과 같은 ｄｐｐ－ｉｖ 억제제를 사용한 유전자형 검사된 당뇨병 환자의 치료
CN102946875A (zh)	2010-05-05	2013-02-27	贝林格尔.英格海姆国际有限公司	组合疗法
WO2011161161A1 (en)	2010-06-24	2011-12-29	Boehringer Ingelheim International Gmbh	Diabetes therapy
AR083878A1 (es)	2010-11-15	2013-03-27	Boehringer Ingelheim Int	Terapia antidiabetica vasoprotectora y cardioprotectora, linagliptina, metodo de tratamiento
US8883800B2 (en)	2011-07-15	2014-11-11	Boehringer Ingelheim International Gmbh	Substituted quinazolines, the preparation thereof and the use thereof in pharmaceutical compositions
US9555001B2 (en)	2012-03-07	2017-01-31	Boehringer Ingelheim International Gmbh	Pharmaceutical composition and uses thereof
JP6218811B2 (ja)	2012-05-14	2017-10-25	ベーリンガーインゲルハイムインターナショナルゲゼルシャフトミットベシュレンクテルハフツング	Ｓｉｒｓ及び／又は敗血症の治療に用いるｄｐｐ−４阻害薬としてのキサンチン誘導体
JP6224084B2 (ja)	2012-05-14	2017-11-01	ベーリンガーインゲルハイムインターナショナルゲゼルシャフトミットベシュレンクテルハフツング	糸球体上皮細胞関連障害及び／又はネフローゼ症候群の治療に用いるｄｐｐ−４阻害薬としてのキサンチン誘導体
WO2013174767A1 (en)	2012-05-24	2013-11-28	Boehringer Ingelheim International Gmbh	A xanthine derivative as dpp -4 inhibitor for use in modifying food intake and regulating food preference
CA2877146C (en)	2012-06-18	2020-10-20	Dart Neuroscience (Cayman) Ltd	Substituted thiophene- and furan-fused azolopyrimidine-5-(6h)-one compounds
EP3110449B1 (de)	2014-02-28	2023-06-28	Boehringer Ingelheim International GmbH	Medizinische verwendung eines dpp-4-inhibitors
CN109310697A (zh)	2016-06-10	2019-02-05	勃林格殷格翰国际有限公司	利格列汀和二甲双胍的组合
IL275817B2 (en) *	2018-01-04	2024-04-01	Impetis Biosciences Ltd	Tricyclic compounds, compositions and medicinal applications thereof
US20210347778A1 (en) *	2018-08-30	2021-11-11	Tera Stone Co., Ltd	Hydrazinopurine compound and triazolopurine compound for inhibiting xanthine oxidase
CN112225761B (zh) *	2020-12-16	2021-03-12	南京颐媛生物医学研究院有限公司	一种嘧啶并三氮唑及其合成方法
CN116964055A (zh) *	2021-03-09	2023-10-27	巴斯夫欧洲公司	杀害虫的三环化合物
BR112023018040A2 (pt) *	2021-03-09	2023-10-03	Basf Se	Compostos, uso dos compostos, mistura pesticida, composições agroquímicas ou veterinárias, métodos para controlar pragas invertebradas e semente

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4593095A (en) *	1983-02-18	1986-06-03	The Johns Hopkins University	Xanthine derivatives
DE3347290A1 (de)	1983-12-28	1985-07-11	Dr. Karl Thomae Gmbh, 7950 Biberach	Neue 2-phenyl-imidazole, ihre herstellung und diese verbindungen enthaltende arzneimittel
DK0417790T3 (da) *	1989-09-14	1997-04-07	Kyowa Hakko Kogyo Kk	S-triazolo(3,4-i)purin-derivater
GB9013750D0 (en) *	1990-06-20	1990-08-08	Pfizer Ltd	Therapeutic agents
NZ238609A (en) *	1990-06-21	1993-12-23	Schering Corp	Polycyclic guanine derivatives; preparation, pharmaceutical compositions,
US5990118A (en) *	1995-02-21	1999-11-23	Yamasa Corporation	Purine compounds and xanthine oxidase inhibitors
US6723719B1 (en) *	1997-04-25	2004-04-20	Pfizer Inc	Pyrazolopyrimidinones which inhibit type 5 cyclic guanosine 3′,5′—monophosphate phosphodiesterase (cGMP PDE5) for the treatment of sexual dysfunction
AU4501199A (en) *	1998-06-03	1999-12-20	Almirall Prodesfarma S.A.	8-phenylxanthine derivatives and their use as phosphodiesterase inhibitors
US7060824B2 (en) *	2000-08-09	2006-06-13	Almirall Prodesfarma, S.A.	Pyrrolotriazolopyrimidinone derivatives

1999
- 1999-07-27 ES ES009901694A patent/ES2166270B1/es not_active Expired - Fee Related
2000
- 2000-07-24 BR BR0012764-7A patent/BR0012764A/pt not_active IP Right Cessation
- 2000-07-24 DE DE60005838T patent/DE60005838T2/de not_active Expired - Lifetime
- 2000-07-24 CN CNB008130760A patent/CN1198825C/zh not_active Expired - Fee Related
- 2000-07-24 TR TR2002/00785T patent/TR200200785T2/xx unknown
- 2000-07-24 WO PCT/EP2000/007062 patent/WO2001007441A1/en not_active Ceased
- 2000-07-24 EE EEP200200046A patent/EE200200046A/xx unknown
- 2000-07-24 DK DK00949400T patent/DK1198464T3/da active
- 2000-07-24 CZ CZ2002311A patent/CZ2002311A3/cs unknown
- 2000-07-24 UA UA2002010660A patent/UA73513C2/uk unknown
- 2000-07-24 SK SK135-2002A patent/SK1352002A3/sk unknown
- 2000-07-24 PT PT00949400T patent/PT1198464E/pt unknown
- 2000-07-24 ES ES00949400T patent/ES2208378T3/es not_active Expired - Lifetime
- 2000-07-24 NZ NZ516780A patent/NZ516780A/en unknown
- 2000-07-24 AT AT00949400T patent/ATE251625T1/de not_active IP Right Cessation
- 2000-07-24 PE PE2000000742A patent/PE20010401A1/es not_active Application Discontinuation
- 2000-07-24 AU AU62772/00A patent/AU777571B2/en not_active Ceased
- 2000-07-24 CA CA002380181A patent/CA2380181A1/en not_active Abandoned
- 2000-07-24 HU HU0202103A patent/HUP0202103A3/hu unknown
- 2000-07-24 PL PL00353827A patent/PL353827A1/xx not_active Application Discontinuation
- 2000-07-24 KR KR1020027001155A patent/KR20020022786A/ko not_active Ceased
- 2000-07-24 IL IL14777000A patent/IL147770A0/xx unknown
- 2000-07-24 JP JP2001512525A patent/JP2003505461A/ja not_active Withdrawn
- 2000-07-24 EP EP00949400A patent/EP1198464B1/de not_active Expired - Lifetime
- 2000-07-24 HK HK02103667.4A patent/HK1044332B/en not_active IP Right Cessation
- 2000-07-24 RU RU2002104935/04A patent/RU2258705C2/ru not_active IP Right Cessation
- 2000-07-26 TW TW089114927A patent/TW568912B/zh active
- 2000-07-26 CO CO00056184A patent/CO5190717A1/es not_active Application Discontinuation
- 2000-07-26 MY MYPI20003424A patent/MY129590A/en unknown
- 2000-07-27 UY UY26258A patent/UY26258A1/es not_active Application Discontinuation
- 2000-07-27 AR ARP000103896A patent/AR024969A1/es not_active Application Discontinuation
2002
- 2002-01-22 ZA ZA200200561A patent/ZA200200561B/en unknown
- 2002-01-24 BG BG06346A patent/BG106346A/xx unknown
- 2002-01-25 US US10/057,847 patent/US7034016B2/en not_active Expired - Fee Related
- 2002-01-25 NO NO20020391A patent/NO20020391L/no unknown

Also Published As

Publication number	Publication date
ES2208378T3 (es)	2004-06-16
TW568912B (en)	2004-01-01
DE60005838T2 (de)	2004-08-19
ZA200200561B (en)	2003-06-25
HK1044332B (en)	2004-10-15
CN1198825C (zh)	2005-04-27
EP1198464B1 (de)	2003-10-08
ES2166270B1 (es)	2003-04-01
NO20020391L (no)	2002-03-25
US20030060627A1 (en)	2003-03-27
CO5190717A1 (es)	2002-08-29
CZ2002311A3 (cs)	2003-01-15
CN1374962A (zh)	2002-10-16
AU6277200A (en)	2001-02-13
HK1044332A1 (en)	2002-10-18
TR200200785T2 (tr)	2002-09-23
US7034016B2 (en)	2006-04-25
BR0012764A (pt)	2002-07-02
ATE251625T1 (de)	2003-10-15
RU2258705C2 (ru)	2005-08-20
AU777571B2 (en)	2004-10-21
AR024969A1 (es)	2002-10-30
JP2003505461A (ja)	2003-02-12
IL147770A0 (en)	2002-08-14
DK1198464T3 (da)	2004-02-16
SK1352002A3 (en)	2003-04-01
MY129590A (en)	2007-04-30
HUP0202103A2 (en)	2002-10-28
ES2166270A1 (es)	2002-04-01
CA2380181A1 (en)	2001-02-01
NO20020391D0 (no)	2002-01-25
EP1198464A1 (de)	2002-04-24
PE20010401A1 (es)	2001-04-16
PL353827A1 (en)	2003-12-01
NZ516780A (en)	2004-01-30
KR20020022786A (ko)	2002-03-27
HUP0202103A3 (en)	2004-12-28
WO2001007441A1 (en)	2001-02-01
UY26258A1 (es)	2000-12-29
DE60005838D1 (de)	2003-11-13
BG106346A (en)	2002-09-30
PT1198464E (pt)	2004-02-27
EE200200046A (et)	2003-04-15

Publication	Publication Date	Title
UA73513C2 (en)	2005-08-15	8-PHENYL-6,9 ûDIHYDRO- [1,2,4] TRIAZOLO [3,4-I] PURIN û5-ON DERIVATIVES, A METHOD FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION BASED THEREON
JP4205168B2 (ja)	2009-01-07	ピリミジン誘導体およびその製造法
AU2010230290B2 (en)	2013-03-14	1-heterocyclyl-1, 5-dihydro-pyrazolo [3, 4-d] pyrimidin-4-one derivatives and their use as PDE9A modulators
BRPI0910690B1 (pt)	2020-10-20	derivados de 1-heterociclil-1,5-di-hidro-pirazolo[3,4-d]pirimidin-4-ona
EP1286997B1 (de)	2004-08-18	6-phenylpyrrolopyrimidindion derivate
EP1492793B1 (de)	2008-01-16	4-(pyrrolopyrimidin-6-yl)benzolsulfonamidderivate
EP1097153B1 (de)	2003-10-01	Triazolo[4,5-d]pyrimidin-verbindungen
EP1307458B1 (de)	2007-10-03	Pyrrolotriazolopyrimidinonderivate
NZ711522A (en)	2021-02-26	6-(5-hydroxy-1h-pyrazol-1-yl)nicotinamide derivatives and their use as phd inhibitors