IL104066A

IL104066A - History of pyridyl, their preparation and pharmaceutical preparations containing them

History of pyridyl, their preparation and pharmaceutical preparations containing them

Info

Publication number: IL104066A
Authority: IL; Israel
Prior art keywords: group; pyridyl; phenyl; hex; formula
Prior art date: 1991-12-14

Application number

IL10406692A

Other languages

English (en)

Hebrew (he)

Other versions

IL104066A0 (en

Original Assignee

Thomae Gmbh Dr K

Priority date

1991-12-14

Filing date

1992-12-11

Publication date

1996-07-23

1991-12-14 Priority claimed from DE4141377A external-priority patent/DE4141377A1/de

1992-12-11 Application filed by Thomae Gmbh Dr K filed Critical Thomae Gmbh Dr K

1993-05-13 Publication of IL104066A0 publication Critical patent/IL104066A0/xx

1996-07-23 Publication of IL104066A publication Critical patent/IL104066A/en

Links

125000004076 pyridyl group Chemical group 0.000 title claims abstract description 12
238000002360 preparation method Methods 0.000 title claims description 20
239000008194 pharmaceutical composition Substances 0.000 title claims description 7
150000001875 compounds Chemical class 0.000 claims abstract description 127
125000000217 alkyl group Chemical group 0.000 claims abstract description 25
125000003545 alkoxy group Chemical group 0.000 claims abstract description 23
239000011203 carbon fibre reinforced carbon Substances 0.000 claims abstract description 14
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 14
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims abstract description 12
230000001404 mediated effect Effects 0.000 claims abstract description 11
125000004414 alkyl thio group Chemical group 0.000 claims abstract description 10
125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims abstract description 10
RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 claims abstract description 9
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract description 8
229960002986 dinoprostone Drugs 0.000 claims abstract description 8
XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 claims abstract description 8
XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 claims abstract description 7
238000004519 manufacturing process Methods 0.000 claims abstract description 7
229910052740 iodine Inorganic materials 0.000 claims abstract description 4
-1 nitromethylene group Chemical group 0.000 claims description 222
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 126
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 61
150000003839 salts Chemical class 0.000 claims description 40
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 30
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 23
238000000034 method Methods 0.000 claims description 22
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 14
229910052739 hydrogen Inorganic materials 0.000 claims description 14
239000001257 hydrogen Substances 0.000 claims description 14
239000000126 substance Substances 0.000 claims description 14
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 13
125000004892 2-methylpropylamino group Chemical group CC(CN*)C 0.000 claims description 12
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
239000000460 chlorine Substances 0.000 claims description 9
229910052801 chlorine Inorganic materials 0.000 claims description 9
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
230000008569 process Effects 0.000 claims description 9
125000003831 tetrazolyl group Chemical group 0.000 claims description 9
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
229940099471 Phosphodiesterase inhibitor Drugs 0.000 claims description 8
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 8
239000003795 chemical substances by application Substances 0.000 claims description 8
125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 8
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
238000011282 treatment Methods 0.000 claims description 8
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
125000004432 carbon atom Chemical group C* 0.000 claims description 7
229910052731 fluorine Inorganic materials 0.000 claims description 7
239000011737 fluorine Substances 0.000 claims description 7
230000002265 prevention Effects 0.000 claims description 7
125000002030 1,2-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([*:2])C([H])=C1[H] 0.000 claims description 6
239000005977 Ethylene Substances 0.000 claims description 6
150000001412 amines Chemical class 0.000 claims description 6
230000032050 esterification Effects 0.000 claims description 6
238000005886 esterification reaction Methods 0.000 claims description 6
125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 6
238000001727 in vivo Methods 0.000 claims description 6
229910052757 nitrogen Inorganic materials 0.000 claims description 6
125000006239 protecting group Chemical group 0.000 claims description 6
SWLNUQSMWKYMJE-UFFVCSGVSA-N (e)-6-[3-[[n-cyano-n'-(2-methylpropyl)carbamimidoyl]amino]phenyl]-6-pyridin-3-ylhex-5-enoic acid Chemical compound CC(C)C\N=C(\NC#N)NC1=CC=CC(C(=C/CCCC(O)=O)\C=2C=NC=CC=2)=C1 SWLNUQSMWKYMJE-UFFVCSGVSA-N 0.000 claims description 5
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 5
125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
206010003210 Arteriosclerosis Diseases 0.000 claims description 5
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims description 5
229930105110 Cyclosporin A Natural products 0.000 claims description 5
108010036949 Cyclosporine Proteins 0.000 claims description 5
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
206010027476 Metastases Diseases 0.000 claims description 5
206010052779 Transplant rejections Diseases 0.000 claims description 5
208000011775 arteriosclerosis disease Diseases 0.000 claims description 5
208000006673 asthma Diseases 0.000 claims description 5
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
229960001265 ciclosporin Drugs 0.000 claims description 5
229930182912 cyclosporin Natural products 0.000 claims description 5
230000018044 dehydration Effects 0.000 claims description 5
238000006297 dehydration reaction Methods 0.000 claims description 5
230000010339 dilation Effects 0.000 claims description 5
208000035475 disorder Diseases 0.000 claims description 5
230000007062 hydrolysis Effects 0.000 claims description 5
238000006460 hydrolysis reaction Methods 0.000 claims description 5
208000028867 ischemia Diseases 0.000 claims description 5
208000017169 kidney disease Diseases 0.000 claims description 5
230000002934 lysing effect Effects 0.000 claims description 5
231100000417 nephrotoxicity Toxicity 0.000 claims description 5
125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
230000035939 shock Effects 0.000 claims description 5
230000009424 thromboembolic effect Effects 0.000 claims description 5
125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
125000004897 3-methylbutylamino group Chemical group CC(CCN*)C 0.000 claims description 4
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 4
206010020751 Hypersensitivity Diseases 0.000 claims description 4
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
125000003282 alkyl amino group Chemical group 0.000 claims description 4
230000007815 allergy Effects 0.000 claims description 4
125000004663 dialkyl amino group Chemical group 0.000 claims description 4
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 4
JUINSXZKUKVTMD-UHFFFAOYSA-N hydrogen azide Chemical compound N=[N+]=[N-] JUINSXZKUKVTMD-UHFFFAOYSA-N 0.000 claims description 4
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 4
229910052727 yttrium Inorganic materials 0.000 claims description 4
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
230000009435 amidation Effects 0.000 claims description 3
238000007112 amidation reaction Methods 0.000 claims description 3
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
229910052794 bromium Inorganic materials 0.000 claims description 3
201000010099 disease Diseases 0.000 claims description 3
239000003814 drug Substances 0.000 claims description 3
238000007327 hydrogenolysis reaction Methods 0.000 claims description 3
125000004130 indan-2-yl group Chemical group [H]C1=C([H])C([H])=C2C(=C1[H])C([H])([H])C([H])(*)C2([H])[H] 0.000 claims description 3
150000007522 mineralic acids Chemical class 0.000 claims description 3
150000007524 organic acids Chemical class 0.000 claims description 3
239000000546 pharmaceutical excipient Substances 0.000 claims description 3
238000007127 saponification reaction Methods 0.000 claims description 3
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 2
125000005236 alkanoylamino group Chemical group 0.000 claims description 2
125000001246 bromo group Chemical group Br* 0.000 claims description 2
125000001589 carboacyl group Chemical group 0.000 claims description 2
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
125000000490 cinnamyl group Chemical group C(C=CC1=CC=CC=C1)* 0.000 claims description 2
208000030499 combat disease Diseases 0.000 claims description 2
125000004122 cyclic group Chemical group 0.000 claims description 2
ARUKYTASOALXFG-UHFFFAOYSA-N cycloheptylcycloheptane Chemical group C1CCCCCC1C1CCCCCC1 ARUKYTASOALXFG-UHFFFAOYSA-N 0.000 claims description 2
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
125000001153 fluoro group Chemical group F* 0.000 claims description 2
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 2
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
238000011321 prophylaxis Methods 0.000 claims description 2
125000001424 substituent group Chemical group 0.000 claims description 2
238000001149 thermolysis Methods 0.000 claims description 2
DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 claims 2
239000000969 carrier Substances 0.000 claims 1
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims 1
230000001225 therapeutic effect Effects 0.000 claims 1
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 abstract description 12
230000000694 effects Effects 0.000 abstract description 9
230000002785 anti-thrombosis Effects 0.000 abstract description 4
230000000144 pharmacologic effect Effects 0.000 abstract description 4
230000015572 biosynthetic process Effects 0.000 abstract description 3
239000003112 inhibitor Substances 0.000 abstract description 3
PXGPLTODNUVGFL-BRIYLRKRSA-N (E,Z)-(1R,2R,3R,5S)-7-(3,5-Dihydroxy-2-((3S)-(3-hydroxy-1-octenyl))cyclopentyl)-5-heptenoic acid Chemical compound CCCCC[C@H](O)C=C[C@H]1[C@H](O)C[C@H](O)[C@@H]1CC=CCCCC(O)=O PXGPLTODNUVGFL-BRIYLRKRSA-N 0.000 abstract description 2
102100029100 Hematopoietic prostaglandin D synthase Human genes 0.000 abstract description 2
101000988802 Homo sapiens Hematopoietic prostaglandin D synthase Proteins 0.000 abstract description 2
239000005557 antagonist Substances 0.000 abstract description 2
210000004072 lung Anatomy 0.000 abstract description 2
BHMBVRSPMRCCGG-OUTUXVNYSA-N prostaglandin D2 Chemical compound CCCCC[C@H](O)\C=C\[C@@H]1[C@@H](C\C=C/CCCC(O)=O)[C@@H](O)CC1=O BHMBVRSPMRCCGG-OUTUXVNYSA-N 0.000 abstract description 2
BHMBVRSPMRCCGG-UHFFFAOYSA-N prostaglandine D2 Natural products CCCCCC(O)C=CC1C(CC=CCCCC(O)=O)C(O)CC1=O BHMBVRSPMRCCGG-UHFFFAOYSA-N 0.000 abstract description 2
238000003786 synthesis reaction Methods 0.000 abstract description 2
XEYBRNLFEZDVAW-DODZYUBVSA-N 7-[(1R,2R,3R)-3-hydroxy-2-[(3S)-3-hydroxyoct-1-enyl]-5-oxocyclopentyl]-5-heptenoic acid Chemical compound CCCCC[C@H](O)C=C[C@H]1[C@H](O)CC(=O)[C@@H]1CC=CCCCC(O)=O XEYBRNLFEZDVAW-DODZYUBVSA-N 0.000 abstract 1
239000000543 intermediate Substances 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 390
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 210
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 209
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 123
238000002844 melting Methods 0.000 description 108
230000008018 melting Effects 0.000 description 108
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 74
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 73
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 71
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 67
239000000741 silica gel Substances 0.000 description 58
229910002027 silica gel Inorganic materials 0.000 description 58
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 57
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 47
239000000243 solution Substances 0.000 description 43
239000011541 reaction mixture Substances 0.000 description 39
239000000203 mixture Substances 0.000 description 34
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 33
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 29
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
239000002904 solvent Substances 0.000 description 29
239000008346 aqueous phase Substances 0.000 description 26
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 26
238000006243 chemical reaction Methods 0.000 description 24
239000003826 tablet Substances 0.000 description 22
239000013543 active substance Substances 0.000 description 21
235000015165 citric acid Nutrition 0.000 description 19
239000006260 foam Substances 0.000 description 19
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
239000003921 oil Substances 0.000 description 18
239000000284 extract Substances 0.000 description 17
239000002253 acid Substances 0.000 description 16
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
239000000725 suspension Substances 0.000 description 15
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 14
OMOVVBIIQSXZSZ-UHFFFAOYSA-N [6-(4-acetyloxy-5,9a-dimethyl-2,7-dioxo-4,5a,6,9-tetrahydro-3h-pyrano[3,4-b]oxepin-5-yl)-5-formyloxy-3-(furan-3-yl)-3a-methyl-7-methylidene-1a,2,3,4,5,6-hexahydroindeno[1,7a-b]oxiren-4-yl] 2-hydroxy-3-methylpentanoate Chemical compound CC12C(OC(=O)C(O)C(C)CC)C(OC=O)C(C3(C)C(CC(=O)OC4(C)COC(=O)CC43)OC(C)=O)C(=C)C32OC3CC1C=1C=COC=1 OMOVVBIIQSXZSZ-UHFFFAOYSA-N 0.000 description 14
235000011167 hydrochloric acid Nutrition 0.000 description 14
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 13
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 13
IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical compound C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 description 13
235000019359 magnesium stearate Nutrition 0.000 description 13
239000001117 sulphuric acid Substances 0.000 description 13
235000011149 sulphuric acid Nutrition 0.000 description 13
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
229960002768 dipyridamole Drugs 0.000 description 12
239000012074 organic phase Substances 0.000 description 12
239000001267 polyvinylpyrrolidone Substances 0.000 description 11
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 11
229920000036 polyvinylpyrrolidone Polymers 0.000 description 11
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 description 10
229960000583 acetic acid Drugs 0.000 description 10
239000002585 base Substances 0.000 description 10
239000002775 capsule Substances 0.000 description 10
XUDOZULIAWNMIU-UHFFFAOYSA-N delta-hexenoic acid Chemical compound OC(=O)CCCC=C XUDOZULIAWNMIU-UHFFFAOYSA-N 0.000 description 10
239000008188 pellet Substances 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
229920002261 Corn starch Polymers 0.000 description 9
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
239000008120 corn starch Substances 0.000 description 9
229960004132 diethyl ether Drugs 0.000 description 9
239000007858 starting material Substances 0.000 description 9
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
KDSNLYIMUZNERS-UHFFFAOYSA-N 2-methylpropanamine Chemical compound CC(C)CN KDSNLYIMUZNERS-UHFFFAOYSA-N 0.000 description 8
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 8
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 8
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 8
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
238000001704 evaporation Methods 0.000 description 8
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