IL106135A - Nicotinic acid esters and pharmaceutical compositions containing them - Google Patents
Nicotinic acid esters and pharmaceutical compositions containing themInfo
- Publication number
- IL106135A IL106135A IL10613593A IL10613593A IL106135A IL 106135 A IL106135 A IL 106135A IL 10613593 A IL10613593 A IL 10613593A IL 10613593 A IL10613593 A IL 10613593A IL 106135 A IL106135 A IL 106135A
- Authority
- IL
- Israel
- Prior art keywords
- group
- formula
- compound
- compounds
- general formula
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 4
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical class OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 58
- 150000003839 salts Chemical class 0.000 claims abstract description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 10
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 9
- 150000002367 halogens Chemical class 0.000 claims abstract description 9
- 210000003169 central nervous system Anatomy 0.000 claims abstract description 8
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 6
- 239000001257 hydrogen Substances 0.000 claims abstract description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 5
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 5
- 125000004950 trifluoroalkyl group Chemical group 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 9
- 239000004480 active ingredient Substances 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- 241001465754 Metazoa Species 0.000 claims description 4
- 238000006555 catalytic reaction Methods 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 claims description 3
- 239000013543 active substance Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims 2
- 229920006395 saturated elastomer Polymers 0.000 abstract 2
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 1
- 150000002391 heterocyclic compounds Chemical class 0.000 abstract 1
- 125000004417 unsaturated alkyl group Chemical group 0.000 abstract 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 208000020016 psychiatric disease Diseases 0.000 description 6
- 102000056834 5-HT2 Serotonin Receptors Human genes 0.000 description 5
- 108091005479 5-HT2 receptors Proteins 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 102000017911 HTR1A Human genes 0.000 description 4
- 101150015707 HTR1A gene Proteins 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical compound C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 102100022738 5-hydroxytryptamine receptor 1A Human genes 0.000 description 3
- 101710138638 5-hydroxytryptamine receptor 1A Proteins 0.000 description 3
- 208000019901 Anxiety disease Diseases 0.000 description 3
- 208000028017 Psychotic disease Diseases 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- -1 acetic Chemical class 0.000 description 3
- 230000036506 anxiety Effects 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- QWCRAEMEVRGPNT-UHFFFAOYSA-N buspirone Chemical compound C1C(=O)N(CCCCN2CCN(CC2)C=2N=CC=CN=2)C(=O)CC21CCCC2 QWCRAEMEVRGPNT-UHFFFAOYSA-N 0.000 description 3
- 229960002495 buspirone Drugs 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 2
- XBLVHTDFJBKJLG-UHFFFAOYSA-N Ethyl nicotinate Chemical compound CCOC(=O)C1=CC=CN=C1 XBLVHTDFJBKJLG-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 230000000949 anxiolytic effect Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- XTKDAFGWCDAMPY-UHFFFAOYSA-N azaperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCN(C=2N=CC=CC=2)CC1 XTKDAFGWCDAMPY-UHFFFAOYSA-N 0.000 description 2
- 229950003616 azaperone Drugs 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 201000009032 substance abuse Diseases 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-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
- ZNDBZNGZPIYESD-UHFFFAOYSA-N (2-nitrophenyl) 2-[4-[4,4-bis(4-fluorophenyl)butyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound [O-][N+](=O)C1=CC=CC=C1OC(=O)C1=CC=CN=C1N1CCN(CCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 ZNDBZNGZPIYESD-UHFFFAOYSA-N 0.000 description 1
- BFBDBZSGOCPXOR-UHFFFAOYSA-N (4-carbamoylphenyl) 2-[4-[4,4-bis(4-fluorophenyl)butyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound C1=CC(C(=O)N)=CC=C1OC(=O)C1=CC=CN=C1N1CCN(CCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 BFBDBZSGOCPXOR-UHFFFAOYSA-N 0.000 description 1
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 1
- TZJUVVIWVWFLCD-UHFFFAOYSA-N 1,1-dioxo-2-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-1,2-benzothiazol-3-one Chemical compound O=S1(=O)C2=CC=CC=C2C(=O)N1CCCCN(CC1)CCN1C1=NC=CC=N1 TZJUVVIWVWFLCD-UHFFFAOYSA-N 0.000 description 1
- VQHQZLSZWREGDG-UHFFFAOYSA-N 2-chloro-4-ethylpyridine-3-carboxylic acid Chemical compound CCC1=CC=NC(Cl)=C1C(O)=O VQHQZLSZWREGDG-UHFFFAOYSA-N 0.000 description 1
- IBRSSZOHCGUTHI-UHFFFAOYSA-N 2-chloropyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=C1Cl IBRSSZOHCGUTHI-UHFFFAOYSA-N 0.000 description 1
- FPCCSQOGAWCVBH-PSQIVULCSA-N 3-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]-1,1,2,2-tetratritioethyl]-1h-quinazoline-2,4-dione Chemical compound O=C1NC2=CC=CC=C2C(=O)N1C([3H])([3H])C([3H])([3H])N(CC1)CCC1C(=O)C1=CC=C(F)C=C1 FPCCSQOGAWCVBH-PSQIVULCSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- VSBVUOFVKIBDGV-UHFFFAOYSA-N 3-methylbutyl 2-[4-[4,4-bis(4-fluorophenyl)butyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound CC(C)CCOC(=O)C1=CC=CN=C1N1CCN(CCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 VSBVUOFVKIBDGV-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
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 1
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 1
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical group NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
- 229940122957 Histamine H2 receptor antagonist Drugs 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
- 239000002841 Lewis acid Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 238000007126 N-alkylation reaction Methods 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 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
- 150000007513 acids Chemical class 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000005227 alkyl sulfonate group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- NNAIYOXJNVGUOM-UHFFFAOYSA-N amperozide Chemical compound C1CN(C(=O)NCC)CCN1CCCC(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 NNAIYOXJNVGUOM-UHFFFAOYSA-N 0.000 description 1
- 229950000388 amperozide Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 125000005228 aryl sulfonate group Chemical group 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- FFSAXUULYPJSKH-UHFFFAOYSA-N butyrophenone Chemical class CCCC(=O)C1=CC=CC=C1 FFSAXUULYPJSKH-UHFFFAOYSA-N 0.000 description 1
- 239000007963 capsule composition Substances 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- OCBVPTLPAJPWNO-UHFFFAOYSA-N cyclohexyl 2-[4-[4,4-bis(4-fluorophenyl)butyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCN1CCN(C=2C(=CC=CN=2)C(=O)OC2CCCCC2)CC1 OCBVPTLPAJPWNO-UHFFFAOYSA-N 0.000 description 1
- PVGDLMLIFWSWAD-UHFFFAOYSA-N cyclooctyl 2-[4-[4,4-bis(4-fluorophenyl)butyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCN1CCN(C=2C(=CC=CN=2)C(=O)OC2CCCCCCC2)CC1 PVGDLMLIFWSWAD-UHFFFAOYSA-N 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 235000019439 ethyl acetate Nutrition 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 229960002464 fluoxetine Drugs 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- MSQACBWWAIBWIC-UHFFFAOYSA-N hydron;piperazine;chloride Chemical compound Cl.C1CNCCN1 MSQACBWWAIBWIC-UHFFFAOYSA-N 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229950003599 ipsapirone Drugs 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940080435 lactose 250 mg Drugs 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- NDCPNKXUTJGQQC-UHFFFAOYSA-N methyl 2-[4-[4,4-bis(4-fluorophenyl)butyl]piperazin-1-yl]pyridine-3-carboxylate Chemical compound COC(=O)C1=CC=CN=C1N1CCN(CCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 NDCPNKXUTJGQQC-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 239000003176 neuroleptic agent Substances 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- 229960002296 paroxetine Drugs 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229940001470 psychoactive drug Drugs 0.000 description 1
- 239000004089 psychotropic agent Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- JUQLTPCYUFPYKE-UHFFFAOYSA-N ritanserin Chemical compound CC=1N=C2SC=CN2C(=O)C=1CCN(CC1)CCC1=C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 JUQLTPCYUFPYKE-UHFFFAOYSA-N 0.000 description 1
- 229950009626 ritanserin Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 230000000862 serotonergic effect Effects 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 239000003772 serotonin uptake inhibitor Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 231100000736 substance abuse Toxicity 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
Landscapes
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9201956A SE9201956D0 (sv) | 1992-06-25 | 1992-06-25 | Novel nicotinicacid esters |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL106135A0 IL106135A0 (en) | 1993-10-20 |
| IL106135A true IL106135A (en) | 1999-01-26 |
Family
ID=20386602
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL10613593A IL106135A (en) | 1992-06-25 | 1993-06-24 | Nicotinic acid esters and pharmaceutical compositions containing them |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US5658910A (fi) |
| EP (2) | EP1120410B1 (fi) |
| JP (1) | JP3306827B2 (fi) |
| KR (1) | KR100302216B1 (fi) |
| CN (1) | CN1085981C (fi) |
| AT (2) | ATE209634T1 (fi) |
| AU (1) | AU681346B2 (fi) |
| BG (1) | BG62000B1 (fi) |
| CA (1) | CA2139112C (fi) |
| CZ (1) | CZ281975B6 (fi) |
| DE (2) | DE69331234T2 (fi) |
| DK (1) | DK0673368T3 (fi) |
| EE (1) | EE03122B1 (fi) |
| ES (1) | ES2169044T3 (fi) |
| FI (1) | FI107151B (fi) |
| HU (2) | HU220613B1 (fi) |
| IL (1) | IL106135A (fi) |
| NO (1) | NO302945B1 (fi) |
| NZ (1) | NZ253823A (fi) |
| PH (1) | PH31417A (fi) |
| PT (1) | PT673368E (fi) |
| RO (1) | RO115725B1 (fi) |
| RU (1) | RU2127732C1 (fi) |
| SE (1) | SE9201956D0 (fi) |
| SK (1) | SK279393B6 (fi) |
| WO (1) | WO1994000434A1 (fi) |
| ZA (1) | ZA934596B (fi) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6632823B1 (en) * | 1997-12-22 | 2003-10-14 | Merck & Co., Inc. | Substituted pyridine compounds useful as modulators of acetylcholine receptors |
| US7045519B2 (en) * | 1998-06-19 | 2006-05-16 | Chiron Corporation | Inhibitors of glycogen synthase kinase 3 |
| AU4956699A (en) | 1998-06-19 | 2000-01-05 | Chiron Corporation | Inhibitors of glycogen synthase kinase 3 |
| AU2019265268C1 (en) | 2018-05-09 | 2022-08-04 | Lg Chem, Ltd. | Novel compound exhibiting enteropeptidase inhibitory activity |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE8701375D0 (sv) * | 1987-04-02 | 1987-04-02 | Leo Ab | Novel pyridyl- and pyrimidyl derivatives |
| SE9201239D0 (sv) * | 1992-04-21 | 1992-04-21 | Kabi Pharmacia Ab | Agents for treating substance abuse disorders |
| SE9202265D0 (sv) * | 1992-07-31 | 1992-07-31 | Kabi Pharmacia Ab | Novel- pyridyl and pyrimidylpiperazine derivatives |
-
1992
- 1992-06-25 SE SE9201956A patent/SE9201956D0/xx unknown
-
1993
- 1993-06-23 DK DK93915075T patent/DK0673368T3/da active
- 1993-06-23 HU HU9403786A patent/HU220613B1/hu not_active IP Right Cessation
- 1993-06-23 WO PCT/SE1993/000565 patent/WO1994000434A1/en active IP Right Grant
- 1993-06-23 EP EP01108668A patent/EP1120410B1/en not_active Expired - Lifetime
- 1993-06-23 DE DE69331234T patent/DE69331234T2/de not_active Expired - Fee Related
- 1993-06-23 EP EP93915075A patent/EP0673368B1/en not_active Expired - Lifetime
- 1993-06-23 ES ES93915075T patent/ES2169044T3/es not_active Expired - Lifetime
- 1993-06-23 SK SK1585-94A patent/SK279393B6/sk not_active IP Right Cessation
- 1993-06-23 US US08/362,475 patent/US5658910A/en not_active Expired - Lifetime
- 1993-06-23 AT AT93915075T patent/ATE209634T1/de not_active IP Right Cessation
- 1993-06-23 NZ NZ253823A patent/NZ253823A/en not_active IP Right Cessation
- 1993-06-23 CZ CZ943274A patent/CZ281975B6/cs not_active IP Right Cessation
- 1993-06-23 KR KR1019940704643A patent/KR100302216B1/ko not_active Expired - Fee Related
- 1993-06-23 AT AT01108668T patent/ATE278671T1/de not_active IP Right Cessation
- 1993-06-23 JP JP50226894A patent/JP3306827B2/ja not_active Expired - Fee Related
- 1993-06-23 AU AU45193/93A patent/AU681346B2/en not_active Ceased
- 1993-06-23 CA CA002139112A patent/CA2139112C/en not_active Expired - Fee Related
- 1993-06-23 RO RO94-02087A patent/RO115725B1/ro unknown
- 1993-06-23 DE DE69333655T patent/DE69333655D1/de not_active Expired - Lifetime
- 1993-06-23 RU RU94046310A patent/RU2127732C1/ru not_active IP Right Cessation
- 1993-06-23 PT PT93915075T patent/PT673368E/pt unknown
- 1993-06-24 IL IL10613593A patent/IL106135A/en not_active IP Right Cessation
- 1993-06-25 ZA ZA934596A patent/ZA934596B/xx unknown
- 1993-06-25 CN CN93116250A patent/CN1085981C/zh not_active Expired - Fee Related
-
1994
- 1994-11-17 EE EE9400400A patent/EE03122B1/xx not_active IP Right Cessation
- 1994-12-22 BG BG99289A patent/BG62000B1/bg unknown
- 1994-12-23 FI FI946085A patent/FI107151B/fi active
- 1994-12-23 NO NO945022A patent/NO302945B1/no not_active IP Right Cessation
-
1995
- 1995-05-23 HU HU95P/P00139P patent/HU210875A9/hu unknown
-
1998
- 1998-06-24 PH PH4640898A patent/PH31417A/en unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2873025B2 (ja) | １‐［モノ―もしくはビス（トリフルオロメチル）‐２‐ピリジニル］ピペラジンを含有する薬剤組成物 | |
| JPH05502682A (ja) | ピペラジン誘導体 | |
| JP3068875B2 (ja) | アミン誘導体、その製造方法、心臓脈管疾患および症状を治療するための医薬 | |
| EP0361271B1 (en) | Pyridyl- and pyrimidyl derivatives | |
| DK161313B (da) | 4-(bis-fluorphenylbutyl)-1-(pyridyl- eller pyrimidinyl)-piperazin- eller -1,4-diazabicycloheptanforbindelser, fremgangsmaade til fremstilling deraf, farmaceutiske praeparater indeholdende disse samt anvendelse af forbindelserne | |
| FI88300C (fi) | Foerfarande foer framstaellning av nya terapeutiskt anvaendbara diazinylpiperidinderivat av cykliska amider och imider | |
| AU681346B2 (en) | Novel nicotinic acid esters | |
| US6326371B1 (en) | Pyrudyl and pyrimidylpiperazine derivatives | |
| GB2162843A (en) | Piperazine derivatives | |
| CA2053980A1 (en) | 4-[4- or 6-(trifluoromethyl-2-pyridinyl)]-1-piperazinyl-alkyl substituted lactams |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FF | Patent granted | ||
| KB | Patent renewed | ||
| HP | Change in proprietorship | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| MM9K | Patent not in force due to non-payment of renewal fees |