CA1305149C - Ester cyclique de l'acide dihydropyridine-5-phosphonique - Google Patents

Ester cyclique de l'acide dihydropyridine-5-phosphonique

Info

Publication number: CA1305149C
Authority: CA; Canada
Prior art keywords: compound; formula; isomer; optical isomer; positions
Prior art date: 1988-01-20
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Fee Related

Application number

CA000556958A

Other languages

English (en)

Inventor

Kiyotomo Seto

Yoshimasa Kamikawaji

Sakuya Tanaka

Ryozo Sakoda

Hiroo Matsumoto

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Nissan Chemical Corp

Original Assignee

Nissan Chemical Corp

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.)

1988-01-20

Filing date

1988-01-20

Publication date

1992-07-14

1988-01-20 Application filed by Nissan Chemical Corp filed Critical Nissan Chemical Corp

1988-01-20 Priority to CA000556958A priority Critical patent/CA1305149C/fr

1992-07-14 Application granted granted Critical

1992-07-14 Publication of CA1305149C publication Critical patent/CA1305149C/fr

2009-07-14 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

150000001875 compounds Chemical class 0.000 claims abstract description 41
230000003287 optical effect Effects 0.000 claims abstract description 23
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 19
HWSUUGHIDOOOOJ-UHFFFAOYSA-N dioxaphosphinane Chemical group C1COOPC1 HWSUUGHIDOOOOJ-UHFFFAOYSA-N 0.000 claims abstract description 11
150000003839 salts Chemical class 0.000 claims abstract description 11
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 5
229910052799 carbon Inorganic materials 0.000 claims abstract description 3
125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 claims abstract description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 55
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 34
239000000203 mixture Substances 0.000 claims description 26
239000000047 product Substances 0.000 claims description 9
238000000034 method Methods 0.000 claims description 6
239000002244 precipitate Substances 0.000 claims description 6
238000001816 cooling Methods 0.000 claims description 4
238000010438 heat treatment Methods 0.000 claims description 4
210000000056 organ Anatomy 0.000 claims description 3
229940124549 vasodilator Drugs 0.000 claims description 3
239000003071 vasodilator agent Substances 0.000 claims description 3
241000124008 Mammalia Species 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
201000010099 disease Diseases 0.000 claims description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
239000000706 filtrate Substances 0.000 claims description 2
238000001704 evaporation Methods 0.000 claims 1
238000001914 filtration Methods 0.000 claims 1
230000001376 precipitating effect Effects 0.000 claims 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
239000000243 solution Substances 0.000 description 19
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
239000002904 solvent Substances 0.000 description 14
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
229940022682 acetone Drugs 0.000 description 10
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
239000013078 crystal Substances 0.000 description 8
239000007858 starting material Substances 0.000 description 7
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
230000000694 effects Effects 0.000 description 6
150000002148 esters Chemical class 0.000 description 6
101150041968 CDC13 gene Proteins 0.000 description 5
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
238000009472 formulation Methods 0.000 description 5
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
230000036772 blood pressure Effects 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
230000000144 pharmacologic effect Effects 0.000 description 4
239000000843 powder Substances 0.000 description 4
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
241000699670 Mus sp. Species 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
239000002253 acid Substances 0.000 description 3
239000004480 active ingredient Substances 0.000 description 3
150000001412 amines Chemical class 0.000 description 3
230000003276 anti-hypertensive effect Effects 0.000 description 3
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
230000037396 body weight Effects 0.000 description 3
239000002775 capsule Substances 0.000 description 3
238000006243 chemical reaction Methods 0.000 description 3
239000004615 ingredient Substances 0.000 description 3
239000007788 liquid Substances 0.000 description 3
229960003512 nicotinic acid Drugs 0.000 description 3
239000011664 nicotinic acid Substances 0.000 description 3
238000010898 silica gel chromatography Methods 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
VJEODMSKVNBGGG-QWRGUYRKSA-N 3-[(4s,6s)-4,6-dimethyl-2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl]-4-(3-nitrophenyl)but-3-en-2-one Chemical compound O1[C@@H](C)C[C@H](C)OP1(=O)C(C(C)=O)=CC1=CC=CC([N+]([O-])=O)=C1 VJEODMSKVNBGGG-QWRGUYRKSA-N 0.000 description 2
YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 description 2
229920002261 Corn starch Polymers 0.000 description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
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 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
241000700159 Rattus Species 0.000 description 2
239000000443 aerosol Substances 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
239000008120 corn starch Substances 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
235000013355 food flavoring agent Nutrition 0.000 description 2
235000011187 glycerol Nutrition 0.000 description 2
239000012442 inert solvent Substances 0.000 description 2
229940090044 injection Drugs 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
239000008101 lactose Substances 0.000 description 2
235000019359 magnesium stearate Nutrition 0.000 description 2
229920000609 methyl cellulose Polymers 0.000 description 2
239000001923 methylcellulose Substances 0.000 description 2
235000010981 methylcellulose Nutrition 0.000 description 2
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
238000000746 purification Methods 0.000 description 2
210000000664 rectum Anatomy 0.000 description 2
239000012266 salt solution Substances 0.000 description 2
238000001228 spectrum Methods 0.000 description 2
239000000829 suppository Substances 0.000 description 2
210000001215 vagina Anatomy 0.000 description 2
GTCCGKPBSJZVRZ-RFZPGFLSSA-N (2r,4r)-pentane-2,4-diol Chemical compound C[C@@H](O)C[C@@H](C)O GTCCGKPBSJZVRZ-RFZPGFLSSA-N 0.000 description 1
GTCCGKPBSJZVRZ-WHFBIAKZSA-N (2s,4s)-pentane-2,4-diol Chemical compound C[C@H](O)C[C@H](C)O GTCCGKPBSJZVRZ-WHFBIAKZSA-N 0.000 description 1
GNWZQVMWSLTQMZ-PHDIDXHHSA-N (4r,6r)-2-methoxy-4,6-dimethyl-1,3,2-dioxaphosphinane Chemical compound COP1O[C@H](C)C[C@@H](C)O1 GNWZQVMWSLTQMZ-PHDIDXHHSA-N 0.000 description 1
UKVYVZLTGQVOPX-IHWYPQMZSA-N (z)-3-aminobut-2-enoic acid Chemical compound C\C(N)=C\C(O)=O UKVYVZLTGQVOPX-IHWYPQMZSA-N 0.000 description 1
RSZLLJSSNWEYJA-HTQZYQBOSA-N 1-[(4r,6r)-4,6-dimethyl-2-oxo-1,3,2$l^{5}-dioxaphosphinan-2-yl]propan-2-one Chemical compound C[C@@H]1C[C@@H](C)OP(=O)(CC(C)=O)O1 RSZLLJSSNWEYJA-HTQZYQBOSA-N 0.000 description 1
WEFSXBPMNKAUDL-UHFFFAOYSA-N 1-iodopropan-2-one Chemical compound CC(=O)CI WEFSXBPMNKAUDL-UHFFFAOYSA-N 0.000 description 1
ITNITUABPMVBJY-UHFFFAOYSA-N 2-(3-nitrophenyl)nicotinic acid Chemical compound OC(=O)C1=CC=CN=C1C1=CC=CC([N+]([O-])=O)=C1 ITNITUABPMVBJY-UHFFFAOYSA-N 0.000 description 1
ZETIVVHRRQLWFW-UHFFFAOYSA-N 3-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC(C=O)=C1 ZETIVVHRRQLWFW-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
206010002383 Angina Pectoris Diseases 0.000 description 1
241000252983 Caecum Species 0.000 description 1
241000700199 Cavia porcellus Species 0.000 description 1
JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
206010020772 Hypertension Diseases 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
241001163743 Perlodes Species 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
241000244155 Taenia Species 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
210000000436 anus Anatomy 0.000 description 1
150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
238000003287 bathing Methods 0.000 description 1
229930188620 butyrolactone Natural products 0.000 description 1
230000002213 calciumantagonistic effect Effects 0.000 description 1
210000001168 carotid artery common Anatomy 0.000 description 1
210000004534 cecum Anatomy 0.000 description 1
230000002490 cerebral effect Effects 0.000 description 1
229950009941 chloralose Drugs 0.000 description 1
230000008602 contraction Effects 0.000 description 1
238000007907 direct compression Methods 0.000 description 1
238000004821 distillation Methods 0.000 description 1
239000012153 distilled water Substances 0.000 description 1
238000011067 equilibration Methods 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
JBTWLSYIZRCDFO-UHFFFAOYSA-N ethyl methyl carbonate Chemical compound CCOC(=O)OC JBTWLSYIZRCDFO-UHFFFAOYSA-N 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
238000002955 isolation Methods 0.000 description 1
239000000463 material Substances 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
210000004165 myocardium Anatomy 0.000 description 1
230000003472 neutralizing effect Effects 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
239000002674 ointment Substances 0.000 description 1
GTCCGKPBSJZVRZ-UHFFFAOYSA-N pentane-2,4-diol Chemical compound CC(O)CC(C)O GTCCGKPBSJZVRZ-UHFFFAOYSA-N 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
229940127557 pharmaceutical product Drugs 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 1
229920000136 polysorbate Polymers 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
238000005507 spraying Methods 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
239000000725 suspension Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
231100000820 toxicity test Toxicity 0.000 description 1
CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical compound COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 description 1
230000024883 vasodilation Effects 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA000556958A 1988-01-20 1988-01-20 Ester cyclique de l'acide dihydropyridine-5-phosphonique Expired - Fee Related CA1305149C (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA000556958A CA1305149C (fr)	1988-01-20	1988-01-20	Ester cyclique de l'acide dihydropyridine-5-phosphonique

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
CA000556958A CA1305149C (fr)	1988-01-20	1988-01-20	Ester cyclique de l'acide dihydropyridine-5-phosphonique

Publications (1)

Publication Number	Publication Date
CA1305149C true CA1305149C (fr)	1992-07-14

Family

ID=4137297

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000556958A Expired - Fee Related CA1305149C (fr)	1988-01-20	1988-01-20	Ester cyclique de l'acide dihydropyridine-5-phosphonique

Country Status (1)

Country	Link
CA (1)	CA1305149C (fr)

1988
- 1988-01-20 CA CA000556958A patent/CA1305149C/fr not_active Expired - Fee Related

Legal Events

Date	Code	Title	Description
1999-07-14	MKLA	Lapsed

Publication	Publication Date	Title
US4885284A (en)	1989-12-05	Dihydropyridine-5-phosphonic acid cyclic propylene ester
KR860001946B1 (ko)	1986-11-01	1, 4-디히드로피리딘 유도체의 제조방법
EP0198456B1 (fr)	1992-06-10	Dérivés de la 1,7-naphtyridine et préparations médicales les contenant
US4224342A (en)	1980-09-23	Guanidinobenzoic acid compounds and process for preparing the same
US4446325A (en)	1984-05-01	1,4-Dihydropyridine compounds
US4839361A (en)	1989-06-13	Dihydropyridine-5-phosphonic acid cyclic propylene ester
DK164551B (da)	1992-07-13	Analogifremgangsmaade til fremstilling af cyclohexylthienyleddikesyreamider eller fysiologisk taalelige syreadditionssalte deraf
CA1305149C (fr)	1992-07-14	Ester cyclique de l'acide dihydropyridine-5-phosphonique
US4843076A (en)	1989-06-27	Dihydropyridine-5-phosphonic acid cyclic ester
HU211579A9 (en)	1995-12-28	2-amino-5-cyano-1,4-dihydropyridines, and their use in medicaments
US4148907A (en)	1979-04-10	Stereoisomers of 1-(1'benzyl-2'pyrryl)-2-di-sec.-butylaminoethanol and pharmaceutical compositions comprising same
HU180617B (en)	1983-03-28	Process for producing 1,2-bis-bracket-nicotinamido-bracket closed-propane,salts and pharmaceutical compositions containing them
EP0230944B1 (fr)	1990-02-07	Esters cycliques de propylène d'acide dihydropyridine-5-phosphonique
JPH0615553B2 (ja)	1994-03-02	ジヒドロピリジン−５−ホスホンアミド酸類
US4703048A (en)	1987-10-27	Novel 1-benzhydryl-4-cinnamylpiperazine derivatives, and pharmaceutical compositions comprising said compounds as active ingredient for treating a cerebrovascular disease
FR2516510A1 (fr)	1983-05-20	Derives de la (trimethoxy-3,4,5-cinnamoyl)-1-aminocarbonylethyl-4-piperazine substituee utilisables en pharmacie et procede pour leur preparation
EP0405525B1 (fr)	1994-09-14	Dérivés de cyanoguanidine
IL28125A (en)	1972-07-26	5- [Arylhydropipridinyl- (and arylhydropyrrolidinyl-) lower alkyl] -2-exazolidinones
US4199582A (en)	1980-04-22	Piperazine containing dihydronaphthalene derivatives and compositions
JPH0211592A (ja)	1990-01-16	光学活性なジヒドロピリジンホスホン酸エステル
US4831049A (en)	1989-05-16	Pyrrolizidine compounds, and their use as antiarrhythmic agents
JPS584749A (ja)	1983-01-11	アミノベンジルアミン誘導体、その製法および薬剤としての用途
KR940003362B1 (ko)	1994-04-21	디히드로피리딘-5-포스폰산 고리형 프로필렌 에스테르
JPS6163688A (ja)	1986-04-01	ジヒドロピリジン−５−ホスホン酸環状エステル類
JPH0699458B2 (ja)	1994-12-07	ジヒドロピリジン−５−ホスホン酸環状エステル類