WO1984004678A1 - Blood pressure-controlling agent - Google Patents
Blood pressure-controlling agent Download PDFInfo
- Publication number
- WO1984004678A1 WO1984004678A1 PCT/JP1984/000255 JP8400255W WO8404678A1 WO 1984004678 A1 WO1984004678 A1 WO 1984004678A1 JP 8400255 W JP8400255 W JP 8400255W WO 8404678 A1 WO8404678 A1 WO 8404678A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- blood pressure
- carbon atoms
- acid residue
- pressure regulating
- halogen atom
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
-
- 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
Definitions
- the present invention relates to a background art of a novel blood pressure regulating drug.
- drugs for hypertension are, for example, thiazide antihypertensive diuretics, vasodilators, or adrenaline J3 receptor blockers or ⁇ -receptors.
- blockers are used, if all drugs are taken for a long time, orthostatic hypotension '', bradycardia or tachycardia, vomiting, nausea, headaches.
- side effects such as suffocation.
- An object of the present invention is to provide a blood pressure regulating drug having no toxicity or side effects. Disclosure of invention
- the present invention relates to the following general formula (I)
- ⁇ ? ⁇ Represents an alkyl group having 1 to 15 carbon atoms, R 4 , R 5 ,
- R ⁇ , R 7 , R 8 and R 9 are the same or different and represent a hydrogen atom, an alkyl group having 1 to 15 carbon atoms, a hydroxyl group or a chromogen atom.
- X represents a halogen atom, a chloric acid residue, a nitric acid residue, or an organic acid residue.
- the trithiazole pentamethine cyanide compound represented by BIJ-Single Formula (I) is effective as a blood pressure regulating drug without toxicity and side effects.
- R 2 and R 3 are n-heptyl groups
- R 4 , R 5 and R s are methyl groups
- R 7 , R 8 and R 9 are hydrogen
- pradodin Compounds in which the atom and X are positive
- FIG. 1 is a graph showing the effect of Bratnin on blood pressure of SH.
- Fig. 2 is a graph showing the effect of plutonin on SHR body weight.
- FIG. 3 is a graph showing the effect of platonin on the blood pressure of a normal rat.
- 8U-1 pratonin has pharmacological actions such as antibacterial action, promoting wound healing, activating retinal hematopoietic organs and endocrine glands, and enhancing Ul body production.
- compound (I) including bratonin, has almost no toxicity or side effects, and it has been shown that it shows an excellent antihypertensive effect, especially when administered orally. It is not known and was first discovered by the present invention.
- the compound represented by the general formula (I) exhibits a slow-acting antihypertensive effect when the blood pressure is increased for some reason (hypertension), and when the blood pressure is normal. It has an excellent blood pressure regulating action, with no significant effect and no acute antihypertensive effect. It does not have serious side effects such as orthostatic hypotension, bradycardia or tachycardia, vomiting, nausea, headache, and dizziness, which are the limitations of conventional drugs for hypertension. It enabled long-term continuous administration of the drug, and was found to be extremely effective against hypertension.
- the blood pressure regulating drug of the present invention containing the compound (I) as an active ingredient makes a very significant contribution as a preventive and therapeutic agent for hypertensive diseases in general. .
- the alkyl group having 1 to 15 carbon atoms represented by R 1 , R 2 or R 3 is, for example, dimethyl or ethyl. , ⁇ -propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, iso-pentyl, sec-pentyl, N-pentyl, tert-pentyl, n-hexyl, isohexyl, sec-hexyl, neohexyl, tert-hexyl, n-heptyl, 5-methyl to key sill, old-click chill, loading Le, decyl, ⁇ Ndeshi Lumpur, de decyl, door Li de Sil, Te Bok La de Sil, pen data de Shi Le of Dogaage we are. or R 4, alkyl group is Oh down et similar to the even and Al kill group table
- Examples of the halogen atom represented by R 4 , R 5 , R 8 , R 7 , R 8, or R 9 include chlor, prom, and anode.
- X represents a halogen atom such as chlor, bromide, or aldehyde, a chloric acid residue, a nitric acid residue, P-toluenesulfonate, nicotinic acid, or nitrosolic acid. And other organic residues.
- R 5 and R 6 are methyl groups and R 7 , R 8 and R 9 are hydrogen atoms is preferable.
- R 1 is a compound in which R 5 and R 6 are methyl groups and R 7 , R 8 and R 9 are hydrogen atoms.
- R 2 and R 3 are the same alkyl group, particularly a heptyl group, and particularly a ⁇ -heptyl group are preferred, and particularly, R i, R 2 and R 3 are ( 1-heptyl group, wherein X is a moiety 'platonin, that is, 4,4 "*-dimethyl-3,3'-di-n-heptyl - ⁇ - [2- (4- Methyl-3- ⁇ -heptylthiazol)]] -2,2 -Dicarposocyanin * Diiodide is preferred.
- Preferred indications of the blood pressure regulating drug of the present invention include, for example, malignant hypertension, essential hypertension, renal hypertension, nervous hypertension, juvenile hypertension, endocrine hypertension, etc.
- the blood pressure regulating drug of the present invention which includes a wide variety of hypertension from mild to severe, etc., can be used as an adult dose (the equivalent of an active ingredient, the same applies hereinafter) of about 10 to 500 ⁇ g at a time. It exerts its effect in a very small amount. In particular, a dosage of 50 to 100 izg Z 1 to 3 days is preferred.
- the blood pressure regulating agent of the present invention which shows sufficient activity by oral administration, can be used as tablets, capsules, powders, granules, liquids and the like. It can also be used as nasal drops, suppositories, etc. Furthermore, transdermal administration in the form of a patch is also possible. There are no particular restrictions on the formulation of the blood pressure regulating drug of the present invention.
- compound (I) was prepared in various dosage forms as described above.
- compound (I) is used as a microcapsule.
- the compound (I) used in the present invention is, for example, as follows.
- the crude product obtained is reacted with a solvent such as ethanol.
- X is a compound other than the raw material
- R 4 , R 5 and R s are methyl groups, and R 7 , R 8 and
- SHR spontaneously hypertensive rat
- O PI Blood pressure, heart rate, and body weight were measured during and after a while.
- the blood pressure was measured using a rat blood pressure tracking device (Narco Pai Sai Systems Co., Ltd.) in a non-invasive manner to measure the systolic pressure of the tail artery. (Manufactured by Kogyo Co., Ltd.).
- Fig. 1 shows the obtained results.
- Fig. 1 (Fig. 2
- the solid line A indicates the group administered with bratnin
- the dashed line B indicates the group administered with saline
- G indicates the administration period.
- Platonin was administered three times a week at a dose of 3 kg / kg.
- Bratonin when given at a dose of 1 g / kg three times a week, had no effect on SHR weight gain and was shown to be a safe drug. Although not shown in the figure, oral administration of 1 to 100 g Z 3 times a week did not affect body weight.
- the administration was performed up to the 8th week. Similarly, the control group has
- Rat blood pressure newly established device (Narcopai Saisei Systems Inc.)
- the heart rate is calculated using a polygraph (Nihon Kohden
- FIG. 3 shows the results.
- Platonin is 1 ii Q /
- the LD e () value was determined by the van ⁇ del ⁇ vaerden method. As a result, intraperitoneal LD-. Value is 54 nig
- blood pressure regulators in various dosage forms were prepared as follows.
- Tablets of the following formula were prepared by a conventional method.
- the following capsule formulation was prepared by a conventional method.
- the powder of the following formulation was prepared by a standard method.
- the following two types of suppositories were prepared in a conventional manner.
- a syrup of the following formulation (single dose 50 g / 5 ml) was prepared by a conventional method.
- a patch having the following formulation was prepared by a conventional method.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Description
Claims
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP58090364A JPS59216819A (ja) | 1983-05-23 | 1983-05-23 | 遅効性経口降圧剤 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1984004678A1 true WO1984004678A1 (en) | 1984-12-06 |
Family
ID=13996481
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP1984/000255 WO1984004678A1 (en) | 1983-05-23 | 1984-05-21 | Blood pressure-controlling agent |
Country Status (7)
Country | Link |
---|---|
EP (1) | EP0144441A4 (ja) |
JP (1) | JPS59216819A (ja) |
AU (1) | AU566836B2 (ja) |
CH (1) | CH662730A5 (ja) |
DE (2) | DE3490243T (ja) |
GB (1) | GB2149663B (ja) |
WO (1) | WO1984004678A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5061637A (en) * | 1987-12-18 | 1991-10-29 | Gerling Institut Pro Schadenforschung, Schadenverhutung Und Sicherheitstechnik Gmbh | Process for the removal and qualitative analytical determination of cyanide in contaminated soils |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2824917B2 (ja) * | 1989-08-30 | 1998-11-18 | 株式会社林原生物化学研究所 | 抗腫瘍剤 |
-
1983
- 1983-05-23 JP JP58090364A patent/JPS59216819A/ja active Granted
-
1984
- 1984-05-21 EP EP19840902059 patent/EP0144441A4/en not_active Ceased
- 1984-05-21 WO PCT/JP1984/000255 patent/WO1984004678A1/ja not_active Application Discontinuation
- 1984-05-21 AU AU29608/84A patent/AU566836B2/en not_active Ceased
- 1984-05-21 CH CH361/85A patent/CH662730A5/de not_active IP Right Cessation
- 1984-05-21 GB GB08500912A patent/GB2149663B/en not_active Expired
- 1984-05-21 DE DE19843490243 patent/DE3490243T/de active Pending
- 1984-05-21 DE DE3490243A patent/DE3490243C2/de not_active Expired - Lifetime
Non-Patent Citations (2)
Title |
---|
CHEMICAL ABSTRACTS Vol. 76, No. 19 (05. 05. 72) (Columbus, Ohio, U.S.A.), SUZUE S., "Effect of Photosensitizing Deys on Blood Pressure" 3rd and 5th Reports, page 56, 1st Step, Abstract No. 76, 108237r and 76, 108239t, Kanko Shikiso 1971, No. 80, and No. 80, 25 * |
See also references of EP0144441A4 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5061637A (en) * | 1987-12-18 | 1991-10-29 | Gerling Institut Pro Schadenforschung, Schadenverhutung Und Sicherheitstechnik Gmbh | Process for the removal and qualitative analytical determination of cyanide in contaminated soils |
Also Published As
Publication number | Publication date |
---|---|
EP0144441A4 (en) | 1986-12-01 |
GB2149663B (en) | 1986-11-19 |
DE3490243T (de) | 1985-05-15 |
AU2960884A (en) | 1984-12-18 |
JPS59216819A (ja) | 1984-12-06 |
CH662730A5 (de) | 1987-10-30 |
AU566836B2 (en) | 1987-10-29 |
EP0144441A1 (en) | 1985-06-19 |
DE3490243C2 (ja) | 1990-02-08 |
GB8500912D0 (en) | 1985-02-20 |
JPH0220608B2 (ja) | 1990-05-10 |
GB2149663A (en) | 1985-06-19 |
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