JP2949366B2 - 心臓疾患の予防または治療剤 - Google Patents
心臓疾患の予防または治療剤Info
- Publication number
- JP2949366B2 JP2949366B2 JP29100290A JP29100290A JP2949366B2 JP 2949366 B2 JP2949366 B2 JP 2949366B2 JP 29100290 A JP29100290 A JP 29100290A JP 29100290 A JP29100290 A JP 29100290A JP 2949366 B2 JP2949366 B2 JP 2949366B2
- Authority
- JP
- Japan
- Prior art keywords
- heart disease
- agent
- compound
- preventing
- addition salt
- Prior art date
- 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 - Lifetime
Links
- 208000019622 heart disease Diseases 0.000 title claims description 16
- 239000002253 acid Substances 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 7
- 230000003449 preventive effect Effects 0.000 claims description 7
- 229940124597 therapeutic agent Drugs 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 3
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 2
- KULBBIWEXOOAHU-UHFFFAOYSA-N methyl 2-(6,7-dihydro-4h-thieno[3,2-c]pyridin-5-yl)acetate Chemical compound C1N(CC(=O)OC)CCC2=C1C=CS2 KULBBIWEXOOAHU-UHFFFAOYSA-N 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 17
- 210000004351 coronary vessel Anatomy 0.000 description 9
- -1 calcium antagonists Substances 0.000 description 5
- 239000007924 injection Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
- 230000004087 circulation Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 208000031225 myocardial ischemia Diseases 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- WJFYLCXWEXZNHU-UHFFFAOYSA-N 2,3,3a,4-tetrahydrothieno[3,2-b]pyridine Chemical class N1C=CC=C2SCCC21 WJFYLCXWEXZNHU-UHFFFAOYSA-N 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 230000006866 deterioration Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000000004 hemodynamic effect Effects 0.000 description 2
- 208000028867 ischemia Diseases 0.000 description 2
- KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical compound COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 229920000573 polyethylene Polymers 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000003218 coronary vasodilator agent Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000004041 inotropic agent Substances 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Description
て、脳血管障害を抜き、ガンに次いで第２位を占めるに
至っている。また、最近、虚血性心疾患に代表される心
臓疾患の羅患年齢は低下し、働きざかりの40代の患者が
増加しつつある。
ロッカー、カルシウムアンタゴニスト、冠血管拡張剤、
強心剤等が用いられている。
いものは副作用が多く、副作用が少ないものは治療効果
が充分でない等の問題があり、臨床的に充分満足できる
ものではなかった。
ついての薬理作用を心臓疾患モデルを用いて検討してき
たところ、下記式（Ｉ）で示されるテトラヒドロチエノ
ピリジン誘導体またはその酸付加塩が優れた心臓疾患の
予防または治療作用を有し、かつ安全性も高いことを見
出し、本発明を完成した。
−（4,5,6,7−テトラヒドロチエノ〔3,2−ｃ〕ピリジン
−５−イル）酢酸メチルエステルまたはその酸付加塩を
有効成分とする心臓疾患の予防または治療剤を提供する
ものである。
る化合物（Ｉ）およびその酸付加塩は、例えば特開昭63
−203684号公報記載の方法に従って製造できる既知の化
合物であるが、心臓疾患に対する予防および治療作用に
ついては全く知られていない。化合物（Ｉ）の酸付加塩
としては、硫酸塩、塩酸塩、リン酸塩、硝酸塩等の無機
酸塩、マレイン酸塩、フマル酸塩、シュウ酸塩等の有機
酸塩が挙げられる。
に示す如く虚血心疾患モデルにおいて優れた冠循環動態
の低下を抑制する作用を有し、心臓疾患、特に狭心症、
心筋梗塞等の虚血性心疾患や心不全の予防または治療剤
として有用である。また、例えば化合物（Ｉ）硫酸塩の
経口投与における急性毒性（LD50,mg/kg）は下記第１表
の通りであり、化合物（Ｉ）は安全性が極めて高いもの
である。
され、その投与量は患者の体重、年齢、性別、投与方
法、体調、症状等により異なるが、経口投与の場合、化
合物（Ｉ）またはその酸付加塩として通常１日10〜100m
g/成人とすればよい。
またはその酸付加塩を配合し、通常の方法で錠剤、顆粒
剤、カプセル剤、懸濁剤、注射剤等の種々の剤型とする
ことができる。経口用の固形製剤を製造するには、化合
物（Ｉ）またはその酸付加塩に賦形剤、更に必要に応じ
て結合剤、崩壊剤、滑沢剤、着色剤、矯味矯臭剤、増量
剤、被覆剤、糖衣剤などを加えた後、常法により錠剤、
顆粒剤、散剤、カプセル剤等とすればよい。注射剤を調
製する場合は、化合物（Ｉ）またはその酸付加塩を注射
用蒸留水等の水性担体にあらかじめ溶解、分散、乳化等
するか、または注射用の粉末にして、用時に溶解等すれ
ばよい。
れに限定されるものではない。
ルで麻酔し、人工呼吸下に開胸して左冠動脈前下行枝を
剥離した。心臓を虚血に陥らせるためにコラーゲンの粉
末を充填した細いカテーテルを左冠動脈前下行枝にその
分枝から挿入した。循環動態は大腿動脈にポリエチレン
製カニューレを挿入して全身血圧と心拍数を測定した。
左冠動脈前下行枝に血流量測定用プローブと左冠動脈前
下行枝末端にポリエチレン製カニューレを挿入してそれ
ぞれ冠血流量と冠動脈血圧を測定した。コラーゲンを充
填したカテーテルを挿入した部位で左冠動脈前下行枝を
その血流量が約20％低下するように狭窄して冠循環不全
モデルを作成した。
る20分前に化合物（Ｉ）の硫酸塩を3mg/kgの用量で静注
し、その後の変化を観察した。対照群には生理食塩水を
投与した。実験の例数は各群10例とした。
圧低下、すなわち冠循環血行動態の悪化を有意に抑制し
た。一方、化合物（Ｉ）は全身血圧と心拍数等の全身循
環動態には影響を与えなかった。以上のことから、化合
物（Ｉ）は虚血時の心臓において冠循環の悪化を抑制す
ることが確認され、化合物（Ｉ）は心臓疾患に有用であ
ることが明らかになった。
Claims (1)
- 【請求項１】次式（Ｉ） で表わされる（Ｓ）−２−（２−クロロフェニル）−２
−（4,5,6,7−テトラヒドロチエノ〔3,2−ｃ〕ピリジン
−５−イル）酢酸メチルエステルまたはその酸付加塩を
有効成分とする心臓疾患の予防または治療剤。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP29100290A JP2949366B2 (ja) | 1990-10-26 | 1990-10-26 | 心臓疾患の予防または治療剤 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP29100290A JP2949366B2 (ja) | 1990-10-26 | 1990-10-26 | 心臓疾患の予防または治療剤 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH04164033A JPH04164033A (ja) | 1992-06-09 |
| JP2949366B2 true JP2949366B2 (ja) | 1999-09-13 |
Family
ID=17763188
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP29100290A Expired - Lifetime JP2949366B2 (ja) | 1990-10-26 | 1990-10-26 | 心臓疾患の予防または治療剤 |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2949366B2 (ja) |
-
1990
- 1990-10-26 JP JP29100290A patent/JP2949366B2/ja not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPH04164033A (ja) | 1992-06-09 |
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