KR19990007900A - 신규한 형태의 (ｅ)-3-[6-[[(2,6-디클로로페닐)-티오]메틸]-3-(2-페닐에톡시)-2-피리디닐]-2-프로펜산 - Google Patents
신규한 형태의 (ｅ)-3-[6-[[(2,6-디클로로페닐)-티오]메틸]-3-(2-페닐에톡시)-2-피리디닐]-2-프로펜산 Download PDFInfo
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- KR19990007900A KR19990007900A KR1019970707423A KR19970707423A KR19990007900A KR 19990007900 A KR19990007900 A KR 19990007900A KR 1019970707423 A KR1019970707423 A KR 1019970707423A KR 19970707423 A KR19970707423 A KR 19970707423A KR 19990007900 A KR19990007900 A KR 19990007900A
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- dichlorophenyl
- thio
- methyl
- phenylethoxy
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- ZJLFOOWTDISDIO-ZRDIBKRKSA-N (e)-3-[6-[(2,6-dichlorophenyl)sulfanylmethyl]-3-(2-phenylethoxy)pyridin-2-yl]prop-2-enoic acid Chemical compound C=1C=C(OCCC=2C=CC=CC=2)C(/C=C/C(=O)O)=NC=1CSC1=C(Cl)C=CC=C1Cl ZJLFOOWTDISDIO-ZRDIBKRKSA-N 0.000 title claims abstract description 10
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 3
- -1 2,6-dichlorophenyl Chemical group 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 125000005975 2-phenylethyloxy group Chemical group 0.000 claims description 13
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 238000010521 absorption reaction Methods 0.000 claims description 5
- 238000002441 X-ray diffraction Methods 0.000 claims description 4
- 238000010586 diagram Methods 0.000 claims description 4
- 238000000113 differential scanning calorimetry Methods 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims 1
- 201000007801 psoriasis 2 Diseases 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 201000004681 Psoriasis Diseases 0.000 description 6
- 238000000034 method Methods 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 239000011888 foil Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 229910052724 xenon Inorganic materials 0.000 description 2
- FHNFHKCVQCLJFQ-UHFFFAOYSA-N xenon atom Chemical compound [Xe] FHNFHKCVQCLJFQ-UHFFFAOYSA-N 0.000 description 2
- MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical compound C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000001559 cyclopropyl group Chemical class [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000003199 leukotriene receptor blocking agent Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
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- 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/65—One oxygen atom attached in position 3 or 5
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
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- 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
- C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/32—Sulfur atoms
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- 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
- C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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Abstract
신규한 물리적 형태의 (Ｅ)-3-[6-[[(2,6-디클로로페닐)-티오]메틸]-3-(2-페닐에톡시)-2-피리디닐]-2-프로펜산 및 치료법에서의 그의 용도가 개시되어 있다.
Description
본 발명은 신규한 물리적 형태의 (Ｅ)-3-[6-[[(2,6-디클로로페닐)-티오]메틸]- 3-(2-페닐에톡시)-2-피리디닐]-2-프로펜산, 그를 함유하는 제약 조성물 및 치료법에서의 그의 용도에 관한 것이다.
(Ｅ)-3-[6-[[(2,6-디클로로페닐)-티오]메틸]-3-(2-페닐에톡시)-2-피리디닐]-2-프로펜산, 즉 하기 구조의 화합물은 루코트라이인 (leukotriene) 길항제로 유용한 화합물로서 본 분야에 공지되어 있다.
특히, 본 화합물은 건선의 치료에 유용한 것으로서 WO94/00437호에 설명되어 있다. 건선으로 고통 받는 환자는 종종 그 치료법의 일부로서 태양광에 노출되고, 그러한 노출은 제약상 활성인 화합물의 분해를 초래할 수 있다. 따라서, 이 화합물을 포함하는 국소 제형은 태양광의 노출에 대해 저항성일 필요가 있다.
(Ｅ)-3-[6-[[(2,6-디클로로페닐)-티오]메틸]-3-(2-페닐에톡시)-2-피리디닐]-2-프로펜산은 상이한 물리적 형태 (또한, 다형으로 공지된)로 존재할 수 있다.
따라서, 본 발명은 첫 번째 관점으로 하기 특성으로 동정되는 형태의 (Ｅ)- 3-[6-[[(2,6-디클로로페닐)-티오]메틸]-3-(2-페닐에톡시)-2-피리디닐]-2-프로펜산을 제공한다.
- 약 697, 743 및 884 cm-1에서의 적외선 흡수 밴드.
- 차등 주사 열량계로 동정하였을 때, 약 140 ℃ (142.2 ℃에서 최소)에서 개시되는 단일 용융 흡열반응.
- 9.2, 16.4, 23.3, 26.8 및 27.3의 x-선 회절 산란도 (Cu 원)
이러한 특성을 갖는 형태를 하기에서 (Ｅ)-3-[6-[[(2,6-디클로로페닐)-티오]메틸]-3-(2-페닐에톡시)-2-피리디닐]-2-프로펜산 형 II로 간주한다.
상기 적외선 흡수 밴드는 누졸 멀 (nujol mull)에서 수득한 것이다.
WO94/00437호에 개시된 다형 형태중 (Ｅ)-3-[6-[[(2,6-디클로로페닐)-티오]메틸]-3-(2-페닐에톡시)-2-피리디닐]-2-프로펜산은 하기 물리적 성질을 갖는다.
- 약 704, 758 및 896 cm-1에서의 적외선 흡수 밴드.
- 차등 주사 열량계로 동정하였을 때, 118 내지 138 ℃에서 소량의 흡열 반응 후 약 140 ℃에서 개시되는 용융 흡열반응.
- 10.1, 20.0, 23.0, 24.0 및 25.4의 x-선 회절 산란도 (Cu 원).
상기 특성을 갖는 다형 형태를 형태 I로 간주한다.
(Ｅ)-3-[6-[[(2,6-디클로로페닐)-티오]메틸]-3-(2-페닐에톡시)-2-피리디닐]-2-프로펜산 형태 II는 앞서 동정된 물리적 형태에 비하여 놀라운 이점을 갖는다. 예를 들면, (Ｅ)-3-[6-[[(2,6-디클로로페닐)-티오]메틸]-3-(2-페닐에톡시)-2-피리디닐]-2-프로펜산 형태 II는 형태 I에 비하여 빛에 대하여 매우 큰 안정성을 나타낸다.
또한, 본 발명은 또 다른 관점으로 치료법, 특히 건선의 치료에 사용되는 (Ｅ)-3-[6-[[(2,6-디클로로페닐)-티오]메틸]-3-(2-페닐에톡시)-2-피리디닐]-2-프로펜산 형태 II를 제공한다. 치료에 사용될 때, (Ｅ)-3-[6-[[(2,6-디클로로페닐)-티오]메틸]-3-(2-페닐에톡시)-2-피리디닐]-2-프로펜산 형태 II는 약학 분야에서 공지된 기술을 사용하여 표준 제약 조성물로 제형될 수 있다.
또 다른 관점에서, 본 발명은 제약상 담체와 함께 (Ｅ)-3-[6-[[(2,6-디클로로페닐)-티오]메틸]-3-(2-페닐에톡시)-2-피리디닐]-2-프로펜산 형태 II를 포함하는 제약 조성물을 제공한다.
실질적으로 순수한 형태의 (Ｅ)-3-[6-[[(2,6-디클로로페닐)-티오]메틸]-3-(2-페닐에톡시)-2-피리디닐]-2-프로펜산 형태 II를 포함하는 제약 조성물이 상기 이점을 나타낸다는 것은 본 분야의 숙련자에게는 명백하다. 실질적으로 순수한 형태란 의미는 적어도 50 % 이상, 바람직하게는 80 - 90 % 이상, 가장 바람직하게는 95 % 이상이 순수하다는 것을 의미한다.
형태 I 및 형태 II의 다형 형태의 혼합물을 포함하는 조성물도 본 발명의 또 다른 관점을 형성한다.
또 다른 관점으로, 본 발명은 건선 치료용 의약의 제조에서의 (Ｅ)-3-[6- [[(2,6-디클로로페닐)-티오]메틸]-3-(2-페닐에톡시)-2-피리디닐]-2-프로펜산 형태 II의 용도를 제공한다. 또한, 본 발명은 필요로 하는 숙주에게 유효량의 (Ｅ)-3-[6- [[(2,6-디클로로페닐)-티오]메틸]-3-(2-페닐에톡시)-2-피리디닐]-2-프로펜산 형태 II를 투여하는 것을 포함하는 건선 치료 방법을 제공한다.
본 발명의 화합물의 투여 범위는 일일 약 5 내지 약 1000 mg의 범위, 바람직하게는 일일 약 10 내지 약 200 mg의 범위이다. 건선 치료를 위한 국소 투여용의 경우, 투여량 범위는 영향받은 부위 및 질환의 심각도에 따라 달라진다.
본 발명에 따라 투여될 때, 허용할 수 없는 독성 효과가 본 발명의 화합물에는 기대되지 않는다.
하기 실시예로 본 발명을 설명한다.
실시예 1
호일로 덮은 50 ml의 원추형 플라스크에 조 (Ｅ)-3-[6-[[(2,6-디클로로페닐)-티오]메틸]-3-(2-페닐에톡시)-2-피리디닐]-2-프로펜산 (WO95/00487에 기재된 방법에 따라 제조) 5.0 g 및 프로판-2-올 25 ml을 부과하였다. 현탁액을 환류하에 가열하고, 그 결과의 용액을 감압하에서 종이를 통하여 마그네틱 막대를 포함하는 호일로 덮은 바이얼에 여과하였다. 바이얼을 밀봉하고 여과물을 3 시간 동안 교반하여 주위 온도로 냉각하였다. 백색의 고체를 여과하고, 배수하고, 디에틸 에테르 (3ml)로 세척하고 (주석 참조), 진공하에서 건조하여 순백색 고체로서 (Ｅ)-3-[6-[[(2,6-디클로로페닐)-티오]메틸]-3-(2-페닐에톡시)-2-피리디닐]-2-프로펜산을 수득하였다 (4.36 g, 88% 수율).
주석: 디에틸 에테르를 사용하여 진공 건조를 도왔다. 냉각의 프로판-2-올을 사용한 세척은 수율에 영향을 주지 않고 생략할 수 있다.
생성물은 하기의 특성을 갖는다.
- 약 697, 743 및 884 cm-1에서의 적외선 흡수 밴드.
- 차등 주사 열량계로 동정하였을 때, 약 140 ℃ (142.2 ℃에서 최소)에서 개시되는 단일 용융 흡열반응.
- 9.2, 16.4, 23.3, 26.8 및 27.3의 x-선 회절 산란도 (Cu 원)
실시예 2
결정 형태의 광 안정성 비교
형태 I 및 형태 II의 시료를 Heraeus Sun Test CPS 광 캐비넷에서 크세논 광 (85,000 lux)에 4 시간 동안 노출하였다. 이 시료를 광노출 전 및 광노출 후에 상대 반응 및 불순물 프로파일에 대하여 HPLC로 분석하였다.
| 시료 | 비노출에 대한 상대 반응 | 주 피크의 면적% | 이량체의 면적% |
| 비노출된 형태 I | 100 % | 99.5 % | 0.1 % |
| 노출된 형태 I | 0.7 % | 1.1 % | 75.8 % |
| 비노출된 형태 II | 100 % | 97.7 % | nd |
| 노출된 형태 II | 96.5 % | 98.1 % | 0.1 % |
| nd: 검출 안됨 |
이량체는 형태 I 화합물의 주요 분해 산물인 (Ｅ)-3-[6-[[(2,6-디클로로페닐)-티오]메틸]-3-(2-페닐에톡시)-2-피리디닐]-2-프로펜산의 시클로부탄 이량체로 간주한다. 이 결과는 형태 II를 크세논 광에 노출 시켰을 때 형태 I에 비하여 현저히 안정하다는 것을 분명히 보여준다. 4 시간의 노출 후에, 형태 I은 거의 완전히 분해된다.
Claims (5)
- 하기 특성으로 동정되는 형태의 (Ｅ)-3-[6-[[(2,6-디클로로페닐)-티오]메틸]- 3-(2-페닐에톡시)-2-피리디닐]-2-프로펜산.- 약 697, 743 및 884 cm-1에서의 적외선 흡수 밴드.- 차등 주사 열량계로 동정하였을 때, 약 140 ℃ (142.2 ℃에서 최소)에서 개시되는 단일 용융 흡열반응.- 9.2, 16.4, 23.3, 26.8 및 27.3의 x-선 회절 산란도 (Cu 원).
- 제약상 허용되는 담체와 함께 제1항에서 설명된 형태의 (Ｅ)-3-[6-[[(2,6-디클로로페닐)-티오]메틸]-3-(2-페닐에톡시)-2-피리디닐]-2-프로펜산을 포함하는 제약 조성물.
- 치료에 사용되는 제1항에서 설명된 형태의 (Ｅ)-3-[6-[[(2,6-디클로로페닐)-티오]메틸]-3-(2-페닐에톡시)-2-피리디닐]-2-프로펜산.
- 건선의 치료 또는 예방에 사용되는 제1항에서 설명된 형태의 (Ｅ)-3-[6- [[(2,6-디클로로페닐)-티오]메틸]-3-(2-페닐에톡시)-2-피리디닐]-2-프로펜산.
- 제약상 허용되는 담체와 함께 (Ｅ)-3-[6-[[(2,6-디클로로페닐)-티오]메틸]- 3-(2-페닐에톡시)-2-피리디닐]-2-프로펜산 형태 I 및 (Ｅ)-3-[6-[[(2,6-디클로로페닐)-티오]메틸]-3-(2-페닐에톡시)-2-피리디닐]-2-프로펜산 형태 II를 포함하는 제약 조성물.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9508137.8A GB9508137D0 (en) | 1995-04-21 | 1995-04-21 | Formulation |
| GB9508137.8 | 1995-04-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR19990007900A true KR19990007900A (ko) | 1999-01-25 |
Family
ID=10773317
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019970707423A KR19990007900A (ko) | 1995-04-21 | 1996-04-02 | 신규한 형태의 (ｅ)-3-[6-[[(2,6-디클로로페닐)-티오]메틸]-3-(2-페닐에톡시)-2-피리디닐]-2-프로펜산 |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US6093828A (ko) |
| EP (1) | EP0821673B1 (ko) |
| JP (1) | JPH11503737A (ko) |
| KR (1) | KR19990007900A (ko) |
| CN (1) | CN1182418A (ko) |
| AT (1) | ATE198883T1 (ko) |
| AU (1) | AU707089B2 (ko) |
| BR (1) | BR9608003A (ko) |
| CA (1) | CA2218322A1 (ko) |
| CZ (1) | CZ333797A3 (ko) |
| DE (1) | DE69611670T2 (ko) |
| DK (1) | DK0821673T3 (ko) |
| ES (1) | ES2154818T3 (ko) |
| GB (1) | GB9508137D0 (ko) |
| GR (1) | GR3035494T3 (ko) |
| HU (1) | HUP9801574A3 (ko) |
| NO (1) | NO309767B1 (ko) |
| NZ (1) | NZ307493A (ko) |
| PL (1) | PL322897A1 (ko) |
| PT (1) | PT821673E (ko) |
| TR (1) | TR199701213T1 (ko) |
| WO (1) | WO1996033174A1 (ko) |
| ZA (1) | ZA963134B (ko) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9602675D0 (en) * | 1996-02-09 | 1996-04-10 | Smithkline Beecham Plc | Process |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2573592A (en) * | 1991-09-19 | 1993-04-27 | Smithkline Beecham Corporation | Pyridine compounds for treating leukotriene-related diseases |
| MA22926A1 (fr) * | 1992-06-30 | 1994-04-01 | Smithkline Beecham Corp | Procede pour la preparation de nouveaux composes. |
| WO1994000433A1 (en) * | 1992-06-30 | 1994-01-06 | Smithkline Beecham Corporation | Process for making phenylthiomethylpyridinylalkenoates |
| GB9313145D0 (en) * | 1993-06-25 | 1993-08-11 | Smithkline Beecham Plc | Process |
-
1995
- 1995-04-21 GB GBGB9508137.8A patent/GB9508137D0/en active Pending
-
1996
- 1996-04-02 CA CA002218322A patent/CA2218322A1/en not_active Abandoned
- 1996-04-02 TR TR97/01213T patent/TR199701213T1/xx unknown
- 1996-04-02 CZ CZ973337A patent/CZ333797A3/cs unknown
- 1996-04-02 US US08/945,372 patent/US6093828A/en not_active Expired - Fee Related
- 1996-04-02 HU HU9801574A patent/HUP9801574A3/hu unknown
- 1996-04-02 NZ NZ307493A patent/NZ307493A/en unknown
- 1996-04-02 WO PCT/EP1996/001466 patent/WO1996033174A1/en not_active Application Discontinuation
- 1996-04-02 BR BR9608003A patent/BR9608003A/pt active Search and Examination
- 1996-04-02 AU AU56859/96A patent/AU707089B2/en not_active Ceased
- 1996-04-02 JP JP8531444A patent/JPH11503737A/ja active Pending
- 1996-04-02 DK DK96914877T patent/DK0821673T3/da active
- 1996-04-02 PT PT96914877T patent/PT821673E/pt unknown
- 1996-04-02 AT AT96914877T patent/ATE198883T1/de active
- 1996-04-02 KR KR1019970707423A patent/KR19990007900A/ko not_active Application Discontinuation
- 1996-04-02 DE DE69611670T patent/DE69611670T2/de not_active Expired - Fee Related
- 1996-04-02 EP EP96914877A patent/EP0821673B1/en not_active Expired - Lifetime
- 1996-04-02 CN CN96193405A patent/CN1182418A/zh active Pending
- 1996-04-02 ES ES96914877T patent/ES2154818T3/es not_active Expired - Lifetime
- 1996-04-02 PL PL96322897A patent/PL322897A1/xx unknown
- 1996-04-19 ZA ZA9603134A patent/ZA963134B/xx unknown
-
1997
- 1997-10-20 NO NO974840A patent/NO309767B1/no not_active IP Right Cessation
-
2001
- 2001-02-28 GR GR20010400337T patent/GR3035494T3/el not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| BR9608003A (pt) | 1999-01-05 |
| ATE198883T1 (de) | 2001-02-15 |
| DE69611670T2 (de) | 2001-08-23 |
| CA2218322A1 (en) | 1996-10-24 |
| EP0821673B1 (en) | 2001-01-24 |
| HUP9801574A3 (en) | 1998-12-28 |
| PL322897A1 (en) | 1998-03-02 |
| DE69611670D1 (en) | 2001-03-01 |
| AU5685996A (en) | 1996-11-07 |
| NO974840D0 (no) | 1997-10-20 |
| PT821673E (pt) | 2001-05-31 |
| DK0821673T3 (da) | 2001-06-18 |
| GR3035494T3 (en) | 2001-05-31 |
| NO309767B1 (no) | 2001-03-26 |
| ES2154818T3 (es) | 2001-04-16 |
| ZA963134B (en) | 1997-02-14 |
| GB9508137D0 (en) | 1995-06-07 |
| TR199701213T1 (ko) | 1998-03-21 |
| AU707089B2 (en) | 1999-07-01 |
| CN1182418A (zh) | 1998-05-20 |
| JPH11503737A (ja) | 1999-03-30 |
| NZ307493A (en) | 1998-07-28 |
| CZ333797A3 (cs) | 1999-01-13 |
| EP0821673A1 (en) | 1998-02-04 |
| HUP9801574A2 (hu) | 1998-11-30 |
| WO1996033174A1 (en) | 1996-10-24 |
| NO974840L (no) | 1997-10-20 |
| US6093828A (en) | 2000-07-25 |
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