CZ220099A3 - Nové sloučeniny s analgetickým účinkem - Google Patents
Nové sloučeniny s analgetickým účinkemInfo
- Publication number
- CZ220099A3 CZ220099A3 CZ992200A CZ220099A CZ220099A3 CZ 220099 A3 CZ220099 A3 CZ 220099A3 CZ 992200 A CZ992200 A CZ 992200A CZ 220099 A CZ220099 A CZ 220099A CZ 220099 A3 CZ220099 A3 CZ 220099A3
- Authority
- CZ
- Czechia
- Prior art keywords
- novel compounds
- compounds exhibiting
- analgetic activity
- analgetic
- activity
- Prior art date
Links
- 230000000202 analgesic effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 title 1
- 230000001747 exhibiting effect Effects 0.000 title 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0446—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0455—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
- C07D207/14—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
- C07D211/56—Nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2123/00—Preparations for testing in vivo
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Physics & Mathematics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Optics & Photonics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9604786A SE9604786D0 (sv) | 1996-12-20 | 1996-12-20 | New compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CZ220099A3 true CZ220099A3 (cs) | 1999-11-17 |
Family
ID=20405139
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CZ992200A CZ220099A3 (cs) | 1996-12-20 | 1997-12-09 | Nové sloučeniny s analgetickým účinkem |
Country Status (31)
| Country | Link |
|---|---|
| US (3) | US6153626A (cs) |
| EP (2) | EP1428821A1 (cs) |
| JP (1) | JP2001507021A (cs) |
| KR (1) | KR20000069600A (cs) |
| CN (2) | CN1154635C (cs) |
| AR (1) | AR010378A1 (cs) |
| AT (1) | ATE266638T1 (cs) |
| AU (1) | AU738002B2 (cs) |
| BR (1) | BR9713785A (cs) |
| CA (1) | CA2274117A1 (cs) |
| CZ (1) | CZ220099A3 (cs) |
| DE (1) | DE69729115T2 (cs) |
| DK (1) | DK0946510T3 (cs) |
| EE (1) | EE03966B1 (cs) |
| ES (1) | ES2219783T3 (cs) |
| HU (1) | HUP0000613A3 (cs) |
| ID (1) | ID21662A (cs) |
| IL (1) | IL130536A0 (cs) |
| IS (1) | IS5078A (cs) |
| MY (1) | MY132705A (cs) |
| NO (1) | NO313632B1 (cs) |
| NZ (1) | NZ336028A (cs) |
| PL (1) | PL188945B1 (cs) |
| PT (1) | PT946510E (cs) |
| RU (1) | RU2193030C2 (cs) |
| SE (1) | SE9604786D0 (cs) |
| SK (1) | SK283300B6 (cs) |
| TR (1) | TR199901411T2 (cs) |
| UA (1) | UA54481C2 (cs) |
| WO (1) | WO1998028270A1 (cs) |
| ZA (1) | ZA9711049B (cs) |
Families Citing this family (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE9504661D0 (sv) | 1995-12-22 | 1995-12-22 | Astra Pharma Inc | New compounds |
| SE9604786D0 (sv) | 1996-12-20 | 1996-12-20 | Astra Pharma Inc | New compounds |
| US6974825B1 (en) | 1996-12-20 | 2005-12-13 | Astrazeneca Canada Inc. | Compounds with analgesic effect |
| TW548271B (en) * | 1996-12-20 | 2003-08-21 | Astra Pharma Inc | Novel piperidine derivatives having an exocyclic double bond with analgesic effects |
| AU2003220725B2 (en) * | 1997-12-24 | 2006-06-01 | Ortho-Mcneil Pharmaceutical, Inc. | 4-[aryl(piperidin-4-yl)] aminobenzamides which bind to the delta-opioid receptor |
| JP4754068B2 (ja) * | 1997-12-24 | 2011-08-24 | オーソ−マクニール・フアーマシユーチカル・インコーポレーテツド | δ−オピオイドレセプターに結合する4−[アリール(ピペリジン−4−イル)]アミノベンズアミド類 |
| US6900228B1 (en) * | 1998-03-10 | 2005-05-31 | Research Triangle Institute | Opiate compounds, methods of making and methods of use |
| EP1512683B1 (en) * | 1998-03-10 | 2011-08-31 | Research Triangle Institute | Novel opiate compounds, methods of making and methods of use |
| US6436959B1 (en) | 1998-12-23 | 2002-08-20 | Ortho-Mcneil Pharmaceutical, Inc. | 4-[aryl(piperidin-4-yl)]aminobenzamides |
| SE9904674D0 (sv) * | 1999-12-20 | 1999-12-20 | Astra Pharma Inc | Novel compounds |
| SE9904675D0 (sv) | 1999-12-20 | 1999-12-20 | Astra Pharma Inc | Novel compounds |
| SE9904673D0 (sv) * | 1999-12-20 | 1999-12-20 | Astra Pharma Inc | Novel compounds |
| CA2395471A1 (en) | 1999-12-22 | 2001-06-28 | Ortho-Mcneil Pharmaceutical, Inc. | 4-[aryl(8-azabicyclo[3.2.1]octan-3-yl)]aminobenzoic acid derivatives |
| AU2001232319B2 (en) * | 2000-02-18 | 2005-01-13 | Meiji Seika Kaisha, Ltd. | Phenoxyalkylamine derivates useful as opioid delta receptor ligands |
| US6552036B2 (en) | 2000-03-03 | 2003-04-22 | Ortho-Mcneil Pharmaceutical, Inc. | 3-(Diarylmethylene)-8-azabicyclo[3.2.1]octane derivatives |
| AU2001242744B2 (en) | 2000-03-24 | 2005-07-21 | Meiji Seika Kaisha Ltd | Diphenylalkylamine derivatives useful as opioid delta receptor ligands |
| SE0001209D0 (sv) | 2000-04-04 | 2000-04-04 | Astrazeneca Canada Inc | Novel compounds |
| WO2002048122A2 (en) * | 2000-12-14 | 2002-06-20 | Ortho-Mcneil Pharmaceutical, Inc. | Benzamidine derivatives |
| CA2436263A1 (en) * | 2000-12-15 | 2002-06-20 | Astrazeneca Ab | New process for the preparation diaryl-4-amino-piperidinyl compounds |
| SE0101769D0 (sv) * | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
| AR035974A1 (es) | 2001-05-18 | 2004-07-28 | Astrazeneca Ab | Derivados de diarilmetil piperazina, procesos para su preparacion, uso de estos derivados para la elaboracion de medicamentos y composicion farmaceutica |
| SE0101773D0 (sv) * | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
| SE0101770D0 (sv) | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
| SE0101771D0 (sv) * | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
| ATE347549T1 (de) | 2001-10-15 | 2006-12-15 | Janssen Pharmaceutica Nv | Neue substituierte 4-phenyl-4-(1h-imidazo-2-yl)- piperidin-derivate und ihre anwendung als selective delta-opioid-agonisten |
| ATE521592T1 (de) * | 2002-03-13 | 2011-09-15 | Janssen Pharmaceutica Nv | Histone-deacetylase-inhibitoren |
| CA2485681C (en) | 2002-05-24 | 2012-10-16 | Millennium Pharmaceuticals, Inc. | Ccr9 inhibitors and methods of use thereof |
| SE0203300D0 (sv) | 2002-11-07 | 2002-11-07 | Astrazeneca Ab | Novel Compounds |
| SE0203303D0 (sv) | 2002-11-07 | 2002-11-07 | Astrazeneca Ab | Novel Compounds |
| SE0203302D0 (sv) | 2002-11-07 | 2002-11-07 | Astrazeneca Ab | Novel Compounds |
| US7741519B2 (en) | 2007-04-23 | 2010-06-22 | Chemocentryx, Inc. | Bis-aryl sulfonamides |
| ATE363470T1 (de) | 2002-11-18 | 2007-06-15 | Chemocentryx Inc | Arylsulfonamide |
| US7420055B2 (en) | 2002-11-18 | 2008-09-02 | Chemocentryx, Inc. | Aryl sulfonamides |
| US7227035B2 (en) | 2002-11-18 | 2007-06-05 | Chemocentryx | Bis-aryl sulfonamides |
| CN1816524B (zh) * | 2003-01-16 | 2012-06-27 | 阿卡蒂亚药品公司 | 用于神经退行性疾病的治疗的选择性五羟色胺2a/2c受体反向激动剂 |
| WO2005003131A1 (en) * | 2003-06-27 | 2005-01-13 | Janssen Pharmaceutica N.V. | Tricyclic delta opioid modulators |
| WO2005075472A1 (en) | 2004-02-03 | 2005-08-18 | Janssen Pharmaceutica, N.V. | 3-(diheteroarylnethylene)-8-azabicyclo[3.2.1]octane and 3-(aryl)(heteroaryl)methylene)-8-azabicyclo[3.2.1]octane derivatives |
| HRP20120343T1 (hr) | 2004-08-02 | 2012-05-31 | Astrazeneca Ab | Derivati diarilmetil piperazina, njihovi pripravci i njihova uporaba |
| CA2574768A1 (en) * | 2004-08-05 | 2006-02-05 | Janssen Pharmaceutica N.V. | Tricyclic delta-opioid modulators |
| AU2005319060A1 (en) * | 2004-12-22 | 2006-06-29 | Janssen Pharmaceutica N.V. | Tricyclic delta-opioid modulators |
| BRPI0519198A2 (pt) * | 2004-12-22 | 2008-12-30 | Janssen Pharmaceutica Nv | moduladores de delta-opiàide tricÍclicos |
| CA2592464A1 (en) * | 2004-12-22 | 2006-06-29 | Janssen Pharmaceutica N.V. | Tricyclic .delta.-opioid modulators |
| CA2594347A1 (en) * | 2005-01-06 | 2006-07-13 | Janssen Pharmaceutica N.V. | Tricyclic d-opioid modulators |
| TWI410406B (zh) | 2005-05-13 | 2013-10-01 | Otsuka Pharma Co Ltd | 吡咯烷化合物 |
| CN101243079A (zh) * | 2005-06-16 | 2008-08-13 | 詹森药业有限公司 | 三环阿片调节剂 |
| JP5219465B2 (ja) * | 2006-11-10 | 2013-06-26 | 大塚製薬株式会社 | 医薬 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4091096A (en) * | 1976-03-19 | 1978-05-23 | Eli Lilly And Company | Dinitroanilines for the control of phytopathogens |
| EG12406A (en) * | 1976-08-12 | 1979-03-31 | Janssen Pharmaceutica Nv | Process for preparing of novel n-aryl-n-(1-l-4-piperidinyl)-arylacetamides |
| SE441448B (sv) * | 1977-05-23 | 1985-10-07 | Pfizer | Sett att framstella hexahydro-gamma-karbolinforeningar |
| DE3200304A1 (de) * | 1981-01-16 | 1982-08-26 | Sandoz-Patent-GmbH, 7850 Lörrach | 3-aminopropoxyaryl-derivate, ihre herstellung und sie enthaltende arzneimittel |
| EP0181793B1 (fr) * | 1984-10-16 | 1988-07-27 | Synthelabo | Dérivés de pipéridine, leur préparation et leur application en thérapeutique |
| YU150489A (sh) | 1989-08-10 | 1992-12-21 | W.L. Gore & Co. Gmbh. | Uređaj za ispitivanje odevnih predmeta na nepromočivost |
| KR940003491B1 (ko) | 1989-08-10 | 1994-04-23 | 리히터 게데온 베기에스제티 기아르 알.티 | 4,4-이중 치환된 피페리딘 유도체와 그 제조방법 및 상기 화합물을 함유하는 약제학적 조성물 |
| SE8904298D0 (sv) * | 1989-12-21 | 1989-12-21 | Astra Ab | New compounds |
| GB9202238D0 (en) * | 1992-02-03 | 1992-03-18 | Wellcome Found | Compounds |
| US5854245A (en) * | 1996-06-28 | 1998-12-29 | Merck & Co., Inc. | Fibrinogen receptor antagonists |
| SE9604786D0 (sv) * | 1996-12-20 | 1996-12-20 | Astra Pharma Inc | New compounds |
| TW548271B (en) * | 1996-12-20 | 2003-08-21 | Astra Pharma Inc | Novel piperidine derivatives having an exocyclic double bond with analgesic effects |
| JP4754068B2 (ja) * | 1997-12-24 | 2011-08-24 | オーソ−マクニール・フアーマシユーチカル・インコーポレーテツド | δ−オピオイドレセプターに結合する4−[アリール(ピペリジン−4−イル)]アミノベンズアミド類 |
| EP1512683B1 (en) | 1998-03-10 | 2011-08-31 | Research Triangle Institute | Novel opiate compounds, methods of making and methods of use |
| US6436959B1 (en) | 1998-12-23 | 2002-08-20 | Ortho-Mcneil Pharmaceutical, Inc. | 4-[aryl(piperidin-4-yl)]aminobenzamides |
-
1996
- 1996-12-20 SE SE9604786A patent/SE9604786D0/xx unknown
-
1997
- 1997-09-12 UA UA99074131A patent/UA54481C2/uk unknown
- 1997-12-09 CN CNB971808376A patent/CN1154635C/zh not_active Expired - Fee Related
- 1997-12-09 ID IDW990536A patent/ID21662A/id unknown
- 1997-12-09 CA CA002274117A patent/CA2274117A1/en not_active Abandoned
- 1997-12-09 EP EP04002901A patent/EP1428821A1/en not_active Withdrawn
- 1997-12-09 US US09/029,468 patent/US6153626A/en not_active Expired - Lifetime
- 1997-12-09 DE DE69729115T patent/DE69729115T2/de not_active Expired - Fee Related
- 1997-12-09 AU AU53513/98A patent/AU738002B2/en not_active Ceased
- 1997-12-09 BR BR9713785-5A patent/BR9713785A/pt unknown
- 1997-12-09 NZ NZ336028A patent/NZ336028A/en unknown
- 1997-12-09 TR TR1999/01411T patent/TR199901411T2/xx unknown
- 1997-12-09 JP JP52867098A patent/JP2001507021A/ja not_active Ceased
- 1997-12-09 RU RU99115746/04A patent/RU2193030C2/ru not_active IP Right Cessation
- 1997-12-09 IL IL13053697A patent/IL130536A0/xx unknown
- 1997-12-09 CN CNA2004100324204A patent/CN1539824A/zh active Pending
- 1997-12-09 EP EP97950539A patent/EP0946510B1/en not_active Expired - Lifetime
- 1997-12-09 ZA ZA9711049A patent/ZA9711049B/xx unknown
- 1997-12-09 DK DK97950539T patent/DK0946510T3/da active
- 1997-12-09 EE EEP199900261A patent/EE03966B1/xx not_active IP Right Cessation
- 1997-12-09 CZ CZ992200A patent/CZ220099A3/cs unknown
- 1997-12-09 WO PCT/SE1997/002051 patent/WO1998028270A1/en not_active Ceased
- 1997-12-09 AT AT97950539T patent/ATE266638T1/de not_active IP Right Cessation
- 1997-12-09 SK SK763-99A patent/SK283300B6/sk unknown
- 1997-12-09 ES ES97950539T patent/ES2219783T3/es not_active Expired - Lifetime
- 1997-12-09 PL PL97334370A patent/PL188945B1/pl not_active IP Right Cessation
- 1997-12-09 PT PT97950539T patent/PT946510E/pt unknown
- 1997-12-09 HU HU0000613A patent/HUP0000613A3/hu unknown
- 1997-12-09 KR KR1019997005586A patent/KR20000069600A/ko not_active Ceased
- 1997-12-19 AR ARP970106076A patent/AR010378A1/es active IP Right Grant
- 1997-12-19 MY MYPI97006174A patent/MY132705A/en unknown
-
1999
- 1999-06-11 IS IS5078A patent/IS5078A/is unknown
- 1999-06-18 NO NO19993023A patent/NO313632B1/no unknown
-
2000
- 2000-08-25 US US09/645,565 patent/US6399635B1/en not_active Expired - Fee Related
-
2002
- 2002-04-15 US US10/121,683 patent/US6710179B2/en not_active Expired - Fee Related
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PD00 | Pending as of 2000-06-30 in czech republic |