SK280837B6 - Tricyklické diazepíny, spôsob ich výroby, ich použitie a farmaceutický prípravok na ich báze - Google Patents

Tricyklické diazepíny, spôsob ich výroby, ich použitie a farmaceutický prípravok na ich báze Download PDF

Info

Publication number
SK280837B6
SK280837B6 SK2984-92A SK298492A SK280837B6 SK 280837 B6 SK280837 B6 SK 280837B6 SK 298492 A SK298492 A SK 298492A SK 280837 B6 SK280837 B6 SK 280837B6
Authority
SK
Slovakia
Prior art keywords
amino
group
dimethylamino
dioxo
alkyl
Prior art date
Application number
SK2984-92A
Other languages
English (en)
Slovak (sk)
Other versions
SK298492A3 (en
Inventor
Joseph J. Hlavka
Phaid-Eng Sum
Yakov Gluzman
Ving J. Lee
Adma A. Ross
Original Assignee
American Cyanamid Company
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.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=25092264&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=SK280837(B6) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by American Cyanamid Company filed Critical American Cyanamid Company
Publication of SK298492A3 publication Critical patent/SK298492A3/sk
Publication of SK280837B6 publication Critical patent/SK280837B6/sk

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/24Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring of the carbon skeleton
    • C07C237/26Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring of the carbon skeleton of a ring being part of a condensed ring system formed by at least four rings, e.g. tetracycline
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/16Amides, e.g. hydroxamic acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D205/00Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D205/02Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D205/04Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D277/00Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20Heterocyclic 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
    • C07D277/32Heterocyclic 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 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
    • C07D277/38Nitrogen atoms
    • C07D277/44Acylated amino or imino radicals
    • C07D277/46Acylated amino or imino radicals by carboxylic acids, or sulfur or nitrogen analogues thereof
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D307/00Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three 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
    • C07D307/68Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D333/00Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/24Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D333/00Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur 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
    • C07D333/30Hetero atoms other than halogen
    • C07D333/34Sulfur atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D333/00Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur 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
    • C07D333/38Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00Systems containing at least three condensed rings
    • C07C2603/02Ortho- or ortho- and peri-condensed systems
    • C07C2603/40Ortho- or ortho- and peri-condensed systems containing four condensed rings
    • C07C2603/42Ortho- or ortho- and peri-condensed systems containing four condensed rings containing only six-membered rings
    • C07C2603/44Naphthacenes; Hydrogenated naphthacenes
    • C07C2603/461,4,4a,5,5a,6,11,12a- Octahydronaphthacenes, e.g. tetracyclines

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)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Peptides Or Proteins (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
  • Furan Compounds (AREA)
  • Moulding By Coating Moulds (AREA)
  • Heterocyclic Compounds Containing Sulfur Atoms (AREA)
  • Pyrrole Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Saccharide Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Hydrogenated Pyridines (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
SK2984-92A 1991-10-04 1992-09-30 Tricyklické diazepíny, spôsob ich výroby, ich použitie a farmaceutický prípravok na ich báze SK280837B6 (sk)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US77157691A 1991-10-04 1991-10-04

Publications (2)

Publication Number Publication Date
SK298492A3 SK298492A3 (en) 1995-03-08
SK280837B6 true SK280837B6 (sk) 2000-08-14

Family

ID=25092264

Family Applications (2)

Application Number Title Priority Date Filing Date
SK2984-92A SK280837B6 (sk) 1991-10-04 1992-09-30 Tricyklické diazepíny, spôsob ich výroby, ich použitie a farmaceutický prípravok na ich báze
SK1149-99A SK284826B6 (sk) 1991-10-04 1992-09-30 7-Nitro-9-substituovaný amino-6-demetyl-6-deoxytetracyklíny a spôsoby ich výroby

Family Applications After (1)

Application Number Title Priority Date Filing Date
SK1149-99A SK284826B6 (sk) 1991-10-04 1992-09-30 7-Nitro-9-substituovaný amino-6-demetyl-6-deoxytetracyklíny a spôsoby ich výroby

Country Status (28)

Country Link
EP (1) EP0536515B1 (fi)
JP (1) JP3186863B2 (fi)
KR (1) KR100269072B1 (fi)
CN (1) CN1048240C (fi)
AT (1) ATE211128T1 (fi)
AU (1) AU654049B2 (fi)
BR (1) BR1100853A (fi)
CA (1) CA2079692C (fi)
CL (1) CL2004001623A1 (fi)
CZ (2) CZ284159B6 (fi)
DE (4) DE69232302T4 (fi)
DK (1) DK0536515T3 (fi)
ES (1) ES2168254T3 (fi)
FI (1) FI114911B (fi)
HK (1) HK1011348A1 (fi)
HU (2) HU219973B (fi)
IL (3) IL119590A (fi)
LU (1) LU91279I2 (fi)
MX (1) MX9205532A (fi)
NL (1) NL300244I2 (fi)
NO (3) NO301472B1 (fi)
NZ (1) NZ244585A (fi)
PL (4) PL172282B1 (fi)
PT (1) PT536515E (fi)
SG (1) SG52361A1 (fi)
SK (2) SK280837B6 (fi)
TW (1) TW275616B (fi)
ZA (1) ZA927607B (fi)

Families Citing this family (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5420272A (en) * 1992-08-13 1995-05-30 American Cyanamid Company 7-(substituted)-8-(substituted)-9-](substituted glycyl)amido]-6-demethyl-6-deoxytetracyclines
US5284963A (en) * 1992-08-13 1994-02-08 American Cyanamid Company Method of producing 7-(substituted)-9-[(substituted glycyl)-amidol]-6-demethyl-6-deoxytetra-cyclines
US5328902A (en) * 1992-08-13 1994-07-12 American Cyanamid Co. 7-(substituted)-9-[(substituted glycyl)amido]-6-demethyl-6-deoxytetracyclines
WO1995022529A1 (en) * 1994-02-17 1995-08-24 Pfizer Inc. 9-(substituted amino)-alpha-6-deoxy-5-oxy tetracycline derivatives, their preparation and their use as antibiotics
DE60027465T2 (de) 1999-09-14 2007-02-01 The Trustees Of Tufts College, Medford Verfahren zur herstellung von substituierten tetracyclinen mit hilfe von auf übergangsmetalle basierten chemien
US8106225B2 (en) 1999-09-14 2012-01-31 Trustees Of Tufts College Methods of preparing substituted tetracyclines with transition metal-based chemistries
CA2404628A1 (en) * 2000-03-31 2001-10-11 Stuart B. Levy 7-and 9-carbamate, urea, thiourea, thiocarbamate, and heteroaryl-amino substituted tetracycline compounds
EP2308863A1 (en) * 2000-05-15 2011-04-13 Paratek Pharmaceuticals, Inc. 7-substituted fused ring tetracycline compounds
CN1690047B (zh) * 2000-07-07 2010-10-06 塔夫茨大学信托人 9-取代的二甲胺四环素化合物
US7094806B2 (en) 2000-07-07 2006-08-22 Trustees Of Tufts College 7, 8 and 9-substituted tetracycline compounds
US7553828B2 (en) 2001-03-13 2009-06-30 Paratek Pharmaceuticals, Inc. 9-aminomethyl substituted minocycline compounds
BR0116935A (pt) 2001-03-13 2005-04-12 Paratek Pharm Innc Composto de tetraciclina, método para tratar um estado responsivo à tetraciclina em um indivìduo, e, composição farmacêutica
AU2002250331A1 (en) 2001-03-13 2002-09-24 Paratek Pharmaceuticals, Inc. 7-pyrollyl tetracycline compounds and methods of use thereof
EP1241160A1 (en) 2001-03-13 2002-09-18 Glaxo Group Limited Tetracycline derivatives and their use as antibiotic agents
AU2002254714C1 (en) * 2001-04-24 2010-01-07 Paratek Pharmaceuticals, Inc. Substituted tetracycline compounds for the treatment of malaria
EP2332550A1 (en) 2001-07-13 2011-06-15 Paratek Pharmaceuticals, Inc. Tetracyclines for the treatment of neurodegenerative diseases
WO2003055441A2 (en) 2001-08-02 2003-07-10 Paratek Pharmaceuticals, Inc. Medicaments
JP2005514410A (ja) 2002-01-08 2005-05-19 パラテック ファーマシューティカルズ インコーポレイテッド 4−デジメチルアミノテトラサイクリン化合物
AU2003220123B2 (en) * 2002-03-08 2009-05-07 Paratek Pharmaceuticals, Inc. Amino-methyl substituted tetracycline compounds
CA2531728A1 (en) 2003-07-09 2005-02-03 Paratek Pharmaceuticals, Inc. Substituted tetracycline compounds
UA83266C2 (en) * 2003-12-08 2008-06-25 Уайет Oxazole derivatives of tetracyclines
CN101027279B (zh) 2004-05-21 2013-03-27 哈佛大学校长及研究员协会 四环素及其类似物的合成
US7534766B2 (en) 2004-11-05 2009-05-19 Wyeth Glucuronide metabolites and epimers thereof of tigecycline
AR057649A1 (es) 2005-05-27 2007-12-12 Wyeth Corp Formas solidas cristalinas de tigeciclina y metodos para preparar las mismas
CA2620600A1 (en) * 2005-08-31 2007-03-08 Wyeth 9-aminocarbonylsubstituted derivatives of glycylcyclines
US20080118979A1 (en) 2006-05-15 2008-05-22 Paratek Pharmaceuticals, Inc. Methods of regulating expression of genes or of gene products using substituted tetracycline compounds
US8518912B2 (en) 2007-11-29 2013-08-27 Actelion Pharmaceuticals Ltd. Phosphonic acid derivates and their use as P2Y12 receptor antagonists
PT2271348T (pt) 2008-03-28 2018-04-16 Paratek Pharm Innc Formulação de comprimido oral de composto de tetraciclina
ITMI20080807A1 (it) 2008-05-05 2009-11-06 Antibioticos Spa Procedimento per la preparazione di tigeciclina in forma amorfa
TW202332671A (zh) 2008-05-23 2023-08-16 美商Prtk Spv2公司 四環素化合物之甲苯磺酸鹽及同素異形體
SG10201806714PA (en) * 2008-08-08 2018-09-27 Tetraphase Pharmaceuticals Inc C7-fluoro substituted tetracycline compounds
WO2010126607A2 (en) 2009-04-30 2010-11-04 President And Fellows Of Harvard College Synthesis of tetracyclines and intermediates thereto
EP2427425B1 (en) 2009-05-08 2017-03-08 Tetraphase Pharmaceuticals, Inc. Tetracycline compounds
US9624166B2 (en) 2009-08-28 2017-04-18 Tetraphase Pharmaceuticals, Inc. Tetracycline compounds
KR101799304B1 (ko) 2010-05-12 2017-11-20 렘펙스 파머수티클스 인코퍼레이티드 테트라사이클린 조성물
CN103635456B (zh) * 2011-07-26 2016-03-09 山东亨利医药科技有限责任公司 替加环素衍生物
EP3461809A1 (en) 2012-08-31 2019-04-03 Tetraphase Pharmaceuticals, Inc. Tetracycline compounds
WO2015071299A2 (en) 2013-11-12 2015-05-21 Galenicum Health S.L. Stable pharmaceutical compositions
KR20240058958A (ko) 2016-10-19 2024-05-07 테트라페이즈 파마슈티컬스, 인코포레이티드 에라바사이클린의 결정질 형태

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3338963A (en) * 1960-10-28 1967-08-29 American Cyanamid Co Tetracycline compounds
US3579579A (en) * 1968-04-18 1971-05-18 American Cyanamid Co Substituted 7- and/or 9-amino-6-demethyl-6-deoxytetracyclines

Also Published As

Publication number Publication date
NO2006015I2 (no) 2011-03-14
NO923857D0 (no) 1992-10-02
NO2017037I1 (no) 2017-08-01
SK114999A3 (en) 2000-07-11
CN1072172A (zh) 1993-05-19
PL172282B1 (pl) 1997-08-29
IL103320A (en) 1998-12-06
ATE211128T1 (de) 2002-01-15
NZ244585A (en) 1995-07-26
NO2017037I2 (no) 2017-08-01
JPH05255219A (ja) 1993-10-05
NO923857L (no) 1993-04-05
FI924454A0 (fi) 1992-10-02
NL300244I1 (nl) 2007-01-02
SG52361A1 (en) 1998-09-28
CZ309397A3 (cs) 1998-09-16
MX9205532A (es) 1993-04-01
DE122006000058I2 (de) 2007-09-13
CZ284159B6 (cs) 1998-08-12
PL173311B1 (pl) 1998-02-27
IL103320A0 (en) 1993-03-15
DK0536515T3 (da) 2002-04-08
DE69232302T4 (de) 2003-02-13
EP0536515A1 (en) 1993-04-14
KR100269072B1 (ko) 2000-10-16
JP3186863B2 (ja) 2001-07-11
CN1048240C (zh) 2000-01-12
NL300244I2 (nl) 2007-01-02
ZA927607B (en) 1993-04-13
DE122006000058I1 (de) 2007-01-18
HUT63145A (en) 1993-07-28
NO301472B1 (no) 1997-11-03
SK298492A3 (en) 1995-03-08
IL119590A (en) 1999-03-12
HU211172A9 (en) 1995-11-28
PL176333B1 (pl) 1999-05-31
HU219973B (hu) 2001-10-28
CL2004001623A1 (es) 2005-06-03
CZ284209B6 (cs) 1998-09-16
FI924454A (fi) 1993-04-05
LU91279I2 (fr) 2006-12-11
PL175957B1 (pl) 1999-03-31
ES2168254T3 (es) 2002-06-16
HU9203110D0 (en) 1992-12-28
AU2618392A (en) 1993-04-08
PT536515E (pt) 2002-05-31
DE69232302D1 (de) 2002-01-31
AU654049B2 (en) 1994-10-20
BR1100853A (pt) 1999-12-07
KR930007894A (ko) 1993-05-20
CA2079692A1 (en) 1993-04-05
CA2079692C (en) 2004-06-08
DE69232302T2 (de) 2002-08-14
PL296143A1 (en) 1993-05-31
TW275616B (fi) 1996-05-11
HK1011348A1 (en) 1999-07-09
EP0536515B1 (en) 2001-12-19
NO2006015I1 (no) 2006-11-27
SK284826B6 (sk) 2005-12-01
FI114911B (fi) 2005-01-31
IL119590A0 (en) 1997-02-18
CZ298492A3 (en) 1993-05-12

Similar Documents

Publication Publication Date Title
SK280837B6 (sk) Tricyklické diazepíny, spôsob ich výroby, ich použitie a farmaceutický prípravok na ich báze
USRE40086E1 (en) Method for treating bacterial infection with novel 7-substituted-9-substituted amino 6-demethyl-6-deoxytetracyclines
JP3639313B2 (ja) 新規な7−(置換)−8−(置換)−9−(置換アミノ)−6−デメチル−6−デオキシテトラシクリン類
EP0535346B1 (en) 9-amino-7-substituted-6-demethyl-6-deoxytetracyclines
SK84893A3 (en) 9-[(substituted glycyl)-6-demethyl]-6-deoxytetracyclines and process for their preparation
SK281866B6 (sk) 7-(substituované)-8-(substituované)-9-[(substituovaný glycyl) amido]-6-demetyl-6-deoxytetracyklíny, medziprodukt a spôsob ich výroby
JPH06206855A (ja) 7−(置換された)−9−[(置換されたグリシル)アミド]−6−デメチル−6−デオキシテトラサイクリン類
USRE40183E1 (en) 7-Substituted-9-substituted amino-6-demethyl-6-deoxytetracyclines
KR20080041722A (ko) 글리실사이클린의 9-아미노카르보닐 치환된 유도체

Legal Events

Date Code Title Description
MK4A Expiry of patent

Expiry date: 20120930

SPCE Expiry of an spc

Spc suppl protection certif: DO. 46; 3-2006

Effective date: 20180401