GB0125259D0 - Novel compounds - Google Patents

Novel compounds

Info

Publication number
GB0125259D0
GB0125259D0 GBGB0125259.2A GB0125259A GB0125259D0 GB 0125259 D0 GB0125259 D0 GB 0125259D0 GB 0125259 A GB0125259 A GB 0125259A GB 0125259 D0 GB0125259 D0 GB 0125259D0
Authority
GB
United Kingdom
Prior art keywords
sub
img
character
tif
novel compounds
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.)
Ceased
Application number
GBGB0125259.2A
Other languages
English (en)
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Glaxo Group Ltd
Original Assignee
Glaxo Group Ltd
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
Application filed by Glaxo Group Ltd filed Critical Glaxo Group Ltd
Priority to GBGB0125259.2A priority Critical patent/GB0125259D0/en
Publication of GB0125259D0 publication Critical patent/GB0125259D0/en
Priority to DE60226334T priority patent/DE60226334T2/de
Priority to AU2002350561A priority patent/AU2002350561A1/en
Priority to EP02785235A priority patent/EP1444248B1/en
Priority to PCT/EP2002/011634 priority patent/WO2003035668A2/en
Priority to JP2003538181A priority patent/JP4495456B2/ja
Priority to US10/492,813 priority patent/US7405206B2/en
Priority to ES02785235T priority patent/ES2304457T3/es
Priority to AT02785235T priority patent/ATE393771T1/de
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
    • C07J31/006—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring not covered by C07J31/003
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • 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]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
    • A61P5/44—Glucocorticosteroids; Drugs increasing or potentiating the activity of glucocorticosteroids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J17/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, having an oxygen-containing hetero ring not condensed with the cyclopenta(a)hydrophenanthrene skeleton

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Pulmonology (AREA)
  • Dermatology (AREA)
  • Immunology (AREA)
  • Diabetes (AREA)
  • Endocrinology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Steroid Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
GBGB0125259.2A 2001-10-20 2001-10-20 Novel compounds Ceased GB0125259D0 (en)

Priority Applications (9)

Application Number Priority Date Filing Date Title
GBGB0125259.2A GB0125259D0 (en) 2001-10-20 2001-10-20 Novel compounds
DE60226334T DE60226334T2 (de) 2001-10-20 2002-10-17 Neue antiphlogistische androstan derivate - 17-carboxy-lactone substituiert mit einer aryl-carboxylic estergruppe in der 17.alpha.-stelle
AU2002350561A AU2002350561A1 (en) 2001-10-20 2002-10-17 Novel anti-inflammatory androstane derivatives -17-carboxy-lactone substituted steroids with an aryl-carboxylic ester in position 17.alpha
EP02785235A EP1444248B1 (en) 2001-10-20 2002-10-17 Novel anti-inflammatory androstane derivatives - 17-carboxy-lactone substituted steroids with an aryl-carboxylic ester in position 17.alpha
PCT/EP2002/011634 WO2003035668A2 (en) 2001-10-20 2002-10-17 Novel anti-inflammatory androstane derivatives -17-carboxy-lactone substituted steroids with an aryl-carboxylic ester in position 17.alpha
JP2003538181A JP4495456B2 (ja) 2001-10-20 2002-10-17 新規の抗炎症性アンドロスタン誘導体
US10/492,813 US7405206B2 (en) 2001-10-20 2002-10-17 Anti-inflammatory androstane derivatives
ES02785235T ES2304457T3 (es) 2001-10-20 2002-10-17 Nuevos antiinflamatorios esteroides derivados de adrostano 17-carboxi-lactona sustituidos con un ester aril-carboxilico en posicion 17-alfa.
AT02785235T ATE393771T1 (de) 2001-10-20 2002-10-17 Neue antiphlogistische androstan derivate - 17- carboxy-lactone substituiert mit einer aryl- carboxylic estergruppe in der 17.alpha.-stelle

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GBGB0125259.2A GB0125259D0 (en) 2001-10-20 2001-10-20 Novel compounds

Publications (1)

Publication Number Publication Date
GB0125259D0 true GB0125259D0 (en) 2001-12-12

Family

ID=9924247

Family Applications (1)

Application Number Title Priority Date Filing Date
GBGB0125259.2A Ceased GB0125259D0 (en) 2001-10-20 2001-10-20 Novel compounds

Country Status (9)

Country Link
US (1) US7405206B2 (enExample)
EP (1) EP1444248B1 (enExample)
JP (1) JP4495456B2 (enExample)
AT (1) ATE393771T1 (enExample)
AU (1) AU2002350561A1 (enExample)
DE (1) DE60226334T2 (enExample)
ES (1) ES2304457T3 (enExample)
GB (1) GB0125259D0 (enExample)
WO (1) WO2003035668A2 (enExample)

Families Citing this family (66)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6858593B2 (en) 2000-08-05 2005-02-22 Smithkline Beecham Corporation Anti-inflammatory androstane derivative compositions
US6777399B2 (en) 2000-08-05 2004-08-17 Smithkline Beecham Corporation Anti-inflammatory androstane derivative compositions
US6858596B2 (en) 2000-08-05 2005-02-22 Smithkline Beecham Corporation Formulation containing anti-inflammatory androstane derivative
CA2417826A1 (en) 2000-08-05 2002-02-14 Glaxo Group Limited 17.beta.-carbothioate 17.alpha.-arylcarbonyloxyloxy androstane derivative as anti-inflammatory agents
GB0019172D0 (en) 2000-08-05 2000-09-27 Glaxo Group Ltd Novel compounds
UA77656C2 (en) 2001-04-07 2007-01-15 Glaxo Group Ltd S-fluoromethyl ester of 6-alpha, 9-alpha-difluoro-17-alpha-[(2-furanylcarbonyl)oxy]-11-beta-hydroxy-16- alpha-methyl-3-oxoandrosta-1,4-dien-17-beta-carbothioacid as anti-inflammatory agent
AR033290A1 (es) 2001-04-30 2003-12-10 Glaxo Group Ltd Derivados antiinflamatorios de androstano
GB2389530B (en) 2002-06-14 2007-01-10 Cipla Ltd Pharmaceutical compositions
AR044519A1 (es) 2003-05-02 2005-09-14 Novartis Ag Derivados de piridin-tiazol amina y de pirimidin-tiazol amina
GB0316290D0 (en) * 2003-07-11 2003-08-13 Glaxo Group Ltd Novel compounds
GB0401334D0 (en) 2004-01-21 2004-02-25 Novartis Ag Organic compounds
GB0411056D0 (en) 2004-05-18 2004-06-23 Novartis Ag Organic compounds
GT200500281A (es) 2004-10-22 2006-04-24 Novartis Ag Compuestos organicos.
GB0424284D0 (en) 2004-11-02 2004-12-01 Novartis Ag Organic compounds
GB0426164D0 (en) 2004-11-29 2004-12-29 Novartis Ag Organic compounds
GB0507577D0 (en) 2005-04-14 2005-05-18 Novartis Ag Organic compounds
GB0510390D0 (en) 2005-05-20 2005-06-29 Novartis Ag Organic compounds
GB0516313D0 (en) 2005-08-08 2005-09-14 Argenta Discovery Ltd Azole derivatives and their uses
RU2442771C2 (ru) 2005-08-08 2012-02-20 Арджента Дискавери Лтд Производные бицикло[2,2,1]гепт-7-иламина и их применения
EP2532677A1 (en) 2005-10-21 2012-12-12 Novartis AG Human antibodies against il13 and therapeutic uses
GB0526244D0 (en) 2005-12-22 2006-02-01 Novartis Ag Organic compounds
TWI374147B (en) * 2006-01-27 2012-10-11 Sun Pharma Advance Res Company Ltd Novel 11β-hydroxyandrosta-4-ene-3-ones
GB0601951D0 (en) 2006-01-31 2006-03-15 Novartis Ag Organic compounds
HRP20120494T1 (hr) 2006-04-21 2012-08-31 Novartis Ag Derivati purina za uporabu kao agonista adenozin a2a receptora
JP2010504933A (ja) 2006-09-29 2010-02-18 ノバルティス アーゲー Pi3k脂質キナーゼ阻害剤としてのピラゾロピリミジン
AU2007342223B2 (en) 2007-01-10 2011-02-24 Irm Llc Compounds and compositions as channel activating protease inhibitors
EP2332933A1 (en) 2007-05-07 2011-06-15 Novartis AG Epithelial sodium channel (ENaC) inhibitors
BRPI0820669A2 (pt) 2007-12-10 2020-08-04 Novartis Ag compostos orgânicos
KR20110040818A (ko) 2008-06-10 2011-04-20 노파르티스 아게 상피 나트륨 채널 차단제로서의 피라진 유도체
PL2379507T3 (pl) 2008-12-30 2014-03-31 Pulmagen Therapeutics Inflammation Ltd Związki sulfonamidu do leczenia zaburzeń układu oddechowego
ES2396023T3 (es) 2009-01-29 2013-02-18 Novartis Ag Bencimidazoles sustituidos para el tratamiento de astrocitomas
TW201111392A (en) 2009-06-16 2011-04-01 Schering Corp Novel [3,2-c] heteroaryl steroids as glucocorticoid receptor agonists, compositions and uses thereof
US8389526B2 (en) 2009-08-07 2013-03-05 Novartis Ag 3-heteroarylmethyl-imidazo[1,2-b]pyridazin-6-yl derivatives
BR112012003262A8 (pt) 2009-08-12 2016-05-17 Novartis Ag compostos de hidrazona heterocíclica e seus usos para tratar câncer e inflamação
UA111579C2 (uk) 2009-08-17 2016-05-25 Інтеллікіне Ллк ГЕТЕРОЦИКЛІЧНІ ПОХІДНІ 2-АМІНОБЕНЗО[d]ОКСАЗОЛУ, ФАРМАЦЕВТИЧНА КОМПОЗИЦІЯ НА ЇХ ОСНОВІ ТА ЇХ ЗАСТОСУВАННЯ ДЛЯ ЛІКУВАННЯ ЗАХВОРЮВАННЯ, ПОВ'АНОГО З РІ3-КІНАЗОЮ
IN2012DN01453A (enExample) 2009-08-20 2015-06-05 Novartis Ag
AU2010310449A1 (en) 2009-10-22 2012-05-03 Vertex Pharmaceuticals Incorporated Compositions for treatment of cystic fibrosis and other chronic diseases
US8247436B2 (en) 2010-03-19 2012-08-21 Novartis Ag Pyridine and pyrazine derivative for the treatment of CF
WO2012034095A1 (en) 2010-09-09 2012-03-15 Irm Llc Compounds and compositions as trk inhibitors
UY33597A (es) 2010-09-09 2012-04-30 Irm Llc Compuestos y composiciones como inhibidores de la trk
US8372845B2 (en) 2010-09-17 2013-02-12 Novartis Ag Pyrazine derivatives as enac blockers
WO2012107500A1 (en) 2011-02-10 2012-08-16 Novartis Ag [1, 2, 4] triazolo [4, 3 -b] pyridazine compounds as inhibitors of the c-met tyrosine kinase
WO2012116237A2 (en) 2011-02-23 2012-08-30 Intellikine, Llc Heterocyclic compounds and uses thereof
BR112013021638A2 (pt) 2011-02-25 2016-08-02 Irm Llc "compostos inibidores de trk, seu uso e composições que os compreendem"
US8883819B2 (en) 2011-09-01 2014-11-11 Irm Llc Bicyclic heterocycle derivatives for the treatment of pulmonary arterial hypertension
UY34329A (es) 2011-09-15 2013-04-30 Novartis Ag Compuestos de triazolopiridina
WO2013038381A1 (en) 2011-09-16 2013-03-21 Novartis Ag Pyridine/pyrazine amide derivatives
JP6165733B2 (ja) 2011-09-16 2017-07-19 ノバルティス アーゲー N−置換ヘテロシクリルカルボキサミド類
WO2013038373A1 (en) 2011-09-16 2013-03-21 Novartis Ag Pyridine amide derivatives
CN103946221B (zh) 2011-09-16 2016-08-03 诺华股份有限公司 用于治疗囊性纤维化的杂环化合物
WO2013038378A1 (en) 2011-09-16 2013-03-21 Novartis Ag Pyridine amide derivatives
US9174994B2 (en) 2011-11-23 2015-11-03 Intellikine, Llc Enhanced treatment regimens using mTor inhibitors
US8809340B2 (en) 2012-03-19 2014-08-19 Novartis Ag Crystalline form
MX371119B (es) 2012-04-03 2020-01-17 Novartis Ag Productos de combinacion con los inhibidores de cinasa de tirosina y su uso.
US9073921B2 (en) 2013-03-01 2015-07-07 Novartis Ag Salt forms of bicyclic heterocyclic derivatives
HK1219421A1 (zh) 2013-03-15 2017-04-07 因特利凯有限责任公司 激酶抑制剂的组合及其用途
US10155001B2 (en) 2013-06-14 2018-12-18 Inserm (Institut National De La Sante Et De La Recherche Medicale) RAC1 inhibitors for inducing bronchodilation
TW201605450A (zh) 2013-12-03 2016-02-16 諾華公司 Mdm2抑制劑與BRAF抑制劑之組合及其用途
KR20160145780A (ko) 2014-04-24 2016-12-20 노파르티스 아게 포스파티딜이노시톨 3-키나제 억제제로서의 아미노 피리딘 유도체
CA2945212A1 (en) 2014-04-24 2015-10-29 Novartis Ag Amino pyrazine derivatives as phosphatidylinositol 3-kinase inhibitors
AU2014391610B2 (en) 2014-04-24 2018-01-25 Novartis Ag Pyrazine derivatives as phosphatidylinositol 3-kinase inhibitors
WO2016011658A1 (en) 2014-07-25 2016-01-28 Novartis Ag Combination therapy
US10195208B2 (en) 2014-07-31 2019-02-05 Novartis Ag Combination therapy
US20200383960A1 (en) 2019-06-10 2020-12-10 Novartis Ag Pyridine and Pyrazine derivative for the Treatment of CF, COPD, and Bronchiectasis
KR20220052934A (ko) 2019-08-28 2022-04-28 노파르티스 아게 치환 1,3-페닐 헤테로아릴 유도체 및 질환 치료에서의 이의 용도
TW202140550A (zh) 2020-01-29 2021-11-01 瑞士商諾華公司 使用抗tslp抗體治療炎性或阻塞性氣道疾病之方法

Family Cites Families (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3828080A (en) * 1972-01-20 1974-08-06 Glaxo Lab Ltd Androstane-17beta-carboxylic acids and processes for the preparation thereof
GB1438940A (en) * 1972-07-19 1976-06-09 Glaxo Lab Ltd 17beta-haloalkoxycarbonyl-17alpha-oxysteroids
CY1359A (en) * 1981-02-02 1987-08-07 Schering Corp Aromatic heterocyclic esters of steroids, their preparation and pharmaceutical compositions containing them
EP0876392B1 (en) * 1995-12-29 2000-07-05 Glaxo Group Limited Lactone derivatives of 17.beta.-carboxy, carbothio and amide androstane derivatives
GB0015876D0 (en) * 2000-06-28 2000-08-23 Novartis Ag Organic compounds
US6759398B2 (en) * 2000-08-05 2004-07-06 Smithkline Beecham Corporation Anti-inflammatory androstane derivative
US6858593B2 (en) * 2000-08-05 2005-02-22 Smithkline Beecham Corporation Anti-inflammatory androstane derivative compositions
US6750210B2 (en) * 2000-08-05 2004-06-15 Smithkline Beecham Corporation Formulation containing novel anti-inflammatory androstane derivative
US6777399B2 (en) * 2000-08-05 2004-08-17 Smithkline Beecham Corporation Anti-inflammatory androstane derivative compositions
US6777400B2 (en) * 2000-08-05 2004-08-17 Smithkline Beecham Corporation Anti-inflammatory androstane derivative compositions
US6858596B2 (en) * 2000-08-05 2005-02-22 Smithkline Beecham Corporation Formulation containing anti-inflammatory androstane derivative
US6787532B2 (en) * 2000-08-05 2004-09-07 Smithkline Beecham Corporation Formulation containing anti-inflammatory androstane derivatives
CA2417826A1 (en) * 2000-08-05 2002-02-14 Glaxo Group Limited 17.beta.-carbothioate 17.alpha.-arylcarbonyloxyloxy androstane derivative as anti-inflammatory agents
GB0019172D0 (en) * 2000-08-05 2000-09-27 Glaxo Group Ltd Novel compounds
GB0103630D0 (en) * 2001-02-14 2001-03-28 Glaxo Group Ltd Chemical compounds
UA77656C2 (en) * 2001-04-07 2007-01-15 Glaxo Group Ltd S-fluoromethyl ester of 6-alpha, 9-alpha-difluoro-17-alpha-[(2-furanylcarbonyl)oxy]-11-beta-hydroxy-16- alpha-methyl-3-oxoandrosta-1,4-dien-17-beta-carbothioacid as anti-inflammatory agent
US20050175545A1 (en) * 2002-02-04 2005-08-11 Keith Biggadike Formulation for inhalation comprising a glucocorticoid and a beta 2-adrenoreceptor agonist
EP1480996A1 (en) * 2002-02-04 2004-12-01 Glaxo Group Limited Amorphous fluticasone 2-furoate, pharmaceutical compositions thereof and its conversion to the crystalline unsolvated form
GB0316290D0 (en) * 2003-07-11 2003-08-13 Glaxo Group Ltd Novel compounds

Also Published As

Publication number Publication date
WO2003035668A2 (en) 2003-05-01
ES2304457T3 (es) 2008-10-16
AU2002350561A1 (en) 2003-05-06
DE60226334D1 (de) 2008-06-12
EP1444248A2 (en) 2004-08-11
JP4495456B2 (ja) 2010-07-07
US7405206B2 (en) 2008-07-29
US20050054622A1 (en) 2005-03-10
DE60226334T2 (de) 2009-06-04
JP2005509642A (ja) 2005-04-14
EP1444248B1 (en) 2008-04-30
ATE393771T1 (de) 2008-05-15
WO2003035668A3 (en) 2003-07-31

Similar Documents

Publication Publication Date Title
AU2002350561A1 (en) Novel anti-inflammatory androstane derivatives -17-carboxy-lactone substituted steroids with an aryl-carboxylic ester in position 17.alpha
IL150085A0 (en) New-p2x7 receptor antagonists for use in the treatment of inflammatory, immune or cardiovascular diseases
PL366198A1 (en) Novel compounds
SE9902987D0 (sv) Novel compounds
PL358281A1 (en) Novel compounds
SE0103836D0 (sv) Novel compounds
HK1056181A1 (zh) 作為抗炎劑的17β-硫代羧酸酯17α-芳基羰氧基氧雄甾烷衍生物
DE60116761D1 (en) Adamantanderivate
MXPA02012033A (es) Derivados de 2-aminocarbonil-9h-purina.
NO20022655L (no) <Beta>-2-adrenerge reseptoragonister
SE0104140D0 (sv) Novel Compounds
SE0202539D0 (sv) Compounds
MY135477A (en) 2-(2,6-dichlorophenyl)-diarylimidazoles
PL367682A1 (en) Dolastatin 10 derivatives
MXPA03002911A (es) Compuestos quimicos.
EE05091B1 (et) Oligosahhariidid, nende valmistamismeetod ja kasutamine ning farmatseutilised kompositsioonid
ZA200110540B (en) Novel diphenyl-piperidine derivate.
MXPA04001968A (es) Agentes antidiabeticos.
GB0104050D0 (en) Chemical compounds
AU2001290480A1 (en) Cyclized benzamide neurokinin antagonists for use in therapy
SE0101038D0 (sv) Novel compounds
AP2001002191A0 (en) 3,3- Biarylpiperine and 2,2-biarylmorpholine derivatives.
GB0120461D0 (en) Novel compounds
SE9902551D0 (sv) Novel compounds
MXPA02012426A (es) Compuestos nuevos.

Legal Events

Date Code Title Description
AT Applications terminated before publication under section 16(1)