AU2017376629B2 - Benzimidazole compounds as c-Kit inhibitors - Google Patents

Benzimidazole compounds as c-Kit inhibitors Download PDF

Info

Publication number
AU2017376629B2
AU2017376629B2 AU2017376629A AU2017376629A AU2017376629B2 AU 2017376629 B2 AU2017376629 B2 AU 2017376629B2 AU 2017376629 A AU2017376629 A AU 2017376629A AU 2017376629 A AU2017376629 A AU 2017376629A AU 2017376629 B2 AU2017376629 B2 AU 2017376629B2
Authority
AU
Australia
Prior art keywords
methyl
cancer
disorder
alkyl
benzo
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
AU2017376629A
Other languages
English (en)
Other versions
AU2017376629A1 (en
Inventor
Nicholas E. Bencivenga
David C. Dalgarno
Joseph M. Gozgit
Wei-Sheng Huang
Anna Kohlmann
Feng Li
Jiwei Qi
William C. Shakespeare
Ranny M. Thomas
Yihan Wang
Yun Zhang
Xiaotian Zhu
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.)
Ariad Pharmaceuticals Inc
Original Assignee
Ariad Pharmaceuticals Inc
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 Ariad Pharmaceuticals Inc filed Critical Ariad Pharmaceuticals Inc
Publication of AU2017376629A1 publication Critical patent/AU2017376629A1/en
Application granted granted Critical
Publication of AU2017376629B2 publication Critical patent/AU2017376629B2/en
Priority to AU2022201082A priority Critical patent/AU2022201082B2/en
Priority to AU2024200624A priority patent/AU2024200624A1/en
Ceased legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/41641,3-Diazoles
    • A61K31/41841,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/06Antiasthmatics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/04Anorexiants; Antiobesity agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/08Antiallergic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D235/00Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/06Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • C07D235/08Radicals containing only hydrogen and carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pulmonology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Rheumatology (AREA)
  • Hematology (AREA)
  • Pain & Pain Management (AREA)
  • Child & Adolescent Psychology (AREA)
  • Obesity (AREA)
  • Diabetes (AREA)
  • Epidemiology (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
AU2017376629A 2016-12-15 2017-12-14 Benzimidazole compounds as c-Kit inhibitors Ceased AU2017376629B2 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU2022201082A AU2022201082B2 (en) 2016-12-15 2022-02-18 Benzimidazole compounds as c-Kit inhibitors
AU2024200624A AU2024200624A1 (en) 2016-12-15 2024-02-01 Benzimidazole compounds as c-Kit inhibitors

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201662434839P 2016-12-15 2016-12-15
US62/434,839 2016-12-15
PCT/US2017/066299 WO2018112140A1 (en) 2016-12-15 2017-12-14 Benzimidazole compounds as c-kit inhibitors

Related Child Applications (1)

Application Number Title Priority Date Filing Date
AU2022201082A Division AU2022201082B2 (en) 2016-12-15 2022-02-18 Benzimidazole compounds as c-Kit inhibitors

Publications (2)

Publication Number Publication Date
AU2017376629A1 AU2017376629A1 (en) 2019-07-04
AU2017376629B2 true AU2017376629B2 (en) 2021-11-25

Family

ID=60888754

Family Applications (3)

Application Number Title Priority Date Filing Date
AU2017376629A Ceased AU2017376629B2 (en) 2016-12-15 2017-12-14 Benzimidazole compounds as c-Kit inhibitors
AU2022201082A Ceased AU2022201082B2 (en) 2016-12-15 2022-02-18 Benzimidazole compounds as c-Kit inhibitors
AU2024200624A Abandoned AU2024200624A1 (en) 2016-12-15 2024-02-01 Benzimidazole compounds as c-Kit inhibitors

Family Applications After (2)

Application Number Title Priority Date Filing Date
AU2022201082A Ceased AU2022201082B2 (en) 2016-12-15 2022-02-18 Benzimidazole compounds as c-Kit inhibitors
AU2024200624A Abandoned AU2024200624A1 (en) 2016-12-15 2024-02-01 Benzimidazole compounds as c-Kit inhibitors

Country Status (13)

Country Link
US (2) US11117883B2 (enExample)
EP (1) EP3555066A1 (enExample)
JP (2) JP7158383B2 (enExample)
KR (1) KR20190092538A (enExample)
CN (3) CN110291081B (enExample)
AU (3) AU2017376629B2 (enExample)
BR (1) BR112019012224A2 (enExample)
CA (1) CA3047107A1 (enExample)
EA (1) EA201991197A1 (enExample)
IL (3) IL314209A (enExample)
MA (1) MA53150A (enExample)
MX (2) MX390348B (enExample)
WO (1) WO2018112140A1 (enExample)

Families Citing this family (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110291081B (zh) * 2016-12-15 2023-01-31 阿瑞雅德制药公司 作为c-kit抑制剂的苯并咪唑化合物
CN109320503B (zh) * 2018-12-10 2022-07-01 怀化学院 苯并咪唑炔胺类化合物的无金属一锅合成方法
CN114364798A (zh) 2019-03-21 2022-04-15 欧恩科斯欧公司 用于治疗癌症的Dbait分子与激酶抑制剂的组合
US20220401436A1 (en) 2019-11-08 2022-12-22 INSERM (Institute National de la Santé et de la Recherche Médicale) Methods for the treatment of cancers that have acquired resistance to kinase inhibitors
US11845723B2 (en) 2019-12-24 2023-12-19 Gilead Sciences, Inc. Diacylglycerol kinase modulating compounds
WO2021148581A1 (en) 2020-01-22 2021-07-29 Onxeo Novel dbait molecule and its use
CR20220396A (es) 2020-02-14 2022-11-14 Jounce Therapeutics Inc Anticuerpos y proteínas de fusión que se unen a ccr8 y usos de estos
CN117377671A (zh) 2021-06-23 2024-01-09 吉利德科学公司 二酰基甘油激酶调节化合物
IL309378A (en) 2021-06-23 2024-02-01 Gilead Sciences Inc Diacylglyercol kinase modulating compounds
AU2022297367B2 (en) 2021-06-23 2025-04-10 Gilead Sciences, Inc. Diacylglyercol kinase modulating compounds
CA3222277A1 (en) 2021-06-23 2022-12-29 Gilead Sciences, Inc. Diacylglyercol kinase modulating compounds
WO2023076983A1 (en) 2021-10-28 2023-05-04 Gilead Sciences, Inc. Pyridizin-3(2h)-one derivatives
PE20241186A1 (es) 2021-10-29 2024-06-03 Gilead Sciences Inc Compuestos de cd73
JP2024545193A (ja) 2021-12-22 2024-12-05 ギリアード サイエンシーズ, インコーポレイテッド Ikarosジンクフィンガーファミリー分解剤及びその使用
AU2022419982A1 (en) 2021-12-22 2024-06-06 Gilead Sciences, Inc. Ikaros zinc finger family degraders and uses thereof
TW202340168A (zh) 2022-01-28 2023-10-16 美商基利科學股份有限公司 Parp7抑制劑
EP4493554A1 (en) 2022-03-17 2025-01-22 Gilead Sciences, Inc. Ikaros zinc finger family degraders and uses thereof
AU2023256670A1 (en) 2022-04-21 2024-10-17 Gilead Sciences, Inc. Kras g12d modulating compounds
WO2024006929A1 (en) 2022-07-01 2024-01-04 Gilead Sciences, Inc. Cd73 compounds
AU2023409398A1 (en) 2022-12-22 2025-06-05 Gilead Sciences, Inc. Prmt5 inhibitors and uses thereof
WO2024215754A1 (en) 2023-04-11 2024-10-17 Gilead Sciences, Inc. Kras modulating compounds
AU2024259556A1 (en) 2023-04-21 2025-10-23 Gilead Sciences, Inc. Prmt5 inhibitors and uses thereof
US20250042922A1 (en) 2023-06-30 2025-02-06 Gilead Sciences, Inc. Kras modulating compounds
TW202519517A (zh) 2023-07-26 2025-05-16 美商基利科學股份有限公司 Parp7抑制劑
WO2025024663A1 (en) 2023-07-26 2025-01-30 Gilead Sciences, Inc. Parp7 inhibitors
US20250109147A1 (en) 2023-09-08 2025-04-03 Gilead Sciences, Inc. Kras g12d modulating compounds
WO2025054347A1 (en) 2023-09-08 2025-03-13 Gilead Sciences, Inc. Kras g12d modulating compounds
WO2025096589A1 (en) 2023-11-03 2025-05-08 Gilead Sciences, Inc. Prmt5 inhibitors and uses thereof
WO2025137640A1 (en) 2023-12-22 2025-06-26 Gilead Sciences, Inc. Azaspiro wrn inhibitors
US20250376484A1 (en) 2024-05-21 2025-12-11 Gilead Sciences, Inc. Prmt5 inhibitors and uses thereof

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2896620A1 (en) * 2012-09-17 2015-07-22 Nanjing Sanhome Pharmaceutical Co., Ltd. Alkynyl heteroaromatic ring compound and application thereof

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5262564A (en) 1992-10-30 1993-11-16 Octamer, Inc. Sulfinic acid adducts of organo nitroso compounds useful as retroviral inactivating agents anti-retroviral agents and anti-tumor agents
UA82395C2 (en) * 2003-08-21 2008-04-10 Оси Фармасьютикалз, Инк. N-substituted benzimidazolyl c-kit inhibitors
US7419995B2 (en) * 2004-12-01 2008-09-02 Osi Pharmaceuticals, Inc. N-substituted benzimidazoyl c-Kit inhibitors and combinatorial benzimidazole library
UA94055C2 (en) * 2005-08-30 2011-04-11 Новартис Аг Substituted benzimidazoles and methods of preparation
EP2493460A4 (en) * 2009-10-30 2013-04-24 Ariad Pharma Inc METHOD AND COMPOSITIONS FOR THE TREATMENT OF CANCER
EA024729B1 (ru) * 2009-11-13 2016-10-31 Джиноско Киназные ингибиторы
EP2694064A1 (en) * 2011-04-07 2014-02-12 Ariad Pharmaceuticals, Incorporated Methods and compositions for treating neurodegenerative diseases
CA3167093A1 (en) * 2012-12-12 2014-06-12 Ariad Pharmaceuticals, Inc. Crystalline form c of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methyl-n-{4-[(4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl}benzamide mono hydrochloride
GB2522226A (en) * 2014-01-17 2015-07-22 Agency Science Tech & Res Heteroaryl alkyne derivatives and uses thereof
CN110291081B (zh) * 2016-12-15 2023-01-31 阿瑞雅德制药公司 作为c-kit抑制剂的苯并咪唑化合物

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2896620A1 (en) * 2012-09-17 2015-07-22 Nanjing Sanhome Pharmaceutical Co., Ltd. Alkynyl heteroaromatic ring compound and application thereof

Also Published As

Publication number Publication date
MX390348B (es) 2025-03-20
IL287517B1 (en) 2024-08-01
CN116178343A (zh) 2023-05-30
IL267260A (en) 2019-08-29
EA201991197A1 (ru) 2020-01-13
EP3555066A1 (en) 2019-10-23
US20220064144A1 (en) 2022-03-03
CA3047107A1 (en) 2018-06-21
CN116283910A (zh) 2023-06-23
AU2024200624A1 (en) 2024-02-22
MX2022002581A (es) 2022-03-22
IL287517B2 (en) 2024-12-01
CN110291081A (zh) 2019-09-27
AU2017376629A1 (en) 2019-07-04
JP2022185110A (ja) 2022-12-13
IL314209A (en) 2024-09-01
AU2022201082A1 (en) 2022-03-10
CN110291081B (zh) 2023-01-31
IL287517A (en) 2021-12-01
KR20190092538A (ko) 2019-08-07
BR112019012224A2 (pt) 2019-11-05
US20200039958A1 (en) 2020-02-06
JP7158383B2 (ja) 2022-10-21
US11117883B2 (en) 2021-09-14
MA53150A (fr) 2021-05-26
IL267260B (en) 2022-10-01
AU2022201082B2 (en) 2023-11-02
MX2019007080A (es) 2019-10-15
JP2020503299A (ja) 2020-01-30
WO2018112140A1 (en) 2018-06-21
IL267260B2 (en) 2023-02-01

Similar Documents

Publication Publication Date Title
AU2022201082B2 (en) Benzimidazole compounds as c-Kit inhibitors
AU2022200741B2 (en) Aminothiazole compounds as c-Kit inhibitors
KR101959590B1 (ko) c-KIT 키나제 억제제로서의 화합물 및 조성물
JP2022548095A (ja) 接着分解剤及びその使用方法
TWI848925B (zh) 肌旋蛋白激酶抑制劑
JP2020503271A (ja) 造血前駆体キナーゼ1(hpk1)阻害剤としてのアニリノピリミジンas
JP2017528491A (ja) 変異イソクエン酸デヒドロゲナーゼ阻害剤としてのピリジニルキノリノン誘導体
JP2018512408A (ja) Phd阻害剤としての縮合二環式ヘテロアリール誘導体
CA3202516A1 (en) Aminothiazole compounds as c-kit inhibitors
NZ795575A (en) Benzimidazole compounds as c-Kit inhibitors
NZ795572A (en) Benzimidazole compounds as c-Kit inhibitors
NZ795495A (en) Aminothiazole compounds as c-Kit inhibitors

Legal Events

Date Code Title Description
FGA Letters patent sealed or granted (standard patent)
MK14 Patent ceased section 143(a) (annual fees not paid) or expired