AU621559B2 - Piperidine-tetra hydrofurane or tetra hydrothiophene spiro derivatives and methods for their preparation - Google Patents

Piperidine-tetra hydrofurane or tetra hydrothiophene spiro derivatives and methods for their preparation Download PDF

Info

Publication number
AU621559B2
AU621559B2 AU23449/88A AU2344988A AU621559B2 AU 621559 B2 AU621559 B2 AU 621559B2 AU 23449/88 A AU23449/88 A AU 23449/88A AU 2344988 A AU2344988 A AU 2344988A AU 621559 B2 AU621559 B2 AU 621559B2
Authority
AU
Australia
Prior art keywords
group
atom
compound
lower alkyl
formula
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
AU23449/88A
Other languages
English (en)
Other versions
AU2344988A (en
Inventor
Masatomi Harada
Hitoshi Nagaoka
Toshinari Tamura
Shinichi Tsukamoto
Shinji Usuda
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.)
Astellas Pharma Inc
Original Assignee
Yamanouchi Pharmaceutical Co 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 Yamanouchi Pharmaceutical Co Ltd filed Critical Yamanouchi Pharmaceutical Co Ltd
Publication of AU2344988A publication Critical patent/AU2344988A/en
Application granted granted Critical
Publication of AU621559B2 publication Critical patent/AU621559B2/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/10—Spiro-condensed systems
    • 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
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • 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
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • 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
    • C07D211/40—Oxygen atoms
    • C07D211/44—Oxygen atoms attached in position 4
    • C07D211/48—Oxygen atoms attached in position 4 having an acyclic carbon atom attached in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/10—Spiro-condensed systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Hydrogenated Pyridines (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
AU23449/88A 1987-10-05 1988-10-05 Piperidine-tetra hydrofurane or tetra hydrothiophene spiro derivatives and methods for their preparation Ceased AU621559B2 (en)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
JP62-252104 1987-10-05
JP25210487 1987-10-05
JP62-286297 1987-11-12
JP28629787 1987-11-12
JP63-84327 1988-04-05
JP8432788 1988-04-05

Publications (2)

Publication Number Publication Date
AU2344988A AU2344988A (en) 1989-04-06
AU621559B2 true AU621559B2 (en) 1992-03-19

Family

ID=27304516

Family Applications (1)

Application Number Title Priority Date Filing Date
AU23449/88A Ceased AU621559B2 (en) 1987-10-05 1988-10-05 Piperidine-tetra hydrofurane or tetra hydrothiophene spiro derivatives and methods for their preparation

Country Status (14)

Country Link
US (4) US4940795A (enExample)
EP (1) EP0311313B1 (enExample)
JP (1) JPH0236183A (enExample)
KR (1) KR970007947B1 (enExample)
CN (1) CN1036653C (enExample)
AT (1) ATE122353T1 (enExample)
AU (1) AU621559B2 (enExample)
CA (1) CA1337817C (enExample)
DE (1) DE3853758T2 (enExample)
DK (1) DK554288A (enExample)
ES (1) ES2074441T3 (enExample)
GR (1) GR3016995T3 (enExample)
HU (1) HU211687A9 (enExample)
NO (1) NO171109C (enExample)

Families Citing this family (47)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE122353T1 (de) * 1987-10-05 1995-05-15 Yamanouchi Pharma Co Ltd Heterozyklische spiroverbindungen und ihre herstellung.
US5412096A (en) * 1987-10-05 1995-05-02 Yamanouchi Pharmaceutical Co., Ltd. Hydrochloride salts of heterocyclic spiro compounds
US5075317A (en) * 1989-06-21 1991-12-24 Fisons Corporation Spirofurane derivatives
US5594000A (en) * 1989-06-21 1997-01-14 Astra Ab Spirofurane derivatives
US5852029A (en) * 1990-04-10 1998-12-22 Israel Institute For Biological Research Aza spiro compounds acting on the cholinergic system with muscarinic agonist activity
US5407938A (en) * 1990-04-10 1995-04-18 Israel Institute For Biological Research Certain 1-methyl-piperidine-4-spiro-4'-(1'-3'-oxazolines) and corresponding -(1',3' thiazolines)
US5534520A (en) * 1990-04-10 1996-07-09 Fisher; Abraham Spiro compounds containing five-membered rings
US5073560A (en) * 1990-07-20 1991-12-17 Fisons Corporation Spiro-isoxazolidine derivatives as cholinergic agents
IE914238A1 (en) * 1990-12-19 1992-07-01 Fisons Corp Novel spirofurane derivatives
US5403931A (en) * 1991-05-15 1995-04-04 Yamanouchi Pharmaceutical Co., Ltd. (-)-(S)-2,8-dimethyl-3-methylene-1-oxa-8-azaspiro[4.5]decane L-tartrate
DE69412067T2 (de) * 1993-01-28 1999-03-25 Merck & Co., Inc., Rahway, N.J. Substituierte spiro-azaringen als tachykinine rezeptor antagonisten
EP0687268B1 (en) * 1993-03-04 1998-05-27 Pfizer Inc. Spiroazacyclic derivatives as substance p antagonists
JP2983141B2 (ja) * 1993-10-06 1999-11-29 株式会社三和化学研究所 新規化合物及び該化合物を有効成分とする脳機能改善剤
JP2002500652A (ja) 1997-05-30 2002-01-08 ニューロサーアチ・アクティーゼルスカブ スピロ−キヌクリジン誘導体、その製造方法及びその使用方法
US6528529B1 (en) 1998-03-31 2003-03-04 Acadia Pharmaceuticals Inc. Compounds with activity on muscarinic receptors
SE9900100D0 (sv) * 1999-01-15 1999-01-15 Astra Ab New compounds
AU7509200A (en) * 1999-08-13 2001-03-13 Aventis Cropscience Gmbh Heterocyclic spiro compounds as pesticides
WO2001078709A2 (en) * 2000-04-12 2001-10-25 Minerva Biotechnologies Corporation Treatment of neurodegenerative disease
JP2003063964A (ja) * 2001-08-28 2003-03-05 Senju Pharmaceut Co Ltd ドライアイまたはドライアイを伴なう疾病の予防治療剤
US20070191815A1 (en) 2004-09-13 2007-08-16 Chrono Therapeutics, Inc. Biosynchronous transdermal drug delivery
KR20080031430A (ko) * 2005-07-26 2008-04-08 센주 세이야꾸 가부시키가이샤 경피적으로 흡수가능한 안과용 제제
EP2258357A3 (en) 2005-08-26 2011-04-06 Braincells, Inc. Neurogenesis with acetylcholinesterase inhibitor
EP2275096A3 (en) 2005-08-26 2011-07-13 Braincells, Inc. Neurogenesis via modulation of the muscarinic receptors
WO2007047978A2 (en) 2005-10-21 2007-04-26 Braincells, Inc. Modulation of neurogenesis by pde inhibition
EP2314289A1 (en) 2005-10-31 2011-04-27 Braincells, Inc. Gaba receptor mediated modulation of neurogenesis
US20100216734A1 (en) 2006-03-08 2010-08-26 Braincells, Inc. Modulation of neurogenesis by nootropic agents
CA2643199A1 (en) * 2006-03-08 2007-09-13 Braincells, Inc. Modulation of neurogenesis by nootropic agents
US7678808B2 (en) 2006-05-09 2010-03-16 Braincells, Inc. 5 HT receptor mediated neurogenesis
US20100009983A1 (en) * 2006-05-09 2010-01-14 Braincells, Inc. 5 ht receptor mediated neurogenesis
EP2021000A2 (en) 2006-05-09 2009-02-11 Braincells, Inc. Neurogenesis by modulating angiotensin
ITMI20061279A1 (it) * 2006-06-30 2008-01-01 Consiglio Nazionale Ricerche Agonisti nicotinici selettivi per il sottotipo recettoriale alfa7,procedimento per la loro preparazione e relative composizioni farmaceutiche
WO2008030651A1 (en) 2006-09-08 2008-03-13 Braincells, Inc. Combinations containing a 4-acylaminopyridine derivative
US20100184806A1 (en) 2006-09-19 2010-07-22 Braincells, Inc. Modulation of neurogenesis by ppar agents
EP2066355A2 (en) * 2006-09-19 2009-06-10 Braincells, Inc. Combination comprising a peroxisome proliferator activated receptor agent and a second neurogenic agent for treating a nervous system disorder, increasing neurodifferentiation and increasing neurogenesis
AU2007299726A1 (en) * 2006-09-22 2008-03-27 Braincells, Inc. Combination comprising an HMG-COA reductase inhibitor and a second neurogenic agent for treating a nervous system disorder and increasing neurogenesis
EP1977746B8 (en) 2007-04-02 2014-09-24 Parkinson's Institute Methods and compositions for reduction of side effects of therapeutic treatments
US9034891B2 (en) 2009-01-26 2015-05-19 Israel Institute For Biological Research Bicyclic heterocyclic spiro compounds
WO2010084499A2 (en) 2009-01-26 2010-07-29 Israel Institute For Biological Research Bicyclic heterocyclic spiro compounds
US20100216805A1 (en) 2009-02-25 2010-08-26 Braincells, Inc. Modulation of neurogenesis using d-cycloserine combinations
EP2882428B1 (en) 2012-07-13 2019-01-16 Pain Therapeutics, Inc. A method of inhibiting tau phosphorylation
US10105487B2 (en) 2013-01-24 2018-10-23 Chrono Therapeutics Inc. Optimized bio-synchronous bioactive agent delivery system
US9433604B2 (en) 2013-10-08 2016-09-06 Pain Therapeutics Inc. Method for inhibiting growth of cancer cells
JP2018511355A (ja) 2015-01-28 2018-04-26 クロノ セラピューティクス インコーポレイテッドＣｈｒｏｎｏ Ｔｈｅｒａｐｅｕｔｉｃｓ Ｉｎｃ． 薬剤送達方法及びシステム
WO2018129304A1 (en) 2017-01-06 2018-07-12 Chrono Therapeutics Inc. Transdermal drug delivery devices and methods
AU2019279884B2 (en) 2018-05-29 2025-01-30 Morningside Venture Investments Limited Drug delivery methods and systems
JP2022507660A (ja) 2018-11-16 2022-01-18 モーニングサイド ベンチャー インベストメンツ リミテッド 温度によって調節される経皮薬剤送達システム
CN115124545B (zh) * 2022-08-31 2023-01-03 南京远淑医药科技有限公司 一种促性腺激素释放激素受体拮抗剂中间体的合成方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU5224286A (en) * 1985-01-16 1986-07-24 Sandoz Ltd. Spiro-dioxolanes, - dithiolanes and-oxothiolanes

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3305556A (en) * 1962-11-23 1967-02-21 Pfizer & Co C Novel hypoglycemic agents
NL124853C (enExample) * 1963-07-19
SU335944A1 (ru) * 1970-12-15 1976-01-25 Научно-исследовательский институт химии Саратовского государственного университета им.Н.Г.Чернышевского Способ получени соединений р да 1-окса6-азаспиро(4,4)нонана
US3784551A (en) * 1971-07-08 1974-01-08 Yoshitomi Pharmaceutical 2-oxo-1,4-dioxa-8-azaspiro (4.5) decanes and related compounds
GB1301254A (enExample) * 1971-07-08 1972-12-29
US3839273A (en) * 1971-11-13 1974-10-01 Sankyo Co N-substituted piperidine derivatives, process for preparing the same and their use as stabilizers
SU434735A1 (ru) * 1972-03-01 1975-12-15 Научно-исследовательский институт химии Саратовского государственного университета им.Н.Г.Чернышевского Способ получени 7-метил-(или 2,7диметил)-2-метокси- -пропионитрил1-окса-6-азаспиро-(4,4)-нонана
SU465399A1 (ru) * 1973-07-19 1975-03-30 Научно-исследовательский институт химии при Саратовском государственном университете им.Н.Г.Чернышевского Способ получени натриевых солей 2-метокси- -карбоксиэтил-1-окса6-азаспиро-(4,4)-нонана
IL48452A (en) * 1975-11-11 1979-07-25 Purdue Frederick Co Spiro (1,3-dioxolane-4,3') quinuclidines,their preparationand pharmaceutical compositions comprising them
US4321379A (en) * 1981-01-28 1982-03-23 American Cyanamid Company 4-Aryl-1-oxa-8-azaspiro[4,5]dec-3-en-2-ones
SU1002294A1 (ru) * 1981-08-14 1983-03-07 Ордена Трудового Красного Знамени Институт Тонкой Органической Химии Им.А.Л.Мнджояна 2,2-Диалкил-3-тиа-8-азаспиро/5,5/ундеканы
US4855290A (en) * 1985-05-10 1989-08-08 State Of Israel, Represented By Prime Minister's Office, Israel Institute For Biological Research Derivatives of quinuclidine
US4981858A (en) * 1987-08-13 1991-01-01 State Of Israel, Represented By The Prime Minister's Office, Israel Institute For Biological Research Optical isomers
ATE122353T1 (de) * 1987-10-05 1995-05-15 Yamanouchi Pharma Co Ltd Heterozyklische spiroverbindungen und ihre herstellung.
US5073560A (en) * 1990-07-20 1991-12-17 Fisons Corporation Spiro-isoxazolidine derivatives as cholinergic agents

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU5224286A (en) * 1985-01-16 1986-07-24 Sandoz Ltd. Spiro-dioxolanes, - dithiolanes and-oxothiolanes

Also Published As

Publication number Publication date
NO884406L (no) 1989-04-06
US5041549A (en) 1991-08-20
ES2074441T3 (es) 1995-09-16
CA1337817C (en) 1995-12-26
DK554288D0 (da) 1988-10-04
HU211687A9 (en) 1995-12-28
GR3016995T3 (en) 1995-11-30
EP0311313B1 (en) 1995-05-10
KR970007947B1 (ko) 1997-05-19
NO171109B (no) 1992-10-19
EP0311313A2 (en) 1989-04-12
NO884406D0 (no) 1988-10-04
US4996210A (en) 1991-02-26
US4940795A (en) 1990-07-10
JPH0544948B2 (enExample) 1993-07-07
DE3853758D1 (de) 1995-06-14
AU2344988A (en) 1989-04-06
ATE122353T1 (de) 1995-05-15
JPH0236183A (ja) 1990-02-06
KR890006649A (ko) 1989-06-15
NO171109C (no) 1993-01-27
EP0311313A3 (en) 1990-12-05
CN1036653C (zh) 1997-12-10
DK554288A (da) 1989-05-26
USRE34653E (en) 1994-07-05
DE3853758T2 (de) 1995-09-07
CN1033629A (zh) 1989-07-05

Similar Documents

Publication Publication Date Title
CA1337817C (en) Heterocyclic spiro compounds and methods for preparing the same
US4879300A (en) Novel piperidine derivatives
US4031222A (en) Trifluoromethylthio (and sulfonyl) derivatives of cyproheptadine analogs
US4210648A (en) II-Aminoacyl-5,11-dihydro-6H-pyrido(2,3-B) (1,4)benzodiazepin-6-ones and salts thereof
US4735944A (en) Spiro-dioxolanes, -dithiolanes and -oxothiolanes, and their use in mental therapy
US5412096A (en) Hydrochloride salts of heterocyclic spiro compounds
JPH06500076A (ja) ピペリジン化合物、その合成およびその使用方法
JPH06500325A (ja) １，２，５，６―テトラヒドロピリジンオキシム誘導体
US4447434A (en) Substituted dibenzodiazepinones
AU624382B2 (en) Compounds with central analgesic activity, process for their preparation and pharmaceutical compositions containing them
US4031223A (en) Trifluoromethylthio derivatives of cyproheptadine
US4104398A (en) 3-Lower alkoxycyproheptadines as serotonin inhibitors
US4507306A (en) cis-4a-Aryl-1,2,3,4,4a,9b-hexahydro-benzofuro[3,2-c]pyridines and their anti-convulsant and analgesic activity
US4734428A (en) Aminoethylimidazole and cytoprotective and gastric antisecretory composition containing the same
AU607966B2 (en) Pilocarpine derivatives
US4021430A (en) Dihydroapovincaminic acid amines
US4132796A (en) Antipsychotic 3-trifluoromethylsulfinyl analogs of cyproheptadine
US4544745A (en) Cis-4a-aryl, 1, 2, 3, 4, 4A, 9B-hexahydro-benzofuro-[3,2-C]- pyridines useful as analgesics
KR850001039B1 (ko) 알로파노일 피페라진 화합물의 제조방법
US4728659A (en) Aminomethyl derivatives and preparation process thereof as well as platelet aggregation inhibitors containing same
US3462427A (en) Novel 1-(cycloalkylidene-ethyl-4-phenyl-piperidines
US4395416A (en) 1-Spiro isobenzofuranic and 1-spiro isobenzothiophenic derivatives the process for preparing the same and their use in therapeutics
US4010161A (en) Piperazinoethyl-N-(2,3-dimethyl-5-oxo-1-phenyl-3Δ-pyrazolin-4-yl)carbamates
CA1248521A (en) 10,11-dihydro-5h-dibenzo [a,d] cycloheptadiene derivatives, their preparation and their use
US4585779A (en) cis-4a-Aryl-1,2,3,4,4a,9b-hexahydro-benzofuro[3,2-c]pyridines and intermediates thereof

Legal Events

Date Code Title Description
MK14 Patent ceased section 143(a) (annual fees not paid) or expired