HUP0104867A3 - Heterocyclic compounds useful in the treatment of inflammatory diseases, process for their preparation, pharmaceutical compositions comprising thereof and their use - Google Patents
Heterocyclic compounds useful in the treatment of inflammatory diseases, process for their preparation, pharmaceutical compositions comprising thereof and their useInfo
- Publication number
- HUP0104867A3 HUP0104867A3 HU0104867A HUP0104867A HUP0104867A3 HU P0104867 A3 HUP0104867 A3 HU P0104867A3 HU 0104867 A HU0104867 A HU 0104867A HU P0104867 A HUP0104867 A HU P0104867A HU P0104867 A3 HUP0104867 A3 HU P0104867A3
- Authority
- HU
- Hungary
- Prior art keywords
- preparation
- treatment
- pharmaceutical compositions
- inflammatory diseases
- heterocyclic compounds
- Prior art date
Links
- 150000002391 heterocyclic compounds Chemical class 0.000 title 1
- 208000027866 inflammatory disease Diseases 0.000 title 1
- 238000000034 method Methods 0.000 title 1
- 239000008194 pharmaceutical composition Substances 0.000 title 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/205—Radicals derived from carbonic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/40—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
- C07K5/06043—Leu-amino acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pulmonology (AREA)
- General Chemical & Material Sciences (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB9828074.6A GB9828074D0 (en) | 1998-12-18 | 1998-12-18 | Therapeutically useful compounds |
PCT/EP1999/010000 WO2000037444A1 (en) | 1998-12-18 | 1999-12-16 | Compounds useful in the treatment of inflammatory diseases |
Publications (2)
Publication Number | Publication Date |
---|---|
HUP0104867A2 HUP0104867A2 (hu) | 2002-04-29 |
HUP0104867A3 true HUP0104867A3 (en) | 2002-06-28 |
Family
ID=10844608
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HU0104867A HUP0104867A3 (en) | 1998-12-18 | 1999-12-16 | Heterocyclic compounds useful in the treatment of inflammatory diseases, process for their preparation, pharmaceutical compositions comprising thereof and their use |
Country Status (26)
Country | Link |
---|---|
US (1) | US6867192B1 (hu) |
EP (1) | EP1140837B1 (hu) |
JP (1) | JP4431282B2 (hu) |
KR (1) | KR20010101258A (hu) |
CN (1) | CN1330637A (hu) |
AR (1) | AR023727A1 (hu) |
AT (1) | ATE273954T1 (hu) |
AU (1) | AU760169B2 (hu) |
BR (1) | BR9916282A (hu) |
CA (1) | CA2355630A1 (hu) |
CO (1) | CO5170533A1 (hu) |
CZ (1) | CZ20012209A3 (hu) |
DE (1) | DE69919580T2 (hu) |
ES (1) | ES2226488T3 (hu) |
GB (1) | GB9828074D0 (hu) |
GT (1) | GT199900217A (hu) |
HK (1) | HK1038744A1 (hu) |
HU (1) | HUP0104867A3 (hu) |
IL (1) | IL142908A0 (hu) |
NO (1) | NO20012995L (hu) |
NZ (1) | NZ511478A (hu) |
PE (1) | PE20001387A1 (hu) |
PL (1) | PL348059A1 (hu) |
TR (1) | TR200101709T2 (hu) |
WO (1) | WO2000037444A1 (hu) |
ZA (1) | ZA200103948B (hu) |
Families Citing this family (46)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CZ20022072A3 (cs) | 1999-12-28 | 2003-05-14 | Pfizer Products Inc. | Nepeptidylové inhibitory VLA-4 dependentní buněčné vazby použitelné pro léčbu zánětlivých, autoimunitních a respiračních onemocnění |
GB0014869D0 (en) * | 2000-06-16 | 2000-08-09 | Glaxo Group Ltd | Novel pharmaceutical formulation |
GB0014883D0 (en) * | 2000-06-16 | 2000-08-09 | Glaxo Group Ltd | Novel pharmaceutical formulation |
GB0014947D0 (en) * | 2000-06-16 | 2000-08-09 | Glaxo Group Ltd | Novel pharmaceutical formulation |
GB0014849D0 (en) * | 2000-06-16 | 2000-08-09 | Glaxo Group Ltd | Pharmaceutical aerosol formulation |
GB0014881D0 (en) * | 2000-06-16 | 2000-08-09 | Glaxo Group Ltd | Pharmaceutical aerosol formulation |
GB0014892D0 (en) * | 2000-06-16 | 2000-08-09 | Glaxo Group Ltd | Novel pharmaceutical formulation |
GB0014851D0 (en) * | 2000-06-16 | 2000-08-09 | Glaxo Group Ltd | Novel pharmaceutical formulation |
GB0127423D0 (en) * | 2001-11-15 | 2002-01-09 | Glaxo Group Ltd | Process |
GB0218630D0 (en) | 2002-08-10 | 2002-09-18 | Tanabe Seiyaku Co | Novel compounds |
EP1633731A2 (en) | 2003-05-20 | 2006-03-15 | Genentech, Inc. | Thiocarbamate inhibitors of alpha-4 integrins |
NZ604082A (en) | 2004-06-04 | 2014-09-26 | Genentech Inc | Method for treating multiple sclerosis |
US8482496B2 (en) | 2006-01-06 | 2013-07-09 | Pixtronix, Inc. | Circuits for controlling MEMS display apparatus on a transparent substrate |
US20070205969A1 (en) | 2005-02-23 | 2007-09-06 | Pixtronix, Incorporated | Direct-view MEMS display devices and methods for generating images thereon |
US8310442B2 (en) | 2005-02-23 | 2012-11-13 | Pixtronix, Inc. | Circuits for controlling display apparatus |
US9158106B2 (en) | 2005-02-23 | 2015-10-13 | Pixtronix, Inc. | Display methods and apparatus |
US9261694B2 (en) | 2005-02-23 | 2016-02-16 | Pixtronix, Inc. | Display apparatus and methods for manufacture thereof |
US7999994B2 (en) | 2005-02-23 | 2011-08-16 | Pixtronix, Inc. | Display apparatus and methods for manufacture thereof |
US8159428B2 (en) | 2005-02-23 | 2012-04-17 | Pixtronix, Inc. | Display methods and apparatus |
US8519945B2 (en) | 2006-01-06 | 2013-08-27 | Pixtronix, Inc. | Circuits for controlling display apparatus |
US7742016B2 (en) | 2005-02-23 | 2010-06-22 | Pixtronix, Incorporated | Display methods and apparatus |
US9082353B2 (en) | 2010-01-05 | 2015-07-14 | Pixtronix, Inc. | Circuits for controlling display apparatus |
US9229222B2 (en) | 2005-02-23 | 2016-01-05 | Pixtronix, Inc. | Alignment methods in fluid-filled MEMS displays |
MY149159A (en) | 2005-11-15 | 2013-07-31 | Hoffmann La Roche | Method for treating joint damage |
US8526096B2 (en) | 2006-02-23 | 2013-09-03 | Pixtronix, Inc. | Mechanical light modulators with stressed beams |
US9176318B2 (en) * | 2007-05-18 | 2015-11-03 | Pixtronix, Inc. | Methods for manufacturing fluid-filled MEMS displays |
AR073295A1 (es) | 2008-09-16 | 2010-10-28 | Genentech Inc | Metodos para tratar la esclerosis multiple progresiva. articulo de fabricacion. |
US8169679B2 (en) | 2008-10-27 | 2012-05-01 | Pixtronix, Inc. | MEMS anchors |
WO2010075249A2 (en) | 2008-12-22 | 2010-07-01 | Genentech, Inc. | A method for treating rheumatoid arthritis with b-cell antagonists |
KR20120139854A (ko) | 2010-02-02 | 2012-12-27 | 픽스트로닉스 인코포레이티드 | 디스플레이 장치를 제어하기 위한 회로 |
JP2013519121A (ja) | 2010-02-02 | 2013-05-23 | ピクストロニックス・インコーポレーテッド | 低温封孔流体充填ディスプレイ装置を製造するための方法 |
WO2013101771A2 (en) | 2011-12-30 | 2013-07-04 | Genentech, Inc. | Compositions and method for treating autoimmune diseases |
AU2013215332A1 (en) | 2012-01-31 | 2014-09-04 | Genentech, Inc. | Anti-Ig-E M1' antibodies and methods using same |
US9134552B2 (en) | 2013-03-13 | 2015-09-15 | Pixtronix, Inc. | Display apparatus with narrow gap electrostatic actuators |
BR112016028081A2 (pt) * | 2014-05-30 | 2017-08-22 | Sphaera Pharma Private Ltd | Novos compostos como agentes antituberculares |
ES2835274T3 (es) | 2015-07-08 | 2021-06-22 | Axerovision Inc | Composiciones farmacéuticas que contienen un antagonista de la integrina alfa 4 para el tratamiento de afecciones inflamatorias oculares |
IL293708A (en) | 2015-10-06 | 2022-08-01 | Genentech Inc | A method for treating multiple sclerosis |
EP3464336B1 (en) * | 2016-06-01 | 2022-03-16 | Athira Pharma, Inc. | Compounds |
CN109722455B (zh) * | 2017-10-31 | 2022-03-11 | 中国科学院天津工业生物技术研究所 | 微生物发酵生产谷内酯的方法、工程菌及应用 |
US20230033021A1 (en) | 2018-06-20 | 2023-02-02 | Progenity, Inc. | Treatment of a disease of the gastrointestinal tract with an integrin inhibitor |
KR20240015737A (ko) | 2018-10-30 | 2024-02-05 | 길리애드 사이언시즈, 인코포레이티드 | 알파4베타7 인테그린 억제제로서의 퀴놀린 유도체 |
EP3873605B1 (en) | 2018-10-30 | 2024-10-23 | Gilead Sciences, Inc. | Compounds for inhibition of alpha4beta7 integrin |
AU2019373242B2 (en) | 2018-10-30 | 2023-07-13 | Gilead Sciences, Inc. | Compounds for inhibition of alpha 4 beta 7 integrin |
CN112969700B (zh) | 2018-10-30 | 2024-08-20 | 吉利德科学公司 | 作为α4β7整合素抑制剂的咪唑并吡啶衍生物 |
CA3148613A1 (en) | 2019-08-14 | 2021-02-18 | Gilead Sciences, Inc. | Phenylalanine derived compounds and their use as inhinitors of alpha 4 beta 7 integrin |
AU2021363705A1 (en) * | 2020-10-21 | 2023-06-15 | Azura Ophthalmics Ltd. | Compounds and methods for the treatment of ocular disorders |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE1593858A1 (de) | 1967-03-02 | 1970-10-29 | Hoechst Ag | Verfahren zur Herstellung tyrosinhaltiger Peptide und deren Derivaten |
US4105602A (en) | 1975-02-10 | 1978-08-08 | Armour Pharmaceutical Company | Synthesis of peptides with parathyroid hormone activity |
US6248713B1 (en) * | 1995-07-11 | 2001-06-19 | Biogen, Inc. | Cell adhesion inhibitors |
AU726585B2 (en) | 1997-05-29 | 2000-11-09 | Merck & Co., Inc. | Biarylalkanoic acids as cell adhesion inhibitors |
WO1998053818A1 (en) * | 1997-05-29 | 1998-12-03 | Merck & Co., Inc. | Sulfonamides as cell adhesion inhibitors |
EP1001764A4 (en) * | 1997-05-29 | 2005-08-24 | Merck & Co Inc | Heterocyclic amides as cell adhesion inhibitors |
ATE256699T1 (de) * | 1997-05-30 | 2004-01-15 | Celltech Therapeutics Ltd | Entzündungshemmende tyrosin-derivate |
-
1998
- 1998-12-18 GB GBGB9828074.6A patent/GB9828074D0/en not_active Ceased
-
1999
- 1999-12-15 CO CO99078241A patent/CO5170533A1/es not_active Application Discontinuation
- 1999-12-15 AR ARP990106429A patent/AR023727A1/es not_active Application Discontinuation
- 1999-12-16 JP JP2000589516A patent/JP4431282B2/ja not_active Expired - Lifetime
- 1999-12-16 US US09/868,395 patent/US6867192B1/en not_active Expired - Lifetime
- 1999-12-16 BR BR9916282-2A patent/BR9916282A/pt not_active IP Right Cessation
- 1999-12-16 IL IL14290899A patent/IL142908A0/xx unknown
- 1999-12-16 EP EP99964583A patent/EP1140837B1/en not_active Expired - Lifetime
- 1999-12-16 NZ NZ511478A patent/NZ511478A/en unknown
- 1999-12-16 WO PCT/EP1999/010000 patent/WO2000037444A1/en not_active Application Discontinuation
- 1999-12-16 CN CN99814654A patent/CN1330637A/zh active Pending
- 1999-12-16 TR TR2001/01709T patent/TR200101709T2/xx unknown
- 1999-12-16 PE PE1999001274A patent/PE20001387A1/es not_active Application Discontinuation
- 1999-12-16 ES ES99964583T patent/ES2226488T3/es not_active Expired - Lifetime
- 1999-12-16 CZ CZ20012209A patent/CZ20012209A3/cs unknown
- 1999-12-16 AU AU30391/00A patent/AU760169B2/en not_active Ceased
- 1999-12-16 HU HU0104867A patent/HUP0104867A3/hu unknown
- 1999-12-16 KR KR1020017007579A patent/KR20010101258A/ko not_active Application Discontinuation
- 1999-12-16 DE DE69919580T patent/DE69919580T2/de not_active Expired - Lifetime
- 1999-12-16 AT AT99964583T patent/ATE273954T1/de not_active IP Right Cessation
- 1999-12-16 CA CA002355630A patent/CA2355630A1/en not_active Abandoned
- 1999-12-16 PL PL99348059A patent/PL348059A1/xx not_active Application Discontinuation
- 1999-12-17 GT GT199900217A patent/GT199900217A/es unknown
-
2001
- 2001-05-15 ZA ZA200103948A patent/ZA200103948B/en unknown
- 2001-06-15 NO NO20012995A patent/NO20012995L/no not_active Application Discontinuation
-
2002
- 2002-01-09 HK HK02100145.2A patent/HK1038744A1/zh unknown
Also Published As
Publication number | Publication date |
---|---|
HUP0104867A2 (hu) | 2002-04-29 |
EP1140837A1 (en) | 2001-10-10 |
PL348059A1 (en) | 2002-05-06 |
PE20001387A1 (es) | 2000-12-22 |
BR9916282A (pt) | 2001-10-02 |
ZA200103948B (en) | 2002-11-15 |
NZ511478A (en) | 2003-08-29 |
CA2355630A1 (en) | 2000-06-29 |
US6867192B1 (en) | 2005-03-15 |
IL142908A0 (en) | 2002-04-21 |
AU3039100A (en) | 2000-07-12 |
NO20012995L (no) | 2001-08-15 |
ATE273954T1 (de) | 2004-09-15 |
HK1038744A1 (zh) | 2002-03-28 |
CZ20012209A3 (cs) | 2001-09-12 |
KR20010101258A (ko) | 2001-11-14 |
DE69919580D1 (de) | 2004-09-23 |
JP2002533326A (ja) | 2002-10-08 |
DE69919580T2 (de) | 2005-09-01 |
EP1140837B1 (en) | 2004-08-18 |
NO20012995D0 (no) | 2001-06-15 |
JP4431282B2 (ja) | 2010-03-10 |
CN1330637A (zh) | 2002-01-09 |
WO2000037444A1 (en) | 2000-06-29 |
AR023727A1 (es) | 2002-09-04 |
CO5170533A1 (es) | 2002-06-27 |
GT199900217A (es) | 2001-06-09 |
TR200101709T2 (tr) | 2001-12-21 |
GB9828074D0 (en) | 1999-02-17 |
ES2226488T3 (es) | 2005-03-16 |
AU760169B2 (en) | 2003-05-08 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
HUP0104867A3 (en) | Heterocyclic compounds useful in the treatment of inflammatory diseases, process for their preparation, pharmaceutical compositions comprising thereof and their use | |
HUP0301101A3 (en) | Novel heterocyclic compounds process for their preparation and pharmaceutical compositions containing them and their use in the treatment of diabetes and related diseases | |
ZA975866B (en) | Novel heterocyclic compounds, process for their preparation and pharmaceutical compositions containing them and their use in the treatment of diabetes and related diseases. | |
HUP0102556A3 (en) | Benzenesulfonamide-derivatives and their use as medicaments and process for the preparation of the compounds | |
IL147217A0 (en) | New spirooxindole derivatives and pharmaceutical compositions containing the same for treatment of pain | |
HUP0204399A3 (en) | Pteridine compounds for the treatment of psoriasis, process for their preparation, pharmaceutical compositions containing them and their use | |
HUP0303296A3 (en) | Carboxamide derivatives and their use in the treatment of thromboembolic diseases and tumours, process for their preparation and pharmaceutical compositions containing them | |
HUP0203542A3 (en) | 3(5)-amino-pyrazole derivatives, process for their preparation, their use and pharmaceutical compositions containing the same | |
IL130424A (en) | Compositions comprising ziprasidone or its hydrochloride monohydrate, their preparation and use thereof in the preparation of medicaments for treating psychosis | |
HUP0400918A3 (en) | Utilization of pyrazoline derivatives in the preparation of pharmaceutical compositions for the prevention and/or treatment of proliferative cell diseases | |
HUP0203142A3 (en) | Benzodiazepine derivatives, process for preparation of the compounds, pharmaceutical compositions containing them and their use | |
HUP0301167A3 (en) | Sulfonyl-pyrrolidine derivatives useful for the treatment of neurological disorders, process for their preparation, pharmaceutical compositions containing them and their use | |
HUP0204226A3 (en) | Quinazoline derivatives, pharmaceutical compositions containing them, their use and process for the preparation of the compounds | |
HUP0204085A3 (en) | New oxabispidine compounds useful in the treatment of cardiac arrhythmias, process for their preparation and pharmaceutical compositions containing them | |
IL204947A0 (en) | Phenylacetamido-thiazole derivatives, process for their preparation and their use in the manufacture of medicaments, pharmaceutical compositions and kits comprising them | |
HUP0105313A3 (en) | Potassium salt of (s)-omeprazole, process for its preparation and pharmaceutical composition containing the same and its use | |
HUP0200553A3 (en) | Use of pyridine derivatives as mglur5 antagonists producing pharmaceutical compositions suitable for the treatment of pain and anxiety | |
HUP0200441A3 (en) | Tetrahydropyran derivatives and their use as therapeutic agents and process for preparation the compounds | |
HUP0203597A3 (en) | Pharmaceutical compositions containing zolmitriptan, process for their preparation and their use | |
HUP0200613A2 (en) | Compounds and methods for treatment of asthma, allergy and inflammatory disorders, pharmaceutical compositions containing them and their use | |
HUP0104963A3 (en) | Compositions for the treatment of skin diseases | |
HUP0401325A3 (en) | Isoxazolopyridinones useful in the treatment of parkinson's disease, process for their preparation and pharmaceutical compositions containing the compounds | |
HUP0300402A3 (en) | Quinolinyl-piperidin-4-ylidene-methyl-benzamide derivatives for the treatment of pain and pharmaceutical compositions containing them | |
GC0000335A (en) | Compositions formed of polyolefins, process for their preparation and use of these compositions | |
IL155174A0 (en) | Methods and compositions for the treatment of inflammatory diseases |