ATE248854T1 - 16-hydroxy-11-(substituierte phenyl)-estra-4,9- dien derivate - Google Patents

16-hydroxy-11-(substituierte phenyl)-estra-4,9- dien derivate

Info

Publication number: ATE248854T1
Authority: AT; Austria
Prior art keywords: estra; hydroxy; substituted phenyl; diene derivatives; diene
Prior art date: 1997-01-15

Application number

AT98906887T

Other languages

English (en)

Inventor

Marinus Bernard Groen

Ronald Gebhard

Original Assignee

Akzo Nobel Nv

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.)

1997-01-15

Filing date

1998-01-13

Publication date

2003-09-15

1998-01-13 Application filed by Akzo Nobel Nv filed Critical Akzo Nobel Nv

2003-09-15 Application granted granted Critical

2003-09-15 Publication of ATE248854T1 publication Critical patent/ATE248854T1/de

Links

-1 16-HYDROXY-11-(SUBSTITUTED PHENYL)-ESTRA-4,9-DIENE Chemical class 0.000 title 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C07J1/0051—Estrane derivatives
- C07J1/0081—Substituted in position 17 alfa and 17 beta
- C07J1/0088—Substituted in position 17 alfa and 17 beta the substituent in position 17 alfa being an unsaturated hydrocarbon group
- C07J1/0096—Alkynyl derivatives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
- 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
- A61P25/20—Hypnotics; Sedatives
- 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
- A61P25/22—Anxiolytics
- 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
- A61P25/24—Antidepressants
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- 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
- 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
- A61P5/46—Drugs for disorders of the endocrine system of the suprarenal hormones for decreasing, blocking or antagonising the activity of glucocorticosteroids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J21/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having an oxygen-containing hetero ring spiro-condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J21/005—Ketals
- C07J21/006—Ketals at position 3
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
- C07J41/0077—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 substituted in position 11-beta by a carbon atom, further substituted by a group comprising at least one further carbon atom
- C07J41/0083—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 substituted in position 11-beta by a carbon atom, further substituted by a group comprising at least one further carbon atom substituted in position 11-beta by an optionally substituted phenyl group not further condensed with other rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J51/00—Normal steroids with unmodified cyclopenta(a)hydrophenanthrene skeleton not provided for in groups C07J1/00 - C07J43/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C07J71/0005—Oxygen-containing hetero ring
- C07J71/001—Oxiranes

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Biomedical Technology (AREA)
Diabetes (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Addiction (AREA)
Psychiatry (AREA)
Endocrinology (AREA)
Physical Education & Sports Medicine (AREA)
Orthopedic Medicine & Surgery (AREA)
Ophthalmology & Optometry (AREA)
Heart & Thoracic Surgery (AREA)
Rheumatology (AREA)
Hematology (AREA)
Obesity (AREA)
Cardiology (AREA)
Pain & Pain Management (AREA)
Urology & Nephrology (AREA)
Emergency Medicine (AREA)
Vascular Medicine (AREA)
Anesthesiology (AREA)
Child & Adolescent Psychology (AREA)
Steroid Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

AT98906887T 1997-01-15 1998-01-13 16-hydroxy-11-(substituierte phenyl)-estra-4,9- dien derivate ATE248854T1 (de)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP97200098		1997-01-15
PCT/EP1998/000377 WO1998031702A1 (en)	1997-01-15	1998-01-13	16-hydroxy-11-(substituted phenyl)-estra-4,9-diene derivatives

Publications (1)

Publication Number	Publication Date
ATE248854T1 true ATE248854T1 (de)	2003-09-15

Family

ID=8227931

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
AT98906887T ATE248854T1 (de)	1997-01-15	1998-01-13	16-hydroxy-11-(substituierte phenyl)-estra-4,9- dien derivate

Country Status (22)

Country	Link
US (1)	US6072068A (de)
EP (1)	EP0973792B1 (de)
JP (1)	JP2001508079A (de)
KR (1)	KR20000070149A (de)
CN (1)	CN1248262A (de)
AR (1)	AR011409A1 (de)
AT (1)	ATE248854T1 (de)
AU (1)	AU736064B2 (de)
BR (1)	BR9807079A (de)
CA (1)	CA2277924A1 (de)
DE (1)	DE69817792T2 (de)
HU (1)	HUP0000901A3 (de)
ID (1)	ID22228A (de)
IL (1)	IL122740A (de)
NO (1)	NO313386B1 (de)
NZ (1)	NZ336790A (de)
PL (1)	PL334518A1 (de)
RU (1)	RU2187510C2 (de)
TR (1)	TR199902367T2 (de)
TW (1)	TW518339B (de)
WO (1)	WO1998031702A1 (de)
ZA (1)	ZA9884B (de)

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AP1542A (en)	1999-04-30	2006-01-31	Pfizer Prod Inc	Glucocorticoid receptor modulators.
US6740645B1 (en) *	1999-09-03	2004-05-25	Research Triangle Institute	17β-acyl-17α-propynyl-11β-(cyclic amino) aryl steroids and their derivatives having antagonist hormonal properties
DE19961219A1 (de) *	1999-12-15	2001-07-19	Jenapharm Gmbh	11beta-Phenylestratrien-Derivate mit Fluoralkylgruppen in der aromatischen Seitenkette, deren Herstellung und diese Verbindungen enthaltende pharmazeutische Zusammensetzungen
US7713989B2 (en)	2000-04-27	2010-05-11	Dow Robert L	Glucocorticoid receptor modulators
IL180679A0 (en) *	2000-10-27	2009-02-11	Pfizer Prod Inc	Process for the preparation of non-steroidal glucocorticoid receptor modulators
ES2262612T3 (es) *	2000-10-28	2006-12-01	Pfizer Products Inc.	Moduladpres del receptor de glucocorticoides.
DE60113032T2 (de)	2000-10-30	2006-07-06	Pfizer Products Inc., Groton	Glukokortikoidrezeptor-Modulatoren
US7250408B2 (en) *	2002-12-16	2007-07-31	Bayer Schering Pharma Ag	Glucocorticoid receptor antagonists for prophylaxis and therapy of glucocorticoid-mediated hypogonadism, of sexual dysfunction and/or infertility
AU2008211613B2 (en)	2007-02-02	2013-05-23	Pfizer Products Inc.	Tricyclic compounds and their use as glucocorticoid receptor modulators
RU2326673C1 (ru) *	2007-02-27	2008-06-20	ФГУ Национальный научный центр наркологии Росздрава	ПРИМЕНЕНИЕ 17α-АЦЕТАТ-21-ПИВАЛОАТ 17α,21-ДИГИДРОКСИПРЕГН-4-ЕН-3,20-ДИОНА В КАЧЕСТВЕ СРЕДСТВА, СНИЖАЮЩЕГО ПАТОЛОГИЧЕСКОЕ ВЛЕЧЕНИЕ К КОКАИНУ
US9512169B2 (en)	2012-07-10	2016-12-06	Bayer Pharma Aktiengesellschaft	3-substituted estra-1,3,5(10),16-tetraene derivatives, methods for the production thereof, pharmaceutical preparations containing same, and use thereof for the production of medicaments
EA201500851A1 (ru)	2013-02-21	2016-02-29	Байер Фарма Акциенгезельшафт	ЭСТРА-1,3,5(10),16-ТЕТРАЕН-3-КАРБОКСАМИДЫ ДЛЯ ИНГИБИРОВАНИЯ 17β-ГИДРОКСИСТЕРОИД-ДЕГИДРОГЕНАЗЫ (AKR1C3)
CN113559075A (zh)	2014-11-17	2021-10-29	康泰科思特生物制药公司	奥那司酮延长释放组合物和方法
AU2016326657B2 (en)	2015-09-25	2019-10-24	Context Biopharma, Inc.	Methods of making onapristone intermediates
EP3389632A4 (de)	2015-12-15	2019-11-06	Context Biopharma Inc.	Amorphe onapristonzusammensetzungen und verfahren zur herstellung davon
WO2017112904A1 (en)	2015-12-23	2017-06-29	Oric Pharmaceuticals, Inc.	Inhibitors of glucocorticoid receptor
EP3394078A4 (de) *	2015-12-23	2019-11-27	Oric Pharmaceuticals, Inc.	Inhibitoren des glucocorticoidrezeptors
JP6995757B2 (ja) *	2015-12-23	2022-01-17	オリックファーマシューティカルズ，インク．	グルココルチコイド受容体の阻害剤
CN106397519A (zh) *	2016-08-30	2017-02-15	天津市中升挑战生物科技有限公司	一种烯丙孕素的制备方法
NZ753142A (en)	2016-10-07	2020-08-28	Oric Pharmaceuticals Inc	Inhibitors of glucocorticoid receptor
WO2018102369A1 (en)	2016-11-30	2018-06-07	Arno Therapeutics, Inc.	Methods for onapristone synthesis dehydration and deprotection
JP2022515528A (ja) *	2018-12-28	2022-02-18	パンダコンサルティングエルエルシー	短時間作用型選択的糖質コルチコイド受容体モジュレーター
WO2023000135A1 (en) *	2021-07-19	2023-01-26	Context Biopharma Inc.	Processes of making onapristone and intermediates thereof
CN114456223B (zh) *	2022-01-24	2023-07-21	湖南科益新生物医药有限公司	3-缩酮的合成方法

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2522328B1 (fr) *	1982-03-01	1986-02-14	Roussel Uclaf	Nouveaux produits derives de la structure 3-ceto 4,9 19-nor steroides, leur procede de preparation et leur application comme medicaments
AU580843B2 (en) *	1985-02-07	1989-02-02	Schering Aktiengesellschaft	11``-phenyl-gonanes, their manufacture and pharmaceutical preparations containing them

1997
- 1997-12-24 IL IL12274097A patent/IL122740A/xx active IP Right Grant
1998
- 1998-01-06 ZA ZA9884A patent/ZA9884B/xx unknown
- 1998-01-12 TW TW087100392A patent/TW518339B/zh not_active IP Right Cessation
- 1998-01-13 CN CN98802618A patent/CN1248262A/zh active Pending
- 1998-01-13 ID IDW990700A patent/ID22228A/id unknown
- 1998-01-13 US US09/341,603 patent/US6072068A/en not_active Expired - Fee Related
- 1998-01-13 AT AT98906887T patent/ATE248854T1/de not_active IP Right Cessation
- 1998-01-13 TR TR1999/02367T patent/TR199902367T2/xx unknown
- 1998-01-13 RU RU99118008/04A patent/RU2187510C2/ru not_active IP Right Cessation
- 1998-01-13 PL PL98334518A patent/PL334518A1/xx unknown
- 1998-01-13 JP JP53369598A patent/JP2001508079A/ja active Pending
- 1998-01-13 EP EP98906887A patent/EP0973792B1/de not_active Expired - Lifetime
- 1998-01-13 KR KR1019997006375A patent/KR20000070149A/ko not_active Ceased
- 1998-01-13 AU AU62935/98A patent/AU736064B2/en not_active Ceased
- 1998-01-13 NZ NZ336790A patent/NZ336790A/en unknown
- 1998-01-13 CA CA002277924A patent/CA2277924A1/en not_active Abandoned
- 1998-01-13 HU HU0000901A patent/HUP0000901A3/hu unknown
- 1998-01-13 DE DE69817792T patent/DE69817792T2/de not_active Expired - Fee Related
- 1998-01-13 WO PCT/EP1998/000377 patent/WO1998031702A1/en not_active Ceased
- 1998-01-13 BR BR9807079-7A patent/BR9807079A/pt not_active IP Right Cessation
- 1998-01-14 AR ARP980100151A patent/AR011409A1/es not_active Application Discontinuation
1999
- 1999-07-14 NO NO19993459A patent/NO313386B1/no not_active IP Right Cessation

Also Published As

Publication number	Publication date
AR011409A1 (es)	2000-08-16
EP0973792A1 (de)	2000-01-26
CN1248262A (zh)	2000-03-22
IL122740A0 (en)	1998-08-16
PL334518A1 (en)	2000-02-28
ID22228A (id)	1999-09-23
NO313386B1 (no)	2002-09-23
TR199902367T2 (xx)	2000-04-21
US6072068A (en)	2000-06-06
EP0973792B1 (de)	2003-09-03
WO1998031702A1 (en)	1998-07-23
NZ336790A (en)	2000-06-23
DE69817792T2 (de)	2004-07-01
NO993459L (no)	1999-09-07
NO993459D0 (no)	1999-07-14
TW518339B (en)	2003-01-21
ZA9884B (en)	1998-07-08
CA2277924A1 (en)	1998-07-23
IL122740A (en)	2003-09-17
HUP0000901A2 (hu)	2000-10-28
AU6293598A (en)	1998-08-07
DE69817792D1 (de)	2003-10-09
KR20000070149A (ko)	2000-11-25
JP2001508079A (ja)	2001-06-19
RU2187510C2 (ru)	2002-08-20
AU736064B2 (en)	2001-07-26
BR9807079A (pt)	2000-04-18
HUP0000901A3 (en)	2001-07-30

Legal Events

Date	Code	Title	Description
2004-03-15	RER	Ceased as to paragraph 5 lit. 3 law introducing patent treaties

Publication	Publication Date	Title
ATE248854T1 (de)	2003-09-15	16-hydroxy-11-(substituierte phenyl)-estra-4,9- dien derivate
DK0763541T3 (da)	2000-02-28	11-(substitueret phenyl)-estra-4,9-dien-derivater
ATE228510T1 (de)	2002-12-15	Substituierte 1,2,3,4-tetrahydronaphthalin derivate
DE69706292D1 (de)	2001-09-27	Chinazoline derivate
FI972026A0 (fi)	1997-05-13	Foerfarande foer estimering av en terminalanordnings hastighet, foerfarande foer cellval och radiosystem
FI980427A0 (fi)	1998-02-25	Foerfarande, arrangemang och anordning foer verifiering
ATE264327T1 (de)	2004-04-15	Substituierte 6,6-heterobicyclische derivate
DE60009147T2 (de)	2005-04-21	Admantan derivate
EE200000192A (et)	2001-04-16	Uus kombinatsioon
ATE273962T1 (de)	2004-09-15	5-phenyl-pyrimidine derivate
ATE277917T1 (de)	2004-10-15	Alkylaminobenzothiazole und -benzoxazole derivate
DE69830739D1 (de)	2005-08-04	2-halo-6-0-substituierte ketolide derivate
DE69928262D1 (de)	2005-12-15	Substituierte chinazoline derivate
ATE230405T1 (de)	2003-01-15	2-phenylpyran-4-one derivate
ATE317389T1 (de)	2006-02-15	4-phenyl-pyrimidine derivate
DE69805974D1 (de)	2002-07-18	5-aroylnaphthalin derivate
ATE241599T1 (de)	2003-06-15	25-hydroxy-16-ene-26,27-bishome-cholecalcerifer l derivate
DE59909590D1 (de)	2004-07-01	Azidfreie, gaserzeugende zusammensetzung
IT1304521B1 (it)	2001-03-19	Bigodino.
HK1023349A (en)	2000-09-08	16-hydroxy-11-(substituted phenyl)-estra-4,9-diene derivatives
FI971391A0 (fi)	1997-04-04	Koppling laemplig foer spaenningsarbete, saerskilt koppling foer ljusbaogs- eller oeverstoemsskydd
ID19473A (id)	1998-07-16	24-homo-26,27-heksafluoro-kolkalsiferol
FI971438A0 (fi)	1997-04-07	Koppling laemplig foer spaennings- eller spaenningsfri arbete, saerskilt koppling foer ljusbaogs- eller oeverstoemsskydd
FI972925A0 (fi)	1997-07-09	Radiopejlingssystem, radiopejlingssaendare och radiopejlingsmottagare
FI973934A0 (fi)	1997-10-10	Skidspaor, spaor foer klassisk skidaokning och fristil