WO2008075012A1 - Cb1 receptor modulators - Google Patents

Cb1 receptor modulators Download PDF

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Publication number
WO2008075012A1
WO2008075012A1 PCT/GB2007/004831 GB2007004831W WO2008075012A1 WO 2008075012 A1 WO2008075012 A1 WO 2008075012A1 GB 2007004831 W GB2007004831 W GB 2007004831W WO 2008075012 A1 WO2008075012 A1 WO 2008075012A1
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WO
WIPO (PCT)
Prior art keywords
phenyl
alkyl
hydrogen
compound
chloro
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
PCT/GB2007/004831
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English (en)
French (fr)
Inventor
Martin Cooper
Jean-Marie Receveur
Thomas Hoegberg
Peter Aadal Nielsen
Jean-Michel Linget
Pia Karina Noeregaard
Anthony Murray
Emelie Bjurling
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.)
7TM Pharma AS
Original Assignee
7TM Pharma AS
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
Priority claimed from GB0625197A external-priority patent/GB0625197D0/en
Priority claimed from GB0717998A external-priority patent/GB0717998D0/en
Priority to NZ578063A priority Critical patent/NZ578063A/en
Priority to CA002673359A priority patent/CA2673359A1/en
Application filed by 7TM Pharma AS filed Critical 7TM Pharma AS
Priority to EA200900838A priority patent/EA017170B1/ru
Priority to MX2009006214A priority patent/MX2009006214A/es
Priority to US12/519,432 priority patent/US8124634B2/en
Priority to EP07848570.3A priority patent/EP2121617B1/en
Priority to AU2007336061A priority patent/AU2007336061B2/en
Priority to BRPI0720732-8A priority patent/BRPI0720732A2/pt
Priority to JP2009542195A priority patent/JP5437812B2/ja
Publication of WO2008075012A1 publication Critical patent/WO2008075012A1/en
Priority to IL198990A priority patent/IL198990A0/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • 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
    • 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
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • 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
    • A61P3/00—Drugs for disorders of the metabolism
    • 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
    • A61P3/06—Antihyperlipidemics
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic 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
    • C07D401/02—Heterocyclic 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
    • C07D401/06—Heterocyclic 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 carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic 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
    • C07D401/14—Heterocyclic 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic 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
    • C07D403/06—Heterocyclic 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 carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Definitions

  • rimonabant are able to modulate energy homeostasis and that CB1 antagonists are able to modulate food intake as well as peripherally block lipogenic processes (Pagotto et al, 2006, Endocrine Reviews, 27, 73-100; Tucci et al, 2006, Curr. Med. Chem. 13, 2669-2680; Lange and Kruse, 2004, Current Opinion in Drug Discovery & Dev., 7, 498-506).
  • the peripheral effects of CB1 antagonists can be mediated by several target organs and mechanisms, e.g.
  • the present invention makes available a class of pyrazole compounds which modulate the activity of the cannabinoid receptor CB1.
  • the following publications relate to other pyrazole compounds having CB1 modulatory activity:
  • R 9 is hydrogen, C 1 -C 4 alkyl, cycloalkyl, fully or partially fluorinated C 1 -C 4 alkyl.
  • the compounds with which this invention is concerned differ in structure from those of PCTEP2005/005726 principally in the identity of the -R 1 - radical and/or -N(R 2 )-R 3 -A 2 group
  • a 4 is a monocyclic carbocyclic or monocyclic heterocyclic ring, having 3 to 8 ring atoms, optionally substituted with one or more of -F, -Cl, -Br, -CN, -CF 3 , C 1 -C 4 alkyl, cycloalkyl, -OR 9 , oxo, -NR 7 R 8 or -SO 2 R 6 ;
  • B 1 when present may be -CO-, -O-, -S-, -SO-, -SO 2 -, -CH 2 -,-CHOH- or -NR 7 ;
  • Another aspect of the invention is a pharmaceutical composition
  • a pharmaceutical composition comprising a compound of formula (I) or a salt, hydrate, solvate or N-oxide thereof, together with one or more pharmaceutically acceptable carriers or excipients.
  • substituted as applied to any moiety herein means substituted with up to four compatible substituents, each of which independently may be, for example, (C 1 -C 6 JaIkVl 1 (C r C 6 )alkoxy, hydroxy, hydroxy(C r C 6 )alkyl, mercapto, mercapto(C 1 -C 6 )alkyl, (d-C 6 )alkylthio, halo (including fluoro, bromo and chloro), fully or partially fluorinated (C-
  • R 4 and/or R 5 have been defined above, but currently preferred are cases where they are independently selected from hydrogen, -F, -CN and -Cl, When A 3 is phenyl or 6-membered heteroaryl, any R 4 and R 5 substituents in the phenyl ring shown in formula (I) as attached to -(CH 2 ) q - and in A 3 , will often be in the para and/or ortho positions of those rings.
  • R-io is hydrogen and R 11 is methyl; or R 10 and R 11 are both methyl; or Ri 0 and R 11 taken together with the carbon atom to which they are attached form a cyclopropyl ring; R 4 , R 5 , R 4 ' and R 5 ' are independently selected from hydrogen, -F, -CN and -Cl; and
  • CB1 inverse agonist or "cannabinoid receptor CB1 inverse agonist” refers to a compound which binds to the receptor and exerts the opposite pharmacological effect as a CB1 receptor agonist does.
  • Inverse agonists are effective against certain types of receptors which have intrinsic activity without the acting of a ligand upon them (also referred to as 'constitutive activity'). This term is well known in the art. It is also well known in the art that such a CB1 inverse agonist can also be named a CB1 antagonist as the general properties of both types are equivalent. Accordingly, in the context of the present invention the term “CB1 antagonist” in general is understood as including both the "CB1 antagonist” as defined above and the "CB 1 inverse agonist”.
  • These dosages are based on an average human subject having a weight of about 60kg to 100kg.
  • the physician will readily be able to determine doses for subjects whose weight falls outside this range, such as infants and the elderly, and especially obese patients.
  • the HN(R 3 )R 2 -A 2 * moiety contains a nucleophilic nitrogen center and the remaining part could include the final substituent, a protected version of the substituent (e.g. an ester) or a group which can be converted to the final substituent using standard procedures known to those skilled in the art (e.g. conversion of nitrile to tetrazole).
  • compounds of Formula I may either be obtained directly following the procedure in scheme 1 or after standard conversions such as removal of protecting groups.
  • Such a procedure may include for instance conversion of a nitrile group to a tetrazole under standard conditions (e.g. by treatment with sodium azide and a weak acid such as dimethylamine hydrochloride in a polar solvent such as DMF) or the conversion of a nitrile group to a carboxylic acid.
  • This latter conversion may either be achieved directly (e.g. by hydrolysis under acidic or basic conditions) or in a two step process involving initial formation of an ester or imidate (e.g. by treatment with an alcohol and anhydrous hydrogen chloride) followed by hydrolysis under standard conditions (e.g. with aqueous sodium hydroxide).
  • the gastrointestinal transit experiment is initiated after overnight food deprivation of the mice.
  • the mice are administered a suspension of 10% charcoal (0.4 ml/mouse orally by gavage). 2.5 % Gum arabic is used as solvent for charcoal.
  • the animals are sacrificed 20 minutes later by cervical dislocation and the small intestine is removed from the cardia to the caecum. The distance covered by the head of the marker is measured and expressed as percent of the total length of the small intestine.
  • the effect of test compounds are evaluated at one or more doses, administered p.o. 45 minutes before R-(+)-WIN 55,212 (2.5 mg/kg) which is administered Lp. 30 minutes before charcoal.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Hematology (AREA)
  • Neurology (AREA)
  • Obesity (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Endocrinology (AREA)
  • Psychiatry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Emergency Medicine (AREA)
  • Child & Adolescent Psychology (AREA)
  • Addiction (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
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  • Reproductive Health (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
PCT/GB2007/004831 2006-12-18 2007-12-17 Cb1 receptor modulators Ceased WO2008075012A1 (en)

Priority Applications (10)

Application Number Priority Date Filing Date Title
BRPI0720732-8A BRPI0720732A2 (pt) 2006-12-18 2007-12-17 Moduladores de receptor cb1
JP2009542195A JP5437812B2 (ja) 2006-12-18 2007-12-17 Ｃｂ１受容体モジュレーター
AU2007336061A AU2007336061B2 (en) 2006-12-18 2007-12-17 CB1 receptor modulators
NZ578063A NZ578063A (en) 2006-12-18 2007-12-17 Cannabinoid CB1 receptor modulators
EA200900838A EA017170B1 (ru) 2006-12-18 2007-12-17 Модуляторы рецептора св1
MX2009006214A MX2009006214A (es) 2006-12-18 2007-12-17 Moduladores del receptor cb1.
US12/519,432 US8124634B2 (en) 2006-12-18 2007-12-17 CB1 receptor modulators
EP07848570.3A EP2121617B1 (en) 2006-12-18 2007-12-17 Cb1 receptor modulators
CA002673359A CA2673359A1 (en) 2006-12-18 2007-12-17 Cb1 receptor modulators
IL198990A IL198990A0 (en) 2006-12-18 2009-05-27 Cb1 receptor modulators

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GB0625197A GB0625197D0 (en) 2006-12-18 2006-12-18 Cannabinoid receptor modulators
GB0625197.9 2006-12-18
GB0717998A GB0717998D0 (en) 2007-09-14 2007-09-14 Canabinoid receptor modulators
GB0717998.9 2007-09-14

Publications (1)

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WO2008075012A1 true WO2008075012A1 (en) 2008-06-26

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Family Applications (3)

Application Number Title Priority Date Filing Date
PCT/GB2007/004831 Ceased WO2008075012A1 (en) 2006-12-18 2007-12-17 Cb1 receptor modulators
PCT/GB2007/004835 Ceased WO2008075013A1 (en) 2006-12-18 2007-12-17 Modulators of cannabinoid receptor
PCT/GB2007/004842 Ceased WO2008075019A1 (en) 2006-12-18 2007-12-17 Modulators of cb1 receptors

Family Applications After (2)

Application Number Title Priority Date Filing Date
PCT/GB2007/004835 Ceased WO2008075013A1 (en) 2006-12-18 2007-12-17 Modulators of cannabinoid receptor
PCT/GB2007/004842 Ceased WO2008075019A1 (en) 2006-12-18 2007-12-17 Modulators of cb1 receptors

Country Status (12)

Country Link
US (2) US8124634B2 (https=)
EP (2) EP2121659B1 (https=)
JP (2) JP5437812B2 (https=)
CN (1) CN103145620A (https=)
AU (2) AU2007336061B2 (https=)
BR (1) BRPI0720732A2 (https=)
CA (2) CA2673359A1 (https=)
EA (1) EA017170B1 (https=)
IL (2) IL198989A0 (https=)
MX (1) MX2009006214A (https=)
NZ (1) NZ578063A (https=)
WO (3) WO2008075012A1 (https=)

Cited By (2)

* Cited by examiner, † Cited by third party
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WO2009074782A1 (en) * 2007-12-10 2009-06-18 7Tm Pharma A/S Cannabinoid receptor modulators
WO2014023367A1 (en) 2012-08-09 2014-02-13 Phenex Pharmaceuticals Ag Carboxamide or sulfonamide substituted nitrogen-containing 5-membered heterocycles as modulators for the orphan nuclear receptor ror gamma

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US7923465B2 (en) 2005-06-02 2011-04-12 Glenmark Pharmaceuticals S.A. Cannabinoid receptor ligands, pharmaceutical compositions containing them, and process for their preparation
US7977358B2 (en) * 2007-07-26 2011-07-12 Hoffmann-La Roche Inc. Pyrazol derivatives
GB0813142D0 (en) 2008-07-17 2008-08-27 Glaxo Group Ltd Novel compounds
GB0813144D0 (en) 2008-07-17 2008-08-27 Glaxo Group Ltd Novel compounds
WO2013010169A1 (en) 2011-07-14 2013-01-17 Cook Medical Technologies Llc A sling to be used in the treatment of obstructive sleep apnea
US9710644B2 (en) 2012-02-01 2017-07-18 Servicenow, Inc. Techniques for sharing network security event information
CA2888030A1 (en) 2012-10-16 2014-11-27 Cook Medical Technologies Llc Method and apparatus for treating obstructive sleep apnea (osa)
EP3498239B1 (en) 2013-08-01 2021-04-21 Cook Medical Technologies LLC Tissue adjustment implant
AU2014306232B2 (en) 2013-08-05 2018-12-06 C2Dx, Inc. Medical devices having a releasable tubular member and methods of using the same
CN104906682A (zh) 2014-01-24 2015-09-16 史蒂文·沙勒布瓦 铰接气囊导管及其使用方法
US9974563B2 (en) 2014-05-28 2018-05-22 Cook Medical Technologies Llc Medical devices having a releasable member and methods of using the same
EP3177219B1 (en) 2014-08-04 2018-09-26 Cook Medical Technologies LLC Medical devices having a releasable tubular member
CN111093572A (zh) 2017-06-29 2020-05-01 库克医学技术有限责任公司 用于重新定位组织的可植入医疗装置
WO2020041322A1 (en) 2018-08-20 2020-02-27 Berkowitz Barry A Novel cannabinoids and cannabinoid acids and their derivatives
CA3166630A1 (en) 2020-01-03 2021-07-08 Berg Llc Polycyclic amides as ube2k modulators for treating cancer
WO2026067383A1 (zh) * 2024-09-27 2026-04-02 上海轻胜谦远生物科技有限公司 咪唑并吡啶衍生物及其用途

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WO1997019063A1 (fr) 1995-11-23 1997-05-29 Sanofi Derives du pyrazole, procede pour leur preparation et compositions pharmaceutiques les contenant
WO1997021682A1 (fr) 1995-12-08 1997-06-19 Sanofi Derives de 3-pyrazolecarboxamide avec une affinite pour le recepteur des cannabinoides
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WO2003020217A2 (en) 2001-08-31 2003-03-13 University Of Connecticut Novel pyrazole analogs acting on cannabinoid receptors
WO2003088968A1 (en) 2002-04-15 2003-10-30 Research Triangle Institute Compounds having unique cb1 receptor binding selectivity and methods for their production and use
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US20040192667A1 (en) 2001-08-31 2004-09-30 University Of Connecticut Novel pyrazole analogs acting on cannabinoid receptors
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