HRP20170532T4 - Derivati kromanila za liječenje mitohondrijske bolesti - Google Patents

Derivati kromanila za liječenje mitohondrijske bolesti Download PDF

Info

Publication number
HRP20170532T4
HRP20170532T4 HRP20170532TT HRP20170532T HRP20170532T4 HR P20170532 T4 HRP20170532 T4 HR P20170532T4 HR P20170532T T HRP20170532T T HR P20170532TT HR P20170532 T HRP20170532 T HR P20170532T HR P20170532 T4 HRP20170532 T4 HR P20170532T4
Authority
HR
Croatia
Prior art keywords
compound
levels
cancer
alkyl
none
Prior art date
Application number
HRP20170532TT
Other languages
English (en)
Inventor
Richard Hendrik Blaauw
Ruben Gerardus George Leenders
Jan Geert Sterk
Pedro Harold Han Hermkens
Original Assignee
Khondrion Ip B.V.
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 PCT/NL2013/050528 external-priority patent/WO2014011047A1/en
Application filed by Khondrion Ip B.V. filed Critical Khondrion Ip B.V.
Publication of HRP20170532T1 publication Critical patent/HRP20170532T1/hr
Publication of HRP20170532T4 publication Critical patent/HRP20170532T4/hr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
    • C07D311/66—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 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 in position 2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations
    • 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
    • C07D413/12—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 chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74—Biological properties of particular ingredients

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Birds (AREA)
  • Epidemiology (AREA)
  • Gerontology & Geriatric Medicine (AREA)
  • Dermatology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Cosmetics (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Claims (20)

1. Spoj opće formule (I): gdje - L je poveznica (linker) koja obuhvaća 1 do 10 po izboru supstituiranih atoma glavnog lanca odabranih između ugljika, dušika i kisika, pri čemu je L odabran između -CH2-CH2-NH-C(O)-CH2-(L2), ili i - R1 i R2 su svaki nezavisno odabrani između vodika i C1 - C6 alkil, ili R1 i R2 su spojeni zajedno da formiraju drugi linker između dušikovog atoma u amidu i kationskog dušikovog atoma, ili R1 je spojen R1' u 4-10 članu cikličnu strukturu i/ili R2 je spojen s R2' u 4-10 članu cikličnu strukturu; i - R3 se odabire između vodika i C1 - C6 alkil, gdje alkilna skupina može biti supstituirana s jednim ili više atoma halogena ili (halo)alkoksi skupinama, ili R3 nije prisutan kada je kationski dušikov atom dio iminske skupine; i - R4 se odabire između vodika i C1 - C6 alkil, gdje alkilni dio može biti supstituiran s jednim ili više atoma halogena ili (halo)alkoksi skupinama; - R5 je spojen s R5' u 4-10 članu cikličnu strukturu i - X- je farmaceutski prikladan anion, gdje spoj nije: (i) spoj formule (I), gdje L = -(CH2)3-(L3), R1 = H, R2 = H, R3 = H, R4 = H i X = Cl; (ii) spoj formule (I), gdje L = -(CH2)3-(L3), R1 = H, R2 = H, R3 = H, R4 = H; X = TFA, koji je S-konfiguracije na položaju 2;
2. Spoj prema zahtjevu 1, gdje X = Cl, I, TFA ili format.
3. Spoj prema bilo kojem od zahtjeva 1-2, gdje - L = -(CH2)2NHC(O)CH2-(L2), R1 = H, R2 = H, R3 = H, R4 = H; X = Cl; ili - L = -(CH2)2NHC(NH2)= (L4), R1 = H, R2 = H, R3 = nema, R4 = H; X = TFA; ili - L = -(CH2)2NHC(O)CH2NHC(NH2)= (L5), R1 = H, R2 = H, R3 = nema, R4 = H; X = TFA; ili - L = -(CH2)3NHC(NH2)= (L6), R1 = H, R2 = H, R3 = nema, R4 = H; X = TFA; ili - L = -(CH2)3- (L3), R1 = H, R2 = Me, R3 = Me, R4 = Me; X = I; ili - L = -(CH2)2NHC(Me)= (L7), R1 = H, R2 = H, R3 = nema, R4 = H; X = Cl; ili - L = -(CH2)2NHC(O)CH2NHC(Me)= (L8), R1 = H, R2 = H, R3 = nema, R4 = H; X = Cl; ili - L = -(CH2)3NHC(Me)= (L9), R1 = H, R2 = H, R3 = nema, R4 = H; X = Cl; ili - L = -(CH2)2NR1’C(NH2)= (L10), R1-R1’ = -(CH2)2- (L1), R2 = H, R3 = nema, R4 = H; X = TFA; ili - L = -C(CO2H)(CH2)3- (L11), R1 = H, R2 = H, R3 = H, R4 = H; X = Cl; ili - L = -C(CO2H)(CH2)3NHC(NH2)=(L12), R1 = H, R2 = H, R3 = nema, R4 = H; X = Cl; ili - L = -C(CO2H)CH2- (L13), R1 = H,R2 = H, R3 = H, R4 = H; X = Cl; ili - L = -C(CO2H)(CH2)2- (L14), R1 = H, R2 = H, R3 = H, R4 = H; X = Cl; ili - L = -C(CO2H)(CH2)3- (L15), R1 = H, R2 = H, R3 = H, R4 = H; X = Cl; ili - L = -C(CO2H)(CH2)3- (L11), R1 = H, R2 = Me, R3 = Me, R4 = H; X = Cl; ili - L = -(CH2)4- (L16), R1 = H, R2 = H, R3 = H, R4 = H; X = Cl; ili - L = -(CH2)5- (L17), R1 = H, R2 = H, R3 = H, R4 = H; X = Cl; ili - L = -(CH2)4- (L16), R1 = H, R2 = Me, R3 = Me, R4 = H; X = Cl; ili - L = -CHR2’C(O)- (L18), R1 = H, R2-R2’ = -(CH2)3- (L3), R3 = H, R4 = H; X = Cl; ili - L = -CHR2’CH2- (L19), R1 = H, R2-R2’ = -(CH2)3- (L3), R3 = H, R4 = H; X = Cl; ili - L = -CHR5CH2NR5’C(Me)= (L20), R1 = H, R2 = H, R5-R5’ = -(CH2)3- (L3), R3 = nema, R4 = H; X = Cl; ili - L = -CHR2’(CH2)2- (L21), R1 = H, R2-R2’ = -(CH2)2- (L1), R3 = H, R4 = H; X = Cl; ili - L = -(CH2)2CHR1’- (L22), R1-R1’ = -(CH2)2- (L1), R2 = H, R3 = H, R4 = H; X = Cl; ili - L = -(CH2)2CHR1’NHC(O)C(Me)- (L23), R1-R1’ = -(CH2)2- (L1), R2 = H, R3 = H, R4 = H; X = Cl; ili - L = -CH2CHR1’- (L24), R1-R1’ = -(CH2)3- (L3), R2 = H, R3 = H, R4 = H; X = Cl; ili - L = -CH2’CHR1’NHC(Me)= (L25), R1-R1’ = -(CH2)3- (L3), R2’ = H, R3 = nema, R4 = H; X = Cl; ili - L = -CHR5(CH2)2CHR5’- (L26), R1 = H, R2 = H, R5-R5’ = -(CH2)2- (L1), R3 = H, R4 = H; X = Cl; ili - L = -CHR2’CH2- (L19), R1 = H, R2-R2’ = -(CH2)3- (L3), R3 = Me, R4 = H; X = Cl; ili - L = -CHR2’CH2- (L19), R1 = H, R2-R2’ = -(CH2)2- (L1), R3 = H, R4 = H; X = Cl; ili - L = -CHR2’(CH2)2- (L21), R1= H, R2-R2’ = -(CH2)2- (L1), R3 = Me, R4 = H; X = Cl.
4. Spoj prema zahtjevu 3, gdje
5. Spoj prema zahtjevu 3, gdje - L = -(CH2)3-(L3), R1 = H, R2 = Me, R3 = Me, R4 = Me; X = I.
6. Spoj opće formule (I): pri čemu je ili
7. Farmaceutski ili kozmetički pripravak koji sadrži spoj prema bilo kojem od zahtjeva 1 - 6 i fiziološki prikladan nosač.
8. Spoj prema bilo kojem od zahtjeva 1 - 6, za uporabu kao lijek.
9. Spoj prema bilo kojem od zahtjeva 1 - 6, za uporabu u modulaciji barem jednog između morfologije mitohondrija i ekspresije OXPHOS enzima.
10. Spoj za uporabu u liječenju, prevenciji ili suprimiranju simptoma povezanih s mitohondrijskim poremećajem, gdje spoj jest spoj opće formule (I): gdje - L je poveznica (linker) koja obuhvaća 1 do 10 po izboru supstituiranih atoma glavnog lanca odabranih između ugljika, dušika i kisika; pri čemu je L odabran između
ili i - R1 i R2 su svaki nezavisno odabrani između vodika i C1 - C6 alkil, ili R1 i R2 su spojeni zajedno da formiraju drugi linker između dušikovog atoma u amidu i kationskog dušikovog atoma, ili R1 je spojen s R1' u 4-10 članu cikličnu strukturu i/ili R2 je spojen R2' u 4-10 članu cikličnu strukturu; i - R3 se odabire između vodika i C1 - C6 alkil, gdje alkilna skupina može biti supstituirana s jednim ili više atoma halogena ili (halo)alkoksi skupinama, ili R3 nije prisutan kada je kationski dušikov atom dio iminske skupine; i - R4 se odabire između vodika i C1 - C6 alkil, gdje alkilna skupina može biti supstituirana s jednim ili više atoma halogena ili (halo)alkoksi skupinama; i - R5 je spojen s R5' u 4-10 članu cikličnu strukturu - X- je farmaceutski prikladan anion.
11. Spoj za uporabu prema zahtjevu 10, gdje
12. Spoj za uporabu prema zahtjevu 10 ili 11, gdje mitohondrijski poremećaj jest poremećaj odabran iz grupe koju čine: mioklonična epilepsija; mioklonična epilepsija s nepravilnim crvenim vlaknima (MERRF); Leberova nasljedna optička neuropatija (LHON); neuropatska ataksija i retinitis pigmentosa (NARP); mitohondrijska miopatija, encefalomiopatija, laktacidoza i napadi nalik na moždani udar (MELAS); Leigh sindrom; Leigh-sličan sindrom; dominantna optička atrofija (DOA); Kearns-Sayre sindrom (KSS); po majci naslijeđeni dijabetes i gluhoća (MIDD); Alpers-Huttenlocher sindrom; spektar ataksija neuropatija; kronična progresivna eksterna oftalmoplegija (CPEO); Pearson sindrom; mitohondrijska Neuro-Gastro-Intestinalna encefalopatija (MNGIE); Sengers sindrom; 3-metilglutakonatna acidurija, senzorineuralna gluhoća, encefalopatija i neuroradiološki nalazi Leigh-sličnog sindroma (MEGDEL); miopatija; mitohondrijska miopatija; kardiomiopatija; i encefalomiopatija, SURFS1 (COX deficijentan Leigh sindrom zbog deficijencije zasićenog proteina kompleksa IV) i izolirane ili kombinirane OXPHOS deficijencije sa do sada neriješenim genetičkim defektom uključujući poremećenu oksidaciju piruvata i ATP plus PCr brzine proizvodnje.
13. Spoj prema bilo kojem od zahtjeva 3 - 6, za uporabu u liječenju, prevenciji ili suprimiranju simptoma povezanih sa stanjem povezanim s disfunkcijom mitohondrija, gdje, poželjno spoj jest spoj prema zahtjevu 5.
14. Spoj za uporabu prema zahtjevu 13, gdje je stanje povezano s disfunkcijom mitohondrija stanje odabrano iz grupe koju čine: Friedreichova ataksija (FRDA); renalna tubularna acidoza; Parkinsonova bolest; Alzheimerova bolest; amiotrofična lateralna skleroza (ALS); Huntingtonova bolest; razvojni pervazivni poremećaji; gubitak sluha; gluhoća; dijabetes; starenje; i nuspojave lijekova koje utječu na funkciju mitohondrija.
15. Spoj za uporabu prema bilo kojem od zahtjeva 10 - 14, gdje se koristi mjerljivi klinički marker za procjenu učinkovitosti liječenja spojem prema pronalasku.
16. Spoj za uporabu prema zahtjevu 15, gdje klinički marker jest jedan ili više markera odabranih iz grupe koju čine razine mliječne kiseline (laktat), bilo iz pune krvi, plazme, cerebrospinalne tekućine, ili cerebralne ventrikularne tekućine; razine piruvatne kiseline (piruvat), bilo iz pune krvi, plazme, cerebrospinalne tekućine, ili cerebralne ventrikularne tekućine; omjeri laktata/piruvata, bilo iz pune krvi, plazme, cerebrospinalne tekućine, ili cerebralne ventrikularne tekućine; aminokiseline, posebno alanin, citrulin i prolin u punoj krvi, plazmi ili cerebrospinalnoj tekućini, organske kiseline u tjelesnim tekućinama; FGF21 u serumu i mišićima skeleta; razine fosfokreatina, razine NADH (NADH + H+) ili NADPH (NADPH + H+); razine NAD ili NADP; razine ATP; anaerobna granica; smanjene razine koenzima Q (CoQred); razine oksidiranog koenzima Q (CoQox; ukupne razine koenzima Q (CoQtot); razine oksidiranog citokroma C; smanjene razine citokroma C; omjer oksidiranog citokroma C/reduciranog citokroma C; razine acetoacetata, razine beta-hidroksi butirata, omjer acetoacetat/betahidroksi butirat, razine 8-hidroksi-2’-deoksigvanozina (8-OHdG); razine reaktivnih kisikovih skupina; i razine potrošnje kisika (VO2), razine proizvodnje ugljikovog dioksida (VCO2), i respiratorni kvocijent (VCO2/VO2).
17. Spoj za uporabu u liječenju, prevenciji ili suprimiranju simptoma povezanih s neoplastičnom bolesti, gdje spoj jest spoj opće formule (I): gdje - L = -(CH2)3-(L3), R1 = H, R2 = Me, R3 = Me, R4 = Me; X = I; ili - L = -(CH2)2- (L1), R1 = H, R2 = Me, R3 = Me, R4 = Me; X = I.
18. Spoj za uporabu prema zahtjevu 17, gdje je neoplastična bolest rak, poželjno rak odabran iz grupe koju čini karcinom bazalnih stanica, rak kostiju, rak crijeva, rak mozga, rak dojke, rak cerviksa, leukemija, rak jetre, rak pluća, limfom, melanom, rak jajnika, rak gušterače, rak prostate ili rak štitnjače.
19. Kozmetički postupak za liječenje ili odgađanje daljnjeg starenja kože u subjekta, postupak obuhvaća korak primjene učinkovite količine pripravka koji sadrži spoj opće formule (I) na kožu subjekta: gdje - L je poveznica (linker) koja obuhvaća 1 do 10 po izboru supstituiranih atoma glavnog lanca odabranih između ugljika, dušika i kisika; i - R1 i R2 su svaki nezavisno odabrani između vodika i C1 - C6 alkil, ili R1 i R2 su spojeni zajedno da formiraju drugi linker između dušikovog atoma u amidu i kationskog dušikovog atoma, ili R1 je spojen s atomom glavnog lanca linkera L u cikličku strukturu i/ili R2 je spojen s atomom glavnog lanca linkera L u cikličku strukturu; i - R3 se odabire između vodika i C1 - C6 alkil, gdje alkilna skupina može biti supstituirana s jednim ili više atoma halogena ili (halo)alkoksi skupinama, ili R3 nije prisutan kada je kationski dušikov atom dio iminske skupine; i - R4 se odabire između vodika i C1 - C6 alkil, gdje alkilna skupina može biti supstituirana s jednim ili više atoma halogena ili (halo)alkoksi skupinama; i - X- je farmaceutski prikladan anion.
20. Postupak prema zahtjevu 19, gdje
HRP20170532TT 2012-07-12 2017-04-03 Derivati kromanila za liječenje mitohondrijske bolesti HRP20170532T4 (hr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201261670644P 2012-07-12 2012-07-12
EP12176128 2012-07-12
PCT/NL2013/050528 WO2014011047A1 (en) 2012-07-12 2013-07-12 Chromanyl derivatives for treating mitochondrial disease
EP13759838.9A EP2872497B2 (en) 2012-07-12 2013-07-12 Chromanyl derivatives for treating mitochondrial disease

Publications (2)

Publication Number Publication Date
HRP20170532T1 HRP20170532T1 (hr) 2017-06-16
HRP20170532T4 true HRP20170532T4 (hr) 2019-12-27

Family

ID=53577992

Family Applications (1)

Application Number Title Priority Date Filing Date
HRP20170532TT HRP20170532T4 (hr) 2012-07-12 2017-04-03 Derivati kromanila za liječenje mitohondrijske bolesti

Country Status (6)

Country Link
US (1) US9388156B2 (hr)
CY (1) CY1119384T1 (hr)
HK (1) HK1209425A1 (hr)
HR (1) HRP20170532T4 (hr)
IN (1) IN2015MN00114A (hr)
MX (1) MX364547B (hr)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2959243T3 (es) * 2017-04-05 2024-02-22 Khondrion Ip B V Nuevo tratamiento de enfermedades mitocondriales
EP3713564B1 (en) * 2017-11-22 2023-11-15 Khondrion Ip B.V. Compounds as mpges-1 inhibitors
AU2018371152B2 (en) * 2017-11-22 2024-02-08 Khondrion Ip B.V. Novel compounds for use in treating depression and migraine
WO2020159576A1 (en) 2019-01-28 2020-08-06 Mitochondria Emotion, Inc. Mitofusin activators and methods of use thereof
CA3127453A1 (en) 2019-01-28 2020-08-06 Mitochondria Emotion, Inc. Trans-4-hydroxycyclohexyl phenyl amide mitofusin activators and methods of use thereof

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AR019190A1 (es) 1998-07-08 2001-12-26 Sod Conseils Rech Applic Derivados de 2-aminopiridinas, productos intermedios para su preparacion, medicamentos y composiciones farmaceuticas que los contienen y su uso para preparar medicamentos
AU2001262200A1 (en) 2000-04-25 2001-11-07 Schering Aktiengesellschaft Benzoxazine derivatives and benzothiazine derivatives having nos-inhibitory and antioxidant properties
JP2002047272A (ja) 2000-07-26 2002-02-12 Dai Ichi Seiyaku Co Ltd ポリアミンアミド誘導体
MX2010004622A (es) 2007-11-06 2010-05-20 Edison Pharmaceuticals Inc Derivados de 4-(p-quinonil)-2-hidroxibutanamida para tratamiento de enfermedades mitocondriales.

Also Published As

Publication number Publication date
MX364547B (es) 2019-04-30
HRP20170532T1 (hr) 2017-06-16
MX2015000488A (es) 2015-04-08
US20150166501A1 (en) 2015-06-18
IN2015MN00114A (hr) 2015-10-16
US9388156B2 (en) 2016-07-12
CY1119384T1 (el) 2018-02-14
HK1209425A1 (zh) 2016-04-01

Similar Documents

Publication Publication Date Title
HRP20170532T4 (hr) Derivati kromanila za liječenje mitohondrijske bolesti
UA110924C2 (uk) Мезоіонні пестициди
PH12019502042A1 (en) Fungicidal composition and method for controlling plant diseases
MY168201A (en) Agricultural And Horticultural Fungicidal Composition
WO2009081152A3 (en) Antimicrobial compounds
CN106699687B (zh) 一种含硒的kga/gac和/或gdh抑制剂化合物
BR0009486A (pt) Compostos que contêm uma amida, utilização desses compostos, composição farmacêutica, processo para o tratamento profilático ou terapêutico de, diabetes do tipo ii e processo para a preparação dos compostos
ATE553095T1 (de) Neue imidazolderivate, deren herstellung und deren verwendung als intermediate zur herstellung von arzneimitteln und pestiziden
WO2010005692A3 (en) Insecticidal cyclic carbonyl amidines
BR112012022125A2 (pt) composto, sal de dicloridrato, composição farmacêutica, uso do composto, e, método para tratar um paciente
BR112015018966A2 (pt) composição de controle de pestes e uso da mesma
NZ593848A (en) Synthesis of 18f-radiolabeled styrylpyridines from tosylate precursors and stable pharmaceutical compositions thereof
UA107324C2 (uk) Похідні 1,2,3-триазолу для застосування як інгібіторів стеароїл-coa десатурази
ATE411296T1 (de) Imidazolinderivate mit cb1-antagonistischer wirkung
ATE499372T1 (de) Azabenzimidalzolderivate, ihre herstellung und ihre verwendung als antikrebsmittel
PT2280706E (pt) Composições compreendendo derivados de benzeno que activam lipase de lipoproteína
NO20063865L (no) Heterocyklisk substituerte 7-amino-4-kinolon-3-karboksylsyrederivater, fremgangsmate for fremstilling derav og deres anvendelse som medikamenter
HK1142898A1 (en) 1, 3-dihydroimidazole- 2 -thione derivatives as inhibitors of dopamine- beta-hydroxylase
BRPI0519578A2 (pt) pirimidinas substituÍdas
Hershko Iron loading and its clinical implications
Limban et al. Synthesis and antimicrobial properties of new 2-((4-ethylphenoxy) methyl) benzoylthioureas
DE602006018359D1 (de) Heterocyclische derivate, deren herstellung und therapeutische verwendung
MA29258B1 (fr) Nouveaux derives d'oximes heterocycliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
BRPI0713951B8 (pt) derivados de quinazolina, e composição farmacêutica
BR112023020114A2 (pt) Derivados microbiocidas de quinolina/quinoxalina benzotiazina