HRP20211483T1 - Derivati 2-(3-(1h-benzo[d]imidazol-1-il)propil)piperidin-3-ola i povezani spojevi kao inhibitori prs za liječenje npr. raka - Google Patents

Derivati 2-(3-(1h-benzo[d]imidazol-1-il)propil)piperidin-3-ola i povezani spojevi kao inhibitori prs za liječenje npr. raka Download PDF

Info

Publication number
HRP20211483T1
HRP20211483T1 HRP20211483TT HRP20211483T HRP20211483T1 HR P20211483 T1 HRP20211483 T1 HR P20211483T1 HR P20211483T T HRP20211483T T HR P20211483TT HR P20211483 T HRP20211483 T HR P20211483T HR P20211483 T1 HRP20211483 T1 HR P20211483T1
Authority
HR
Croatia
Prior art keywords
piperidin
propyl
benzo
imidazol
chloro
Prior art date
Application number
HRP20211483TT
Other languages
English (en)
Inventor
Bong-Yong Lee
Min-Jae Cho
Hyung-Geun Lee
Myung-gi JUNG
Yunju OH
Original Assignee
Daewoong 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 Daewoong Pharmaceutical Co., Ltd. filed Critical Daewoong Pharmaceutical Co., Ltd.
Publication of HRP20211483T1 publication Critical patent/HRP20211483T1/hr

Links

Classifications

    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
    • 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]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • 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
    • C07D401/04—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 directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom 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
    • C07D413/14—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
    • 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
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
    • C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
    • C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
    • C07D473/12—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3 with methyl radicals in positions 1, 3, and 7, e.g. caffeine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Claims (15)

1. Spoj predstavljen sljedećom kemijskom formulom 1, ili njegova farmaceutski prihvatljiva sol: [image] u kemijskoj formuli 1, n je 1 ili 2, L je -CH2CH2-, -CH=C(R')-, ili -C≡C-, pri čemu R' je vodik, C1-4 alkil, ili halogen, X1 je CR1R2, NR1, ili -CO-, X2 je CR3R4, ili NR3, naznačen time što R1 do R4 su svaki neovisno vodik, C1-4 alkil, C1-4 hidroksialkil, hidroksi, amino, karboksi, -COO(C1-4 alkil), -CONH2, -CONH(C1-4 alkil), -CON (C1-4 alkil)2, ili pirazolil nesupstituiran ili supstituiran s C1-4 haloalkil; ili R1 i R3, zajedno jedan s drugim, povezuju X1 i X2 dvostrukom vezom, i A je benzenski, piridinski, pirimidinski ili pirimidindionski prsten, pri čemu A je nesupstituiran ili supstituiran s jednim do tri supstituenta koji su svaki neovisno odabrani iz skupine koju čine supstituent prstenastog tipa odabran iz skupine koju čine furanil, imidazolil, izoksazolil, fenil, pirazolil, piridinonil, piridinil, pirolil, tiazolil, i tiofenil; C1-4 alkil; C1-4 alkoksi; C1-4 haloalkil; C1-4 haloalkoksi; halogen; di(C1-4 alkil)amino; nitro; -COO(C1-4 alkil); dihidropiranil; morfolino; piperidinil; i pirolidinil; i pri čemu je supstituent prstenastog tipa nesupstituiran ili supstituiran s jednim ili dva supstituenta svaki neovisno odabran iz skupine koju čine C1-5 alkil, C1-4 haloalkil, C3-6 cikloalkil, jednovalentni C2-5 alkilen karbonata, -COO(C1-4 alkil), halogen, cijano, tiazolil, i (1,3-dioksolan-2-il)metil.
2. Spoj ili njegova farmaceutski prihvatljiva sol prema patentnom zahtjevu 1, naznačen time što, A je nesupstituiran ili supstituiran s jednim do tri supstituenta koji su svaki neovisno odabrani iz skupine koju čine C1-4 alkil; C1-4 alkoksi; C1-4 haloalkil; halogen; fenil nesupstituiran ili supstituiran s halogenom, ili C1-4 haloalkil; pirazolil nesupstituiran ili supstituiran s C1-5 alkilom, tiazolil, ili C1-4 haloalkil; tiofenil nesupstituiran ili supstituiran s C1-5 alkilom, ili -COO(C1-4 alkil); pirolil nesupstituiran ili supstituiran s C1-5 alkilom i/ili-COO(C1-4 alkil); di(C1-4 alkil)amino; morfolino; piperidinil; furanil; i pirolidinil.
3. Spoj ili njegova farmaceutski prihvatljiva sol prema patentnom zahtjevu 1, naznačen time što L je -CH2CH2-, -CH=CH-, -CH=CF-, -CH=C(CH3)-, ili -C≡C-.
4. Spoj ili njegova farmaceutski prihvatljiva sol prema patentnom zahtjevu 1, naznačen time što je spoj predstavljen kemijskom formulom 1 predstavljen sljedećim kemijskim formulama 1-1 do 1-5: [image] [image] u kemijskim formulama 1-1 do 1-5, n, L, R1 do R4 i A su kako je definirano u zahtjevu 1.
5. Spoj ili njegova farmaceutski prihvatljiva sol prema patentnom zahtjevu 1, naznačen time što su R1 do R4 svaki neovisno vodik, metil, hidroksimetil, hidroksi, amino, karboksi, -COOCH3, -CONH2, -CONHCH3, ili -CON(CH3)2; ili R1 i R3, zajedno jedan s drugim, vežu X1 i X2 dvostrukom vezom.
6. Spoj ili njegova farmaceutski prihvatljiva sol prema patentnom zahtjevu 1, naznačen time što A je benzenski, piridinski, pirimidinski ili pirimidindionski prsten, i A je nesupstituiran ili supstituiran s jednim do tri supstituenta koji su svaki neovisno odabrani iz skupine koju čine metil, izobutil, metoksi, trifluormetil, fluor, klor, brom, fenil, fenil supstituiran s fluorom, fenil supstituiran s klorom, fenil supstituiran s trifluorometilom, tiofenil, tiofenil supstituiran s metilom, tiofenil supstituiran s -COOCH3, pirazolil supstituiran s difluorometilom, pirazolil supstituiran s metilom, pirazolil supstituiran s tiazolilom, pirolil supstituiran s metilom i -COOCH2CH3, furanil, dimetilamino, dietilamino, metiletilamino, morfolino, piperidinil, i pirolidinil.
7. Spoj ili njegova farmaceutski prihvatljiva sol prema patentnom zahtjevu 1, naznačen time što A je benzen, i A je nesupstituiran ili supstituiran s jednim do tri supstituenta koji su svaki neovisno odabrani iz skupine koju čine C1-4 alkil; C1-4 alkoksi; halogen; i fenil nesupstituiran ili supstituiran s halogen ili C1-4 haloalkil.
8. Spoj ili njegova farmaceutski prihvatljiva sol prema patentnom zahtjevu 1, naznačen time što A je piridin, i A je nesupstituiran ili supstituiran s jednim ili dva supstituenta svaki neovisno odabran iz skupine koju čine C1-4 alkil; C1-4 alkoksi; halogen; i fenil supstituiran s halogenom.
9. Spoj ili njegova farmaceutski prihvatljiva sol prema patentnom zahtjevu 1, naznačen time što A je pirimidin, i A je supstituiran sa supstituentom odabranim iz skupine koju čine halogen; di(C1-4 alkil)amino; morfolino; piperidinil; i pirolidinil.
10. Spoj ili njegova farmaceutski prihvatljiva sol prema patentnom zahtjevu 1, naznačen time što A je pirimidindion, i A je nesupstituiran ili supstituiran s jednim ili dva C1-4 alkila.
11. Spoj ili njegova farmaceutski prihvatljiva sol, naznačen time što je spoj izabran iz skupine koju čine: 1) (2R,3S)-2-(3-(6-klor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 2) (2R,3S)-2-(3-(4-brom-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 3) (2R,3S)-2-(3-(5-brom-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 4) (2R,3S)-2-(3-(6-brom-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 5) (2R,3S)-2-(3-(7-brom-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 6) (2R,3S)-2-(3-(4-fluor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 7) (2R,3S)-2-(3-(5-fluor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 8) (2R,3S)-2-(3-(6-fluor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 9) (2R,3S)-2-(3-(7-fluor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 10) (2R,3S)-2-(3-(4-klor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 11) (2R,3S)-2-(3-(5-klor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 12) (2R,3S)-2-(3-(7-klor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 13) (2R,3S)-2-(3-(6-metil-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 14) (2R,3S)-2-(3-(5-metil-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 15) (2R,3S)-2-(3-(6-(trifluormetil)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 16) (2R,3S)-2-(3-(7-(trifluormetil)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 17) (2R,3S)-2-(3-(7-(trifluormetoksi)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 18) (2R,3S)-2-(3-(4-(pirolidin-1-il)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 19) (2R,3S)-2-(3-(4-(piperidin-1-il)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 20) (2R,3S)-2-(3-(4-(3-fluorfenil)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 21) (2R,3S)-2-(3-(4-(3-klorfenil)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 22) (2R,3S)-2-(3-(5-(3-fluorfenil)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 23) (2R,3S)-2-(3-(6-(2-fluorfenil)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 24) (2R,3S)-2-(3-(6-(3-fluorfenil)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 25) (2R,3S)-2-(3-(6-(4-fluorfenil)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 26) (2R,3S)-2-(3-(7-(2-fluorfenil)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 27) (2R,3S)-2-(3-(7-(3-fluorfenil)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 28) (2R,3S)-2-(3-(7-(4-fluorfenil)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 29) (2R,3S)-2-(3-(5-(1H-pirazol-4-il)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 30) (2R,3S)-2-(3-(6-(1H-pirazol-4-il)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 31) (2R,3S)-2-(3-(7-(1H-pirazol-4-il)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 32) (2R,3S)-2-(3-(6-klor-5-fluor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 33) (2R,3S)-2-(3-(6-brom-5-fluor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 34) (2R,3S)-2-(3-(5-klor-6-fluor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 35) (2R,3S)-2-(3-(5-brom-6-fluor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 36) (2R,3S)-2-(3-(6-brom-5-klor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 37) (2R,3S)-2-(3-(6-klor-5-metoksi-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 38) (2R,3S)-2-(3-(6-fluor-5-metoksi-1 H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 39) (2R,3S)-2-(3-(5-fluor-6-metil-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 40) (2R,3S)-2-(3-(4,5-diklor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 41) (2S,3S)-2-(3-(4,5-diklor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 42) (2S,3R)-2-(3-(4,5-diklor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 43) (2R,3R)-2-(3-(4,5-diklor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 44) (2R,3S)-2-(3-(4-klor-5-metil-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 45) (2R,3S)-2-(3-(5-brom-4-metil-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 46) (2R,3S)-2-(3-(5-klor-4-metil-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 47) (2R,3S)-2-(3-(5-brom-4-fluor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 48) (2R,3S)-2-(3-(6-brom-7-fluor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 49) (2R,3S)-2-(3-(4,5-difluor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 50) (2R,3S)-2-(3-(6,7-difluor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 51) (2R,3S)-2-(3-(4,5-dimetil-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 52) (2R,3S)-2-(3-(5,6-difluor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 53) (2R,3S)-2-(3-(5,6-diklor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 54) (2R,3S)-2-(3-(5,6-dibrom-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 55) (2R,3S)-2-(3-(5,6-dimetil-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 56) (2R,3S)-2-(3-(6,7-diklor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 57) (2R,3S)-2-(3-(4,6-difluor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 58) (2R,3S)-2-(3-(5,7-difluor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 59) (2R,3S)-2-(3-(4-klor-5-metoksi-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 60) (2R,3S)-2-(3-(7-klor-6-metoksi-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 61) (2R,3S)-2-(3-(6-klor-4-metil-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 62) (2R,3S)-2-(3-(4-klor-5-fluor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 63) (2R,3S)-2-(3-(6-brom-4-metil-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 64) (2R,3S)-2-(3-(5-fluor-4-metil-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 65) (2R,3S)-2-(3-(6-fluor-7-metil-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 66) (2R,3S)-2-(3-(4-klor-5-(trifluormetil)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 67) (2R,3S)-2-(3-(7-klor-6-(trifluormetil)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 68) metil 7-brom-1-(3-((2R,3S)-3-hidroksipiperidin-2-il)propil)-1H-benzo[d]imidazol-5-karboksilat, 69) (2R,3S)-2-(3-(7-brom-5-klor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 70) (2R,3S)-2-(3-(5-brom-7-klor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 71) (2R,3S)-2-(3-(7-brom-5-(trifluormetil)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 72) (2R,3S)-2-(3-(6-brom-4-fluor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 73) (2R,3S)-2-(3-(5-brom-7-fluor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 74) (2R,3S)-2-(3-(7-klor-4-fluor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 75) (2R,3S)-2-(3-(5-brom-4-nitro-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 76) (2R,3S)-2-(3-(6-brom-7-nitro-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 77) (2R,3S)-2-(3-(4-klor-5-nitro-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 78) (2R,3S)-2-(3-(7-klor-5-(trifluormetil)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 79) (2R,3S)-2-(3-(5-klor-7-fluor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 80) (2R,3S)-2-(3-(5,7-diklor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 81) (2R,3S)-2-(3-(5-klor-7-(1H-pirazol-4-il)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 82) (2R,3S)-2-(3-(7-(1H-pirazol-4-il)-5-(trifluormetil)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 83) (2R,3S)-2-(3-(5-klor-7-(3-fluorfenil)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 84) (2R,3S)-2-(3-(7-(3-fluorfenil)-5-(trifluormetil)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 85) (2R,3S)-2-(3-(5-klor-7-(2-metiltiazol-5-il)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 86) (2R,3S)-2-(3-(5-klor-7-(piridin-3-il)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 87) (2R,3S)-2-(3-(5-klor-7-(5-fluorpiridin-3-il)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 88) 5-(5-klor-1-(3-((2R,3S)-3-hidroksipiperidin-2-il)propil)-1H-benzo[d]imidazol-7-il)-1-metilpiridin-2(1H)-on, 89) (2R,3S)-2-(3-(5-klor-7-(1-(difluormetil)-1H-pirazol-4-il)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 90) (2R,3S)-2-(3-(5-klor-7-(izoksazol-3-il)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 91) (2R,3S)-2-(3-(5-klor-7-(tiofen-3-il)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 92) (2R,3S)-2-(3-(5-klor-7-(2-metiltiofen-3-il)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 93) (2R,3S)-2-(3-(5-klor-7-(3,5-dimetilizoksazol-4-il)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 94) (2R,3S)-2-(3-(5-klor-7-(3,6-dihidro-2H-piran-4-il)-1 H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 95) (2R,3S)-2-(3-(7-(1-((1,3-dioksolan-2-il)metil)-1H-pirazol-4-il)-5-klor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 96) (2R,3S)-2-(3-(5-klor-7-(1-metil-1H-imidazol-5-il)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 97) (2R,3S)-2-(3-(5-klor-7-(1-metil-1H-pirazol-4-il)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 98) (2R,3S)-2-(3-(7-(pirolidin-1-il)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 99) (2R,3S)-2-(3-(5-klor-7-(pirolidin-1-il)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 100) (2R,3S)-2-(3-(5-klor-7-(2-ciklopropiltiazol-5-il)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 101) (2R,3S)-2-(3-(5-klor-7-(1-(tiazol-2-il)-1H-pirazol-4-il)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 102) (2R,3S)-2-(3-(5-klor-7-(1-(oksetan-3-il)-1H-pirazol-4-il)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 103) (2R,3S)-2-(3-(5-klor-7-(2-(tetrahidro-2H-piran-4-il)tiazol-4-il)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 104) (2R,3S)-2-(3-(5-klor-7-(furan-3-il)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 105) 4-(5-klor-1-(3-((2R,3S)-3-hidroksipiperidin-2-il)propil)-1H-benzo[d]imidazol-7-il)tiazole-2-karbonitril, 106) (2R,3S)-2-(3-(7-(1-(tert-butil)-1H-pirazol-4-il)-5-klor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 107) (2R,3S)-2-(3-(5-klor-7-(1-izopentil-1H-pirazol-4-il)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 108) (2R,3S)-2-(3-(5-klor-7-(1-izopropil-1H-pirazol-4-il)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 109) (2R,3S)-2-(3-(5-klor-7-(4-metiltiofen-3-il)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 110) etil 3-(5-klor-1-(3-((2R,3S)-3-hidroksipiperidin-2-il)propil)-1H-benzo[d]imidazol-7-il)furan-2-karboksilat, 111) metil 4-(5-klor-1-(3-((2R,3S)-3-hidroksipiperidin-2-il)propil)-1H-benzo[d]imidazol-7-il)tiofen-2-karboksilat, 112) (2R,3S)-2-(3-(5-klor-7-(1-(2-fluoretil)-1H-pirazol-4-il)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 113) (2R,3S)-2-(3-(7-(1-butil-1H-pirazol-4-il)-5-klor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 114) (2R,3S)-2-(3-(5-klor-7-(2,5-dimetiltiofen-3-il)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 115) (2R,3S)-2-(3-(5-klor-7-(1-izobutil-1H-pirazol-4-il)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 116) etil 4-(5-klor-1-(3-((2R,3S)-3-hidroksipiperidin-2-il)propil)-1H-benzo[d]imidazol-7-il)-1-metil-1H-pirol-2-karboksilat, 117) (2R,3S)-2-(3-(5-klor-1H-imidazo[4,5-b]piridin-1-il)propil)piperidin-3-ol, 118) (2R,3S)-2-(3-(5-klor-3H-imidazo[4,5-b]piridin-3-il)propil)piperidin-3-ol, 119) (2R,3S)-2-(3-(5-brom-1H-imidazo[4,5-b]piridin-1-il)propil)piperidin-3-ol, 120) (2R,3S)-2-(3-(6-brom-1H-imidazo[4,5-b]piridin-1-il)propil)piperidin-3-ol, 121) (2R,3S)-2-(3-(5-metil-1H-imidazo[4,5-b]piridin-1-il)propil)piperidin-3-ol, 122) (2R,3S)-2-(3-(6-klor-1H-imidazo[4,5-c]piridin-1-il)propil)piperidin-3-ol. 123) (2R,3S)-2-(3-(6-klor-3H-imidazo[4,5-c]piridin-3-il)propil)piperidin-3-ol, 124) (2R,3S)-2-(3-(6-brom-1H-imidazo[4,5-c]piridin-1-il)propil)piperidin-3-ol, 125) (2R,3S)-2-(3-(6-brom-3H-imidazo[4,5-c]piridin-3-il)propil)piperidin-3-ol, 126) (2R,3S)-2-(3-(7-klor-1H-imidazo[4,5-b]piridin-1-il)propil)piperidin-3-ol, 127) (2R,3S)-2-(3-(5,6-diklor-1H-imidazo[4,5-b]piridin-1-il)propil)piperidin-3-ol, 128) (2R,3S)-2-(3-(7-brom-1H-imidazo[4,5-c]piridin-1-il)propil)piperidin-3-ol, 129) (2R,3S)-2-(3-(5-(trifluormetil)-3H-imidazo[4,5-b]piridin-3-il)propil)piperidin-3-ol, 130) (2R,3S)-2-(3-(6,7-diklor-3H-imidazo[4,5-b]piridin-3-il)propil)piperidin-3-ol, 131) (2R,3S)-2-(3-(6-klor-7-metil-3H-imidazo[4,5-b]piridin-3-il)propil)piperidin-3-ol, 132) (2R,3S)-2-(3-(6-brom-7-metil-3H-imidazo[4,5-b]piridin-3-il)propil)piperidin-3-ol, 133) (2R,3S)-2-(3-(6-brom-7-klor-3H-imidazo[4,5-b]piridin-3-il)propil)piperidin-3-ol, 134) (2R,3S)-2-(3-(7-klor-6-(3-klorfenil)-3H-imidazo[4,5-b]piridin-3-il)propil)piperidin-3-ol, 135) (2R,3S)-2-(3-(2-klor-7H-purin-7-il)propil)piperidin-3-ol, 136) (2R,3S)-2-(3-(2-klor-9H-purin-9-il)propil)piperidin-3-ol, 137) (2R,3S)-2-(3-(6-(dimetilamino)-9H-purin-9-il)propil)piperidin-3-ol, 138) (2R,3S)-2-(3-(6-(dietilamino)-9H-purin-9-il)propil)piperidin-3-ol, 139) (2R,3S)-2-(3-(6-(etil(metil)amino)-9H-purin-9-il)propil)piperidin-3-ol, 140) (2R,3S)-2-(3-(6-morfolino-9H-purin-9-il)propil)piperidin-3-ol, 141) (2R,3S)-2-(3-(6-(piperidin-1-il)-9H-purin-9-il)propil)piperidin-3-ol, 142) (2R,3S)-2-(3-(6-(pirolidin-1-il)-9H-purin-9-il)propil)piperidin-3-ol, 143) 1-(3-((2R,3S)-3-hidroksipiperidin-2-il)propil)-1H-benzo[d]imidazol-2-ol, 144) 5,6-diklor-1-(3-((2R,3S)-3-hidroksipiperidin-2-il)propil)-1H-benzo[d]imidazol-2-ol, 145) (2R,3S)-2-(3-(2-(hidroksimetil)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 146) (2R,3S)-2-(3-(2-(hidroksimetil)-4,5-dimetil-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 147) (2R,3S)-2-(3-(5,6-diklor-2-(hidroksimetil)-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 148) (2R,3S)-2-(3-(2-amino-5,6-diklor-1H-benzo[d]imidazol-1-il)propil)piperidin-3-ol, 149) metil 7-brom-1-(3-((2R,3S)-3-hidroksipiperidin-2-il)propil)-1H-indol-3-karboksilat, 150) metil 5-brom-1-(3-((2R,3S)-3-hidroksipiperidin-2-il)propil)-1H-indol-3-karboksilat, 151) metil 6-brom-1-(3-((2R,3S)-3-hidroksipiperidin-2-il)propil)-1H-indol-3-karboksilat, 152) metil 4-klor-1-(3-((2R,3S)-3-hidroksipiperidin-2-il)propil)-1H-indol-3-karboksilat, 153) metil 6-klor-1-(3-((2R,3S)-3-hidroksipiperidin-2-il)propil)-1H-indol-3-karboksilat, 154) metil 7-klor-1-(3-((2R,3S)-3-hidroksipiperidin-2-il)propil)-1H-indol-3-karboksilat, 155) (2R,3S)-2-(3-(5-klor-3-ciklopropil-1H-indazol-1-il)propil)piperidin-3-ol, 156) (2R,3S)-2-(3-(5-klor-3-(trifluormetil)-1H-indazol-1-il)propil)piperidin-3-ol, 157) (2R,3S)-2-(3-(5-klor-3-(1-(difluormetil)-1H-pirazol-4-il)-1H-indazol-1-il)propil)piperidin-3-ol, 158) (2R,3S)-2-(3-(6-klor-3-(1-(difluormetil)-1H-pirazol-4-il)-1H-indazol-1-il)propil)piperidin-3-ol, 159) 1-(3-((2R,3S)-3-hidroksipiperidin-2-il)propil)-3-metil-1H-benzo[d]imidazol-2(3H)-on, 160) 5-brom-1-(3-((2R,3S)-3-hidroksipiperidin-2-il)propil)-1H-benzo[d]imidazol-2(3H)-on, 161) 6-brom-1-(3-((2R,3S)-3-hidroksipiperidin-2-il)propil)-1H-benzo[d]imidazol-2(3H)-on, 162) 7-(3-((2R,3S)-3-hidroksipiperidin-2-il)propil)-1,3-dimetil-1H-purin-2,6(3H,7H)-dione, 163) 7-(3-((2R,3S)-3-hidroksipiperidin-2-il)propil)-3-metil-1H-purin-2,6(3H,7H)-dione, 164) 9-(3-((2R,3S)-3-hidroksipiperidin-2-il)propil)-1-metil-1H-purin-2,6(3H,9H)-dione, 165) 7-(3-((2R,3S)-3-hidroksipiperidin-2-il)propil)-3-izobutil-1-metil-1H-purin-2,6(3H,7H)-dione, 166) (2R,3S)-2-((E)-3-(5,6-diklor-1H-benzo[d]imidazol-1-il)prop-1-enil)piperidin-3-ol, 167) (2R,3S)-2-((E)-3-(5-fluor-4-metil-1H-benzo[d]imidazol-1-il)prop-1-enil)piperidin-3-ol, 168) (2R,3S)-2-((E)-3-(5-brom-4-metil-1H-benzo[d]imidazol-1-il)prop-1-enil)piperidin-3-ol, 169) (2R,3S)-2-((E)-3-(5,6-dimetil-1H-benzo[d]imidazol-1-il)prop-1-enil)piperidin-3-ol, 170) (2R,3S)-2-((E)-3-(5,6-dibrom-1H-benzo[d]imidazol-1-il)prop-1-enil)piperidin-3-ol, 171) (2R,3S)-2-((E)-3-(5,6-difluor-1H-benzo[d]imidazol-1-il)prop-1-enil)piperidin-3-ol, 172) (2R,3S)-2-((E)-3-(4,5-dimetil-1H-benzo[d]imidazol-1-il)prop-1-enil)piperidin-3-ol, 173) (2R,3S)-2-((E)-3-(5-klor-4-metil-1H-benzo[d]imidazol-1-il)prop-1-enil)piperidin-3-ol, 174) (2R,3S)-2-((E)-3-(4,5-diklor-1H-benzo[d]imidazol-1-il)prop-1-en-1-il)piperidin-3-ol, 175) (2R,3S)-2-((E)-3-(4-klor-5-metil-1H-benzo[d]imidazol-1-il)prop-1-en-1-il)piperidin-3-ol, 176) (2R,3S)-2-((E)-3-(5-brom-4-nitro-1H-benzo[d]imidazol-1-il)prop-1-en-1-il)piperidin-3-ol, 177) (2R,3S)-2-((E)-3-(6-brom-7-nitro-1H-benzo[d]imidazol-1-il)prop-1-en-1-il)piperidin-3-ol, 178) (2R,3S)-2-((E)-3-(4-klor-5-nitro-1H-benzo[d]imidazol-1-il)prop-1-en-1-il)piperidin-3-ol, 179) (2R,3S)-2-((E)-3-(4,6-difluor-1H-benzo[d]imidazol-1-il)prop-1-en-1-il)piperidin-3-ol, 180) (2R,3S)-2-((E)-3-(6-klor-4-metil-1H-benzo[d]imidazol-1-il)prop-1-en-1-il)piperidin-3-ol, 181) (2R,3S)-2-((E)-3-(7-klor-5-(trifluormetil)-1H-benzo[d]imidazol-1-il)prop-1-en-1-il)piperidin-3-ol, 182) (2R,3S)-2-((E)-3-(5,7-diklor-1H-benzo[d]imidazol-1-il)prop-1-en-1-il)piperidin-3-ol, 183) (2R,3S)-2-((E)-3-(5-klor-7-fluor-1H-benzo[d]imidazol-1-il)prop-1-en-1-il)piperidin-3-ol, 184) (2R,3S)-2-((E)-3-(5-brom-1H-imidazo[4,5-b]piridin-1-il)prop-1-enil)piperidin-3-ol, 185) (2R,3S)-2-((E)-3-(7-klor-6-(3-klorfenil)-3H-imidazo[4,5-b]piridin-3-il)prop-1-enil)piperidin-3-ol, 186) (2R,3S)-2-((E)-3-(6-brom-7-metil-3H-imidazo[4,5-b]piridin-3-il)prop-1-enil)piperidin-3-ol, 187) (2R,3S)-2-((E)-3-(6-brom-7-klor-3H-imidazo[4,5-b]piridin-3-il)prop-1-enil)piperidin-3-ol, 188) (2R,3S)-2-((E)-3-(6-klor-7-metil-3H-imidazo[4,5-b]piridin-3-il)prop-1-enil)piperidin-3-ol, 189) (2R,3S)-2-((E)-3-(6,7-diklor-3H-imidazo[4,5-b]piridin-3-il)prop-1-enil)piperidin-3-ol, 190) (2R,3S)-2-((E)-3-(6-(3-klorfenil)-1H-benzo[d]imidazol-1-il)prop-1-enil)piperidin-3-ol, 191) (2R,3S)-2-((E)-3-(6-(3-fluorfenil)-1H-benzo[d]imidazol-1-il)prop-1-enil)piperidin-3-ol, 192) (2R,3S)-2-((E)-3-(6-(3-(trifluormetil)fenil)-1H-benzo[d]imidazol-1-il)prop-1-enil)piperidin-3-ol, 193) (2R,3S)-2-((E)-3-(5-brom-6,7-difluor-2-metil-1H-benzo[d]imidazol-1-il)prop-1-enil)piperidin-3-ol, 194) (2R,3S)-2-((E)-3-(indolin-1-il)prop-1-enil)piperidin-3-ol, 195) (2R,3S)-2-((E)-3-(5-klorindolin-1-il)prop-1-enil)piperidin-3-ol, 196) (2R,3S)-2-((E)-3-(1H-pirolo[2,3-b]piridin-1-il)prop-1-enil)piperidin-3-ol, 197) (2R,3S)-2-((E)-3-(6-klor-1H-indol-1-il)prop-1-enil)piperidin-3-ol, 198) (2R,3S)-2-((E)-3-(6-klor-1H-indazol-1-il)prop-1-enil)piperidin-3-ol, 199) (2R,3S)-2-((E)-3-(4-klor-7H-pirolo[2,3-d]pirimidin-7-il)prop-1-enil)piperidin-3-ol, 200) (2R,3S)-2-((E)-3-(5-klor-1H-pirazolo[3,4-b]piridin-1-il)prop-1-enil)piperidin-3-ol, 201) (2R,3S)-2-((E)-3-(3,5-dimetil-1H-indazol-1-il)prop-1-enil)piperidin-3-ol, 202) metil 7-brom-1-((E)-3-((2R,3S)-3-hidroksipiperidin-2-il)alil)-1H-indol-3-karboksilat, 203) 7-brom-1-((E)-3-((2R,3S)-3-hidroksipiperidin-2-il)alil)-1H-indol-3-karboksilna kiselina, 204) 5-brom-1-((E)-3-((2R,3S)-3-hidroksipiperidin-2-il)alil)-1H-indol-3-karboksilna kiselina, 205) 4-klor-1-((E)-3-((2R,3S)-3-hidroksipiperidin-2-il)alil)-1H-indol-3-karboksilna kiselina, 206) 6-klor-1-((E)-3-((2R,3S)-3-hidroksipiperidin-2-il)alil)-1H-indol-3-karboksilna kiselina, 207) 7-klor-1-((E)-3-((2R,3S)-3-hidroksipiperidin-2-il)alil)-1H-indol-3-karboksilna kiselina, 208) 6-fluor-1-((E)-3-((2R,3S)-3-hidroksipiperidin-2-il)alil)-1H-indol-3-karboksilna kiselina, 209) 1-((E)-3-((2R,3S)-3-hidroksipiperidin-2-il)alil)-1H-indol-3-karboksilna kiselina, 210) metil 4-klor-1-((E)-3-((2R,3S)-3-hidroksipiperidin-2-il)alil)-1H-indol-3-karboksilat, 211) metil 6-klor-1-((E)-3-((2R,3S)-3-hidroksipiperidin-2-il)alil)-1H-indol-3-karboksilat, 212) metil 7-klor-1-((E)-3-((2R,3S)-3-hidroksipiperidin-2-il)alil)-1H-indol-3-karboksilat, 213) metil 5-brom-1-((E)-3-((2R,3S)-3-hidroksipiperidin-2-il)alil)-1H-indol-3-karboksilat, 214) metil 6-brom-1-((E)-3-((2R,3S)-3-hidroksipiperidin-2-il)alil)-1H-indol-3-karboksilat, 215) 5-brom-1-((E)-3-((2R,3S)-3-hidroksipiperidin-2-il)alil)-N-metil-1H-indol-3-karboksamid, 216) 5-brom-1-((E)-3-((2R,3S)-3-hidroksipiperidin-2-il)alil)-N,N-dimetil-1H-indol-3-karboksamid, 217) (2R,3S)-2-((Z)-3-(5-klor-4-metil-1H-benzo[d]imidazol-1-il)-2-fluorprop-1-enil)piperidin-3-ol, 218) (2R,3S)-2-((Z)-3-(5-brom-4-metil-1H-benzo[d]imidazol-1-il)-2-fluorprop-1-enil)piperidin-3-ol, 219) (2R,3S)-2-((Z)-3-(5,6-diklor-1H-benzo[d]imidazol-1-il)-2-fluorprop-1-enil)piperidin-3-ol, 220) (2R,3S)-2-((Z)-3-(5,6-diklor-2-(hidroksimetil)-1H-benzo[d]imidazol-1-il)-2-fluorprop-1-enil)piperidin-3-ol, 221) (2R,3S)-2-((E)-3-(5-klor-4-metil-1H-benzo[d]imidazol-1-il)-2-metilprop-1-enil)piperidin-3-ol, 222) (2R,3S)-2-((E)-3-(5-brom-4-metil-1H-benzo[d]imidazol-1-il)-2-metilprop-1-enil)piperidin-3-ol, 223) (2R,3S)-2-((E)-3-(5,6-diklor-1H-benzo[d]imidazol-1-il)-2-metilprop-1-enil)piperidin-3-ol, 224) (2R,3S)-2-((E)-3-(5,6-diklor-2-(hidroksimetil)-1H-benzo[d]imidazol-1-il)-2-metilprop-1-enil)piperidin-3-ol, 225) (2R,3S)-2-(3-(5,6-diklor-1H-benzo[d]imidazol-1-il)prop-1-inil)piperidin-3-ol, 226) (2R,3S)-2-(3-(5-brom-4-metil-1H-benzo[d]imidazol-1-il)prop-1-inil)piperidin-3-ol, 227) (2R,3S)-2-(3-(5-klor-4-metil-1H-benzo[d]imidazol-1-il)prop-1-inil)piperidin-3-ol, 228) (2R,3S)-2-(3-(5,6-dibrom-1H-benzo[d]imidazol-1-il)prop-1-inil)piperidin-3-ol, 229) (2R,3S)-2-(3-(5-fluor-4-metil-1H-benzo[d]imidazol-1-il)prop-1-inil)piperidin-3-ol, i 230) (2R,3S)-2-((E)-3-(5,6-diklor-1H-benzo[d]imidazol-1-il)prop-1-enil)pirolidin-3-ol.
12. Farmaceutski pripravak za uporabu u prevenciji ili liječenju karcinoma, upalnih bolesti, autoimunih bolesti ili fibroze, naznačen time što sadrži spoj prema bilo kojem od zahtjeva 1 do 11 ili njegovu farmaceutski prihvatljivu sol.
13. Postupak za pripravu spoja predstavljenog sljedećom kemijskom formulom 1 naznačen time što obuhvaća korake: reagiranje spoja predstavljenog sljedećom kemijskom formulom 1-A sa spojem predstavljenim sljedećom kemijskom formulom 1-B u prisutnosti baze za pripravu spoja predstavljenog sljedećom kemijskom formulom 1-C; i reagiranje spoja predstavljenog kemijskom formulom 1-C u prisutnosti kiseline za pripravu spoja predstavljenog sljedećom kemijskom formulom 1: [image] u kemijskim formulama 1, 1-A, 1-B, i 1-C, n, L, X1, X2 i A su kako je definirano u zahtjevu 1, X je halogen, i R' i R" su svaki neovisno zaštitna skupina.
14. Postupak za pripravu spoja predstavljenog sljedećom kemijskom formulom 1-1 naznačen time što obuhvaća korake: reagiranje spoja predstavljenog sljedećom kemijskom formulom 2-A sa spojem predstavljenim sljedećom kemijskom formulom 2-B u prisutnosti baze za pripravu spoja predstavljenog sljedećom kemijskom formulom 2-C; reagiranje aminske skupine i nitro skupine spoja predstavljenog kemijskom formulom 2-C da se dobije prsten, čime se dobiva spoj predstavljen sa sljedećom kemijskom formulom 2-D; i reagiranje spoja predstavljenog kemijskom formulom 2-D u prisutnosti kiseline za pripravu spoja predstavljenog sljedećom kemijskom formulom 1-1: [image] u kemijskim formulama 1-1, 2-A, 2-B, 2-C, i 2-D, n, L, R2 i A su kako je definirano u zahtjevu 1, i R' i R" su svaki neovisno zaštitna skupina.
15. Postupak za pripravu spoja predstavljenog sljedećom kemijskom formulom 3 naznačen time što obuhvaća korake: reagiranje spoja predstavljenog sljedećom kemijskom formulom 3-A sa (karbetoksimetilen)trifenilfosforanom radi priprave spoja predstavljenog sljedećom kemijskom formulom 3-B; hidrogeniranje spoja predstavljenog sljedećom kemijskom formulom 3-B za pripravu spoja predstavljenog sljedećom kemijskom formulom 3-C; hidroliziranje spoja predstavljenog kemijskom formulom 3-C za pripravu spoja predstavljenog sljedećom kemijskom formulom 3-D; podvrgavanje spoja predstavljenog kemijskom formulom 3-D reakciji redukcije karbonila za pripravu spoja predstavljenog sljedećom kemijskom formulom 3-E; bromiranje spoja predstavljenog kemijskom formulom 3-E za pripravu spoja predstavljenog sljedećom kemijskom formulom 3-F; podvrgavanje spoja predstavljenog kemijskom formulom 3-F azidnoj reakciji radi priprave spoja predstavljenog sljedećom kemijskom formulom 3-G; i aminiranje spoja predstavljenog kemijskom formulom 3-G za pripravu spoja predstavljenog sljedećom kemijskom formulom 3: [image] [image] u kemijskim formulama 3, 3-A, 3-B, 3-C, 3-D, 3-E, 3-F, i 3-G, n je kako je definiran u zahtjevu 1, i R' i R" su svaki neovisno zaštitna skupina.
HRP20211483TT 2017-02-07 2018-02-07 Derivati 2-(3-(1h-benzo[d]imidazol-1-il)propil)piperidin-3-ola i povezani spojevi kao inhibitori prs za liječenje npr. raka HRP20211483T1 (hr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
KR20170016971 2017-02-07
PCT/KR2018/001625 WO2018147626A1 (en) 2017-02-07 2018-02-07 Novel heterocyclic compound, its preparation method, and pharmaceutical composition comprising the same
EP18750794.2A EP3580208B1 (en) 2017-02-07 2018-02-07 2-(3-(1h-benzo[d]imidazol-1-yl)propyl)piperidin-3-ol derivatives and related compounds as prs inhibitors for treating e.g. cancer

Publications (1)

Publication Number Publication Date
HRP20211483T1 true HRP20211483T1 (hr) 2021-12-24

Family

ID=63107680

Family Applications (1)

Application Number Title Priority Date Filing Date
HRP20211483TT HRP20211483T1 (hr) 2017-02-07 2018-02-07 Derivati 2-(3-(1h-benzo[d]imidazol-1-il)propil)piperidin-3-ola i povezani spojevi kao inhibitori prs za liječenje npr. raka

Country Status (31)

Country Link
US (1) US10981917B2 (hr)
EP (1) EP3580208B1 (hr)
JP (1) JP6785384B2 (hr)
KR (1) KR102084772B1 (hr)
CN (1) CN110191882B (hr)
AR (1) AR110963A1 (hr)
AU (1) AU2018218965B2 (hr)
BR (1) BR112019016291A2 (hr)
CA (1) CA3049643C (hr)
CL (1) CL2019002019A1 (hr)
CO (1) CO2019007834A2 (hr)
DO (1) DOP2019000193A (hr)
EC (1) ECSP19051409A (hr)
ES (1) ES2899665T3 (hr)
HR (1) HRP20211483T1 (hr)
HU (1) HUE056218T2 (hr)
MA (1) MA47469B1 (hr)
MX (1) MX2019009185A (hr)
MY (1) MY196538A (hr)
PE (1) PE20191477A1 (hr)
PH (1) PH12019501811A1 (hr)
PL (1) PL3580208T3 (hr)
PT (1) PT3580208T (hr)
RS (1) RS62541B1 (hr)
RU (1) RU2733384C1 (hr)
SA (1) SA519402180B1 (hr)
SG (1) SG11201906436VA (hr)
SI (1) SI3580208T1 (hr)
TN (1) TN2019000204A1 (hr)
TW (4) TWI694070B (hr)
WO (1) WO2018147626A1 (hr)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018213211A1 (en) * 2017-05-15 2018-11-22 The Regents Of The University Of Michigan Pyrrolo[2,3-c]pyridines and related analogs as lsd-1 inhibitors
KR102346187B1 (ko) * 2019-12-26 2021-12-31 울산과학기술원 디히드로퓨란 유도체 및 이의 합성 방법
WO2022240035A1 (ko) 2021-05-13 2022-11-17 주식회사 대웅제약 섬유화증의 예방 또는 치료용 약학적 조성물
BR112023023670A2 (pt) 2021-05-13 2024-01-30 Daewoong Pharmaceutical Co Ltd Composição farmacêutica para prevenir ou tratar fibrose
CN117693343A (zh) 2021-07-23 2024-03-12 株式会社大熊制药 用于预防或治疗***性硬化症的药物组合物
KR20230047910A (ko) * 2021-10-01 2023-04-10 주식회사유한양행 바이사이클릭 융합환 유도체 또는 이의 염 및 이를 포함하는 약학 조성물
KR20230092630A (ko) * 2021-12-17 2023-06-26 주식회사 대웅제약 (2R, 3S)-2-(벤조[d]이미다졸일프로필)피페리딘-3-올 유도체의 제조 방법
TW202334112A (zh) * 2021-12-17 2023-09-01 南韓商大熊製藥股份有限公司 (2R, 3S)-2-(3-(4,5-二氯-1H-苯并[d]咪唑-1-基)丙基)哌啶-3-醇的新穎酸加成鹽及晶形
WO2023239166A1 (ko) * 2022-06-08 2023-12-14 주식회사 대웅제약 아르기나아제 저해제 및 이를 포함하는 약학적 조성물
WO2024080777A1 (ko) * 2022-10-12 2024-04-18 주식회사 대웅제약 신장염의 예방 또는 치료용 약학적 조성물

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB8900719D0 (en) 1989-01-13 1989-03-08 Nycomed As Compounds
DE59504622D1 (de) 1994-10-31 1999-02-04 Merck Patent Gmbh Benzylpiperidinderivate mit hoher Affinität zu Bindungsstellen von Aminosäure-Rezeptoren
IL114951A (en) 1995-08-15 1999-08-17 Hadasit Med Res Service Quinazolinone-containing pharmaceutical compositions for prevention of neovascularization
WO1997034895A1 (de) * 1996-03-15 1997-09-25 Novartis Ag NEUE N-7 HETEROCYCLYL-PYRROLO[2,3-d]PYRIMIDINE UND IHRE VERWENDUNG
CN1333028C (zh) * 1999-08-20 2007-08-22 Csl硅树脂公司 用作防腐蚀涂层的单组分有机聚硅氧烷橡胶组合物
MXPA03008180A (es) 2001-03-15 2003-12-12 Astrazeneca Ab Inhibidores de metaloproteinasa.
US7307088B2 (en) * 2002-07-09 2007-12-11 Amgen Inc. Substituted anthranilic amide derivatives and methods of use
CN101247853B (zh) 2005-04-13 2014-11-12 轴突公司 具有nos抑制活性的取代的吲哚化合物
EP1939199A4 (en) * 2005-09-22 2010-10-20 Dainippon Sumitomo Pharma Co NEW ADENINE CONNECTION
WO2008101867A1 (en) 2007-02-19 2008-08-28 Smithkline Beecham Corporation Purine derivatives as immunomodulators
KR101649881B1 (ko) * 2008-08-11 2016-08-30 글락소스미스클라인 엘엘씨 신규의 아데닌 유도체
CA2737219C (en) 2008-08-11 2017-02-28 Tracy Keller Halofuginone analogs for inhibition of trna synthetases and uses thereof
US20130338201A1 (en) 2009-11-02 2013-12-19 Ahr Pharmaceuticals, Inc. Method of Cancer Treatment with 2-(1H-Indole-3-Carbonyl)-Thiazole-4-Carboxylic Acid Methyl Ester
AU2013237881B2 (en) 2012-03-29 2017-10-12 Akashi Therapeutics, Inc. Dosage forms of halofuginone and methods of use
WO2014145576A2 (en) 2013-03-15 2014-09-18 Northwestern University Substituted pyrrolo(2,3-d)pyrimidines for the treatment of cancer
WO2015199418A2 (ko) * 2014-06-23 2015-12-30 주식회사 대웅제약 신규한 헤테로고리 화합물
KR102277538B1 (ko) * 2015-06-08 2021-07-14 주식회사 대웅제약 신규한 헤테로 고리 화합물, 이의 제조 방법 및 이를 포함하는 약학적 조성물

Also Published As

Publication number Publication date
TWI782525B (zh) 2022-11-01
CA3049643C (en) 2021-07-06
MY196538A (en) 2023-04-19
TN2019000204A1 (en) 2021-01-07
HUE056218T2 (hu) 2022-02-28
SA519402180B1 (ar) 2022-02-14
KR20180091770A (ko) 2018-08-16
TWI772759B (zh) 2022-08-01
CN110191882B (zh) 2022-09-13
TW202132279A (zh) 2021-09-01
WO2018147626A1 (en) 2018-08-16
US10981917B2 (en) 2021-04-20
MA47469A (fr) 2021-06-02
SG11201906436VA (en) 2019-08-27
RS62541B1 (sr) 2021-12-31
BR112019016291A2 (pt) 2020-04-07
PL3580208T3 (pl) 2021-12-27
TW201831463A (zh) 2018-09-01
EP3580208A4 (en) 2020-08-26
JP2020506197A (ja) 2020-02-27
SI3580208T1 (sl) 2021-11-30
CO2019007834A2 (es) 2019-07-31
AU2018218965B2 (en) 2020-06-18
EP3580208A1 (en) 2019-12-18
AU2018218965A1 (en) 2019-07-25
TWI694070B (zh) 2020-05-21
MA47469B1 (fr) 2021-11-30
DOP2019000193A (es) 2019-08-15
CL2019002019A1 (es) 2019-12-13
MX2019009185A (es) 2019-09-26
TW202030185A (zh) 2020-08-16
EP3580208B1 (en) 2021-09-01
TW201922723A (zh) 2019-06-16
RU2733384C1 (ru) 2020-10-01
JP6785384B2 (ja) 2020-11-18
NZ755300A (en) 2021-10-29
PT3580208T (pt) 2021-11-18
KR102084772B1 (ko) 2020-03-04
AR110963A1 (es) 2019-05-22
PH12019501811A1 (en) 2020-09-14
US20190359617A1 (en) 2019-11-28
CA3049643A1 (en) 2018-08-16
ES2899665T3 (es) 2022-03-14
TWI700280B (zh) 2020-08-01
PE20191477A1 (es) 2019-10-16
CN110191882A (zh) 2019-08-30
ECSP19051409A (es) 2019-07-31

Similar Documents

Publication Publication Date Title
HRP20211483T1 (hr) Derivati 2-(3-(1h-benzo[d]imidazol-1-il)propil)piperidin-3-ola i povezani spojevi kao inhibitori prs za liječenje npr. raka
AU2019203444B2 (en) Bicyclic lactams and methods of use thereof
Cherukupalli et al. An insight on synthetic and medicinal aspects of pyrazolo [1, 5-a] pyrimidine scaffold
AU2007209689B2 (en) Pyrrolo [3,2-c] pyridine-4-one 2-indolinone protein kinase inhibitors
Abdellatif et al. New advances in synthesis and clinical aspects of pyrazolo [3, 4-d] pyrimidine scaffolds
JP2017524734A5 (hr)
AU2013249041A1 (en) Benzothiazol- 6 -yl acetic acid derivatives and their use for treating an HIV infection
HRP20120105T1 (hr) Aminoheterociklički spojevi
HRP20120174T1 (hr) Derivat policikličnog cinamida
NZ529205A (en) Substituted azaindoles as inhibitors of protein kinases, and process for their preparation
RU2018112230A (ru) Бициклические соединения в качестве ингибиторов atx
KR20110039307A (ko) 이미다조피리딘-2-온 유도체
CA2694401A1 (en) Polycyclic compound
HRP20140632T1 (hr) Derivati 2-arimidazola kao inhibitori pde10a enzima
HRP20140898T1 (hr) Heteroaromatski derivati fenilimidazola kao inhibitori enzima pde10a
Asati et al. Pyrazolopyrimidines as anticancer agents: A review on structural and target-based approaches
HRP20131210T1 (hr) Heteroaromatski aril triazol derivati kao inhibitori pde10a enzima
JP2007526285A5 (hr)
ES2689325T3 (es) Derivados de carbamoilo de carbonilamino-pirazoles bicíclicos como pro-fármacos
US20240109900A1 (en) Azabicyclic shp2 inhibitors
Martin et al. A review on the antimicrobial activity of 1, 2, 4-triazole derivatives
JPWO2020252353A5 (hr)
JPWO2020065614A5 (hr)
JPWO2020065613A5 (hr)