HRP20220429T1 - Novi antagonisti receptora bradikinina b2 - Google Patents

Novi antagonisti receptora bradikinina b2 Download PDF

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HRP20220429T1
HRP20220429T1 HRP20220429TT HRP20220429T HRP20220429T1 HR P20220429 T1 HRP20220429 T1 HR P20220429T1 HR P20220429T T HRP20220429T T HR P20220429TT HR P20220429 T HRP20220429 T HR P20220429T HR P20220429 T1 HRP20220429 T1 HR P20220429T1
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Christoph Gibson
Joern SAUPE
Horst-Dieter Ambrosi
Lars Ole HAUSTEDT
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Pharvaris Netherlands B.V.
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    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/04Heterocyclic 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
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    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
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    • A61K31/47Quinolines; Isoquinolines
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/14Heterocyclic 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
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    • C07ORGANIC CHEMISTRY
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    • C07D405/00Heterocyclic 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
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
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    • C07DHETEROCYCLIC COMPOUNDS
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    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
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Claims (15)

1. Spoj opće formule (I): [image] ili njegova sol, naznačen time što A predstavlja skupinu: [image] A1 je N, ili CH; A2 je N, ili C-RA2; A3 je N, ili C-RA3; A4 je NH, O, ili S; A5 je N-RA5; RA1 predstavlja vodikov atom ili metilnu skupinu; RA2 i RA3 svaki, neovisno jedan o drugom, predstavlja vodikov atom, atom halogena, OH, CN, NH2; (C1-C3)alkil, koji može biti supstituiran s jednom ili više, identičnih ili različitih, skupina odabranih od atoma halogena, OH, =O, i NH2; (C1-C3)alkoksi, koja može biti supstituirana s jednom ili više, identičnih ili različitih, skupina odabranih od atoma halogena, OH, =O, i NH2; (C2-C5)alkoksialkil, koja može biti supstituirana s jednom ili više, identičnih ili različitih, skupina odabranih od atoma halogena, OH, =O, i NH2; C(O)NRB1RB2; ili NRB1RB2; RB1, RB2 i RA5 svaki, neovisno jedan o drugom, predstavlja vodikov atom ili skupinu (C1-C3)alkil, koja može biti supstituirana s jednom ili više, identičnih ili različitih, skupina odabranih od atoma halogena, OH, =O, i NH2; R1 predstavlja skupinu (C1-C3)alkil ili (C2-C5)alkoksialkil, koja alkilna skupina ili alkoksialkilna skupina može biti supstituirana s jednom ili više, identičnih ili različitih, skupina odabranih od atoma deuterija, atoma halogena, OH, =O, i NH2; R2 predstavlja vodikov atom ili atom deuterija; R3 predstavlja vodikov atom, skupinu (C1-C3)alkil, ili skupinu (C1-C3)haloalkil; E predstavlja CRE1RE2RE3 ili Hce; Hce predstavlja mono- ili biciklički, djelomično nezasićeni ili aromatski heterocikl koji ima 3 do 10 C atoma i 1 do 4 heteroatoma koji su svaki, neovisno jedan o drugom, odabrani od N, O ili S, koji heterocikl je nesupstituiran ili može biti mono-, di- ili trisupstituiran, u svakoj prilici neovisno, s atomom halogena, OH, G, NRC1RC2 i/ili =O; RC1 i RC2 svaki, neovisno jedan o drugom, predstavlja vodikov atom ili skupinu (C1-C3)alkil; G predstavlja skupinu (C1-C6)alkil, u kojoj 1 do 7 H atoma može, u svakoj prilici neovisno, biti zamijenjeno s atomom halogena, ORG1, CN, NRG2RG3 ili (C3-C6)cikloalkil, i/ili u kojoj se jedna CH2 skupina, ili dvije nesusjedne CH2 skupine, mogu zamijeniti sa O, C(O), OC(O), C(O)O, C(O)NH, NH, S, SO, SO2 i/ili sa skupinom CH=CH; RG1, RG2, i RG3 svaki, neovisno jedan o drugom, predstavlja vodikov atom, skupinu (C1-C4)alkil, (C1-C4) haloalkil, (C1-C4) hidroksialkil, (C1-C4) heteroalkil, ili (C3-C6) cikloalkil; RE1 i RE2 svaki, neovisno jedan o drugom, predstavlja vodikov atom, atom halogena, ili G; ili RE1 i RE2 uzeti zajedno tvore =O ili Cyc; RE3 predstavlja vodikov atom, atom halogena, G, OG ili OH; i Cyc predstavlja mono- ili bicikličku, zasićenu ili djelomično nezasićenu 3- do 10-članu cikloalkilnu skupinu ili 4- do 10-članu heterocikloalkilnu skupinu koja ima 1 do 3 heteroatoma koji su svaki, neovisno jedan o drugom, odabrani od N, O ili S, koja cikloalkilna ili heterocikloalkilna skupina je nesupstituirana ili može biti mono-, di-, tri-, ili tetrasupstituirana, u svakoj prilici neovisno, s atomom halogena, OH, G, NRC1RC2 i/ili =O.
2. Spoj ili sol prema patentnom zahtjevu 1, naznačen time što R1 predstavlja skupinu (C1-C2)alkil ili skupinu (C2-C4)alkoksialkil, navedena alkilna skupina ili alkoksialkilna skupina može biti supstituirana s jednom ili više, identičnih ili različitih, skupina odabranih od atoma deuterija, atoma halogena, i OH.
3. Spoj ili sol prema patentnom zahtjevu 1 ili 2, naznačen time što R3 predstavlja vodikov atom ili metilnu skupinu.
4. Spoj ili sol prema bilo kojem od patentnih zahtjeva 1 do 3, naznačen time što E je CRE1RE2RE3; RE1 predstavlja vodikov atom, fluorov atom, metil ili etil; i svaki RE2 i RE3 je definiran kao u zahtjevu 1.
5. Spoj ili sol prema bilo kojem od patentnih zahtjeva 1 do 4, naznačen time što RE2 predstavlja vodikov atom, fluorov atom, skupinu (C1-C6)alkil, poželjno skupinu (C1-C3)alkil, u kojoj 1 do 4 H atoma mogu, u svakoj prilici neovisno, biti zamijenjeni atomom fluora, OH, =O, ili NRC1RC2; skupinu (C1-C6)alkoksi, poželjno skupinu (C1-C3)alkoksi, u kojoj 1 do 4 H atoma mogu, u svakoj prilici neovisno, biti zamijenjeni atomom fluora, OH, =O, NRC1RC2 ili ciklopropilom; ili skupinu (C2-C5)alkoksialkil, u kojoj 1 do 5 H atoma mogu, u svakoj prilici neovisno, biti zamijenjeni atomom fluora, OH, =O, NRC1RC2 ili ciklopropilom; i svaki RC1 i RC2 je definiran kao u zahtjevu 1.
6. Spoj ili sol prema bilo kojem od patentnih zahtjeva 1 do 5, naznačen time što RE3 predstavlja vodikov atom, fluorov atom, OH, skupinu (C1-C6)alkil, poželjno skupinu (C1-C3)alkil, u kojoj 1 do 5 H atoma mogu, u svakoj prilici neovisno, biti zamijenjeni atomom fluora, OH, =O, ili NRC1RC2; skupinu (C1-C6)alkoksi, u kojoj 1 do 5 H atoma mogu, u svakoj prilici neovisno, biti zamijenjeni atomom fluora, OH, =O, NRC1RC2 ili ciklopropil; skupinu (C2-C5)alkoksialkil, u kojoj 1 do 5 H atoma mogu, u svakoj prilici neovisno, biti zamijenjeni atomom fluora, OH, =O, NRC1RC2 ili ciklopropilom; i svaki RC1 i RC2 je definiran kao u zahtjevu 1.
7. Spoj ili sol prema bilo kojem od patentnih zahtjeva 1 do 3, naznačen time što E je CRE1RE2RE3; i RE1 i RE2 su uzeti zajedno tako da tvore =O ili Cyc, pri čemu je Cyc odabran iz niza koji čine ciklopropil, ciklobutil, ciklopentil, oksetanil, tetrahidrofuranil, tetrahidro-2H-piranil, 1,3-dioksolanil, morfolinil, azetidinil pirolidinil, piperidinil, piperazinil, (imidazolidin-2-on)il i (oksazolidin-2-on)il, te je supstituiran ili može biti mono-, di- ili trisupstituiran, u svakoj prilici neovisno, s atomom halogena, OH, G, NRC1RC2 i/ili =O; i svaki od RC1, RC2 i RE3 je definiran kao u zahtjevu 1.
8. Spoj ili sol prema patentnom zahtjevu 7, naznačen time što RE3 predstavlja vodikov atom, fluorov atom, OH ili skupinu (C1-C3)alkil.
9. Spoj ili sol prema bilo kojem od patentnih zahtjeva 1 do 3, naznačen time što E je Hce, i Hce predstavlja monociklički, djelomično nezasićeni ili aromatski heterocikl koji ima 3 do 5 C atoma i 1 do 3 N atom(a); 3 do 5 C atoma, 1-2 N atom(a) i 1 O atom; ili 3 do 5 C atoma, 1-2 N atom(a) i 1 S atom; koji heterocikl je nesupstituiran ili može biti mono-, di- ili trisupstituiran, u svakoj prilici neovisno, s atomom halogena, OH, (C1-C3)alkilom, (C1-C3)haloalkilom, (C1-C3)alkoksi, (C1-C3)haloalkoksi i/ili =O.
10. Spoj ili sol prema bilo kojem od patentnih zahtjeva 1 do 6, i 9, naznačen time što E predstavlja skupinu: [image] [image] [image] [image] [image]
11. Spoj ili sol prema bilo kojem od patentnih zahtjeva 1 do 10, naznačen time što je spoj odabran iz skupine: [image] [image] [image] [image] [image] [image] [image] [image]
12. Farmaceutski pripravak koji sadrži jedan ili više spojeva prema bilo kojem od patentnih zahtjeva 1 do 11 i, po izboru, najmanje jednu tvar nosača, pomoćnu tvar i/ili pomoćno sredstvo.
13. Farmaceutski pripravak prema patentnom zahtjevu 12, naznačen time što je farmaceutski pripravak formuliran kao aerosol, krema, gel, pilula, kapsula, sirup, otopina, transdermalni flaster ili uređaj za isporuku lijeka.
14. Kombinirani pripravak naznačen time što sadrži najmanje jedan spoj prema bilo kojem od zahtjeva 1 do 11 i najmanje jedan daljnji aktivni farmaceutski sastojak.
15. Spoj prema bilo kojem od patentnih zahtjeva 1 do 11, farmaceutski pripravak prema zahtjevu 12, ili kombinirani pripravak prema zahtjevu 14 za upotrebu kao lijek.
HRP20220429TT 2017-11-24 2018-11-23 Novi antagonisti receptora bradikinina b2 HRP20220429T1 (hr)

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EP17203675 2017-11-24
EP18818992.2A EP3713928B1 (en) 2017-11-24 2018-11-23 Novel bradykinin b2 receptor antagonists
PCT/EP2018/082338 WO2019101906A1 (en) 2017-11-24 2018-11-23 Novel bradykinin b2 receptor antagonists

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US (3) US10836748B2 (hr)
EP (2) EP3998259A1 (hr)
JP (2) JP7164619B2 (hr)
KR (1) KR102413321B1 (hr)
CN (1) CN111433196B (hr)
AR (1) AR113839A1 (hr)
AU (1) AU2018371186B2 (hr)
BR (1) BR112020010298A2 (hr)
CA (1) CA3082948A1 (hr)
CY (1) CY1125348T1 (hr)
DK (1) DK3713928T3 (hr)
EA (1) EA202091256A1 (hr)
ES (1) ES2908409T3 (hr)
HR (1) HRP20220429T1 (hr)
HU (1) HUE058217T2 (hr)
IL (1) IL274883B2 (hr)
LT (1) LT3713928T (hr)
MA (1) MA50804B1 (hr)
MX (1) MX2020005287A (hr)
NZ (1) NZ764304A (hr)
PH (1) PH12020550683A1 (hr)
PL (1) PL3713928T3 (hr)
PT (1) PT3713928T (hr)
RS (1) RS63087B1 (hr)
SG (1) SG11202004653TA (hr)
SI (1) SI3713928T1 (hr)
TW (1) TWI768156B (hr)
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KR20230107269A (ko) 2020-11-12 2023-07-14 파르바리스 게엠베하 혈관부종의 예방 및 치료
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US11261173B2 (en) 2022-03-01
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MA50804A (fr) 2020-09-30
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PH12020550683A1 (en) 2021-03-15
RS63087B1 (sr) 2022-04-29
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WO2019101906A1 (en) 2019-05-31
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