DK2935227T3 - Diazolamider som ccr1-receptorantagonister - Google Patents

Diazolamider som ccr1-receptorantagonister Download PDF

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DK2935227T3
DK2935227T3 DK13866291.1T DK13866291T DK2935227T3 DK 2935227 T3 DK2935227 T3 DK 2935227T3 DK 13866291 T DK13866291 T DK 13866291T DK 2935227 T3 DK2935227 T3 DK 2935227T3
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compound
mmol
alkyl
ccr1
compounds
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DK13866291.1T
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Xi Chen
Dean R Dragoli
Pingchen Fan
Juan C Jaen
Yandong Li
Jay P Powers
Viengkham Malathong
Sreenivas Punna
Hiroko Tanaka
Penglie Zhang
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Chemocentryx Inc
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    • 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
    • A61K31/415—1,2-Diazoles
    • A61K31/4155—1,2-Diazoles non condensed and containing further heterocyclic rings
    • 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
    • A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
    • A—HUMAN NECESSITIES
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    • 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
    • A61K31/4192—1,2,3-Triazoles
    • 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
    • A61K31/4196—1,2,4-Triazoles
    • 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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
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    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
    • 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
    • C07D231/14—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 hetero atoms or 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 to ring carbon atoms
    • C07D231/38—Nitrogen atoms
    • C07D231/40—Acylated on said nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or 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 to ring carbon atoms
    • C07D233/88—Nitrogen atoms, e.g. allantoin
    • 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
    • C07D401/12—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 chain containing hetero atoms as chain links
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    • 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
    • C07D403/12—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 chain containing hetero atoms as chain links
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    • 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

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  • Urology & Nephrology (AREA)
  • Transplantation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Hydrogenated Pyridines (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Plural Heterocyclic Compounds (AREA)

Claims (15)

1. Forbindelse repræsenteret ved strukturen (Ib2):
hvor hvert A uafhængigt er udvalgt fra gruppen bestående af N og CH; A1 er N eller C(R5); A2 er N eller C(R7); R1 er Cl eller F; R3 er udvalgt fra gruppen bestående af Ci-8-alkyl, Ci-8-haloalkyl, Ci-8-hydroxyalkyl, hvor alkyldelene af R3 eventuelt endvidere er substitueret med 1-3 Ra; R , R og R hver uafhængigt er udvalgt fra gruppen bestående af H, halogen, CN, Ci-8-alkyl, C3-8-cycloalkyl, C2_8-alkenyl, C2_8-alkynyl, Ci.8-haloalkyl, Ci_8-hydroxyalkyl, -ORa, -C02Ra, -NRaRb, -CONRaRb, aryl, 5- eller 6-leddet heteroaryl og 3-, 4-, 5- eller 6-leddet heterocycloalkan, hvor heteroatomeme til stede som ringtoppunkter af heteroaryl- og heterocycloalkanringene er udvalgt fra N, O og S, og hvor alkyl-, cycloalkyl-, aryl-, heteroaryl- og heterocycloalkandelene af R5, R7 og R8 eventuelt endvidere er substitueret med 1-3 Ra; og hvert Ra og Rb uafhængigt er udvalgt fra gruppen bestående af hydrogen, hydroxyl, halogen, cyano, Ci_8-alkyl, Ci_8-alkoxy, Ci.8-haloalkyl, C3_6-cycloalkyl, C3_6-cycloalkylalkyl, amino, Ci-8-alkylamino, di-Ci.8-alkylamino, carboxamid, carboxy-Ci-4-alkylester, carboxylsyre og -S02-Ci-8-alkyl, eller et farmaceutisk acceptabelt salt, hydrat, solvat, en rotamer eller et N-oxid deraf.
2. Forbindelse ifølge krav 1, repræsenteret ved strukturen: eller
eller
3. Forbindelse ifølge krav 1, repræsenteret ved strukturen:
hvor R1 er Cl eller F.
4. Forbindelse ifølge krav 1, repræsenteret ved strukturen:
5. Forbindelse ifølge et hvilket som helst af kravene 1 eller 2, eller 4, hvor R er Ci_g-alkyl.
6. Forbindelse ifølge krav 1, der er:
eller et farmaceutisk acceptabelt salt, hydrat, solvat, en rotamer eller et N-oxid deraf.
7. Forbindelse ifølge krav 1, der er:
eller et farmaceutisk acceptabelt salt, hydrat, solvat, en rotamer eller et N-oxid deraf.
8. Forbindelse ifølge krav 1, der er:
eller et farmaceutisk acceptabelt salt, hydrat, solvat, en rotamer eller et N-oxid deraf.
9. Forbindelse ifølge krav 1, der er:
eller et farmaceutisk acceptabelt salt, hydrat, solvat, en rotamer eller et N-oxid deraf.
10. Farmaceutisk sammensætning, der omfatter forbindelsen ifølge et hvilket som helst af de foregående krav og en farmaceutisk acceptabel excipiens eller bærer.
11. Forbindelse som defineret i et hvilket som helst af kravene 1 til 9 til anvendelse i en fremgangsmåde til behandling af en CCRl-medieret sygdom eller tilstand omfattende administration til en person med behov derfor af en terapeutisk effektiv mængde af forbindelsen; hvor den CCR1-medierede sygdom eller tilstand er en inflammatorisk tilstand; eller den CCR1-medierede sygdom eller tilstand er en immunregulatorisk forstyrrelse.
12. Forbindelse til anvendelse ifølge krav 11, hvor den CCR1-medierede sygdom eller tilstand er udvalgt fra gruppen bestående af transplantatafvisning, dermatitis, eksem, urticaria, vasculitis, inflammatorisk tarmsygdom, fødevareallergi, astma, Alzheimer s sygdom, Parkinsons sygdom, psoriasis, lupus erythematosus, apopleksi, restenose og encephalomyelitis.
13. Forbindelse til anvendelse ifølge krav 11, hvor den CCR1-medierede sygdom eller tilstand er udvalgt fra gruppen bestående af rheumatoid arthritis, multipel sklerose, osteoarthritis, multipelt myelom og osteoporose.
14. Forbindelse til anvendelse ifølge krav 11, hvor administrationen er oral, parenteral, rektal, transdermal, sublingual, nasal eller topisk.
15. Forbindelse til anvendelse ifølge krav 11, hvor forbindelsen administreres i kombination med et antiinflammatorisk middel, et smertestillende middel, et antiproliferativt middel, en metabolisk hæmmer, en leukocytmigrationshæmmer eller en immunmodulator.
DK13866291.1T 2012-12-21 2013-12-20 Diazolamider som ccr1-receptorantagonister DK2935227T3 (da)

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US201261745444P 2012-12-21 2012-12-21
PCT/US2013/077257 WO2014100735A2 (en) 2012-12-21 2013-12-20 Diazole amides

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DK2935227T3 true DK2935227T3 (da) 2017-12-04

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US (3) US9169248B2 (da)
EP (1) EP2935227B1 (da)
JP (1) JP6306607B2 (da)
CN (1) CN104918921B (da)
AU (1) AU2013364038B2 (da)
CA (1) CA2894715C (da)
DK (1) DK2935227T3 (da)
ES (1) ES2648994T3 (da)
MX (1) MX2015007853A (da)
PT (1) PT2935227T (da)
WO (1) WO2014100735A2 (da)

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WO2016202758A1 (en) 2015-06-18 2016-12-22 Bayer Pharma Aktiengesellschaft Substituted 2-(1h-pyrazol-1-yl)-1h-benzimidazole compounds
WO2016202759A1 (en) * 2015-06-18 2016-12-22 Bayer Pharma Aktiengesellschaft Cytotoxic substituted 2-(1 h-pyrazol-1 -yl)-1,3-benzothiazole compounds for the treatment of cancer
EP3439653B1 (en) * 2016-04-07 2021-01-20 ChemoCentryx, Inc. Reducing tumor burden by administering ccr1 antagonists in combination with pd-1 inhibitors or pd-l1 inhibitors
BR112021025888A2 (pt) 2019-07-10 2022-04-26 Chemocentryx Inc Indanos como inibidores de pd-l1

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CN104918921B (zh) 2017-09-22
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