CA2758934A1 - 4-azetidinyl-1-phenyl-cyclohexane antagonists of ccr2 - Google Patents
4-azetidinyl-1-phenyl-cyclohexane antagonists of ccr2 Download PDFInfo
- Publication number
- CA2758934A1 CA2758934A1 CA2758934A CA2758934A CA2758934A1 CA 2758934 A1 CA2758934 A1 CA 2758934A1 CA 2758934 A CA2758934 A CA 2758934A CA 2758934 A CA2758934 A CA 2758934A CA 2758934 A1 CA2758934 A1 CA 2758934A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- prepared
- phenyl
- azetidin
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
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- 239000005557 antagonist Substances 0.000 title description 19
- VOBLMJKUYJTNEK-UHFFFAOYSA-N 1-(4-phenylcyclohexyl)azetidine Chemical compound C1CCN1C1CCC(C=2C=CC=CC=2)CC1 VOBLMJKUYJTNEK-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 339
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- -1 -C.ident.CH Chemical group 0.000 claims description 184
- 125000000217 alkyl group Chemical group 0.000 claims description 143
- 229910052731 fluorine Inorganic materials 0.000 claims description 39
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 38
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 35
- 150000003839 salts Chemical class 0.000 claims description 34
- 101710155857 C-C motif chemokine 2 Proteins 0.000 claims description 31
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 31
- 239000012453 solvate Substances 0.000 claims description 29
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 26
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 25
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- 229940002612 prodrug Drugs 0.000 claims description 24
- 239000000651 prodrug Substances 0.000 claims description 24
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 23
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- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 14
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 13
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 claims description 11
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- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 claims description 4
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- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
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- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 4
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- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 230000004968 inflammatory condition Effects 0.000 claims description 3
- 125000002757 morpholinyl group Chemical group 0.000 claims description 3
- 125000004193 piperazinyl group Chemical group 0.000 claims description 3
- 125000003386 piperidinyl group Chemical group 0.000 claims description 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
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- 239000003638 chemical reducing agent Substances 0.000 claims description 2
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- DUPKTFVNPHZWNC-UHFFFAOYSA-N tert-butyl n-[3-(8-hydroxy-1,4-dioxaspiro[4.5]decan-8-yl)phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CC(C2(O)CCC3(CC2)OCCO3)=C1 DUPKTFVNPHZWNC-UHFFFAOYSA-N 0.000 description 1
- RVGRTRHVBFCARF-UHFFFAOYSA-N tert-butyl n-[3-[1-hydroxy-4-[3-[[2-[[3-(trifluoromethyl)benzoyl]amino]acetyl]amino]azetidin-1-yl]cyclohexyl]phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CC(C2(O)CCC(CC2)N2CC(C2)NC(=O)CNC(=O)C=2C=C(C=CC=2)C(F)(F)F)=C1 RVGRTRHVBFCARF-UHFFFAOYSA-N 0.000 description 1
- NLFXTKIWZDONRR-UHFFFAOYSA-N tert-butyl n-[4-(1-hydroxy-4-oxocyclohexyl)phenyl]carbamate Chemical compound C1=CC(NC(=O)OC(C)(C)C)=CC=C1C1(O)CCC(=O)CC1 NLFXTKIWZDONRR-UHFFFAOYSA-N 0.000 description 1
- FYTMPPOAWMMTGA-UHFFFAOYSA-N tert-butyl n-[4-(4-oxocyclohexen-1-yl)phenyl]carbamate Chemical compound C1=CC(NC(=O)OC(C)(C)C)=CC=C1C1=CCC(=O)CC1 FYTMPPOAWMMTGA-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/04—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
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- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
- A61K31/36—Compounds containing methylenedioxyphenyl groups, e.g. sesamin
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- 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
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
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| KR101743280B1 (ko) | 2010-06-17 | 2017-06-02 | 얀센 파마슈티카 엔.브이. | Ccr2의 사이클로헥실-아제티디닐 길항제 |
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| EP3613435A1 (en) | 2015-01-28 | 2020-02-26 | Universite De Bordeaux | Chemokine receptor cxcr4 inhibitors for treating and/or preventing chronic obstructive pulmonary disease |
| KR102622891B1 (ko) | 2015-05-21 | 2024-01-08 | 케모센트릭스, 인크. | Ccr2 조절제 |
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| US20190269664A1 (en) | 2018-01-08 | 2019-09-05 | Chemocentryx, Inc. | Methods of treating solid tumors with ccr2 antagonists |
| ES2991280T3 (es) | 2018-01-08 | 2024-12-03 | Chemocentryx Inc | Antagonistas de CCR2 para el tratamiento del linfoma cutáneo de linfocitos T |
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| NZ595432A (en) | 2013-12-20 |
| US20100267689A1 (en) | 2010-10-21 |
| JP5675773B2 (ja) | 2015-02-25 |
| WO2010121046A1 (en) | 2010-10-21 |
| KR20120006544A (ko) | 2012-01-18 |
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