CA2545384A1

CA2545384A1 - Utilisation d'heterocycles amines a six elements contenant de l'azote substitues comme antagonistes du recepteur vanilloide de type 1 pour le traitement de la douleur

Utilisation d'heterocycles amines a six elements contenant de l'azote substitues comme antagonistes du recepteur vanilloide de type 1 pour le traitement de la douleur Download PDF

Info

Publication number: CA2545384A1
Authority: CA; Canada
Prior art keywords: amine; pyrimidin; quinolin; trifluoromethylphenyl; methyl
Prior art date: 2003-11-10
Legal status : Abandoned

Application number

CA002545384A

Other languages

English (en)

Inventor

Gregory John Hollingworth

Brian A. Jones

Edward Giles Mciver

Christopher Richard Moyes

Lauren Rogers

Current Assignee

Organon Pharma UK Ltd

Original Assignee

Individual

Priority date

2003-11-10

Filing date

2004-11-09

Publication date

2005-05-26

2003-11-10 Priority claimed from GB0326217A external-priority patent/GB0326217D0/en

2004-04-05 Priority claimed from GB0407748A external-priority patent/GB0407748D0/en

2004-11-09 Application filed by Individual filed Critical Individual

2005-05-26 Publication of CA2545384A1 publication Critical patent/CA2545384A1/fr

Status Abandoned legal-status Critical Current

Links

208000002193 Pain Diseases 0.000 title claims abstract description 27
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 title claims description 4
108010025083 TRPV1 receptor Proteins 0.000 title description 2
239000002464 receptor antagonist Substances 0.000 title 1
229940044551 receptor antagonist Drugs 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 172
-1 haloC1-4alkyl Chemical group 0.000 claims abstract description 140
238000000034 method Methods 0.000 claims abstract description 125
125000001424 substituent group Chemical group 0.000 claims abstract description 46
229910052736 halogen Inorganic materials 0.000 claims abstract description 40
150000003839 salts Chemical class 0.000 claims abstract description 38
150000002367 halogens Chemical class 0.000 claims abstract description 37
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 37
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical group N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims abstract description 28
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 27
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 26
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 26
125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 25
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 24
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 23
229910052717 sulfur Inorganic materials 0.000 claims abstract description 20
229910052760 oxygen Inorganic materials 0.000 claims abstract description 19
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical group C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims abstract description 18
125000005842 heteroatom Chemical group 0.000 claims abstract description 18
AWJUIBRHMBBTKR-UHFFFAOYSA-N iso-quinoline Chemical group C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims abstract description 16
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 16
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims abstract description 13
239000005557 antagonist Substances 0.000 claims abstract description 12
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims abstract description 12
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 12
125000004076 pyridyl group Chemical group 0.000 claims abstract description 11
JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical group C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 claims abstract description 9
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Chemical group C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims abstract description 9
239000003814 drug Substances 0.000 claims abstract description 9
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 8
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims abstract description 6
125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 6
229910052727 yttrium Inorganic materials 0.000 claims abstract description 6
208000021302 gastroesophageal reflux disease Diseases 0.000 claims abstract description 5
238000004519 manufacturing process Methods 0.000 claims abstract description 5
206010011224 Cough Diseases 0.000 claims abstract description 4
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract 15
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract 9
125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims abstract 2
238000002560 therapeutic procedure Methods 0.000 claims abstract 2
OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 claims description 98
125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 29
238000011282 treatment Methods 0.000 claims description 19
125000004093 cyano group Chemical group *C#N 0.000 claims description 12
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
229920006395 saturated elastomer Polymers 0.000 claims description 7
125000001072 heteroaryl group Chemical group 0.000 claims description 5
UFWIBTONFRDIAS-UHFFFAOYSA-N naphthalene-acid Natural products C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 4
125000001624 naphthyl group Chemical group 0.000 claims description 4
PZCRKZLFCWMTKG-UHFFFAOYSA-N 4-quinolin-8-yl-n-[4-(trifluoromethyl)phenyl]-1,3,5-triazin-2-amine Chemical compound C1=CC(C(F)(F)F)=CC=C1NC1=NC=NC(C=2C3=NC=CC=C3C=CC=2)=N1 PZCRKZLFCWMTKG-UHFFFAOYSA-N 0.000 claims description 3
125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 3
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
208000035475 disorder Diseases 0.000 claims description 3
150000002527 isonitriles Chemical class 0.000 claims description 3
SZAQKMSBGFBBAA-UHFFFAOYSA-N nitroazaniumylidynemethane Chemical compound [O-][N+](=O)[N+]#[C-] SZAQKMSBGFBBAA-UHFFFAOYSA-N 0.000 claims description 3
239000000546 pharmaceutical excipient Substances 0.000 claims description 3
150000003248 quinolines Chemical class 0.000 claims description 3
CVXNHMFXHOTDOQ-CALCHBBNSA-N 2-[[(2r,6s)-2,6-dimethylmorpholin-4-yl]methyl]-5-methyl-6-quinolin-7-yl-n-[5-(trifluoromethyl)pyridin-2-yl]pyrimidin-4-amine Chemical compound C1[C@@H](C)O[C@@H](C)CN1CC1=NC(NC=2N=CC(=CC=2)C(F)(F)F)=C(C)C(C=2C=C3N=CC=CC3=CC=2)=N1 CVXNHMFXHOTDOQ-CALCHBBNSA-N 0.000 claims description 2
JYKAIVNYHYIYHA-UHFFFAOYSA-N 4-quinolin-7-yl-n-[4-(trifluoromethyl)phenyl]pyrimidin-2-amine Chemical compound C1=CC(C(F)(F)F)=CC=C1NC1=NC=CC(C=2C=C3N=CC=CC3=CC=2)=N1 JYKAIVNYHYIYHA-UHFFFAOYSA-N 0.000 claims description 2
LBHUUELJNCXDAQ-UHFFFAOYSA-N 4-quinolin-8-yl-n-[4-(trifluoromethyl)phenyl]pyrimidin-2-amine Chemical compound C1=CC(C(F)(F)F)=CC=C1NC1=NC=CC(C=2C3=NC=CC=C3C=CC=2)=N1 LBHUUELJNCXDAQ-UHFFFAOYSA-N 0.000 claims description 2
LXQBAENJKIOUFC-UHFFFAOYSA-N 5-fluoro-6-(8-methylquinolin-7-yl)-n-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine Chemical compound C1=CC2=CC=CN=C2C(C)=C1C(C=1F)=NC=NC=1NC1=CC=C(C(F)(F)F)C=C1 LXQBAENJKIOUFC-UHFFFAOYSA-N 0.000 claims description 2
UCPNLZWQCRCQFM-UHFFFAOYSA-N 5-methyl-6-quinolin-7-yl-2-(trifluoromethyl)-n-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine Chemical compound N1=C(C(F)(F)F)N=C(C=2C=C3N=CC=CC3=CC=2)C(C)=C1NC1=CC=C(C(F)(F)F)C=C1 UCPNLZWQCRCQFM-UHFFFAOYSA-N 0.000 claims description 2
DNZUQJMTFWXIEH-UHFFFAOYSA-N 5-methyl-6-quinolin-7-yl-n-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine Chemical compound N1=CN=C(C=2C=C3N=CC=CC3=CC=2)C(C)=C1NC1=CC=C(C(F)(F)F)C=C1 DNZUQJMTFWXIEH-UHFFFAOYSA-N 0.000 claims description 2
VQWCAFXKKAIPON-UHFFFAOYSA-N 5-nitro-6-quinolin-7-yl-n-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine Chemical compound N1=CN=C(C=2C=C3N=CC=CC3=CC=2)C([N+](=O)[O-])=C1NC1=CC=C(C(F)(F)F)C=C1 VQWCAFXKKAIPON-UHFFFAOYSA-N 0.000 claims description 2
GJUPPYGFEKFANC-UHFFFAOYSA-N 5-quinolin-7-yl-n-[4-(trifluoromethyl)phenyl]pyridazin-3-amine Chemical compound C1=CC(C(F)(F)F)=CC=C1NC1=CC(C=2C=C3N=CC=CC3=CC=2)=CN=N1 GJUPPYGFEKFANC-UHFFFAOYSA-N 0.000 claims description 2
AEDBXCWXMXHSPR-UHFFFAOYSA-N 5-quinolin-8-yl-n-[4-(trifluoromethyl)phenyl]pyridazin-3-amine Chemical compound C1=CC(C(F)(F)F)=CC=C1NC1=CC(C=2C3=NC=CC=C3C=CC=2)=CN=N1 AEDBXCWXMXHSPR-UHFFFAOYSA-N 0.000 claims description 2
BBRIJUCACMIKOR-UHFFFAOYSA-N 6-(3-methylquinolin-7-yl)-n-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine Chemical compound C1=CC2=CC(C)=CN=C2C=C1C(N=CN=1)=CC=1NC1=CC=C(C(F)(F)F)C=C1 BBRIJUCACMIKOR-UHFFFAOYSA-N 0.000 claims description 2
RHVYTHGBCYEYPH-UHFFFAOYSA-N 6-quinolin-6-yl-n-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine Chemical compound C1=CC(C(F)(F)F)=CC=C1NC1=CC(C=2C=C3C=CC=NC3=CC=2)=NC=N1 RHVYTHGBCYEYPH-UHFFFAOYSA-N 0.000 claims description 2
SHIXISZOCCBTMX-UHFFFAOYSA-N 6-quinolin-7-yl-4-n-[4-(trifluoromethyl)phenyl]pyrimidine-4,5-diamine Chemical compound N1=CN=C(C=2C=C3N=CC=CC3=CC=2)C(N)=C1NC1=CC=C(C(F)(F)F)C=C1 SHIXISZOCCBTMX-UHFFFAOYSA-N 0.000 claims description 2
NEEPGTWHWWTDCR-UHFFFAOYSA-N 6-quinolin-7-yl-n-[4-(trifluoromethyl)phenyl]pyrazin-2-amine Chemical compound C1=CC(C(F)(F)F)=CC=C1NC1=CN=CC(C=2C=C3N=CC=CC3=CC=2)=N1 NEEPGTWHWWTDCR-UHFFFAOYSA-N 0.000 claims description 2
FXIUTEWCABQYEY-UHFFFAOYSA-N 6-quinolin-7-yl-n-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine Chemical compound C1=CC(C(F)(F)F)=CC=C1NC1=CC(C=2C=C3N=CC=CC3=CC=2)=NC=N1 FXIUTEWCABQYEY-UHFFFAOYSA-N 0.000 claims description 2
FGZFOUYPEABZIZ-UHFFFAOYSA-N 6-quinolin-7-yl-n-[5-(trifluoromethyl)pyridin-2-yl]pyrimidin-4-amine Chemical compound N1=CC(C(F)(F)F)=CC=C1NC1=CC(C=2C=C3N=CC=CC3=CC=2)=NC=N1 FGZFOUYPEABZIZ-UHFFFAOYSA-N 0.000 claims description 2
XGSBEKRLYITAMF-UHFFFAOYSA-N 6-quinolin-7-yl-n-[6-(trifluoromethyl)pyridin-3-yl]pyrimidin-4-amine Chemical compound C1=NC(C(F)(F)F)=CC=C1NC1=CC(C=2C=C3N=CC=CC3=CC=2)=NC=N1 XGSBEKRLYITAMF-UHFFFAOYSA-N 0.000 claims description 2
RLLOTYMLVFQQMJ-UHFFFAOYSA-N 6-quinolin-8-yl-n-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine Chemical compound C1=CC(C(F)(F)F)=CC=C1NC1=CC(C=2C3=NC=CC=C3C=CC=2)=NC=N1 RLLOTYMLVFQQMJ-UHFFFAOYSA-N 0.000 claims description 2
JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical group CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 claims description 2
241001465754 Metazoa Species 0.000 claims description 2
NHFDIUPJVYYTLG-UHFFFAOYSA-N carbononitridic isocyanide Chemical compound [C-]#[N+]C#N NHFDIUPJVYYTLG-UHFFFAOYSA-N 0.000 claims description 2
125000005843 halogen group Chemical group 0.000 claims description 2
DMEUDSHBHKHLPD-UHFFFAOYSA-N pyrazin-2-amine Chemical compound NC1=CN=C=C[N]1 DMEUDSHBHKHLPD-UHFFFAOYSA-N 0.000 claims description 2
125000002098 pyridazinyl group Chemical group 0.000 claims description 2
150000003230 pyrimidines Chemical class 0.000 claims description 2
238000003419 tautomerization reaction Methods 0.000 claims description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 7
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 4
125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 3
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 3
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 3
125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 2
FNYNNOFVQSQVMD-UHFFFAOYSA-N 2-(2-morpholin-4-ylethoxy)-6-quinolin-7-yl-n-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine Chemical compound C1=CC(C(F)(F)F)=CC=C1NC1=CC(C=2C=C3N=CC=CC3=CC=2)=NC(OCCN2CCOCC2)=N1 FNYNNOFVQSQVMD-UHFFFAOYSA-N 0.000 claims 1
LMWYAZVKADXZQS-UHFFFAOYSA-N 2-(4-phenylpiperazin-1-yl)-6-quinolin-7-yl-n-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine Chemical compound C1=CC(C(F)(F)F)=CC=C1NC1=CC(C=2C=C3N=CC=CC3=CC=2)=NC(N2CCN(CC2)C=2C=CC=CC=2)=N1 LMWYAZVKADXZQS-UHFFFAOYSA-N 0.000 claims 1
YQJOTJOKTCWJBF-UHFFFAOYSA-N 2-(cyclopropylmethoxy)-6-quinolin-7-yl-n-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine Chemical compound C1=CC(C(F)(F)F)=CC=C1NC1=CC(C=2C=C3N=CC=CC3=CC=2)=NC(OCC2CC2)=N1 YQJOTJOKTCWJBF-UHFFFAOYSA-N 0.000 claims 1
NRVQKSOZICIWQT-UHFFFAOYSA-N 2-(methoxymethyl)-5-methyl-6-quinolin-7-yl-n-[5-(trifluoromethyl)pyridin-2-yl]pyrimidin-4-amine Chemical compound CC=1C(C=2C=C3N=CC=CC3=CC=2)=NC(COC)=NC=1NC1=CC=C(C(F)(F)F)C=N1 NRVQKSOZICIWQT-UHFFFAOYSA-N 0.000 claims 1
OMDPSXQAODWDIT-UHFFFAOYSA-N 2-chloro-6-quinolin-7-yl-n-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine Chemical compound C1=CC(C(F)(F)F)=CC=C1NC1=CC(C=2C=C3N=CC=CC3=CC=2)=NC(Cl)=N1 OMDPSXQAODWDIT-UHFFFAOYSA-N 0.000 claims 1
KUCYGIQOOFGUQM-UHFFFAOYSA-N 2-methoxy-6-quinolin-7-yl-n-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine Chemical compound C=1C(C=2C=C3N=CC=CC3=CC=2)=NC(OC)=NC=1NC1=CC=C(C(F)(F)F)C=C1 KUCYGIQOOFGUQM-UHFFFAOYSA-N 0.000 claims 1
HNNZRHVOGSMGNS-UHFFFAOYSA-N 2-methyl-6-quinolin-7-yl-4-n-[4-(trifluoromethyl)phenyl]pyrimidine-4,5-diamine Chemical compound NC=1C(C=2C=C3N=CC=CC3=CC=2)=NC(C)=NC=1NC1=CC=C(C(F)(F)F)C=C1 HNNZRHVOGSMGNS-UHFFFAOYSA-N 0.000 claims 1
FHOCPELHEACFNS-UHFFFAOYSA-N 2-methyl-6-quinolin-7-yl-n-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine Chemical compound C=1C(C=2C=C3N=CC=CC3=CC=2)=NC(C)=NC=1NC1=CC=C(C(F)(F)F)C=C1 FHOCPELHEACFNS-UHFFFAOYSA-N 0.000 claims 1
YUXNBOKZNDFMNE-UHFFFAOYSA-N 2-methylsulfonyl-6-quinolin-7-yl-n-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine Chemical compound C=1C(C=2C=C3N=CC=CC3=CC=2)=NC(S(=O)(=O)C)=NC=1NC1=CC=C(C(F)(F)F)C=C1 YUXNBOKZNDFMNE-UHFFFAOYSA-N 0.000 claims 1
DIWAYUIJVOASBS-UHFFFAOYSA-N 2-morpholin-4-yl-6-quinolin-7-yl-n-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine Chemical compound C1=CC(C(F)(F)F)=CC=C1NC1=CC(C=2C=C3N=CC=CC3=CC=2)=NC(N2CCOCC2)=N1 DIWAYUIJVOASBS-UHFFFAOYSA-N 0.000 claims 1
BXQHTFKCAGHXAU-UHFFFAOYSA-N 2-tert-butyl-5-methyl-6-quinolin-7-yl-n-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine Chemical compound N1=C(C(C)(C)C)N=C(C=2C=C3N=CC=CC3=CC=2)C(C)=C1NC1=CC=C(C(F)(F)F)C=C1 BXQHTFKCAGHXAU-UHFFFAOYSA-N 0.000 claims 1
IFTUAYFNIZODBA-UHFFFAOYSA-N 4-methyl-6-quinolin-7-yl-n-[4-(trifluoromethyl)phenyl]-1,3,5-triazin-2-amine Chemical compound N=1C(C=2C=C3N=CC=CC3=CC=2)=NC(C)=NC=1NC1=CC=C(C(F)(F)F)C=C1 IFTUAYFNIZODBA-UHFFFAOYSA-N 0.000 claims 1
HKLWBZDOGZKLTA-UHFFFAOYSA-N 5-bromo-6-quinolin-7-yl-n-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine Chemical compound C1=CC(C(F)(F)F)=CC=C1NC1=NC=NC(C=2C=C3N=CC=CC3=CC=2)=C1Br HKLWBZDOGZKLTA-UHFFFAOYSA-N 0.000 claims 1
IKDUCCCBMNZALJ-UHFFFAOYSA-N 5-fluoro-6-(8-fluoroquinolin-7-yl)-n-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine Chemical compound N1=CN=C(C=2C(=C3N=CC=CC3=CC=2)F)C(F)=C1NC1=CC=C(C(F)(F)F)C=C1 IKDUCCCBMNZALJ-UHFFFAOYSA-N 0.000 claims 1
QNWIJFBQRHPPSP-UHFFFAOYSA-N 5-fluoro-6-quinolin-7-yl-n-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine Chemical compound N1=CN=C(C=2C=C3N=CC=CC3=CC=2)C(F)=C1NC1=CC=C(C(F)(F)F)C=C1 QNWIJFBQRHPPSP-UHFFFAOYSA-N 0.000 claims 1
GYSHYWKCHKRUHO-UHFFFAOYSA-N 5-methoxy-6-quinolin-7-yl-n-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine Chemical compound N1=CN=C(C=2C=C3N=CC=CC3=CC=2)C(OC)=C1NC1=CC=C(C(F)(F)F)C=C1 GYSHYWKCHKRUHO-UHFFFAOYSA-N 0.000 claims 1
MZNHZUDIBJRNMR-UHFFFAOYSA-N 5-methyl-2-(2-methylpyrrolidin-1-yl)-6-quinolin-7-yl-n-[5-(trifluoromethyl)pyridin-2-yl]pyrimidin-4-amine Chemical compound CC1CCCN1C1=NC(NC=2N=CC(=CC=2)C(F)(F)F)=C(C)C(C=2C=C3N=CC=CC3=CC=2)=N1 MZNHZUDIBJRNMR-UHFFFAOYSA-N 0.000 claims 1
MGXUOTOKVOFNQN-UHFFFAOYSA-N 5-methyl-2-methylsulfanyl-6-quinolin-7-yl-n-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine Chemical compound CC=1C(C=2C=C3N=CC=CC3=CC=2)=NC(SC)=NC=1NC1=CC=C(C(F)(F)F)C=C1 MGXUOTOKVOFNQN-UHFFFAOYSA-N 0.000 claims 1
ZIITVBCLVNXSJF-UHFFFAOYSA-N 5-methyl-2-methylsulfanyl-6-quinolin-7-yl-n-[5-(trifluoromethyl)pyridin-2-yl]pyrimidin-4-amine Chemical compound CC=1C(C=2C=C3N=CC=CC3=CC=2)=NC(SC)=NC=1NC1=CC=C(C(F)(F)F)C=N1 ZIITVBCLVNXSJF-UHFFFAOYSA-N 0.000 claims 1
SOLYSNOXFVWGDQ-UHFFFAOYSA-N 5-methyl-2-methylsulfonyl-6-quinolin-7-yl-n-[5-(trifluoromethyl)pyridin-2-yl]pyrimidin-4-amine Chemical compound N1=C(S(C)(=O)=O)N=C(C=2C=C3N=CC=CC3=CC=2)C(C)=C1NC1=CC=C(C(F)(F)F)C=N1 SOLYSNOXFVWGDQ-UHFFFAOYSA-N 0.000 claims 1
QERBFNAJVZHYTI-UHFFFAOYSA-N 5-methyl-2-morpholin-4-yl-6-quinolin-7-yl-n-[5-(trifluoromethyl)pyridin-2-yl]pyrimidin-4-amine Chemical compound N1=C(N2CCOCC2)N=C(C=2C=C3N=CC=CC3=CC=2)C(C)=C1NC1=CC=C(C(F)(F)F)C=N1 QERBFNAJVZHYTI-UHFFFAOYSA-N 0.000 claims 1
CXHCGWTVIFBZLM-UHFFFAOYSA-N 5-methyl-6-(1,5-naphthyridin-3-yl)-n-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine Chemical compound N1=CN=C(C=2C=C3N=CC=CC3=NC=2)C(C)=C1NC1=CC=C(C(F)(F)F)C=C1 CXHCGWTVIFBZLM-UHFFFAOYSA-N 0.000 claims 1
AVAMMFHQFZIOET-UHFFFAOYSA-N 5-methyl-6-(1,8-naphthyridin-2-yl)-n-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine Chemical compound N1=CN=C(C=2N=C3N=CC=CC3=CC=2)C(C)=C1NC1=CC=C(C(F)(F)F)C=C1 AVAMMFHQFZIOET-UHFFFAOYSA-N 0.000 claims 1
NBXYPVHDDZXAKE-UHFFFAOYSA-N 5-methyl-6-(1-methylbenzimidazol-5-yl)-n-[4-(trifluoromethyl)phenyl]pyrimidin-4-amine Chemical compound N1=CN=C(C=2C=C3N=CN(C)C3=CC=2)C(C)=C1NC1=CC=C(C(F)(F)F)C=C1 NBXYPVHDDZXAKE-UHFFFAOYSA-N 0.000 claims 1
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