CA2523439C - Pyrimidine derivatives useful for the treatment of diseases mediated by crth2 - Google Patents
Pyrimidine derivatives useful for the treatment of diseases mediated by crth2 Download PDFInfo
- Publication number
- CA2523439C CA2523439C CA2523439A CA2523439A CA2523439C CA 2523439 C CA2523439 C CA 2523439C CA 2523439 A CA2523439 A CA 2523439A CA 2523439 A CA2523439 A CA 2523439A CA 2523439 C CA2523439 C CA 2523439C
- Authority
- CA
- Canada
- Prior art keywords
- amino
- benzyl
- acetic acid
- pyrimidinyl
- dimethylamino
- 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.)
- Expired - Fee Related
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 22
- 150000003230 pyrimidines Chemical class 0.000 title claims abstract description 19
- 201000010099 disease Diseases 0.000 title claims abstract description 17
- 238000011282 treatment Methods 0.000 title claims abstract description 17
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title description 3
- 230000001404 mediated effect Effects 0.000 title 1
- 230000000694 effects Effects 0.000 claims abstract description 74
- 102000009389 Prostaglandin D receptors Human genes 0.000 claims abstract description 25
- 108050000258 Prostaglandin D receptors Proteins 0.000 claims abstract description 25
- 150000003839 salts Chemical class 0.000 claims abstract description 19
- 239000004480 active ingredient Substances 0.000 claims abstract description 12
- 208000032671 Allergic granulomatous angiitis Diseases 0.000 claims abstract description 8
- 208000006344 Churg-Strauss Syndrome Diseases 0.000 claims abstract description 8
- 206010012438 Dermatitis atopic Diseases 0.000 claims abstract description 8
- 208000018428 Eosinophilic granulomatosis with polyangiitis Diseases 0.000 claims abstract description 8
- 206010039085 Rhinitis allergic Diseases 0.000 claims abstract description 8
- 201000010105 allergic rhinitis Diseases 0.000 claims abstract description 8
- 208000006673 asthma Diseases 0.000 claims abstract description 8
- 201000008937 atopic dermatitis Diseases 0.000 claims abstract description 8
- 201000009890 sinusitis Diseases 0.000 claims abstract description 8
- 208000016557 Acute basophilic leukemia Diseases 0.000 claims abstract description 7
- 206010052568 Urticaria chronic Diseases 0.000 claims abstract description 7
- 208000024376 chronic urticaria Diseases 0.000 claims abstract description 7
- 206010024378 leukocytosis Diseases 0.000 claims abstract description 7
- 206010010744 Conjunctivitis allergic Diseases 0.000 claims abstract description 6
- 208000002205 allergic conjunctivitis Diseases 0.000 claims abstract description 6
- 208000024998 atopic conjunctivitis Diseases 0.000 claims abstract description 6
- 241000124008 Mammalia Species 0.000 claims abstract description 4
- 208000010668 atopic eczema Diseases 0.000 claims abstract description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 193
- -1 nitro, guanidino, pyrrolyl Chemical group 0.000 claims description 179
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 98
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 72
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 57
- 229910052736 halogen Inorganic materials 0.000 claims description 37
- 229910052739 hydrogen Inorganic materials 0.000 claims description 37
- 239000001257 hydrogen Substances 0.000 claims description 29
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 24
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 23
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 20
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 19
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 16
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 15
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 13
- 150000002367 halogens Chemical group 0.000 claims description 12
- 150000002148 esters Chemical class 0.000 claims description 11
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 125000001072 heteroaryl group Chemical group 0.000 claims description 9
- 239000000651 prodrug Substances 0.000 claims description 9
- 229940002612 prodrug Drugs 0.000 claims description 9
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 8
- 150000002825 nitriles Chemical group 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 125000002541 furyl group Chemical group 0.000 claims description 7
- 125000001041 indolyl group Chemical group 0.000 claims description 7
- 125000001624 naphthyl group Chemical group 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 125000005493 quinolyl group Chemical group 0.000 claims description 6
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 5
- 125000004750 (C1-C6) alkylaminosulfonyl group Chemical group 0.000 claims description 4
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 4
- 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims description 4
- XEOSTBFUCNZKGS-UHFFFAOYSA-N 2-[4,6-bis(dimethylamino)-2-[[4-[[4-(trifluoromethyl)benzoyl]amino]phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound CN(C)C1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)C=3C=CC(=CC=3)C(F)(F)F)=CC=2)=N1 XEOSTBFUCNZKGS-UHFFFAOYSA-N 0.000 claims description 4
- KXPAVCJDTRYMRP-UHFFFAOYSA-N 2-[4,6-dichloro-2-[[4-(naphthalene-2-carbonylamino)phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound N1=C(Cl)C(CC(=O)O)=C(Cl)N=C1CC(C=C1)=CC=C1NC(=O)C1=CC=C(C=CC=C2)C2=C1 KXPAVCJDTRYMRP-UHFFFAOYSA-N 0.000 claims description 4
- XSGQONMWVRQSTD-UHFFFAOYSA-N 2-[4-(dimethylamino)-2-[[4-(naphthalene-2-carbonylamino)phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound C1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)C=3C=C4C=CC=CC4=CC=3)=CC=2)=N1 XSGQONMWVRQSTD-UHFFFAOYSA-N 0.000 claims description 4
- SETQVYMZHIVBRU-UHFFFAOYSA-N 2-[4-(dimethylamino)-2-[[4-(phenylmethoxycarbonylamino)phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound C1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)OCC=3C=CC=CC=3)=CC=2)=N1 SETQVYMZHIVBRU-UHFFFAOYSA-N 0.000 claims description 4
- OGZNYVIPIIDZLY-UHFFFAOYSA-N 2-[4-(dimethylamino)-6-morpholin-4-yl-2-[[4-(naphthalene-2-carbonylamino)phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound OC(=O)CC=1C(N(C)C)=NC(CC=2C=CC(NC(=O)C=3C=C4C=CC=CC4=CC=3)=CC=2)=NC=1N1CCOCC1 OGZNYVIPIIDZLY-UHFFFAOYSA-N 0.000 claims description 4
- CUNNBJJEJUDKNN-UHFFFAOYSA-N 2-[4-chloro-6-(dimethylamino)-2-[[4-(naphthalene-2-carbonylamino)phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound ClC1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)C=3C=C4C=CC=CC4=CC=3)=CC=2)=N1 CUNNBJJEJUDKNN-UHFFFAOYSA-N 0.000 claims description 4
- 125000001589 carboacyl group Chemical group 0.000 claims description 4
- WNSNYYLIQITQFJ-UHFFFAOYSA-N n-[4-[[4-chloro-6-(dimethylamino)-5-(2h-tetrazol-5-ylmethyl)pyrimidin-2-yl]methyl]phenyl]naphthalene-2-carboxamide Chemical compound CN(C)C1=NC(CC=2C=CC(NC(=O)C=3C=C4C=CC=CC4=CC=3)=CC=2)=NC(Cl)=C1CC1=NN=NN1 WNSNYYLIQITQFJ-UHFFFAOYSA-N 0.000 claims description 4
- YPFWOLUEYTWRKX-UHFFFAOYSA-N n-[4-[[5-(2-amino-2-oxoethyl)-4-chloro-6-(dimethylamino)pyrimidin-2-yl]methyl]phenyl]naphthalene-2-carboxamide Chemical compound ClC1=C(CC(N)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)C=3C=C4C=CC=CC4=CC=3)=CC=2)=N1 YPFWOLUEYTWRKX-UHFFFAOYSA-N 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 4
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 3
- QLEXLARZQWPJAH-UHFFFAOYSA-N 2-[4-(dimethylamino)-2-[[4-[(4-fluorophenyl)methoxycarbonylamino]phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound C1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)OCC=3C=CC(F)=CC=3)=CC=2)=N1 QLEXLARZQWPJAH-UHFFFAOYSA-N 0.000 claims description 3
- OCXZEAWOZHRQKP-UHFFFAOYSA-N 2-[4-chloro-2-[[4-(naphthalene-2-carbonylamino)phenyl]methyl]-6-pyrrolidin-1-ylpyrimidin-5-yl]acetic acid Chemical compound OC(=O)CC1=C(Cl)N=C(CC=2C=CC(NC(=O)C=3C=C4C=CC=CC4=CC=3)=CC=2)N=C1N1CCCC1 OCXZEAWOZHRQKP-UHFFFAOYSA-N 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 2
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 2
- BRAVLCWGFGRYAJ-UHFFFAOYSA-N 2-[2-[(4-benzamidophenyl)methyl]-4-[[2-(cyclopentylamino)-2-oxoethyl]-methylamino]pyrimidin-5-yl]acetic acid Chemical compound N=1C(CC=2C=CC(NC(=O)C=3C=CC=CC=3)=CC=2)=NC=C(CC(O)=O)C=1N(C)CC(=O)NC1CCCC1 BRAVLCWGFGRYAJ-UHFFFAOYSA-N 0.000 claims description 2
- YBKWXSXHGJHDKJ-UHFFFAOYSA-N 2-[2-[(4-benzamidophenyl)methyl]-4-chloro-6-[[2-(cyclopentylamino)-2-oxoethyl]-methylamino]pyrimidin-5-yl]acetic acid Chemical compound N=1C(CC=2C=CC(NC(=O)C=3C=CC=CC=3)=CC=2)=NC(Cl)=C(CC(O)=O)C=1N(C)CC(=O)NC1CCCC1 YBKWXSXHGJHDKJ-UHFFFAOYSA-N 0.000 claims description 2
- VNJYZANVNXLMBK-UHFFFAOYSA-N 2-[2-[1-[4-[(3,4-dichlorobenzoyl)amino]phenyl]ethyl]-4-(dimethylamino)pyrimidin-5-yl]acetic acid Chemical compound N=1C=C(CC(O)=O)C(N(C)C)=NC=1C(C)C(C=C1)=CC=C1NC(=O)C1=CC=C(Cl)C(Cl)=C1 VNJYZANVNXLMBK-UHFFFAOYSA-N 0.000 claims description 2
- WFSKXLWLRRRIJO-UHFFFAOYSA-N 2-[2-[1-[4-[(4-chlorobenzoyl)amino]phenyl]ethyl]-4-(dimethylamino)pyrimidin-5-yl]acetic acid Chemical compound N=1C=C(CC(O)=O)C(N(C)C)=NC=1C(C)C(C=C1)=CC=C1NC(=O)C1=CC=C(Cl)C=C1 WFSKXLWLRRRIJO-UHFFFAOYSA-N 0.000 claims description 2
- HSJTTYZHQSKFMU-UHFFFAOYSA-N 2-[2-[[4-(1-benzofuran-2-carbonylamino)phenyl]methyl]-4-chloro-6-[[2-(cyclopentylamino)-2-oxoethyl]-methylamino]pyrimidin-5-yl]acetic acid Chemical compound N=1C(CC=2C=CC(NC(=O)C=3OC4=CC=CC=C4C=3)=CC=2)=NC(Cl)=C(CC(O)=O)C=1N(C)CC(=O)NC1CCCC1 HSJTTYZHQSKFMU-UHFFFAOYSA-N 0.000 claims description 2
- OQGHYGCQIHVPKX-UHFFFAOYSA-N 2-[2-[[4-(3,3-dimethylbutanoylamino)phenyl]methyl]-4-pyrrolidin-1-ylpyrimidin-5-yl]acetic acid Chemical compound C1=CC(NC(=O)CC(C)(C)C)=CC=C1CC1=NC=C(CC(O)=O)C(N2CCCC2)=N1 OQGHYGCQIHVPKX-UHFFFAOYSA-N 0.000 claims description 2
- QWKZLHMASPOSDC-UHFFFAOYSA-N 2-[2-[[4-(benzylcarbamoylamino)phenyl]methyl]-4-(dimethylamino)pyrimidin-5-yl]acetic acid Chemical compound C1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)NCC=3C=CC=CC=3)=CC=2)=N1 QWKZLHMASPOSDC-UHFFFAOYSA-N 0.000 claims description 2
- BLYDFBFHXASRNY-UHFFFAOYSA-N 2-[2-[[4-(benzylcarbamoylamino)phenyl]methyl]-4-chloro-6-[[2-(cyclopentylamino)-2-oxoethyl]-methylamino]pyrimidin-5-yl]acetic acid Chemical compound N=1C(CC=2C=CC(NC(=O)NCC=3C=CC=CC=3)=CC=2)=NC(Cl)=C(CC(O)=O)C=1N(C)CC(=O)NC1CCCC1 BLYDFBFHXASRNY-UHFFFAOYSA-N 0.000 claims description 2
- VIACNMLRKMDHEV-UHFFFAOYSA-N 2-[2-[[4-(naphthalene-2-carbonylamino)phenyl]methyl]-4-pyrrolidin-1-ylpyrimidin-5-yl]acetic acid Chemical compound OC(=O)CC1=CN=C(CC=2C=CC(NC(=O)C=3C=C4C=CC=CC4=CC=3)=CC=2)N=C1N1CCCC1 VIACNMLRKMDHEV-UHFFFAOYSA-N 0.000 claims description 2
- BLGFEKQGRRINTG-UHFFFAOYSA-N 2-[2-[[4-[(3,4-dichlorobenzoyl)amino]phenyl]methyl]-4,6-bis(dimethylamino)pyrimidin-5-yl]acetic acid Chemical compound CN(C)C1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)C=3C=C(Cl)C(Cl)=CC=3)=CC=2)=N1 BLGFEKQGRRINTG-UHFFFAOYSA-N 0.000 claims description 2
- ANWJXEFKLMMCHP-UHFFFAOYSA-N 2-[2-[[4-[(3,4-dichlorobenzoyl)amino]phenyl]methyl]-4-(dimethylamino)-6-methylpyrimidin-5-yl]acetic acid Chemical compound CC1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)C=3C=C(Cl)C(Cl)=CC=3)=CC=2)=N1 ANWJXEFKLMMCHP-UHFFFAOYSA-N 0.000 claims description 2
- IVOAQFSTFIFFRD-UHFFFAOYSA-N 2-[2-[[4-[(3,4-dichlorobenzoyl)amino]phenyl]methyl]-4-(dimethylamino)-6-morpholin-4-ylpyrimidin-5-yl]acetic acid Chemical compound N=1C(N2CCOCC2)=C(CC(O)=O)C(N(C)C)=NC=1CC(C=C1)=CC=C1NC(=O)C1=CC=C(Cl)C(Cl)=C1 IVOAQFSTFIFFRD-UHFFFAOYSA-N 0.000 claims description 2
- WULJEVKZTZYJFW-UHFFFAOYSA-N 2-[2-[[4-[(3,4-dichlorobenzoyl)amino]phenyl]methyl]-4-(dimethylamino)pyrimidin-5-yl]acetic acid Chemical compound C1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)C=3C=C(Cl)C(Cl)=CC=3)=CC=2)=N1 WULJEVKZTZYJFW-UHFFFAOYSA-N 0.000 claims description 2
- OXZAIUCHPIZYDI-UHFFFAOYSA-N 2-[2-[[4-[(3,4-dichlorobenzoyl)amino]phenyl]methyl]-4-methyl-6-pyrrolidin-1-ylpyrimidin-5-yl]acetic acid Chemical compound N=1C(N2CCCC2)=C(CC(O)=O)C(C)=NC=1CC(C=C1)=CC=C1NC(=O)C1=CC=C(Cl)C(Cl)=C1 OXZAIUCHPIZYDI-UHFFFAOYSA-N 0.000 claims description 2
- LOCILIUQLADHQZ-UHFFFAOYSA-N 2-[2-[[4-[(3-chlorobenzoyl)amino]phenyl]methyl]-4-(dimethylamino)pyrimidin-5-yl]acetic acid Chemical compound C1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)C=3C=C(Cl)C=CC=3)=CC=2)=N1 LOCILIUQLADHQZ-UHFFFAOYSA-N 0.000 claims description 2
- QBCSHZVZVUKCQO-UHFFFAOYSA-N 2-[2-[[4-[(4-acetamidobenzoyl)amino]phenyl]methyl]-4-chloro-6-pyrrolidin-1-ylpyrimidin-5-yl]acetic acid Chemical compound C1=CC(NC(=O)C)=CC=C1C(=O)NC(C=C1)=CC=C1CC1=NC(Cl)=C(CC(O)=O)C(N2CCCC2)=N1 QBCSHZVZVUKCQO-UHFFFAOYSA-N 0.000 claims description 2
- AARBEQQNTOZBTL-UHFFFAOYSA-N 2-[2-[[4-[(4-bromobenzoyl)amino]phenyl]methyl]-4-chloro-6-(dimethylamino)pyrimidin-5-yl]acetic acid Chemical compound ClC1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)C=3C=CC(Br)=CC=3)=CC=2)=N1 AARBEQQNTOZBTL-UHFFFAOYSA-N 0.000 claims description 2
- ZBWYVWIGXMTAMQ-UHFFFAOYSA-N 2-[2-[[4-[(4-chlorobenzoyl)amino]phenyl]methyl]-4-(dimethylamino)-6-pyrrolidin-1-ylpyrimidin-5-yl]acetic acid Chemical compound N=1C(N2CCCC2)=C(CC(O)=O)C(N(C)C)=NC=1CC(C=C1)=CC=C1NC(=O)C1=CC=C(Cl)C=C1 ZBWYVWIGXMTAMQ-UHFFFAOYSA-N 0.000 claims description 2
- LACBHKONDFDLLO-UHFFFAOYSA-N 2-[2-[[4-[(4-chlorobenzoyl)amino]phenyl]methyl]-4-(dimethylamino)pyrimidin-5-yl]acetic acid Chemical compound C1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)C=3C=CC(Cl)=CC=3)=CC=2)=N1 LACBHKONDFDLLO-UHFFFAOYSA-N 0.000 claims description 2
- YTMBTJPYTXLXLT-UHFFFAOYSA-N 2-[2-[[4-[(4-chlorobenzoyl)amino]phenyl]methyl]-4-pyrrolidin-1-ylpyrimidin-5-yl]acetic acid Chemical compound N1=C(N2CCCC2)C(CC(=O)O)=CN=C1CC(C=C1)=CC=C1NC(=O)C1=CC=C(Cl)C=C1 YTMBTJPYTXLXLT-UHFFFAOYSA-N 0.000 claims description 2
- PTVJXKKBDDFIEH-UHFFFAOYSA-N 2-[2-[[4-[(4-fluorobenzoyl)amino]phenyl]methyl]-4-pyrrolidin-1-ylpyrimidin-5-yl]acetic acid Chemical compound N1=C(N2CCCC2)C(CC(=O)O)=CN=C1CC(C=C1)=CC=C1NC(=O)C1=CC=C(F)C=C1 PTVJXKKBDDFIEH-UHFFFAOYSA-N 0.000 claims description 2
- YAUYYYFLGPQZJN-UHFFFAOYSA-N 2-[2-[[4-[(4-tert-butylcyclohexanecarbonyl)amino]phenyl]methyl]-4-chloro-6-(dimethylamino)pyrimidin-5-yl]acetic acid Chemical compound ClC1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)C3CCC(CC3)C(C)(C)C)=CC=2)=N1 YAUYYYFLGPQZJN-UHFFFAOYSA-N 0.000 claims description 2
- VIADXYASLLIBBI-NTEUORMPSA-N 2-[2-[[4-[[(e)-3-(4-chlorophenyl)prop-2-enoyl]amino]phenyl]methyl]-4,6-bis(dimethylamino)pyrimidin-5-yl]acetic acid Chemical compound CN(C)C1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)\C=C\C=3C=CC(Cl)=CC=3)=CC=2)=N1 VIADXYASLLIBBI-NTEUORMPSA-N 0.000 claims description 2
- ONUBVPYJYUPJMQ-NTEUORMPSA-N 2-[2-[[4-[[(e)-3-(4-chlorophenyl)prop-2-enoyl]amino]phenyl]methyl]-4-(dimethylamino)-6-pyrrolidin-1-ylpyrimidin-5-yl]acetic acid Chemical compound N=1C(N2CCCC2)=C(CC(O)=O)C(N(C)C)=NC=1CC(C=C1)=CC=C1NC(=O)\C=C\C1=CC=C(Cl)C=C1 ONUBVPYJYUPJMQ-NTEUORMPSA-N 0.000 claims description 2
- FLVDJNIFQHPSAB-KPKJPENVSA-N 2-[2-[[4-[[(e)-3-(4-chlorophenyl)prop-2-enoyl]amino]phenyl]methyl]-4-(dimethylamino)pyrimidin-5-yl]acetic acid Chemical compound C1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)\C=C\C=3C=CC(Cl)=CC=3)=CC=2)=N1 FLVDJNIFQHPSAB-KPKJPENVSA-N 0.000 claims description 2
- NRDKCQHKFLCXRT-UHFFFAOYSA-N 2-[2-[[4-[[benzyl(methyl)carbamoyl]amino]phenyl]methyl]-4-(dimethylamino)pyrimidin-5-yl]acetic acid Chemical compound C1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)N(C)CC=3C=CC=CC=3)=CC=2)=N1 NRDKCQHKFLCXRT-UHFFFAOYSA-N 0.000 claims description 2
- HRFIBVDUAZPDBR-UHFFFAOYSA-N 2-[4,6-bis(dimethylamino)-2-[[4-(naphthalene-2-carbonylamino)phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound CN(C)C1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)C=3C=C4C=CC=CC4=CC=3)=CC=2)=N1 HRFIBVDUAZPDBR-UHFFFAOYSA-N 0.000 claims description 2
- UEZPEEKSXSVHHW-NTCAYCPXSA-N 2-[4,6-bis(dimethylamino)-2-[[4-[[(e)-3-phenylprop-2-enoyl]amino]phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound CN(C)C1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)\C=C\C=3C=CC=CC=3)=CC=2)=N1 UEZPEEKSXSVHHW-NTCAYCPXSA-N 0.000 claims description 2
- IEQWOVCCLCITJC-UHFFFAOYSA-N 2-[4-(dimethylamino)-2-[1-[4-(naphthalene-2-carbonylamino)phenyl]ethyl]pyrimidin-5-yl]acetic acid Chemical compound C=1C=C(NC(=O)C=2C=C3C=CC=CC3=CC=2)C=CC=1C(C)C1=NC=C(CC(O)=O)C(N(C)C)=N1 IEQWOVCCLCITJC-UHFFFAOYSA-N 0.000 claims description 2
- JBCJIXHGOBOQOI-UHFFFAOYSA-N 2-[4-(dimethylamino)-2-[1-[4-(quinoline-2-carbonylamino)phenyl]ethyl]pyrimidin-5-yl]acetic acid Chemical compound C=1C=C(NC(=O)C=2N=C3C=CC=CC3=CC=2)C=CC=1C(C)C1=NC=C(CC(O)=O)C(N(C)C)=N1 JBCJIXHGOBOQOI-UHFFFAOYSA-N 0.000 claims description 2
- HFENOWNHMIFNFE-UHFFFAOYSA-N 2-[4-(dimethylamino)-2-[1-[4-[(4-fluorobenzoyl)amino]phenyl]ethyl]pyrimidin-5-yl]acetic acid Chemical compound N=1C=C(CC(O)=O)C(N(C)C)=NC=1C(C)C(C=C1)=CC=C1NC(=O)C1=CC=C(F)C=C1 HFENOWNHMIFNFE-UHFFFAOYSA-N 0.000 claims description 2
- IYJAOVLMZKODOB-NTEUORMPSA-N 2-[4-(dimethylamino)-2-[1-[4-[[(e)-3-phenylprop-2-enoyl]amino]phenyl]ethyl]pyrimidin-5-yl]acetic acid Chemical compound N=1C=C(CC(O)=O)C(N(C)C)=NC=1C(C)C(C=C1)=CC=C1NC(=O)\C=C\C1=CC=CC=C1 IYJAOVLMZKODOB-NTEUORMPSA-N 0.000 claims description 2
- MGHRGVKVSCHTFH-UHFFFAOYSA-N 2-[4-(dimethylamino)-2-[1-[4-[[4-(trifluoromethyl)benzoyl]amino]phenyl]ethyl]pyrimidin-5-yl]acetic acid Chemical compound N=1C=C(CC(O)=O)C(N(C)C)=NC=1C(C)C(C=C1)=CC=C1NC(=O)C1=CC=C(C(F)(F)F)C=C1 MGHRGVKVSCHTFH-UHFFFAOYSA-N 0.000 claims description 2
- WXBFZIGGWGVNCY-UHFFFAOYSA-N 2-[4-(dimethylamino)-2-[[4-(naphthalene-2-carbonylamino)phenyl]methyl]-6-propan-2-ylpyrimidin-5-yl]acetic acid Chemical compound CN(C)C1=C(CC(O)=O)C(C(C)C)=NC(CC=2C=CC(NC(=O)C=3C=C4C=CC=CC4=CC=3)=CC=2)=N1 WXBFZIGGWGVNCY-UHFFFAOYSA-N 0.000 claims description 2
- WZQHWHBFSVGSTJ-UHFFFAOYSA-N 2-[4-(dimethylamino)-2-[[4-(quinoline-2-carbonylamino)phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound C1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)C=3N=C4C=CC=CC4=CC=3)=CC=2)=N1 WZQHWHBFSVGSTJ-UHFFFAOYSA-N 0.000 claims description 2
- ZSKOFFLYTKCEIM-UHFFFAOYSA-N 2-[4-(dimethylamino)-2-[[4-[(3-methoxybenzoyl)amino]phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound COC1=CC=CC(C(=O)NC=2C=CC(CC=3N=C(C(CC(O)=O)=CN=3)N(C)C)=CC=2)=C1 ZSKOFFLYTKCEIM-UHFFFAOYSA-N 0.000 claims description 2
- PBUBGDUPQPHGCQ-UHFFFAOYSA-N 2-[4-(dimethylamino)-2-[[4-[(3-phenoxybenzoyl)amino]phenyl]methyl]-6-pyrrolidin-1-ylpyrimidin-5-yl]acetic acid Chemical compound N=1C(N2CCCC2)=C(CC(O)=O)C(N(C)C)=NC=1CC(C=C1)=CC=C1NC(=O)C(C=1)=CC=CC=1OC1=CC=CC=C1 PBUBGDUPQPHGCQ-UHFFFAOYSA-N 0.000 claims description 2
- MGGOTZPTECHQAR-UHFFFAOYSA-N 2-[4-(dimethylamino)-2-[[4-[(3-phenylbenzoyl)amino]phenyl]methyl]-6-pyrrolidin-1-ylpyrimidin-5-yl]acetic acid Chemical compound N=1C(N2CCCC2)=C(CC(O)=O)C(N(C)C)=NC=1CC(C=C1)=CC=C1NC(=O)C(C=1)=CC=CC=1C1=CC=CC=C1 MGGOTZPTECHQAR-UHFFFAOYSA-N 0.000 claims description 2
- JAOFGXGCUKKDCF-UHFFFAOYSA-N 2-[4-(dimethylamino)-2-[[4-[(4-fluorobenzoyl)amino]phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound C1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)C=3C=CC(F)=CC=3)=CC=2)=N1 JAOFGXGCUKKDCF-UHFFFAOYSA-N 0.000 claims description 2
- SHPWFAJUVZRUIY-UHFFFAOYSA-N 2-[4-(dimethylamino)-2-[[4-[(4-methoxybenzoyl)amino]phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound C1=CC(OC)=CC=C1C(=O)NC(C=C1)=CC=C1CC1=NC=C(CC(O)=O)C(N(C)C)=N1 SHPWFAJUVZRUIY-UHFFFAOYSA-N 0.000 claims description 2
- JQMMXIYSINFBCU-UHFFFAOYSA-N 2-[4-(dimethylamino)-2-[[4-[(4-nitrophenyl)methoxycarbonylamino]phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound C1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)OCC=3C=CC(=CC=3)[N+]([O-])=O)=CC=2)=N1 JQMMXIYSINFBCU-UHFFFAOYSA-N 0.000 claims description 2
- RQZCDOIOWMSAAL-UHFFFAOYSA-N 2-[4-(dimethylamino)-2-[[4-[(4-phenoxybenzoyl)amino]phenyl]methyl]-6-pyrrolidin-1-ylpyrimidin-5-yl]acetic acid Chemical compound N=1C(N2CCCC2)=C(CC(O)=O)C(N(C)C)=NC=1CC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1OC1=CC=CC=C1 RQZCDOIOWMSAAL-UHFFFAOYSA-N 0.000 claims description 2
- QAAHQJRWEYVWSL-UHFFFAOYSA-N 2-[4-(dimethylamino)-2-[[4-[(4-phenylbenzoyl)amino]phenyl]methyl]-6-pyrrolidin-1-ylpyrimidin-5-yl]acetic acid Chemical compound N=1C(N2CCCC2)=C(CC(O)=O)C(N(C)C)=NC=1CC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1C1=CC=CC=C1 QAAHQJRWEYVWSL-UHFFFAOYSA-N 0.000 claims description 2
- KZCGWNVWJRIYQZ-MDWZMJQESA-N 2-[4-(dimethylamino)-2-[[4-[[(e)-3-(4-methoxyphenyl)prop-2-enoyl]amino]phenyl]methyl]-6-morpholin-4-ylpyrimidin-5-yl]acetic acid Chemical compound C1=CC(OC)=CC=C1\C=C\C(=O)NC(C=C1)=CC=C1CC1=NC(N(C)C)=C(CC(O)=O)C(N2CCOCC2)=N1 KZCGWNVWJRIYQZ-MDWZMJQESA-N 0.000 claims description 2
- DLPWHXJHKLBDDS-KPKJPENVSA-N 2-[4-(dimethylamino)-2-[[4-[[(e)-3-[4-(trifluoromethyl)phenyl]prop-2-enoyl]amino]phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound C1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)\C=C\C=3C=CC(=CC=3)C(F)(F)F)=CC=2)=N1 DLPWHXJHKLBDDS-KPKJPENVSA-N 0.000 claims description 2
- WIOSZSAVCVGCRK-JLHYYAGUSA-N 2-[4-(dimethylamino)-2-[[4-[[(e)-3-phenylprop-2-enoyl]amino]phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound C1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)\C=C\C=3C=CC=CC=3)=CC=2)=N1 WIOSZSAVCVGCRK-JLHYYAGUSA-N 0.000 claims description 2
- GSHAEHFCCIKSRP-UHFFFAOYSA-N 2-[4-(dimethylamino)-2-[[4-[[4-(trifluoromethoxy)benzoyl]amino]phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound C1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)C=3C=CC(OC(F)(F)F)=CC=3)=CC=2)=N1 GSHAEHFCCIKSRP-UHFFFAOYSA-N 0.000 claims description 2
- DJSYVPDFYKAFFR-UHFFFAOYSA-N 2-[4-(dimethylamino)-2-[[4-[[4-(trifluoromethyl)benzoyl]amino]phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound C1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)C=3C=CC(=CC=3)C(F)(F)F)=CC=2)=N1 DJSYVPDFYKAFFR-UHFFFAOYSA-N 0.000 claims description 2
- QCPVMOCGIQWSRP-UHFFFAOYSA-N 2-[4-(dimethylamino)-6-(methoxymethyl)-2-[[4-(naphthalene-2-carbonylamino)phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound CN(C)C1=C(CC(O)=O)C(COC)=NC(CC=2C=CC(NC(=O)C=3C=C4C=CC=CC4=CC=3)=CC=2)=N1 QCPVMOCGIQWSRP-UHFFFAOYSA-N 0.000 claims description 2
- JOJTVPWAEDPARE-UHFFFAOYSA-N 2-[4-(dimethylamino)-6-(methoxymethyl)-2-[[4-[[4-(trifluoromethyl)benzoyl]amino]phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound CN(C)C1=C(CC(O)=O)C(COC)=NC(CC=2C=CC(NC(=O)C=3C=CC(=CC=3)C(F)(F)F)=CC=2)=N1 JOJTVPWAEDPARE-UHFFFAOYSA-N 0.000 claims description 2
- SBKQRLWONFKCFV-UHFFFAOYSA-N 2-[4-(dimethylamino)-6-ethyl-2-[[4-(naphthalene-2-carbonylamino)phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound CN(C)C1=C(CC(O)=O)C(CC)=NC(CC=2C=CC(NC(=O)C=3C=C4C=CC=CC4=CC=3)=CC=2)=N1 SBKQRLWONFKCFV-UHFFFAOYSA-N 0.000 claims description 2
- PVUSLECUHKYKFI-UHFFFAOYSA-N 2-[4-(dimethylamino)-6-ethyl-2-[[4-[[4-(trifluoromethyl)benzoyl]amino]phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound CN(C)C1=C(CC(O)=O)C(CC)=NC(CC=2C=CC(NC(=O)C=3C=CC(=CC=3)C(F)(F)F)=CC=2)=N1 PVUSLECUHKYKFI-UHFFFAOYSA-N 0.000 claims description 2
- OMDIJQIRAXUPFB-UHFFFAOYSA-N 2-[4-(dimethylamino)-6-methyl-2-[[4-(naphthalene-2-carbonylamino)phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound CC1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)C=3C=C4C=CC=CC4=CC=3)=CC=2)=N1 OMDIJQIRAXUPFB-UHFFFAOYSA-N 0.000 claims description 2
- DINJPARSGWZJLN-JLHYYAGUSA-N 2-[4-(dimethylamino)-6-morpholin-4-yl-2-[[4-[[(e)-3-phenylprop-2-enoyl]amino]phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound N=1C(N2CCOCC2)=C(CC(O)=O)C(N(C)C)=NC=1CC(C=C1)=CC=C1NC(=O)\C=C\C1=CC=CC=C1 DINJPARSGWZJLN-JLHYYAGUSA-N 0.000 claims description 2
- GEJHDNYRGZSUTQ-UHFFFAOYSA-N 2-[4-(dimethylamino)-6-morpholin-4-yl-2-[[4-[[4-(trifluoromethyl)benzoyl]amino]phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound N=1C(N2CCOCC2)=C(CC(O)=O)C(N(C)C)=NC=1CC(C=C1)=CC=C1NC(=O)C1=CC=C(C(F)(F)F)C=C1 GEJHDNYRGZSUTQ-UHFFFAOYSA-N 0.000 claims description 2
- MRMSMOWNKYPGHI-UHFFFAOYSA-N 2-[4-(dimethylamino)-6-propan-2-yl-2-[[4-[[4-(trifluoromethyl)benzoyl]amino]phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound CN(C)C1=C(CC(O)=O)C(C(C)C)=NC(CC=2C=CC(NC(=O)C=3C=CC(=CC=3)C(F)(F)F)=CC=2)=N1 MRMSMOWNKYPGHI-UHFFFAOYSA-N 0.000 claims description 2
- BKHLPFXCOHVKNA-UHFFFAOYSA-N 2-[4-(dimethylamino)-6-pyrrolidin-1-yl-2-[[4-[[4-(trifluoromethyl)benzoyl]amino]phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound N=1C(N2CCCC2)=C(CC(O)=O)C(N(C)C)=NC=1CC(C=C1)=CC=C1NC(=O)C1=CC=C(C(F)(F)F)C=C1 BKHLPFXCOHVKNA-UHFFFAOYSA-N 0.000 claims description 2
- FZZZSCVAJSHOTP-UHFFFAOYSA-N 2-[4-[[2-(cyclopentylamino)-2-oxoethyl]-methylamino]-2-[[4-(naphthalene-2-carbonylamino)phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound N=1C(CC=2C=CC(NC(=O)C=3C=C4C=CC=CC4=CC=3)=CC=2)=NC=C(CC(O)=O)C=1N(C)CC(=O)NC1CCCC1 FZZZSCVAJSHOTP-UHFFFAOYSA-N 0.000 claims description 2
- BUVUXCNBRMWLTA-DTQAZKPQSA-N 2-[4-[[2-(cyclopentylamino)-2-oxoethyl]-methylamino]-2-[[4-[[(e)-3-phenylprop-2-enoyl]amino]phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound N=1C(CC=2C=CC(NC(=O)\C=C\C=3C=CC=CC=3)=CC=2)=NC=C(CC(O)=O)C=1N(C)CC(=O)NC1CCCC1 BUVUXCNBRMWLTA-DTQAZKPQSA-N 0.000 claims description 2
- OXWLKJXZSSGDRN-UHFFFAOYSA-N 2-[4-[carboxymethyl(methyl)amino]-6-chloro-2-[[4-(naphthalene-2-carbonylamino)phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound ClC1=C(CC(O)=O)C(N(CC(O)=O)C)=NC(CC=2C=CC(NC(=O)C=3C=C4C=CC=CC4=CC=3)=CC=2)=N1 OXWLKJXZSSGDRN-UHFFFAOYSA-N 0.000 claims description 2
- MGOYNGXEMSANKG-UHFFFAOYSA-N 2-[4-[methyl-(2-oxo-2-pyrrolidin-1-ylethyl)amino]-2-[[4-(naphthalene-2-carbonylamino)phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound N=1C(CC=2C=CC(NC(=O)C=3C=C4C=CC=CC4=CC=3)=CC=2)=NC=C(CC(O)=O)C=1N(C)CC(=O)N1CCCC1 MGOYNGXEMSANKG-UHFFFAOYSA-N 0.000 claims description 2
- WEUSPEBVRKDRLM-UHFFFAOYSA-N 2-[4-chloro-2-[[4-(naphthalene-2-carbonylamino)phenyl]methyl]-6-piperidin-1-ylpyrimidin-5-yl]acetic acid Chemical compound OC(=O)CC1=C(Cl)N=C(CC=2C=CC(NC(=O)C=3C=C4C=CC=CC4=CC=3)=CC=2)N=C1N1CCCCC1 WEUSPEBVRKDRLM-UHFFFAOYSA-N 0.000 claims description 2
- ZNTGLJGJOQBPOJ-UHFFFAOYSA-N 2-[4-chloro-2-[[4-[(2-cyclohexylacetyl)amino]phenyl]methyl]-6-[[2-(cyclopentylamino)-2-oxoethyl]-methylamino]pyrimidin-5-yl]acetic acid Chemical compound N=1C(CC=2C=CC(NC(=O)CC3CCCCC3)=CC=2)=NC(Cl)=C(CC(O)=O)C=1N(C)CC(=O)NC1CCCC1 ZNTGLJGJOQBPOJ-UHFFFAOYSA-N 0.000 claims description 2
- JCPPYXISAHHCPF-UHFFFAOYSA-N 2-[4-chloro-2-[[4-[(3,4-dichlorobenzoyl)amino]phenyl]methyl]-6-(dimethylamino)pyrimidin-5-yl]acetic acid Chemical compound ClC1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)C=3C=C(Cl)C(Cl)=CC=3)=CC=2)=N1 JCPPYXISAHHCPF-UHFFFAOYSA-N 0.000 claims description 2
- PICHTDWCXIURKN-UHFFFAOYSA-N 2-[4-chloro-2-[[4-[(3,4-difluorobenzoyl)amino]phenyl]methyl]-6-(dimethylamino)pyrimidin-5-yl]acetic acid Chemical compound ClC1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)C=3C=C(F)C(F)=CC=3)=CC=2)=N1 PICHTDWCXIURKN-UHFFFAOYSA-N 0.000 claims description 2
- DOHVYOHYPAGMAF-UHFFFAOYSA-N 2-[4-chloro-2-[[4-[(3,4-dimethoxybenzoyl)amino]phenyl]methyl]-6-(dimethylamino)pyrimidin-5-yl]acetic acid Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NC(C=C1)=CC=C1CC1=NC(Cl)=C(CC(O)=O)C(N(C)C)=N1 DOHVYOHYPAGMAF-UHFFFAOYSA-N 0.000 claims description 2
- QKSKYWATPYQNRY-UHFFFAOYSA-N 2-[4-chloro-2-[[4-[(3-chloro-4-methoxybenzoyl)amino]phenyl]methyl]-6-pyrrolidin-1-ylpyrimidin-5-yl]acetic acid Chemical compound C1=C(Cl)C(OC)=CC=C1C(=O)NC(C=C1)=CC=C1CC1=NC(Cl)=C(CC(O)=O)C(N2CCCC2)=N1 QKSKYWATPYQNRY-UHFFFAOYSA-N 0.000 claims description 2
- GXRGQPPSNFDVRG-UHFFFAOYSA-N 2-[4-chloro-2-[[4-[(3-chlorobenzoyl)amino]phenyl]methyl]-6-(dimethylamino)pyrimidin-5-yl]acetic acid Chemical compound ClC1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)C=3C=C(Cl)C=CC=3)=CC=2)=N1 GXRGQPPSNFDVRG-UHFFFAOYSA-N 0.000 claims description 2
- DJZFUDKILTZUGL-UHFFFAOYSA-N 2-[4-chloro-2-[[4-[(4-chlorobenzoyl)amino]phenyl]methyl]-6-(dimethylamino)pyrimidin-5-yl]acetic acid Chemical compound ClC1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)C=3C=CC(Cl)=CC=3)=CC=2)=N1 DJZFUDKILTZUGL-UHFFFAOYSA-N 0.000 claims description 2
- WXARHGJSLJJRPG-UHFFFAOYSA-N 2-[4-chloro-2-[[4-[(4-chlorobenzoyl)amino]phenyl]methyl]-6-pyrrolidin-1-ylpyrimidin-5-yl]acetic acid Chemical compound N1=C(N2CCCC2)C(CC(=O)O)=C(Cl)N=C1CC(C=C1)=CC=C1NC(=O)C1=CC=C(Cl)C=C1 WXARHGJSLJJRPG-UHFFFAOYSA-N 0.000 claims description 2
- HVTPKJKYFNCJTQ-UHFFFAOYSA-N 2-[4-chloro-2-[[4-[(4-cyanobenzoyl)amino]phenyl]methyl]-6-[[2-(cyclopentylamino)-2-oxoethyl]-methylamino]pyrimidin-5-yl]acetic acid Chemical compound N=1C(CC=2C=CC(NC(=O)C=3C=CC(=CC=3)C#N)=CC=2)=NC(Cl)=C(CC(O)=O)C=1N(C)CC(=O)NC1CCCC1 HVTPKJKYFNCJTQ-UHFFFAOYSA-N 0.000 claims description 2
- SLPMFCFFPOSDJT-UHFFFAOYSA-N 2-[4-chloro-2-[[4-[(4-methoxy-3,5-dimethylbenzoyl)amino]phenyl]methyl]-6-pyrrolidin-1-ylpyrimidin-5-yl]acetic acid Chemical compound C1=C(C)C(OC)=C(C)C=C1C(=O)NC(C=C1)=CC=C1CC1=NC(Cl)=C(CC(O)=O)C(N2CCCC2)=N1 SLPMFCFFPOSDJT-UHFFFAOYSA-N 0.000 claims description 2
- MADNSGWBZDSODE-UHFFFAOYSA-N 2-[4-chloro-2-[[4-[(4-methoxy-3-nitrobenzoyl)amino]phenyl]methyl]-6-pyrrolidin-1-ylpyrimidin-5-yl]acetic acid Chemical compound C1=C([N+]([O-])=O)C(OC)=CC=C1C(=O)NC(C=C1)=CC=C1CC1=NC(Cl)=C(CC(O)=O)C(N2CCCC2)=N1 MADNSGWBZDSODE-UHFFFAOYSA-N 0.000 claims description 2
- RJIDXIAMEKHXNS-UHFFFAOYSA-N 2-[4-chloro-2-[[4-[(4-methylsulfanylbenzoyl)amino]phenyl]methyl]-6-pyrrolidin-1-ylpyrimidin-5-yl]acetic acid Chemical compound C1=CC(SC)=CC=C1C(=O)NC(C=C1)=CC=C1CC1=NC(Cl)=C(CC(O)=O)C(N2CCCC2)=N1 RJIDXIAMEKHXNS-UHFFFAOYSA-N 0.000 claims description 2
- GYUDXTUDABEZFS-UHFFFAOYSA-N 2-[4-chloro-2-[[4-[(4-nitrobenzoyl)amino]phenyl]methyl]-6-pyrrolidin-1-ylpyrimidin-5-yl]acetic acid Chemical compound N1=C(N2CCCC2)C(CC(=O)O)=C(Cl)N=C1CC(C=C1)=CC=C1NC(=O)C1=CC=C([N+]([O-])=O)C=C1 GYUDXTUDABEZFS-UHFFFAOYSA-N 0.000 claims description 2
- RGPFGWBVFSTDOG-UHFFFAOYSA-N 2-[4-chloro-2-[[4-[(4-phenoxybenzoyl)amino]phenyl]methyl]-6-pyrrolidin-1-ylpyrimidin-5-yl]acetic acid Chemical compound N1=C(N2CCCC2)C(CC(=O)O)=C(Cl)N=C1CC(C=C1)=CC=C1NC(=O)C(C=C1)=CC=C1OC1=CC=CC=C1 RGPFGWBVFSTDOG-UHFFFAOYSA-N 0.000 claims description 2
- NCBINUVTUKRPQC-UHFFFAOYSA-N 2-[4-chloro-2-[[4-[(4-propan-2-yloxybenzoyl)amino]phenyl]methyl]-6-pyrrolidin-1-ylpyrimidin-5-yl]acetic acid Chemical compound C1=CC(OC(C)C)=CC=C1C(=O)NC(C=C1)=CC=C1CC1=NC(Cl)=C(CC(O)=O)C(N2CCCC2)=N1 NCBINUVTUKRPQC-UHFFFAOYSA-N 0.000 claims description 2
- DHEFFVDIXZXMLI-KPKJPENVSA-N 2-[4-chloro-2-[[4-[[(e)-3-(4-chlorophenyl)prop-2-enoyl]amino]phenyl]methyl]-6-(dimethylamino)pyrimidin-5-yl]acetic acid Chemical compound ClC1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=CC(NC(=O)\C=C\C=3C=CC(Cl)=CC=3)=CC=2)=N1 DHEFFVDIXZXMLI-KPKJPENVSA-N 0.000 claims description 2
- RADBTWDKEJPKEO-KPKJPENVSA-N 2-[4-chloro-2-[[4-[[(e)-3-(4-chlorophenyl)prop-2-enoyl]amino]phenyl]methyl]-6-pyrrolidin-1-ylpyrimidin-5-yl]acetic acid Chemical compound N1=C(N2CCCC2)C(CC(=O)O)=C(Cl)N=C1CC(C=C1)=CC=C1NC(=O)\C=C\C1=CC=C(Cl)C=C1 RADBTWDKEJPKEO-KPKJPENVSA-N 0.000 claims description 2
- FEQHBGJZYPBKBZ-UHFFFAOYSA-N 2-[4-chloro-6-(2,5-dihydropyrrol-1-yl)-2-[[4-(naphthalene-2-carbonylamino)phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound OC(=O)CC1=C(Cl)N=C(CC=2C=CC(NC(=O)C=3C=C4C=CC=CC4=CC=3)=CC=2)N=C1N1CC=CC1 FEQHBGJZYPBKBZ-UHFFFAOYSA-N 0.000 claims description 2
- JDIZIXSBVMDTGP-UHFFFAOYSA-N 2-[4-chloro-6-(3-hydroxypyrrolidin-1-yl)-2-[[4-(naphthalene-2-carbonylamino)phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound C1C(O)CCN1C1=NC(CC=2C=CC(NC(=O)C=3C=C4C=CC=CC4=CC=3)=CC=2)=NC(Cl)=C1CC(O)=O JDIZIXSBVMDTGP-UHFFFAOYSA-N 0.000 claims description 2
- VHSVZJXHYNEFJG-UHFFFAOYSA-N 2-[4-chloro-6-(diethylamino)-2-[[4-(naphthalene-2-carbonylamino)phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound ClC1=C(CC(O)=O)C(N(CC)CC)=NC(CC=2C=CC(NC(=O)C=3C=C4C=CC=CC4=CC=3)=CC=2)=N1 VHSVZJXHYNEFJG-UHFFFAOYSA-N 0.000 claims description 2
- RXKPEAXSSMKIKT-UHFFFAOYSA-N 2-[4-chloro-6-(dimethylamino)-2-[[3-(naphthalene-2-carbonylamino)phenyl]methyl]pyrimidin-5-yl]acetic acid Chemical compound ClC1=C(CC(O)=O)C(N(C)C)=NC(CC=2C=C(NC(=O)C=3C=C4C=CC=CC4=CC=3)C=CC=2)=N1 RXKPEAXSSMKIKT-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
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- 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
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/14—Decongestants or antiallergics
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- A—HUMAN NECESSITIES
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- A61P27/16—Otologicals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/30—Halogen atoms or nitro radicals
-
- 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
-
- 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
- C07D403/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D403/12—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
-
- 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
- C07D405/02—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 two hetero rings
- C07D405/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Ophthalmology & Optometry (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Otolaryngology (AREA)
- Dermatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP03009384A EP1471057B1 (en) | 2003-04-25 | 2003-04-25 | Pyrimidinylacetic acid derivatives useful for the treatment of diseases mediated by CRTH2 |
| EP03009384.3 | 2003-04-25 | ||
| PCT/EP2004/003910 WO2004096777A1 (en) | 2003-04-25 | 2004-04-14 | Pyrimidine derivatives useful for the treatment of diseases mediated by crth2 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2523439A1 CA2523439A1 (en) | 2004-11-11 |
| CA2523439C true CA2523439C (en) | 2012-06-19 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2523439A Expired - Fee Related CA2523439C (en) | 2003-04-25 | 2004-04-14 | Pyrimidine derivatives useful for the treatment of diseases mediated by crth2 |
Country Status (32)
Families Citing this family (59)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE0301010D0 (sv) | 2003-04-07 | 2003-04-07 | Astrazeneca Ab | Novel compounds |
| ATE316077T1 (de) | 2003-04-25 | 2006-02-15 | Actimis Pharmaceuticals Inc | Pyrimidin-essigsäure derivate geeignet zur behandlung von crth2-bedingten krankheiten |
| SA04250253B1 (ar) | 2003-08-21 | 2009-11-10 | استرازينيكا ايه بي | احماض فينوكسي اسيتيك مستبدلة باعتبارها مركبات صيدلانية لعلاج الامراض التنفسية مثل الربو ومرض الانسداد الرئوي المزمن |
| EP3718564B1 (en) * | 2003-12-23 | 2023-10-11 | Genentech, Inc. | Novel anti-il 13 antibodies and uses thereof |
| EP1718649B1 (en) | 2004-01-31 | 2009-06-10 | Actimis Pharmaceuticals, Inc., | Imidazo 1,2-c pyrimidinylacetic acid derivatives |
| ES2304010T3 (es) | 2004-03-11 | 2008-09-01 | Actelion Pharmaceuticals Ltd. | Derivados de tetrahidropiridoindol. |
| GB0415320D0 (en) | 2004-07-08 | 2004-08-11 | Astrazeneca Ab | Novel compounds |
| GB0418830D0 (en) | 2004-08-24 | 2004-09-22 | Astrazeneca Ab | Novel compounds |
| ATE517085T1 (de) | 2004-11-23 | 2011-08-15 | Astrazeneca Ab | Zur behandlung von atemwegserkrankungen geeignete phenoxyessigsäurederivate |
| DK1871374T3 (da) | 2005-04-21 | 2011-12-05 | Merck Serono Sa | 2,3-substituerede pyrazinsulfonamider som CRTH2-inhibitorer |
| MX2007014256A (es) | 2005-05-24 | 2008-03-26 | Serono Lab | Derivados espiro triciclicos como moduladores crth2. |
| PE20110118A1 (es) | 2005-10-04 | 2011-03-08 | Aventis Pharma Inc | Compuestos de pirimidina amida como inhibidores de pgds |
| US8148572B2 (en) | 2005-10-06 | 2012-04-03 | Astrazeneca Ab | Compounds |
| TW200745003A (en) | 2005-10-06 | 2007-12-16 | Astrazeneca Ab | Novel compounds |
| WO2007062677A1 (en) * | 2005-11-30 | 2007-06-07 | 7Tm Pharma A/S | Thiazolyl- and pyrimidinyl-acetic acids and their use as crth2 receptor ligands |
| AU2007256597A1 (en) * | 2006-06-09 | 2007-12-13 | Icos Corporation | Substituted phenyl acetic acids as DP-2 antagonists |
| EP2132196A1 (en) * | 2007-02-26 | 2009-12-16 | Pfizer Products Inc. | Nicotinamide derivatives as inhibitors of h-pgds and their use for treating prostaglandin d2 mediated diseases |
| CN101772489B (zh) * | 2007-06-21 | 2013-02-20 | 艾克提麦斯医药品有限公司 | 一种crth2拮抗剂的胺盐 |
| CN103172573A (zh) * | 2007-06-21 | 2013-06-26 | 艾克提麦斯医药品有限公司 | Crth2 拮抗剂的微粒 |
| UA100983C2 (ru) | 2007-07-05 | 2013-02-25 | Астразенека Аб | Бифенилоксипропановая кислота как модулятор crth2 и интермедиаты |
| ATE547407T1 (de) * | 2007-09-25 | 2012-03-15 | Actimis Pharmaceuticals Inc | Alkylthiopyrimidine als crth2-antagonisten |
| AU2008305633B2 (en) * | 2007-09-25 | 2013-09-12 | Actimis Pharmaceuticals, Inc. | 2-S-benzyl substituted pyrimidines as CRTH2 antagonists |
| EP2257524B1 (en) | 2008-02-01 | 2016-01-06 | Brickell Biotech, Inc. | N,n-disubstituted aminoalkylbiphenyl antagonists of prostaglandin d2 receptors |
| JP2011512359A (ja) | 2008-02-14 | 2011-04-21 | アミラ ファーマシューティカルズ，インク． | プロスタグランジンｄ２受容体のアンタゴニストとしての環式ジアリールエーテル化合物 |
| US8497381B2 (en) | 2008-02-25 | 2013-07-30 | Panmira Pharmaceuticals, Llc | Antagonists of prostaglandin D2 receptors |
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