MXPA05011399A - Derivados de pirimidina utilies para el tratamiento de enfermedades mediadas por crth2. - Google Patents
Derivados de pirimidina utilies para el tratamiento de enfermedades mediadas por crth2.Info
- Publication number
- MXPA05011399A MXPA05011399A MXPA05011399A MXPA05011399A MXPA05011399A MX PA05011399 A MXPA05011399 A MX PA05011399A MX PA05011399 A MXPA05011399 A MX PA05011399A MX PA05011399 A MXPA05011399 A MX PA05011399A MX PA05011399 A MXPA05011399 A MX PA05011399A
- Authority
- MX
- Mexico
- Prior art keywords
- amino
- benzyl
- acid
- pyrimidinyl
- dimethylamino
- Prior art date
Links
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 24
- 201000010099 disease Diseases 0.000 title claims abstract description 21
- 150000003230 pyrimidines Chemical class 0.000 title claims abstract description 21
- 238000011282 treatment Methods 0.000 title claims abstract description 19
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title description 5
- 230000001404 mediated effect Effects 0.000 title description 2
- 230000000694 effects Effects 0.000 claims abstract description 59
- 102000009389 Prostaglandin D receptors Human genes 0.000 claims abstract description 27
- 108050000258 Prostaglandin D receptors Proteins 0.000 claims abstract description 27
- 150000003839 salts Chemical class 0.000 claims abstract description 19
- 208000026935 allergic disease Diseases 0.000 claims abstract description 15
- 210000003979 eosinophil Anatomy 0.000 claims abstract description 14
- 239000004480 active ingredient Substances 0.000 claims abstract description 13
- 210000003651 basophil Anatomy 0.000 claims abstract description 10
- 206010010744 Conjunctivitis allergic Diseases 0.000 claims abstract description 7
- 206010012438 Dermatitis atopic Diseases 0.000 claims abstract description 7
- 206010039085 Rhinitis allergic Diseases 0.000 claims abstract description 7
- 210000001744 T-lymphocyte Anatomy 0.000 claims abstract description 7
- 208000002205 allergic conjunctivitis Diseases 0.000 claims abstract description 7
- 201000010105 allergic rhinitis Diseases 0.000 claims abstract description 7
- 208000006673 asthma Diseases 0.000 claims abstract description 7
- 208000024998 atopic conjunctivitis Diseases 0.000 claims abstract description 7
- 201000008937 atopic dermatitis Diseases 0.000 claims abstract description 7
- 201000009890 sinusitis Diseases 0.000 claims abstract description 7
- 208000016557 Acute basophilic leukemia Diseases 0.000 claims abstract description 6
- 208000032671 Allergic granulomatous angiitis Diseases 0.000 claims abstract description 6
- 208000006344 Churg-Strauss Syndrome Diseases 0.000 claims abstract description 6
- 208000018428 Eosinophilic granulomatosis with polyangiitis Diseases 0.000 claims abstract description 6
- 210000004241 Th2 cell Anatomy 0.000 claims abstract description 6
- 206010052568 Urticaria chronic Diseases 0.000 claims abstract description 6
- 208000024376 chronic urticaria Diseases 0.000 claims abstract description 6
- 210000000265 leukocyte Anatomy 0.000 claims abstract description 5
- 238000011321 prophylaxis Methods 0.000 claims abstract description 5
- 102000011652 Formyl peptide receptors Human genes 0.000 claims abstract description 4
- 108010076288 Formyl peptide receptors Proteins 0.000 claims abstract description 4
- 241000124008 Mammalia Species 0.000 claims abstract description 4
- 206010024378 leukocytosis Diseases 0.000 claims abstract description 4
- 206010009900 Colitis ulcerative Diseases 0.000 claims abstract description 3
- 208000011231 Crohn disease Diseases 0.000 claims abstract description 3
- 201000004624 Dermatitis Diseases 0.000 claims abstract description 3
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims abstract description 3
- 201000004681 Psoriasis Diseases 0.000 claims abstract description 3
- 201000006704 Ulcerative Colitis Diseases 0.000 claims abstract description 3
- 206010003246 arthritis Diseases 0.000 claims abstract description 3
- 208000010668 atopic eczema Diseases 0.000 claims abstract description 3
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims abstract description 3
- 208000019693 Lung disease Diseases 0.000 claims abstract 2
- 230000003042 antagnostic effect Effects 0.000 claims abstract 2
- 230000001684 chronic effect Effects 0.000 claims abstract 2
- 230000000414 obstructive effect Effects 0.000 claims abstract 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 496
- -1 nitro, guanidino, pyrrolyl Chemical group 0.000 claims description 345
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 249
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 214
- 150000001875 compounds Chemical class 0.000 claims description 196
- 239000002253 acid Substances 0.000 claims description 176
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 152
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 94
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 80
- 125000000217 alkyl group Chemical group 0.000 claims description 71
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 57
- 125000006312 cyclopentyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 52
- 238000000034 method Methods 0.000 claims description 36
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 31
- 239000001257 hydrogen Substances 0.000 claims description 29
- 229910052739 hydrogen Inorganic materials 0.000 claims description 29
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
- 125000003545 alkoxy group Chemical group 0.000 claims description 24
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 24
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 21
- 125000003118 aryl group Chemical group 0.000 claims description 17
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 16
- 125000002999 4-(trifluoromethyl)benzoyl group Chemical group FC(C1=CC=C(C(=O)*)C=C1)(F)F 0.000 claims description 16
- 125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 claims description 15
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 14
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 150000002367 halogens Chemical group 0.000 claims description 13
- 150000002431 hydrogen Chemical class 0.000 claims description 13
- 239000000460 chlorine Chemical group 0.000 claims description 12
- 150000002148 esters Chemical class 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 125000003282 alkyl amino group Chemical group 0.000 claims description 11
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 10
- 239000000651 prodrug Substances 0.000 claims description 10
- 229940002612 prodrug Drugs 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 125000001072 heteroaryl group Chemical group 0.000 claims description 9
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 claims description 9
- 150000001408 amides Chemical class 0.000 claims description 8
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 241001024304 Mino Species 0.000 claims description 7
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 7
- 125000001624 naphthyl group Chemical group 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 125000001999 4-Methoxybenzoyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C(*)=O 0.000 claims description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 6
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 6
- 125000003705 anilinocarbonyl group Chemical group O=C([*])N([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 229940124003 CRTH2 antagonist Drugs 0.000 claims description 5
- 125000003647 acryloyl group Chemical group O=C([*])C([H])=C([H])[H] 0.000 claims description 5
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 5
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 125000002541 furyl group Chemical group 0.000 claims description 5
- 125000001041 indolyl group Chemical group 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 239000005557 antagonist Substances 0.000 claims description 4
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 4
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
- 125000005493 quinolyl group Chemical group 0.000 claims description 4
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 3
- 125000002672 4-bromobenzoyl group Chemical group BrC1=CC=C(C(=O)*)C=C1 0.000 claims description 3
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 3
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 2
- BJWSMNONLBPUSX-UHFFFAOYSA-N 2-[4-(dimethylamino)-2-[[4-(naphthalene-2-carbonylamino)phenyl]methyl]-6-piperidin-1-ylpyrimidin-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=1N1CCCCC1 BJWSMNONLBPUSX-UHFFFAOYSA-N 0.000 claims description 2
- VZQIUAMJIMFSOW-UHFFFAOYSA-N 2-[4-(dimethylamino)-2-[[4-(naphthalene-2-carbonylamino)phenyl]methyl]-6-pyrrolidin-1-ylpyrimidin-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=1N1CCCC1 VZQIUAMJIMFSOW-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
- 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
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- 101710120037 Toxin CcdB Proteins 0.000 claims description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
- 229940024606 amino acid Drugs 0.000 claims description 2
- 150000001413 amino acids Chemical class 0.000 claims description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 2
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims description 2
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
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- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
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- 208000035475 disorder Diseases 0.000 claims 3
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- 230000004075 alteration Effects 0.000 claims 2
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- WONLCOCARDVMTP-UHFFFAOYSA-N (2-aminophenyl)-[4-(trifluoromethoxy)phenyl]methanone Chemical compound NC1=CC=CC=C1C(=O)C1=CC=C(OC(F)(F)F)C=C1 WONLCOCARDVMTP-UHFFFAOYSA-N 0.000 claims 1
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 1
- XKXLBHSNDSFICW-ZHACJKMWSA-N (e)-1-(2-aminophenyl)-3-phenylprop-2-en-1-one Chemical compound NC1=CC=CC=C1C(=O)\C=C\C1=CC=CC=C1 XKXLBHSNDSFICW-ZHACJKMWSA-N 0.000 claims 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- ZSSFQQJWTVRIMO-UHFFFAOYSA-N 2-[4-chloro-6-[[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(Cl)=C(CC(O)=O)C=1N(C)CC(=O)NC1CCCC1 ZSSFQQJWTVRIMO-UHFFFAOYSA-N 0.000 claims 1
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- JVXXKQIRGQDWOJ-UHFFFAOYSA-N naphthalene-2-carboxamide Chemical compound C1=CC=CC2=CC(C(=O)N)=CC=C21 JVXXKQIRGQDWOJ-UHFFFAOYSA-N 0.000 claims 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
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- 125000006639 cyclohexyl carbonyl group Chemical group 0.000 description 1
- 125000006638 cyclopentyl carbonyl group Chemical group 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
- 125000006255 cyclopropyl carbonyl group Chemical group [H]C1([H])C([H])([H])C1([H])C(*)=O 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
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- 238000011161 development Methods 0.000 description 1
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
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- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 125000006260 ethylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])C([H])([H])[H] 0.000 description 1
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- 125000004997 halocarbonyl group Chemical group 0.000 description 1
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- 238000005658 halogenation reaction Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000006517 heterocyclyl carbonyl group Chemical group 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
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- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000006262 isopropyl amino sulfonyl group Chemical group 0.000 description 1
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
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- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000011344 liquid material Substances 0.000 description 1
- FKBSHNBSEUWDAC-UHFFFAOYSA-L lithium sodium dihydroxide Chemical compound [Li+].[OH-].[OH-].[Na+] FKBSHNBSEUWDAC-UHFFFAOYSA-L 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
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- 239000002184 metal Substances 0.000 description 1
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- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- GBDLKARXLYOYOG-UHFFFAOYSA-N methyl 2-[2-[(4-aminophenyl)methyl]-4,6-bis(dimethylamino)pyrimidin-5-yl]acetate Chemical compound N1=C(N(C)C)C(CC(=O)OC)=C(N(C)C)N=C1CC1=CC=C(N)C=C1 GBDLKARXLYOYOG-UHFFFAOYSA-N 0.000 description 1
- QCBNWWUBWLLBLW-UHFFFAOYSA-N methyl 2-[2-[(4-aminophenyl)methyl]-4,6-dichloropyrimidin-5-yl]acetate Chemical compound N1=C(Cl)C(CC(=O)OC)=C(Cl)N=C1CC1=CC=C(N)C=C1 QCBNWWUBWLLBLW-UHFFFAOYSA-N 0.000 description 1
- WJAXESRMUMNNIY-UHFFFAOYSA-N methyl 2-[2-[(4-aminophenyl)methyl]-4-methyl-6-pyrrolidin-1-ylpyrimidin-5-yl]acetate Chemical compound N1=C(N2CCCC2)C(CC(=O)OC)=C(C)N=C1CC1=CC=C(N)C=C1 WJAXESRMUMNNIY-UHFFFAOYSA-N 0.000 description 1
- VHJKSCQQYCOPHR-UHFFFAOYSA-N methyl 2-[4-chloro-2-[[4-(naphthalene-2-carbonylamino)phenyl]methyl]-6-pyrrolidin-1-ylpyrimidin-5-yl]acetate Chemical compound COC(=O)CC1=C(Cl)N=C(CC=2C=CC(NC(=O)C=3C=C4C=CC=CC4=CC=3)=CC=2)N=C1N1CCCC1 VHJKSCQQYCOPHR-UHFFFAOYSA-N 0.000 description 1
- ITCYNWZKTHQHHA-UHFFFAOYSA-N methyl 2-[4-hydroxy-2-[(4-nitrophenyl)methyl]-6-oxo-1h-pyrimidin-5-yl]acetate Chemical compound N1=C(O)C(CC(=O)OC)=C(O)N=C1CC1=CC=C([N+]([O-])=O)C=C1 ITCYNWZKTHQHHA-UHFFFAOYSA-N 0.000 description 1
- UDSUZQCSWWADQM-UHFFFAOYSA-N methyl 2-[4-methyl-2-[(4-nitrophenyl)methyl]-6-pyrrolidin-1-ylpyrimidin-5-yl]acetate Chemical compound N1=C(N2CCCC2)C(CC(=O)OC)=C(C)N=C1CC1=CC=C([N+]([O-])=O)C=C1 UDSUZQCSWWADQM-UHFFFAOYSA-N 0.000 description 1
- NVCHUNVJIWZRRR-UHFFFAOYSA-N methyl 2-[6-methyl-2-[(4-nitrophenyl)methyl]-4-oxo-1h-pyrimidin-5-yl]acetate Chemical compound N1=C(O)C(CC(=O)OC)=C(C)N=C1CC1=CC=C([N+]([O-])=O)C=C1 NVCHUNVJIWZRRR-UHFFFAOYSA-N 0.000 description 1
- 125000006261 methyl amino sulfonyl group Chemical group [H]N(C([H])([H])[H])S(*)(=O)=O 0.000 description 1
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- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
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- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
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- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
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- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
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- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- 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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- 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
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- 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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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
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- C—CHEMISTRY; METALLURGY
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- 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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- C07D403/00—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
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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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- 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
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Applications Claiming Priority (2)
| 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 |
| PCT/EP2004/003910 WO2004096777A1 (en) | 2003-04-25 | 2004-04-14 | Pyrimidine derivatives useful for the treatment of diseases mediated by crth2 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA05011399A true MXPA05011399A (es) | 2006-05-31 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MXPA05011399A MXPA05011399A (es) | 2003-04-25 | 2004-04-14 | Derivados de pirimidina utilies para el tratamiento de enfermedades mediadas por crth2. |
Country Status (32)
Families Citing this family (59)
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| SE0301010D0 (sv) | 2003-04-07 | 2003-04-07 | Astrazeneca Ab | Novel compounds |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
| JP2011518130A (ja) | 2008-04-02 | 2011-06-23 | 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受容体のアミノアルキルフェニルアンタゴニスト |
| WO2010003120A2 (en) | 2008-07-03 | 2010-01-07 | Amira Pharmaceuticals, Inc. | Antagonists of prostaglandin d2 receptors |
| JP5586606B2 (ja) * | 2008-09-02 | 2014-09-10 | アクチミス ファーマシューティカルズ インコーポレーテッド | Ｃｒｔｈ２アンタゴニストとしての同位体富化されたピリミジン−５−イル酢酸誘導体 |
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| US8383654B2 (en) | 2008-11-17 | 2013-02-26 | Panmira Pharmaceuticals, Llc | Heterocyclic antagonists of prostaglandin D2 receptors |
| JPWO2010074244A1 (ja) * | 2008-12-25 | 2012-06-21 | 大正製薬株式会社 | イソキノリン誘導体 |
| WO2010089391A1 (en) | 2009-02-09 | 2010-08-12 | Boehringer Ingelheim International Gmbh | New pharmaceutical compositions for treatment of respiratory and gastrointestinal disorders |
| AU2010212970A1 (en) | 2009-02-12 | 2011-08-18 | Merck Serono S.A. | Phenoxy acetic acid derivatives |
| WO2010094643A1 (en) * | 2009-02-17 | 2010-08-26 | Glaxo Group Limited | Quinoline derivatives and their uses for rhinitis and urticaria |
| GB0908394D0 (en) | 2009-05-15 | 2009-06-24 | Univ Leuven Kath | Novel viral replication inhibitors |
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| GB0913636D0 (en) | 2009-08-05 | 2009-09-16 | Univ Leuven Kath | Novel viral replication inhibitors |
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| MX2012006003A (es) * | 2009-11-24 | 2012-06-19 | Boehringer Ingelheim Int | Procedimiento para preparar un polimorfo de la sal de colina de [4,6-bis(dimetilamino)-2-(4-{[4-(trifluorometil)-benzoil]amino}be ncil)pirimidin-5-ilo]. |
| CA2782085A1 (en) | 2010-01-06 | 2011-07-14 | Panmira Pharmaceuticals, Llc | Dp2 antagonist and uses thereof |
| AU2011209286B2 (en) | 2010-01-27 | 2016-02-11 | Gb007, Inc. | Pyrazole compounds as CRTH2 antagonists |
| CN103119024A (zh) | 2010-06-23 | 2013-05-22 | 大正制药株式会社 | 异喹啉衍生物 |
| EP2590944B1 (en) | 2010-07-05 | 2015-09-30 | Actelion Pharmaceuticals Ltd. | 1-phenyl-substituted heterocyclyl derivatives and their use as prostaglandin d2 receptor modulators |
| EP2598145A1 (en) | 2010-07-28 | 2013-06-05 | Boehringer Ingelheim International GmbH | Pharmaceutical composition for treatment of respiratory and inflammatory diseases |
| WO2012013566A1 (en) | 2010-07-28 | 2012-02-02 | Boehringer Ingelheim International Gmbh | Pharmaceutical compositions for treatment of respiratory and inflammatory diseases |
| WO2012054691A2 (en) | 2010-10-20 | 2012-04-26 | Valspar Sourcing, Inc. | Water-based coating system with improved adhesion to a wide range of coated and uncoated substrates including muffler grade stainless steel |
| EP2640705A2 (en) | 2010-11-15 | 2013-09-25 | Katholieke Universiteit Leuven | Novel antiviral compounds |
| EP2457900A1 (en) | 2010-11-25 | 2012-05-30 | Almirall, S.A. | New pyrazole derivatives having CRTh2 antagonistic behaviour |
| TWI527809B (zh) | 2011-01-24 | 2016-04-01 | 百靈佳殷格翰國際股份有限公司 | 作為ｃｒｔｈ２拮抗劑之吡唑化合物 |
| JP5999387B2 (ja) | 2011-03-25 | 2016-09-28 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｃｒｔｈ２拮抗薬としてのピラゾール化合物 |
| RS56326B1 (sr) * | 2011-05-16 | 2017-12-29 | Actimis Pharmaceuticals Inc | Postupak za pripremu [4,6-bis-dimetilamino-2-[4-(4-trifluorometilbenzoil-amino)benzil]pirimidin-5-il]sirćetne kiseline |
| WO2013088109A1 (en) | 2011-12-16 | 2013-06-20 | Oxagen Limited | Combination of crth2 antagonist and a proton pump inhibitor for the treatment of eosinophilic esophagitis |
| ES2624379T3 (es) | 2011-12-21 | 2017-07-14 | Idorsia Pharmaceuticals Ltd | Derivados de heterociclilo y su uso como moduladores del receptor de prostaglandina D2 |
| US9169270B2 (en) | 2012-07-05 | 2015-10-27 | Actelion Pharmaceuticals Ltd. | 1-phenyl-substituted heterocyclyl derivatives and their use as prostaglandin D2 receptor modulators |
| US20140148470A1 (en) * | 2012-11-23 | 2014-05-29 | Boehringer Ingelheim International Gmbh | Pyrimidine compounds for treating hairloss |
| TWI695831B (zh) | 2014-09-13 | 2020-06-11 | 香港商南北兄弟藥業投資有限公司 | Ｃｒｔｈ２拮抗劑化合物及其用途 |
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| GB9125842D0 (en) * | 1991-12-04 | 1992-02-05 | Ici Plc | Heterocyclic derivatives |
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| CA2263198A1 (en) * | 1996-09-06 | 1998-03-12 | Nippon Kayaku Kabushiki Kaisha | Novel acetamide derivatives and protease inhibitors |
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| EP1413306A1 (en) * | 2002-10-21 | 2004-04-28 | Warner-Lambert Company LLC | Tetrahydroquinoline derivatives as CRTH2 antagonists |
| ES2401079T3 (es) | 2002-12-20 | 2013-04-16 | Amgen Inc. | Moduladores del asma y de la inflamación alérgica |
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| 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 |
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2004
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