ES2375614T3 - Derivados de espiro tric�?clicos como moduladores de crth2 - Google Patents

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Publication number

ES2375614T3

ES2375614T3 ES06763238T ES06763238T ES2375614T3 ES 2375614 T3 ES2375614 T3 ES 2375614T3 ES 06763238 T ES06763238 T ES 06763238T ES 06763238 T ES06763238 T ES 06763238T ES 2375614 T3 ES2375614 T3 ES 2375614T3

Authority

ES

Spain

Prior art keywords

chloro

indole

pyrrolidin

acetic acid

trioxospiro

Prior art date

2005-05-24

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.)

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• 102000009389 Prostaglandin D receptors Human genes 0.000 title claims description 45
• 108050000258 Prostaglandin D receptors Proteins 0.000 title claims description 45
• 101001005711 Homo sapiens MARVEL domain-containing protein 2 Proteins 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 261
• -1 hydroxy, amino, aminocarbonyl Chemical group 0.000 claims abstract description 224
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 87
• 125000003118 aryl group Chemical group 0.000 claims abstract description 64
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 58
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 27
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 26
• 150000002367 halogens Chemical class 0.000 claims abstract description 26
• 239000001257 hydrogen Substances 0.000 claims abstract description 25
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 25
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 20
• 150000003839 salts Chemical class 0.000 claims abstract description 20
• 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 18
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 17
• 125000003545 alkoxy group Chemical group 0.000 claims abstract description 11
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract description 10
• 125000002837 carbocyclic group Chemical group 0.000 claims abstract description 10
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 10
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 9
• 125000004442 acylamino group Chemical group 0.000 claims abstract description 8
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 8
• QECVIPBZOPUTRD-UHFFFAOYSA-N N=S(=O)=O Chemical compound N=S(=O)=O QECVIPBZOPUTRD-UHFFFAOYSA-N 0.000 claims abstract description 7
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 6
• 229910052717 sulfur Inorganic materials 0.000 claims abstract description 6
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims abstract description 5
• 125000005842 heteroatom Chemical group 0.000 claims abstract description 5
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 5
• 125000006528 (C2-C6) alkyl group Chemical group 0.000 claims abstract description 3
• 239000002253 acid Substances 0.000 claims description 162
• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 139
• 238000000034 method Methods 0.000 claims description 108
• CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 claims description 104
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 74
• 125000003003 spiro group Chemical group 0.000 claims description 65
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 25
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 20
• 230000002757 inflammatory effect Effects 0.000 claims description 19
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 18
• 208000026935 allergic disease Diseases 0.000 claims description 17
• 201000010099 disease Diseases 0.000 claims description 17
• 230000029936 alkylation Effects 0.000 claims description 15
• 238000005804 alkylation reaction Methods 0.000 claims description 15
• 239000003814 drug Substances 0.000 claims description 15
• 208000017520 skin disease Diseases 0.000 claims description 14
• 230000000694 effects Effects 0.000 claims description 13
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 12
• 239000008194 pharmaceutical composition Substances 0.000 claims description 12
• 208000006673 asthma Diseases 0.000 claims description 11
• 208000024376 chronic urticaria Diseases 0.000 claims description 11
• 208000010247 contact dermatitis Diseases 0.000 claims description 11
• 230000008569 process Effects 0.000 claims description 11
• 206010012442 Dermatitis contact Diseases 0.000 claims description 10
• 206010048768 Dermatosis Diseases 0.000 claims description 10
• 208000017983 photosensitivity disease Diseases 0.000 claims description 10
• 101100439663 Arabidopsis thaliana CHR7 gene Proteins 0.000 claims description 9
• 208000002551 irritable bowel syndrome Diseases 0.000 claims description 9
• 238000002360 preparation method Methods 0.000 claims description 9
• 125000003852 3-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Cl)=C1[H])C([H])([H])* 0.000 claims description 8
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 8
• 208000010201 Exanthema Diseases 0.000 claims description 7
• 150000001412 amines Chemical class 0.000 claims description 7
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
• 201000005884 exanthem Diseases 0.000 claims description 7
• 208000004296 neuralgia Diseases 0.000 claims description 7
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 7
• 208000021722 neuropathic pain Diseases 0.000 claims description 7
• 230000002265 prevention Effects 0.000 claims description 7
• 206010037844 rash Diseases 0.000 claims description 7
• 206010010744 Conjunctivitis allergic Diseases 0.000 claims description 6
• 201000002481 Myositis Diseases 0.000 claims description 6
• 206010051246 Photodermatosis Diseases 0.000 claims description 6
• 206010039085 Rhinitis allergic Diseases 0.000 claims description 6
• 206010052568 Urticaria chronic Diseases 0.000 claims description 6
• 201000009961 allergic asthma Diseases 0.000 claims description 6
• 208000002205 allergic conjunctivitis Diseases 0.000 claims description 6
• 208000002029 allergic contact dermatitis Diseases 0.000 claims description 6
• 201000010105 allergic rhinitis Diseases 0.000 claims description 6
• 208000024998 atopic conjunctivitis Diseases 0.000 claims description 6
• 229940079593 drug Drugs 0.000 claims description 6
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 6
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 6
• 201000006417 multiple sclerosis Diseases 0.000 claims description 6
• 201000008482 osteoarthritis Diseases 0.000 claims description 6
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 6
• DTHXODZAZAIWJB-UHFFFAOYSA-N 2-(1-benzyl-5'-chloro-2,2',5-trioxospiro[imidazolidine-4,3'-indole]-1'-yl)acetic acid Chemical compound C12=CC(Cl)=CC=C2N(CC(=O)O)C(=O)C1(C1=O)NC(=O)N1CC1=CC=CC=C1 DTHXODZAZAIWJB-UHFFFAOYSA-N 0.000 claims description 5
• 230000007062 hydrolysis Effects 0.000 claims description 5
• 238000006460 hydrolysis reaction Methods 0.000 claims description 5
• SKLDVYDFQCXARY-UHFFFAOYSA-N 2-[5-chloro-1'-[(2-fluorophenyl)methyl]-2,2',5'-trioxospiro[indole-3,3'-pyrrolidine]-1-yl]acetic acid Chemical compound C12=CC(Cl)=CC=C2N(CC(=O)O)C(=O)C1(C1=O)CC(=O)N1CC1=CC=CC=C1F SKLDVYDFQCXARY-UHFFFAOYSA-N 0.000 claims description 4
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 4
• 125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 claims description 4
• 230000001363 autoimmune Effects 0.000 claims description 4
• SIFGTWUNWFVQMI-UHFFFAOYSA-N 2-[1'-benzyl-2,2',5'-trioxo-5-(trifluoromethoxy)spiro[indole-3,3'-pyrrolidine]-1-yl]acetic acid Chemical compound C12=CC(OC(F)(F)F)=CC=C2N(CC(=O)O)C(=O)C1(C1=O)CC(=O)N1CC1=CC=CC=C1 SIFGTWUNWFVQMI-UHFFFAOYSA-N 0.000 claims description 3
• KCCHKYLQIKGUPB-UHFFFAOYSA-N 2-[5-chloro-2,2',5'-trioxo-1'-(1-phenylethyl)spiro[indole-3,3'-pyrrolidine]-1-yl]acetic acid Chemical compound O=C1CC2(C3=CC(Cl)=CC=C3N(CC(O)=O)C2=O)C(=O)N1C(C)C1=CC=CC=C1 KCCHKYLQIKGUPB-UHFFFAOYSA-N 0.000 claims description 3
• MUISNBWDZPNXDE-UHFFFAOYSA-N 2-[5-chloro-2,2',5'-trioxo-1'-(pyridin-3-ylmethyl)spiro[indole-3,3'-pyrrolidine]-1-yl]acetic acid Chemical compound C12=CC(Cl)=CC=C2N(CC(=O)O)C(=O)C1(C1=O)CC(=O)N1CC1=CC=CN=C1 MUISNBWDZPNXDE-UHFFFAOYSA-N 0.000 claims description 3
• MAIOCNMQTWAEBE-UHFFFAOYSA-N 2-[5-chloro-2,2',5'-trioxo-1'-(thiophen-2-ylmethyl)spiro[indole-3,3'-pyrrolidine]-1-yl]acetic acid Chemical compound C12=CC(Cl)=CC=C2N(CC(=O)O)C(=O)C1(C1=O)CC(=O)N1CC1=CC=CS1 MAIOCNMQTWAEBE-UHFFFAOYSA-N 0.000 claims description 3
• KWYXKZZDLCISSC-UHFFFAOYSA-N 2-[5-chloro-2,2',5'-trioxo-1'-[(4-phenoxyphenyl)methyl]spiro[indole-3,3'-pyrrolidine]-1-yl]acetic acid Chemical compound C12=CC(Cl)=CC=C2N(CC(=O)O)C(=O)C1(C1=O)CC(=O)N1CC(C=C1)=CC=C1OC1=CC=CC=C1 KWYXKZZDLCISSC-UHFFFAOYSA-N 0.000 claims description 3
• BMLVYMFLBDCCQI-UHFFFAOYSA-N 4-(1'-benzyl-6-chloro-2,2',5'-trioxospiro[indole-3,3'-pyrrolidine]-1-yl)butanoic acid Chemical compound C12=CC=C(Cl)C=C2N(CCCC(=O)O)C(=O)C1(C1=O)CC(=O)N1CC1=CC=CC=C1 BMLVYMFLBDCCQI-UHFFFAOYSA-N 0.000 claims description 3
• HIJZDZLPNFKWAV-UHFFFAOYSA-N 4-[5-chloro-1'-[(2-fluorophenyl)methyl]-2,2',5'-trioxospiro[indole-3,3'-pyrrolidine]-1-yl]butanoic acid Chemical compound C12=CC(Cl)=CC=C2N(CCCC(=O)O)C(=O)C1(C1=O)CC(=O)N1CC1=CC=CC=C1F HIJZDZLPNFKWAV-UHFFFAOYSA-N 0.000 claims description 3
• NRPFMALMXVEMQL-UHFFFAOYSA-N 4-[5-chloro-1'-[(4-fluorophenyl)methyl]-2,2',5'-trioxospiro[indole-3,3'-pyrrolidine]-1-yl]butanoic acid Chemical compound C12=CC(Cl)=CC=C2N(CCCC(=O)O)C(=O)C1(C1=O)CC(=O)N1CC1=CC=C(F)C=C1 NRPFMALMXVEMQL-UHFFFAOYSA-N 0.000 claims description 3
• NOLYCSGPQXLBPU-UHFFFAOYSA-N 4-[5-chloro-1'-[(4-methoxyphenyl)methyl]-2,2',5'-trioxospiro[indole-3,3'-pyrrolidine]-1-yl]butanoic acid Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C2(C3=CC(Cl)=CC=C3N(CCCC(O)=O)C2=O)CC1=O NOLYCSGPQXLBPU-UHFFFAOYSA-N 0.000 claims description 3
• XGABWFHBDDEURD-UHFFFAOYSA-N 4-[5-chloro-2,2',5'-trioxo-1'-[[4-(trifluoromethyl)phenyl]methyl]spiro[indole-3,3'-pyrrolidine]-1-yl]butanoic acid Chemical compound C12=CC(Cl)=CC=C2N(CCCC(=O)O)C(=O)C1(C1=O)CC(=O)N1CC1=CC=C(C(F)(F)F)C=C1 XGABWFHBDDEURD-UHFFFAOYSA-N 0.000 claims description 3
• 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 3
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 3
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 3
• 239000003085 diluting agent Substances 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 235000019256 formaldehyde Nutrition 0.000 claims description 3
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
• 229940124530 sulfonamide Drugs 0.000 claims description 3
• 150000003456 sulfonamides Chemical class 0.000 claims description 3
• 125000006507 2,4-difluorobenzyl group Chemical group [H]C1=C(F)C([H])=C(F)C(=C1[H])C([H])([H])* 0.000 claims description 2
• BDWQUHFLKUXBHZ-UHFFFAOYSA-N 2-(1'-benzyl-5-chloro-2,2'-dioxospiro[indole-3,4'-pyrrolidine]-1-yl)acetic acid Chemical compound C12=CC(Cl)=CC=C2N(CC(=O)O)C(=O)C1(CC1=O)CN1CC1=CC=CC=C1 BDWQUHFLKUXBHZ-UHFFFAOYSA-N 0.000 claims description 2
• SKLDVYDFQCXARY-HXUWFJFHSA-N 2-[(3r)-5-chloro-1'-[(2-fluorophenyl)methyl]-2,2',5'-trioxospiro[indole-3,3'-pyrrolidine]-1-yl]acetic acid Chemical compound C([C@@]1(C(=O)N(C2=CC=C(Cl)C=C21)CC(=O)O)C1=O)C(=O)N1CC1=CC=CC=C1F SKLDVYDFQCXARY-HXUWFJFHSA-N 0.000 claims description 2
• IJRKCYVJCJRDTH-OAQYLSRUSA-N 2-[(3r)-5-chloro-1'-[(3-methoxyphenyl)methyl]-2,2',5'-trioxospiro[indole-3,3'-pyrrolidine]-1-yl]acetic acid Chemical compound COC1=CC=CC(CN2C([C@@]3(C4=CC(Cl)=CC=C4N(CC(O)=O)C3=O)CC2=O)=O)=C1 IJRKCYVJCJRDTH-OAQYLSRUSA-N 0.000 claims description 2
• IXKFWNVFUXXEFY-HXUWFJFHSA-N 2-[(3r)-5-chloro-1'-[(5-chloro-2-fluorophenyl)methyl]-2,2',5'-trioxospiro[indole-3,3'-pyrrolidine]-1-yl]acetic acid Chemical compound C([C@@]1(C(=O)N(C2=CC=C(Cl)C=C21)CC(=O)O)C1=O)C(=O)N1CC1=CC(Cl)=CC=C1F IXKFWNVFUXXEFY-HXUWFJFHSA-N 0.000 claims description 2
• ZCDQMYGMUJCSPB-FQEVSTJZSA-N 2-[(3s)-1'-benzyl-5-chloro-2,2',5'-trioxospiro[indole-3,3'-pyrrolidine]-1-yl]acetic acid Chemical compound C([C@]1(C(=O)N(C2=CC=C(Cl)C=C21)CC(=O)O)C1=O)C(=O)N1CC1=CC=CC=C1 ZCDQMYGMUJCSPB-FQEVSTJZSA-N 0.000 claims description 2
• VPIOMNUUAVOVBL-UHFFFAOYSA-N 2-[1'-(naphthalen-1-ylmethyl)-2,2',5'-trioxo-5-(trifluoromethoxy)spiro[indole-3,3'-pyrrolidine]-1-yl]acetic acid Chemical compound C12=CC(OC(F)(F)F)=CC=C2N(CC(=O)O)C(=O)C11C(=O)N(CC=2C3=CC=CC=C3C=CC=2)C(=O)C1 VPIOMNUUAVOVBL-UHFFFAOYSA-N 0.000 claims description 2
• MIZGYGQQDQJKQN-UHFFFAOYSA-N 2-[1'-[(2-fluorophenyl)methyl]-2,2',5'-trioxo-5-(trifluoromethoxy)spiro[indole-3,3'-pyrrolidine]-1-yl]acetic acid Chemical compound C12=CC(OC(F)(F)F)=CC=C2N(CC(=O)O)C(=O)C1(C1=O)CC(=O)N1CC1=CC=CC=C1F MIZGYGQQDQJKQN-UHFFFAOYSA-N 0.000 claims description 2
• FNYXTMPTHWWJIN-UHFFFAOYSA-N 2-[1'-[(3-fluorophenyl)methyl]-2,2',5'-trioxo-5-(trifluoromethoxy)spiro[indole-3,3'-pyrrolidine]-1-yl]acetic acid Chemical compound C12=CC(OC(F)(F)F)=CC=C2N(CC(=O)O)C(=O)C1(C1=O)CC(=O)N1CC1=CC=CC(F)=C1 FNYXTMPTHWWJIN-UHFFFAOYSA-N 0.000 claims description 2
• FRNKZMPGRLAFSU-UHFFFAOYSA-N 2-[1'-[(4-carbamoylphenyl)methyl]-5-chloro-2,2',5'-trioxospiro[indole-3,3'-pyrrolidine]-1-yl]acetic acid Chemical compound C1=CC(C(=O)N)=CC=C1CN1C(=O)C2(C3=CC(Cl)=CC=C3N(CC(O)=O)C2=O)CC1=O FRNKZMPGRLAFSU-UHFFFAOYSA-N 0.000 claims description 2
• BJZGPBBZPOZEAY-UHFFFAOYSA-N 2-[1'-[(4-chlorophenyl)methyl]-2,2',5'-trioxo-5-(trifluoromethoxy)spiro[indole-3,3'-pyrrolidine]-1-yl]acetic acid Chemical compound C12=CC(OC(F)(F)F)=CC=C2N(CC(=O)O)C(=O)C1(C1=O)CC(=O)N1CC1=CC=C(Cl)C=C1 BJZGPBBZPOZEAY-UHFFFAOYSA-N 0.000 claims description 2
• OMZNSFXGTFCYFB-UHFFFAOYSA-N 2-[1'-[(4-fluorophenyl)methyl]-2,2',5'-trioxo-5-(trifluoromethoxy)spiro[indole-3,3'-pyrrolidine]-1-yl]acetic acid Chemical compound C12=CC(OC(F)(F)F)=CC=C2N(CC(=O)O)C(=O)C1(C1=O)CC(=O)N1CC1=CC=C(F)C=C1 OMZNSFXGTFCYFB-UHFFFAOYSA-N 0.000 claims description 2
• MERNDDFNKCVMGC-UHFFFAOYSA-N 2-[1'-[(4-methoxyphenyl)methyl]-2,2',5'-trioxo-5-(trifluoromethoxy)spiro[indole-3,3'-pyrrolidine]-1-yl]acetic acid Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C2(C3=CC(OC(F)(F)F)=CC=C3N(CC(O)=O)C2=O)CC1=O MERNDDFNKCVMGC-UHFFFAOYSA-N 0.000 claims description 2
• ROGMHOCRIGQYMM-UHFFFAOYSA-N 2-[2,2',5'-trioxo-5-(trifluoromethoxy)-1'-[[3-(trifluoromethyl)phenyl]methyl]spiro[indole-3,3'-pyrrolidine]-1-yl]acetic acid Chemical compound C12=CC(OC(F)(F)F)=CC=C2N(CC(=O)O)C(=O)C1(C1=O)CC(=O)N1CC1=CC=CC(C(F)(F)F)=C1 ROGMHOCRIGQYMM-UHFFFAOYSA-N 0.000 claims description 2
• RBHSFPBPZVMKMC-UHFFFAOYSA-N 2-[5'-chloro-1-[(2-fluorophenyl)methyl]-2,2',5-trioxospiro[imidazolidine-4,3'-indole]-1'-yl]acetic acid Chemical compound C12=CC(Cl)=CC=C2N(CC(=O)O)C(=O)C1(C1=O)NC(=O)N1CC1=CC=CC=C1F RBHSFPBPZVMKMC-UHFFFAOYSA-N 0.000 claims description 2
• AHJHZJYPIYKOIX-UHFFFAOYSA-N 2-[5'-chloro-1-[(5-methyl-3-phenyl-1,2-oxazol-4-yl)methyl]-2,2',5-trioxospiro[imidazolidine-4,3'-indole]-1'-yl]acetic acid Chemical compound O=C1NC2(C3=CC(Cl)=CC=C3N(CC(O)=O)C2=O)C(=O)N1CC1=C(C)ON=C1C1=CC=CC=C1 AHJHZJYPIYKOIX-UHFFFAOYSA-N 0.000 claims description 2
• VEEDEOIGYMFLIJ-UHFFFAOYSA-N 2-[5-chloro-1'-(1,3-oxazol-2-ylmethyl)-2,2',5'-trioxospiro[indole-3,3'-pyrrolidine]-1-yl]acetic acid Chemical compound C12=CC(Cl)=CC=C2N(CC(=O)O)C(=O)C1(C1=O)CC(=O)N1CC1=NC=CO1 VEEDEOIGYMFLIJ-UHFFFAOYSA-N 0.000 claims description 2
• RAJFUMSJKMAFSR-UHFFFAOYSA-N 2-[5-chloro-1'-(furan-3-ylmethyl)-2,2',5'-trioxospiro[indole-3,3'-pyrrolidine]-1-yl]acetic acid Chemical compound C12=CC(Cl)=CC=C2N(CC(=O)O)C(=O)C1(C1=O)CC(=O)N1CC=1C=COC=1 RAJFUMSJKMAFSR-UHFFFAOYSA-N 0.000 claims description 2
• JVKOATTXUZLONV-UHFFFAOYSA-N 2-[5-chloro-1'-(imidazo[1,2-a]pyridin-2-ylmethyl)-2,2',5'-trioxospiro[indole-3,3'-pyrrolidine]-1-yl]acetic acid Chemical compound C12=CC(Cl)=CC=C2N(CC(=O)O)C(=O)C11C(=O)N(CC=2N=C3C=CC=CN3C=2)C(=O)C1 JVKOATTXUZLONV-UHFFFAOYSA-N 0.000 claims description 2
• XLHVLCAWJHDPNA-UHFFFAOYSA-N 2-[5-chloro-1'-(isoquinolin-1-ylmethyl)-2,2',5'-trioxospiro[indole-3,3'-pyrrolidine]-1-yl]acetic acid Chemical compound C12=CC(Cl)=CC=C2N(CC(=O)O)C(=O)C11C(=O)N(CC=2C3=CC=CC=C3C=CN=2)C(=O)C1 XLHVLCAWJHDPNA-UHFFFAOYSA-N 0.000 claims description 2
• RJOQDNCZKQYIFC-UHFFFAOYSA-N 2-[5-chloro-1'-[(1-methylbenzimidazol-2-yl)methyl]-2,2',5'-trioxospiro[indole-3,3'-pyrrolidine]-1-yl]acetic acid Chemical compound C1=CC=C2N(C)C(CN3C(C4(CC3=O)C3=CC(Cl)=CC=C3N(CC(O)=O)C4=O)=O)=NC2=C1 RJOQDNCZKQYIFC-UHFFFAOYSA-N 0.000 claims description 2
• HIUAOLPQRYMOSK-UHFFFAOYSA-N 2-[5-chloro-1'-[(2,4-dichlorophenyl)methyl]-2,2',5'-trioxospiro[indole-3,3'-pyrrolidine]-1-yl]acetic acid Chemical compound C12=CC(Cl)=CC=C2N(CC(=O)O)C(=O)C1(C1=O)CC(=O)N1CC1=CC=C(Cl)C=C1Cl HIUAOLPQRYMOSK-UHFFFAOYSA-N 0.000 claims description 2
• VITIJZLHMBHKEV-UHFFFAOYSA-N 2-[5-chloro-1'-[(2,5-dichlorophenyl)methyl]-2,2',5'-trioxospiro[indole-3,3'-pyrrolidine]-1-yl]acetic acid Chemical compound C12=CC(Cl)=CC=C2N(CC(=O)O)C(=O)C1(C1=O)CC(=O)N1CC1=CC(Cl)=CC=C1Cl VITIJZLHMBHKEV-UHFFFAOYSA-N 0.000 claims description 2
• OSWKOYHLOHUIKD-UHFFFAOYSA-N 2-[5-chloro-1'-[(2-chloro-4-fluorophenyl)methyl]-2,2',5'-trioxospiro[indole-3,3'-pyrrolidine]-1-yl]acetic acid Chemical compound C12=CC(Cl)=CC=C2N(CC(=O)O)C(=O)C1(C1=O)CC(=O)N1CC1=CC=C(F)C=C1Cl OSWKOYHLOHUIKD-UHFFFAOYSA-N 0.000 claims description 2
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