OA12550A - Quinazolines as MMP-13 inhibitors. - Google Patents
Quinazolines as MMP-13 inhibitors. Download PDFInfo
- Publication number
- OA12550A OA12550A OA1200300200A OA1200300200A OA12550A OA 12550 A OA12550 A OA 12550A OA 1200300200 A OA1200300200 A OA 1200300200A OA 1200300200 A OA1200300200 A OA 1200300200A OA 12550 A OA12550 A OA 12550A
- Authority
- OA
- OAPI
- Prior art keywords
- methyl
- dioxo
- methoxy
- ylmethyl
- compound
- Prior art date
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- 239000003112 inhibitor Substances 0.000 title abstract description 19
- 150000003246 quinazolines Chemical class 0.000 title description 4
- 102100027995 Collagenase 3 Human genes 0.000 title 1
- 108050005238 Collagenase 3 Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 758
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 187
- 125000003118 aryl group Chemical group 0.000 claims abstract description 92
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 89
- 239000001257 hydrogen Substances 0.000 claims abstract description 88
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 67
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 60
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 57
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 37
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 36
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 33
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 33
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 26
- 239000001301 oxygen Substances 0.000 claims abstract description 26
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 26
- 239000005864 Sulphur Substances 0.000 claims abstract description 24
- 150000003839 salts Chemical class 0.000 claims abstract description 21
- 239000011159 matrix material Substances 0.000 claims abstract description 20
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 11
- 102000005741 Metalloproteases Human genes 0.000 claims abstract description 9
- 108010006035 Metalloproteases Proteins 0.000 claims abstract description 9
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 8
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 5
- 238000000034 method Methods 0.000 claims description 269
- 239000002253 acid Substances 0.000 claims description 135
- IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 claims description 120
- -1 cycloaliyl Chemical group 0.000 claims description 96
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- 125000004430 oxygen atom Chemical group O* 0.000 claims description 72
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 66
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 54
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 54
- 230000008569 process Effects 0.000 claims description 53
- 229910052736 halogen Inorganic materials 0.000 claims description 51
- 150000002367 halogens Chemical class 0.000 claims description 50
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- 125000004429 atom Chemical group 0.000 claims description 45
- 125000005605 benzo group Chemical group 0.000 claims description 44
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- 238000010992 reflux Methods 0.000 claims description 40
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 37
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- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 26
- TXQWFIVRZNOPCK-UHFFFAOYSA-N pyridin-4-ylmethanamine Chemical compound NCC1=CC=NC=C1 TXQWFIVRZNOPCK-UHFFFAOYSA-N 0.000 claims description 26
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 25
- 238000004519 manufacturing process Methods 0.000 claims description 24
- 229910052727 yttrium Inorganic materials 0.000 claims description 24
- 125000004076 pyridyl group Chemical group 0.000 claims description 21
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- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 20
- ZILSBZLQGRBMOR-UHFFFAOYSA-N 1,3-benzodioxol-5-ylmethanamine Chemical compound NCC1=CC=C2OCOC2=C1 ZILSBZLQGRBMOR-UHFFFAOYSA-N 0.000 claims description 19
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 19
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 18
- 125000001544 thienyl group Chemical group 0.000 claims description 17
- 125000005871 1,3-benzodioxolyl group Chemical group 0.000 claims description 16
- FPQVGDGSRVMNMR-JCTPKUEWSA-N [[(z)-(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy-(dimethylamino)methylidene]-dimethylazanium;tetrafluoroborate Chemical compound F[B-](F)(F)F.CCOC(=O)C(\C#N)=N/OC(N(C)C)=[N+](C)C FPQVGDGSRVMNMR-JCTPKUEWSA-N 0.000 claims description 16
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- 125000002883 imidazolyl group Chemical group 0.000 claims description 14
- UQAHBOKPZNLKRF-UHFFFAOYSA-N (2-methoxypyridin-4-yl)methanamine Chemical compound COC1=CC(CN)=CC=N1 UQAHBOKPZNLKRF-UHFFFAOYSA-N 0.000 claims description 13
- 239000012190 activator Substances 0.000 claims description 13
- 125000003282 alkyl amino group Chemical group 0.000 claims description 13
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 claims description 13
- 150000002431 hydrogen Chemical class 0.000 claims description 13
- GRRIMVWABNHKBX-UHFFFAOYSA-N (3-methoxyphenyl)methanamine Chemical compound COC1=CC=CC(CN)=C1 GRRIMVWABNHKBX-UHFFFAOYSA-N 0.000 claims description 12
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 12
- 125000000928 benzodioxinyl group Chemical group O1C(=COC2=C1C=CC=C2)* 0.000 claims description 12
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- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 12
- 150000002148 esters Chemical class 0.000 claims description 12
- 125000002541 furyl group Chemical group 0.000 claims description 12
- 125000001041 indolyl group Chemical group 0.000 claims description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 11
- HDOUGSFASVGDCS-UHFFFAOYSA-N pyridin-3-ylmethanamine Chemical compound NCC1=CC=CN=C1 HDOUGSFASVGDCS-UHFFFAOYSA-N 0.000 claims description 11
- 201000010099 disease Diseases 0.000 claims description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
- 201000008482 osteoarthritis Diseases 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 9
- 125000005843 halogen group Chemical group 0.000 claims description 9
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 9
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- 206010064930 age-related macular degeneration Diseases 0.000 claims description 8
- 206010003246 arthritis Diseases 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 208000002780 macular degeneration Diseases 0.000 claims description 8
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
- JPYQFYIEOUVJDU-UHFFFAOYSA-N beclamide Chemical compound ClCCC(=O)NCC1=CC=CC=C1 JPYQFYIEOUVJDU-UHFFFAOYSA-N 0.000 claims description 7
- 125000004601 benzofurazanyl group Chemical group N1=C2C(=NO1)C(=CC=C2)* 0.000 claims description 7
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 claims description 6
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 6
- 125000001624 naphthyl group Chemical group 0.000 claims description 6
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 6
- 201000001320 Atherosclerosis Diseases 0.000 claims description 5
- 201000004681 Psoriasis Diseases 0.000 claims description 5
- 208000006673 asthma Diseases 0.000 claims description 5
- 230000005764 inhibitory process Effects 0.000 claims description 5
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- 208000028169 periodontal disease Diseases 0.000 claims description 5
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- WWABBFPTGJZEDN-UHFFFAOYSA-N quinazoline-6-carboxylic acid Chemical compound N1=CN=CC2=CC(C(=O)O)=CC=C21 WWABBFPTGJZEDN-UHFFFAOYSA-N 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 4
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 claims description 4
- 208000001132 Osteoporosis Diseases 0.000 claims description 4
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- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
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- 229910052721 tungsten Inorganic materials 0.000 claims description 4
- DIIIISSCIXVANO-UHFFFAOYSA-N 1,2-Dimethylhydrazine Chemical compound CNNC DIIIISSCIXVANO-UHFFFAOYSA-N 0.000 claims description 3
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- 206010019280 Heart failures Diseases 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
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- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 2
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- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
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Classifications
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- 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
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/525—Isoalloxazines, e.g. riboflavins, vitamin B2
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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CN111116494B (zh) * | 2019-12-31 | 2022-08-16 | 江苏中旗科技股份有限公司 | 一类含喹唑啉二酮结构的酰胺类化合物、其制备方法与应用 |
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-
2002
- 2002-02-08 PA PA20028539401A patent/PA8539401A1/es unknown
- 2002-02-11 CZ CZ20032142A patent/CZ20032142A3/cs unknown
- 2002-02-11 MX MXPA03007248A patent/MXPA03007248A/es unknown
- 2002-02-11 KR KR10-2003-7010659A patent/KR20030074827A/ko not_active Application Discontinuation
- 2002-02-11 PL PL02367396A patent/PL367396A1/xx not_active Application Discontinuation
- 2002-02-11 EA EA200300792A patent/EA200300792A1/ru unknown
- 2002-02-11 AP APAP/P/2003/002841A patent/AP2003002841A0/en unknown
- 2002-02-11 HU HU0303164A patent/HUP0303164A2/hu unknown
- 2002-02-11 WO PCT/EP2002/001979 patent/WO2002064572A1/en not_active Application Discontinuation
- 2002-02-11 IL IL15710902A patent/IL157109A0/xx unknown
- 2002-02-11 SK SK1001-2003A patent/SK10012003A3/sk unknown
- 2002-02-11 OA OA1200300200A patent/OA12550A/en unknown
- 2002-02-11 CN CNA028050142A patent/CN1537105A/zh active Pending
- 2002-02-11 CA CA002437122A patent/CA2437122A1/en not_active Abandoned
- 2002-02-11 JP JP2002564505A patent/JP2004523546A/ja not_active Abandoned
- 2002-02-11 EP EP02722137A patent/EP1368324A1/en not_active Withdrawn
- 2002-02-11 EE EEP200300384A patent/EE200300384A/xx unknown
- 2002-02-11 BR BR0207268-8A patent/BR0207268A/pt not_active IP Right Cessation
- 2002-02-13 UY UY27173A patent/UY27173A1/es not_active Application Discontinuation
- 2002-02-13 PE PE2002000118A patent/PE20021005A1/es not_active Application Discontinuation
- 2002-02-13 AR ARP020100470A patent/AR032676A1/es not_active Application Discontinuation
- 2002-02-13 SV SV2002000876A patent/SV2003000876A/es not_active Application Discontinuation
- 2002-02-13 US US10/075,954 patent/US20020193377A1/en not_active Abandoned
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2003
- 2003-07-08 TN TNPCT/EP2002/001979A patent/TNSN03045A1/en unknown
- 2003-07-24 IS IS6886A patent/IS6886A/is unknown
- 2003-08-04 ZA ZA2003/06008A patent/ZA200306008B/en unknown
- 2003-08-12 MA MA27274A patent/MA26994A1/fr unknown
- 2003-08-13 EC EC2003004730A patent/ECSP034730A/es unknown
- 2003-08-13 NO NO20033593A patent/NO20033593D0/no not_active Application Discontinuation
- 2003-08-13 BG BG108091A patent/BG108091A/xx unknown
Also Published As
Publication number | Publication date |
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PE20021005A1 (es) | 2002-11-27 |
US20020193377A1 (en) | 2002-12-19 |
PL367396A1 (en) | 2005-02-21 |
WO2002064572A1 (en) | 2002-08-22 |
SK10012003A3 (sk) | 2004-09-08 |
NO20033593L (no) | 2003-08-13 |
MXPA03007248A (es) | 2005-02-14 |
MA26994A1 (fr) | 2004-12-20 |
BG108091A (en) | 2004-12-30 |
CA2437122A1 (en) | 2002-08-22 |
PA8539401A1 (es) | 2002-10-28 |
NO20033593D0 (no) | 2003-08-13 |
EA200300792A1 (ru) | 2004-02-26 |
ECSP034730A (es) | 2003-12-01 |
HUP0303164A2 (hu) | 2004-01-28 |
EE200300384A (et) | 2003-12-15 |
KR20030074827A (ko) | 2003-09-19 |
SV2003000876A (es) | 2003-08-19 |
IL157109A0 (en) | 2004-02-08 |
EP1368324A1 (en) | 2003-12-10 |
CN1537105A (zh) | 2004-10-13 |
TNSN03045A1 (en) | 2005-12-23 |
AR032676A1 (es) | 2003-11-19 |
UY27173A1 (es) | 2002-09-30 |
CZ20032142A3 (cs) | 2004-12-15 |
BR0207268A (pt) | 2005-03-15 |
JP2004523546A (ja) | 2004-08-05 |
IS6886A (is) | 2003-07-24 |
ZA200306008B (en) | 2005-01-26 |
AP2003002841A0 (en) | 2003-09-30 |
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