ES2225086T3 - Nuevos derivados de guanidina como inhibidores de adhesion celular. - Google Patents
Nuevos derivados de guanidina como inhibidores de adhesion celular.Info
- Publication number
- ES2225086T3 ES2225086T3 ES00905022T ES00905022T ES2225086T3 ES 2225086 T3 ES2225086 T3 ES 2225086T3 ES 00905022 T ES00905022 T ES 00905022T ES 00905022 T ES00905022 T ES 00905022T ES 2225086 T3 ES2225086 T3 ES 2225086T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- residue
- aryl
- formula
- cycloalkyl
- 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 - Lifetime
Links
- 239000003112 inhibitor Substances 0.000 title claims abstract description 17
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical class NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 title claims description 14
- 230000021164 cell adhesion Effects 0.000 title abstract description 5
- 229940083094 guanine derivative acting on arteriolar smooth muscle Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 121
- 150000003839 salts Chemical class 0.000 claims abstract description 55
- 238000000034 method Methods 0.000 claims abstract description 33
- 238000011321 prophylaxis Methods 0.000 claims abstract description 22
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 19
- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 14
- 238000002360 preparation method Methods 0.000 claims abstract description 14
- 239000000825 pharmaceutical preparation Substances 0.000 claims abstract description 13
- 239000002464 receptor antagonist Substances 0.000 claims abstract description 5
- 229940044551 receptor antagonist Drugs 0.000 claims abstract description 5
- -1 hydroxy, amino Chemical group 0.000 claims description 121
- 125000003118 aryl group Chemical group 0.000 claims description 80
- 239000002253 acid Substances 0.000 claims description 77
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 45
- 125000001072 heteroaryl group Chemical group 0.000 claims description 44
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 42
- 239000000203 mixture Substances 0.000 claims description 34
- 125000000217 alkyl group Chemical group 0.000 claims description 29
- 229910052736 halogen Inorganic materials 0.000 claims description 23
- 150000002367 halogens Chemical class 0.000 claims description 23
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 23
- 229910052760 oxygen Inorganic materials 0.000 claims description 22
- 229910052717 sulfur Inorganic materials 0.000 claims description 21
- 125000005842 heteroatom Chemical group 0.000 claims description 19
- 125000002619 bicyclic group Chemical group 0.000 claims description 16
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 15
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 125000002950 monocyclic group Chemical group 0.000 claims description 15
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 14
- 108010031318 Vitronectin Proteins 0.000 claims description 13
- 102100035140 Vitronectin Human genes 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 11
- 206010028980 Neoplasm Diseases 0.000 claims description 11
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 9
- 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims description 9
- 125000003277 amino group Chemical group 0.000 claims description 9
- 150000001450 anions Chemical class 0.000 claims description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 125000000524 functional group Chemical group 0.000 claims description 7
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 6
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 5
- 229910052740 iodine Inorganic materials 0.000 claims description 5
- 125000004043 oxo group Chemical group O=* 0.000 claims description 5
- 206010027476 Metastases Diseases 0.000 claims description 4
- 239000002243 precursor Substances 0.000 claims description 4
- 230000004614 tumor growth Effects 0.000 claims description 4
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 3
- 206010038923 Retinopathy Diseases 0.000 claims description 3
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 3
- 208000037803 restenosis Diseases 0.000 claims description 3
- 125000003837 (C1-C20) alkyl group Chemical group 0.000 claims description 2
- 125000000539 amino acid group Chemical group 0.000 claims description 2
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 2
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims description 2
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 2
- 208000017169 kidney disease Diseases 0.000 claims description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 2
- 125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 claims 1
- 229940078581 Bone resorption inhibitor Drugs 0.000 claims 1
- 230000009401 metastasis Effects 0.000 claims 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
- 210000002997 osteoclast Anatomy 0.000 abstract description 20
- 208000006386 Bone Resorption Diseases 0.000 abstract description 17
- 102100022337 Integrin alpha-V Human genes 0.000 abstract description 17
- 108010048673 Vitronectin Receptors Proteins 0.000 abstract description 17
- 230000024279 bone resorption Effects 0.000 abstract description 17
- 239000004480 active ingredient Substances 0.000 abstract description 12
- 201000010099 disease Diseases 0.000 abstract description 12
- 239000003814 drug Substances 0.000 abstract description 7
- 230000008569 process Effects 0.000 abstract description 6
- 239000000651 prodrug Substances 0.000 abstract description 2
- 229940002612 prodrug Drugs 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 69
- 239000002904 solvent Substances 0.000 description 32
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- 150000002148 esters Chemical class 0.000 description 26
- 238000006243 chemical reaction Methods 0.000 description 23
- 238000004519 manufacturing process Methods 0.000 description 22
- 239000000243 solution Substances 0.000 description 22
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 20
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 18
- 238000004587 chromatography analysis Methods 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 14
- 238000012360 testing method Methods 0.000 description 14
- 239000002699 waste material Substances 0.000 description 14
- 238000011282 treatment Methods 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 210000000988 bone and bone Anatomy 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- 235000001014 amino acid Nutrition 0.000 description 10
- 150000001413 amino acids Chemical class 0.000 description 10
- 239000005557 antagonist Substances 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- 239000012074 organic phase Substances 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- 235000011152 sodium sulphate Nutrition 0.000 description 10
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 9
- 125000004432 carbon atom Chemical group C* 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- 102000005962 receptors Human genes 0.000 description 9
- 108020003175 receptors Proteins 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 7
- 150000007513 acids Chemical class 0.000 description 7
- 150000002357 guanidines Chemical class 0.000 description 7
- 150000004702 methyl esters Chemical class 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- PEHDFSFYZKSKGH-UHFFFAOYSA-N 1,4,5,6-tetrahydropyrimidin-2-amine Chemical compound NC1=NCCCN1 PEHDFSFYZKSKGH-UHFFFAOYSA-N 0.000 description 6
- 239000007821 HATU Substances 0.000 description 6
- 125000004429 atom Chemical group 0.000 description 6
- 201000011510 cancer Diseases 0.000 description 6
- 150000001735 carboxylic acids Chemical class 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 229940011871 estrogen Drugs 0.000 description 6
- 239000000262 estrogen Substances 0.000 description 6
- 125000000623 heterocyclic group Chemical group 0.000 description 6
- 239000006187 pill Substances 0.000 description 6
- 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 description 5
- 208000020084 Bone disease Diseases 0.000 description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
- 241000282414 Homo sapiens Species 0.000 description 5
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 5
- 230000029936 alkylation Effects 0.000 description 5
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- 150000001602 bicycloalkyls Chemical group 0.000 description 5
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- 108010059557 kistrin Proteins 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- ZTYNVDHJNRIRLL-FWZKYCSMSA-N rhodostomin Chemical compound C([C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(N[C@@H]2C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(=O)N3CCC[C@H]3C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N3CCC[C@H]3C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CSSC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H](CC=2NC=NC=2)C(O)=O)[C@@H](C)O)=O)CSSC[C@H]2C(=O)N[C@H]3CSSC[C@@H](C(NCC(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H]2CCCN2C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H]2NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H]4CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)CN)CSSC2)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N2CCC[C@H]2C(=O)N[C@H](C(N4)=O)CSSC[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC3=O)C(=O)N[C@@H](CCCCN)C(=O)N1)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=CC=C1 ZTYNVDHJNRIRLL-FWZKYCSMSA-N 0.000 description 5
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- 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
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
- C07D239/06—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D239/08—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms directly attached in position 2
- C07D239/12—Nitrogen atoms not forming part of a nitro radical
- C07D239/16—Nitrogen atoms not forming part of a nitro radical acylated on said nitrogen atoms
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Ophthalmology & Optometry (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Compositions Of Macromolecular Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP99102916A EP1028114A1 (en) | 1999-02-13 | 1999-02-13 | Novel guanidine derivatives as inhibitors of cell adhesion |
| EP99102916 | 1999-02-13 | ||
| PCT/EP2000/000895 WO2000047564A1 (en) | 1999-02-13 | 2000-02-04 | Novel guanidine derivatives as inhibitors of cell adhesion |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2225086T3 true ES2225086T3 (es) | 2005-03-16 |
Family
ID=8237555
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES00905022T Expired - Lifetime ES2225086T3 (es) | 1999-02-13 | 2000-02-04 | Nuevos derivados de guanidina como inhibidores de adhesion celular. |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US6340679B1 (enExample) |
| EP (2) | EP1028114A1 (enExample) |
| JP (1) | JP4642242B2 (enExample) |
| AT (1) | ATE273285T1 (enExample) |
| AU (1) | AU768206B2 (enExample) |
| CA (1) | CA2371789C (enExample) |
| DE (1) | DE60012890T2 (enExample) |
| ES (1) | ES2225086T3 (enExample) |
| IL (1) | IL144725A0 (enExample) |
| MX (1) | MXPA01008072A (enExample) |
| WO (1) | WO2000047564A1 (enExample) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19629816A1 (de) * | 1996-07-24 | 1998-01-29 | Hoechst Ag | Neue Cycloalkyl-Derivate als Inhibitoren der Knochenresorption und Vitronectinrezeptor-Antagonisten |
| US6972296B2 (en) | 1999-05-07 | 2005-12-06 | Encysive Pharmaceuticals Inc. | Carboxylic acid derivatives that inhibit the binding of integrins to their receptors |
| JP2003506491A (ja) | 1999-08-13 | 2003-02-18 | バイオジェン インコーポレイテッド | 細胞接着インヒビター |
| CN100560131C (zh) | 2001-10-22 | 2009-11-18 | 斯克里普斯研究学院 | 抗体靶向化合物 |
| DK1682537T3 (da) * | 2003-11-05 | 2012-07-09 | Sarcode Bioscience Inc | Modulatorer af celleadhæsion |
| US7196112B2 (en) | 2004-07-16 | 2007-03-27 | Biogen Idec Ma Inc. | Cell adhesion inhibitors |
| ES2530780T3 (es) * | 2005-05-17 | 2015-03-05 | Sarcode Bioscience Inc | Composiciones y métodos para el tratamiento de trastornos oculares |
| WO2007048127A2 (en) * | 2005-10-20 | 2007-04-26 | The Scripps Research Institute | Fc labeling for immunostaining and immunotargeting |
| CA3105972A1 (en) * | 2007-10-19 | 2009-04-30 | Novartis Ag | Compositions and methods for treatment of diabetic retinopathy |
| JP2011516607A (ja) * | 2008-04-15 | 2011-05-26 | サーコード コーポレイション | 胃腸系へのｌｆａ−１アンタゴニストの送達 |
| WO2009139817A2 (en) | 2008-04-15 | 2009-11-19 | Sarcode Corporation | Crystalline pharmaceutical and methods of preparation and use thereof |
| US20090257957A1 (en) * | 2008-04-15 | 2009-10-15 | John Burnier | Aerosolized LFA-1 antagonists for use in localized treatment of immune related disorders |
| JP2011521896A (ja) * | 2008-04-15 | 2011-07-28 | サーコード コーポレイション | 免疫関連障害に対する局部治療に使用するための局所ｌｆａ−１アンタゴニスト |
| WO2010093706A2 (en) | 2009-02-10 | 2010-08-19 | The Scripps Research Institute | Chemically programmed vaccination |
| WO2011050175A1 (en) | 2009-10-21 | 2011-04-28 | Sarcode Corporation | Crystalline pharmaceutical and methods of preparation and use thereof |
| WO2014018748A1 (en) | 2012-07-25 | 2014-01-30 | Sarcode Bioscience Inc. | Lfa-1 inhibitor and polymorph thereof |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5204350A (en) | 1991-08-09 | 1993-04-20 | Merck & Co., Inc. | Method of inhibiting osteoclast-mediated bone resorption by administration of n-heterocyclicalkyl-substituted phenyl derivatives |
| US5217994A (en) | 1991-08-09 | 1993-06-08 | Merck & Co., Inc. | Method of inhibiting osteoclast-mediated bone resorption by administration of aminoalkyl-substituted phenyl derivatives |
| US5250679A (en) | 1991-10-18 | 1993-10-05 | Genentech, Inc. | Nonpeptidyl platelet aggregation inhibitors having specificity for the GPIIb III.sub. receptor |
| AU674553B2 (en) | 1992-10-14 | 1997-01-02 | Merck & Co., Inc. | Fibrinogen receptor antagonists |
| EP0673247A4 (en) | 1992-12-01 | 1996-05-01 | Merck & Co Inc | FIBRINOGEN RECEPTOR ANTAGONISTS. |
| ATE227567T1 (de) | 1994-05-27 | 2002-11-15 | Merck & Co Inc | Präparate zur hemmung der durch osteoklasten vermittelten knochenresorption |
| ZA955391B (en) | 1994-06-29 | 1996-02-09 | Smithkline Beecham Corp | Vitronectin receptor antagonists |
| AU702661B2 (en) | 1994-06-29 | 1999-02-25 | Smithkline Beecham Corporation | Vitronectin receptor antagonists |
| AU726793B2 (en) | 1995-08-14 | 2000-11-23 | Scripps Research Institute, The | Methods and compositions useful for inhibition of alpha v beta 5 mediated angiogenesis |
| DE19548709A1 (de) * | 1995-12-23 | 1997-07-03 | Merck Patent Gmbh | Tyrosinderivate |
| SK176898A3 (en) * | 1996-06-28 | 1999-05-07 | Merck Patent Gmbh | Phenylalamine derivatives as integrin inhibitors |
| DE19629816A1 (de) * | 1996-07-24 | 1998-01-29 | Hoechst Ag | Neue Cycloalkyl-Derivate als Inhibitoren der Knochenresorption und Vitronectinrezeptor-Antagonisten |
| EP0933367A1 (en) * | 1997-12-19 | 1999-08-04 | Hoechst Marion Roussel Deutschland GmbH | Novel acylguanidine derivates as inhibitors of bone resorption and as vitronectin receptor antagonists |
| SK10632000A3 (sk) | 1998-01-23 | 2001-02-12 | Aventis Pharma Deutschland Gmbh | Sulfónamidové deriváty ako inhibítory resorpcie kostí a inhibítory bunkovej adhézie |
-
1999
- 1999-02-13 EP EP99102916A patent/EP1028114A1/en not_active Withdrawn
-
2000
- 2000-02-04 MX MXPA01008072A patent/MXPA01008072A/es not_active IP Right Cessation
- 2000-02-04 CA CA002371789A patent/CA2371789C/en not_active Expired - Lifetime
- 2000-02-04 IL IL14472500A patent/IL144725A0/xx unknown
- 2000-02-04 AT AT00905022T patent/ATE273285T1/de not_active IP Right Cessation
- 2000-02-04 JP JP2000598485A patent/JP4642242B2/ja not_active Expired - Lifetime
- 2000-02-04 ES ES00905022T patent/ES2225086T3/es not_active Expired - Lifetime
- 2000-02-04 DE DE60012890T patent/DE60012890T2/de not_active Expired - Lifetime
- 2000-02-04 AU AU26699/00A patent/AU768206B2/en not_active Ceased
- 2000-02-04 EP EP00905022A patent/EP1155003B1/en not_active Expired - Lifetime
- 2000-02-04 WO PCT/EP2000/000895 patent/WO2000047564A1/en not_active Ceased
- 2000-02-11 US US09/502,577 patent/US6340679B1/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| EP1028114A1 (en) | 2000-08-16 |
| ATE273285T1 (de) | 2004-08-15 |
| WO2000047564A1 (en) | 2000-08-17 |
| EP1155003B1 (en) | 2004-08-11 |
| AU768206B2 (en) | 2003-12-04 |
| IL144725A0 (en) | 2002-06-30 |
| DE60012890T2 (de) | 2005-08-25 |
| CA2371789C (en) | 2009-04-14 |
| AU2669900A (en) | 2000-08-29 |
| EP1155003A1 (en) | 2001-11-21 |
| JP2002536438A (ja) | 2002-10-29 |
| MXPA01008072A (es) | 2002-07-30 |
| CA2371789A1 (en) | 2000-08-17 |
| JP4642242B2 (ja) | 2011-03-02 |
| US6340679B1 (en) | 2002-01-22 |
| DE60012890D1 (de) | 2004-09-16 |
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