AP1269A - Novel salfonamide derivatives as inhibitors of bone resorption and as inhibitors of cell adhesion. - Google Patents

Novel salfonamide derivatives as inhibitors of bone resorption and as inhibitors of cell adhesion. Download PDF

Info

Publication number: AP1269A
Authority: AP; ARIPO
Prior art keywords: alkyl; radical; aryl; formula; heteroaryl
Prior art date: 1998-01-23

Application number

APAP/P/2000/001863A

Other languages

English (en)

Other versions

AP2000001863A0 (en

Inventor

Anuschirvan Peyman

David Will

Jochen Knolle

Karl-Heinz Scheunemann

Denis Carniato

Jean-Francois Gourvest

Thomas R Gadek

Robert Mcdowell

Sarah C Bodary

Robert Andrew Cuthbertson

Original Assignee

Aventis Pharma Deutschland Gmbh

Genentech Inc

Priority date (The priority date 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 date listed.)

1998-01-23

Filing date

1999-01-16

Publication date

2004-04-03

1999-01-16 Application filed by Aventis Pharma Deutschland Gmbh, Genentech Inc filed Critical Aventis Pharma Deutschland Gmbh

2000-09-30 Publication of AP2000001863A0 publication Critical patent/AP2000001863A0/xx

2004-04-03 Application granted granted Critical

2004-04-03 Publication of AP1269A publication Critical patent/AP1269A/en

Links

208000006386 Bone Resorption Diseases 0.000 title claims abstract description 22
230000024279 bone resorption Effects 0.000 title claims abstract description 22
239000003112 inhibitor Substances 0.000 title claims abstract description 18
230000021164 cell adhesion Effects 0.000 title abstract description 4
150000001875 compounds Chemical class 0.000 claims abstract description 173
150000003839 salts Chemical class 0.000 claims abstract description 63
239000000651 prodrug Substances 0.000 claims abstract description 58
229940002612 prodrug Drugs 0.000 claims abstract description 58
238000000034 method Methods 0.000 claims abstract description 50
238000011321 prophylaxis Methods 0.000 claims abstract description 20
102100022337 Integrin alpha-V Human genes 0.000 claims abstract description 19
108010048673 Vitronectin Receptors Proteins 0.000 claims abstract description 19
230000008569 process Effects 0.000 claims abstract description 18
238000002560 therapeutic procedure Methods 0.000 claims abstract description 17
239000000825 pharmaceutical preparation Substances 0.000 claims abstract description 13
238000002360 preparation method Methods 0.000 claims abstract description 13
208000001132 Osteoporosis Diseases 0.000 claims abstract description 12
239000002464 receptor antagonist Substances 0.000 claims abstract description 6
229940044551 receptor antagonist Drugs 0.000 claims abstract description 6
-1 cyano, hydroxyl Chemical group 0.000 claims description 148
150000003254 radicals Chemical class 0.000 claims description 130
229910052739 hydrogen Inorganic materials 0.000 claims description 50
239000001257 hydrogen Substances 0.000 claims description 50
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 37
229920006395 saturated elastomer Polymers 0.000 claims description 37
239000000203 mixture Substances 0.000 claims description 35
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 30
125000002837 carbocyclic group Chemical group 0.000 claims description 28
229910052736 halogen Inorganic materials 0.000 claims description 26
150000002367 halogens Chemical class 0.000 claims description 25
125000004433 nitrogen atom Chemical group N* 0.000 claims description 22
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 21
239000002253 acid Substances 0.000 claims description 17
125000004043 oxo group Chemical group O=* 0.000 claims description 17
150000005840 aryl radicals Chemical class 0.000 claims description 16
125000000623 heterocyclic group Chemical group 0.000 claims description 15
229910052757 nitrogen Inorganic materials 0.000 claims description 14
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 13
125000006708 (C5-C14) heteroaryl group Chemical group 0.000 claims description 12
125000004432 carbon atom Chemical group C* 0.000 claims description 12
239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 12
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 11
125000005915 C6-C14 aryl group Chemical group 0.000 claims description 11
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
125000001424 substituent group Chemical group 0.000 claims description 11
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
150000001450 anions Chemical class 0.000 claims description 10
125000004093 cyano group Chemical group *C#N 0.000 claims description 10
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
206010028980 Neoplasm Diseases 0.000 claims description 9
125000000524 functional group Chemical group 0.000 claims description 9
125000000217 alkyl group Chemical group 0.000 claims description 8
150000002357 guanidines Chemical class 0.000 claims description 8
229910052717 sulfur Inorganic materials 0.000 claims description 8
CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 7
SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 7
229910052740 iodine Inorganic materials 0.000 claims description 7
229910052760 oxygen Inorganic materials 0.000 claims description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
239000002243 precursor Substances 0.000 claims description 6
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
125000004429 atom Chemical group 0.000 claims description 5
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
150000002148 esters Chemical class 0.000 claims description 5
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
239000001301 oxygen Substances 0.000 claims description 5
239000011593 sulfur Substances 0.000 claims description 5
206010027476 Metastases Diseases 0.000 claims description 4
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
235000019260 propionic acid Nutrition 0.000 claims description 4
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 4
230000004614 tumor growth Effects 0.000 claims description 4
125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 claims description 3
206010003210 Arteriosclerosis Diseases 0.000 claims description 3
208000024172 Cardiovascular disease Diseases 0.000 claims description 3
206010038923 Retinopathy Diseases 0.000 claims description 3
208000011775 arteriosclerosis disease Diseases 0.000 claims description 3
230000009401 metastasis Effects 0.000 claims description 3
208000037803 restenosis Diseases 0.000 claims description 3
125000003545 alkoxy group Chemical group 0.000 claims description 2
230000003110 anti-inflammatory effect Effects 0.000 claims description 2
125000004494 ethyl ester group Chemical group 0.000 claims description 2
239000012634 fragment Substances 0.000 claims description 2
208000017169 kidney disease Diseases 0.000 claims description 2
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
UFWIBTONFRDIAS-UHFFFAOYSA-N naphthalene-acid Natural products C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims 1
210000002997 osteoclast Anatomy 0.000 abstract description 20
239000004480 active ingredient Substances 0.000 abstract description 15
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 11
201000010099 disease Diseases 0.000 abstract description 10
229940124530 sulfonamide Drugs 0.000 abstract description 5
150000003456 sulfonamides Chemical class 0.000 abstract description 5
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 88
239000000047 product Substances 0.000 description 77
239000000243 solution Substances 0.000 description 47
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
239000002904 solvent Substances 0.000 description 43
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 40
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 29
210000004027 cell Anatomy 0.000 description 27
238000006243 chemical reaction Methods 0.000 description 27
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 25
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
238000001819 mass spectrum Methods 0.000 description 23
238000000524 positive electrospray ionisation mass spectrometry Methods 0.000 description 23
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 18
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
230000015572 biosynthetic process Effects 0.000 description 15
239000000872 buffer Substances 0.000 description 14
239000012074 organic phase Substances 0.000 description 14
238000003786 synthesis reaction Methods 0.000 description 13
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
239000000741 silica gel Substances 0.000 description 12
229910002027 silica gel Inorganic materials 0.000 description 12
210000000988 bone and bone Anatomy 0.000 description 10
239000000460 chlorine Substances 0.000 description 10
125000005842 heteroatom Chemical group 0.000 description 10
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
229910052938 sodium sulfate Inorganic materials 0.000 description 9
235000011152 sodium sulphate Nutrition 0.000 description 9
238000011282 treatment Methods 0.000 description 9
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
150000001732 carboxylic acid derivatives Chemical class 0.000 description 8
239000003814 drug Substances 0.000 description 8
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
238000012360 testing method Methods 0.000 description 8
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
239000005557 antagonist Substances 0.000 description 7
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 6
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
125000003118 aryl group Chemical group 0.000 description 6
239000000969 carrier Substances 0.000 description 6
229940011871 estrogen Drugs 0.000 description 6
239000000262 estrogen Substances 0.000 description 6
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
125000002950 monocyclic group Chemical group 0.000 description 6
229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
239000011780 sodium chloride Substances 0.000 description 6
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 6
239000003826 tablet Substances 0.000 description 6
PEHDFSFYZKSKGH-UHFFFAOYSA-N 1,4,5,6-tetrahydropyrimidin-2-amine Chemical compound NC1=NCCCN1 PEHDFSFYZKSKGH-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
125000002252 acyl group Chemical group 0.000 description 5
239000002585 base Substances 0.000 description 5
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
210000002805 bone matrix Anatomy 0.000 description 5
150000001735 carboxylic acids Chemical class 0.000 description 5
229910052801 chlorine Inorganic materials 0.000 description 5
125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 5
230000005764 inhibitory process Effects 0.000 description 5
230000003993 interaction Effects 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 description 4
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CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
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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 description 4
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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 3
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AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
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230000002378 acidificating effect Effects 0.000 description 3
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KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
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UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
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XFBGZLJYAYMLNB-QHCPKHFHSA-N tert-butyl (2s)-3-[[4-(3-methoxy-3-oxopropyl)benzoyl]amino]-2-(naphthalen-1-ylsulfonylamino)propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C(=O)NC[C@@H](C(=O)OC(C)(C)C)NS(=O)(=O)C1=CC=CC2=CC=CC=C12 XFBGZLJYAYMLNB-QHCPKHFHSA-N 0.000 description 1
PBEAPEOHEHNJRZ-NRFANRHFSA-N tert-butyl (2s)-3-[[4-(3-methoxy-3-oxopropyl)benzoyl]amino]-2-(phenylmethoxycarbonylamino)propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1C(=O)NC[C@@H](C(=O)OC(C)(C)C)NC(=O)OCC1=CC=CC=C1 PBEAPEOHEHNJRZ-NRFANRHFSA-N 0.000 description 1
PPGHSGBIVNQSKC-QHCPKHFHSA-N tert-butyl (2s)-3-[[4-[3-oxo-3-(1,4,5,6-tetrahydropyrimidin-2-ylamino)propyl]benzoyl]amino]-2-(quinolin-8-ylsulfonylamino)propanoate Chemical compound C([C@@H](C(=O)OC(C)(C)C)NS(=O)(=O)C=1C2=NC=CC=C2C=CC=1)NC(=O)C(C=C1)=CC=C1CCC(=O)NC1=NCCCN1 PPGHSGBIVNQSKC-QHCPKHFHSA-N 0.000 description 1
OVQUNCLVRIQJMQ-DEOSSOPVSA-N tert-butyl (2s)-3-[[4-[3-oxo-3-(1,4,5,6-tetrahydropyrimidin-2-ylamino)propyl]benzoyl]amino]-2-[[2-(1,4,5,6-tetrahydropyrimidin-2-ylcarbamoyl)phenyl]sulfonylamino]propanoate Chemical compound C([C@@H](C(=O)OC(C)(C)C)NS(=O)(=O)C=1C(=CC=CC=1)C(=O)NC=1NCCCN=1)NC(=O)C(C=C1)=CC=C1CCC(=O)NC1=NCCCN1 OVQUNCLVRIQJMQ-DEOSSOPVSA-N 0.000 description 1
GUTOOFAUODQZRP-LBPRGKRZSA-N tert-butyl (2s)-3-amino-2-(phenylmethoxycarbonylamino)propanoate Chemical compound CC(C)(C)OC(=O)[C@H](CN)NC(=O)OCC1=CC=CC=C1 GUTOOFAUODQZRP-LBPRGKRZSA-N 0.000 description 1
125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
VNNLHYZDXIBHKZ-UHFFFAOYSA-N thiophene-2-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CS1 VNNLHYZDXIBHKZ-UHFFFAOYSA-N 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
239000001993 wax Substances 0.000 description 1
238000005303 weighing Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1
125000004933 β-carbolinyl group Chemical group C1(=NC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
- C07C311/19—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/18—Sulfonamides
- 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
- 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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
- 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
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- 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
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/36—Sulfur atoms
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/30—Hetero atoms other than halogen
- C07D333/34—Sulfur atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Epidemiology (AREA)
Rheumatology (AREA)
Physical Education & Sports Medicine (AREA)
Orthopedic Medicine & Surgery (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Ophthalmology & Optometry (AREA)
Pain & Pain Management (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Plural Heterocyclic Compounds (AREA)
Pyridine Compounds (AREA)

APAP/P/2000/001863A 1998-01-23 1999-01-16 Novel salfonamide derivatives as inhibitors of bone resorption and as inhibitors of cell adhesion. AP1269A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US1248998A	1998-01-23	1998-01-23
PCT/EP1999/000242 WO1999037621A1 (en)	1998-01-23	1999-01-16	Novel sulfonamide derivatives as inhibitors of bone resorption and as inhibitors of cell adhesion

Publications (2)

Publication Number	Publication Date
AP2000001863A0 AP2000001863A0 (en)	2000-09-30
AP1269A true AP1269A (en)	2004-04-03

Family

ID=21755208

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
APAP/P/2000/001863A AP1269A (en)	1998-01-23	1999-01-16	Novel salfonamide derivatives as inhibitors of bone resorption and as inhibitors of cell adhesion.

Country Status (25)

Country	Link
EP (1)	EP1049677A1 (no)
JP (1)	JP2002501054A (no)
KR (1)	KR20010034319A (no)
CN (1)	CN1177832C (no)
AP (1)	AP1269A (no)
AR (1)	AR014456A1 (no)
AU (1)	AU752882B2 (no)
BG (1)	BG104630A (no)
BR (1)	BR9907735A (no)
CA (1)	CA2318221A1 (no)
EA (1)	EA003102B1 (no)
HR (1)	HRP20000493A2 (no)
HU (1)	HUP0100520A3 (no)
ID (1)	ID26219A (no)
IL (1)	IL137423A0 (no)
NO (1)	NO318795B1 (no)
NZ (1)	NZ505613A (no)
PL (1)	PL341871A1 (no)
SK (1)	SK10632000A3 (no)
TR (1)	TR200002160T2 (no)
TW (1)	TWI247742B (no)
UA (1)	UA63990C2 (no)
WO (1)	WO1999037621A1 (no)
YU (1)	YU47200A (no)
ZA (1)	ZA99476B (no)

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AU747784B2 (en) *	1998-07-29	2002-05-23	Merck & Co., Inc.	Integrin receptor antagonists
EP1028114A1 (en)	1999-02-13	2000-08-16	Aventis Pharma Deutschland GmbH	Novel guanidine derivatives as inhibitors of cell adhesion
EP1065208A1 (en) *	1999-07-02	2001-01-03	Aventis Pharma Deutschland GmbH	Substituted purine derivatives as inhibitors of cell adhesion
EP1065207A1 (en) *	1999-07-02	2001-01-03	Aventis Pharma Deutschland GmbH	Naphthyridine derivatives, processes for their preparation, their use, and pharmaceutical compositions comprising them
EP1070707A1 (en)	1999-07-21	2001-01-24	Aventis Pharma Deutschland GmbH	1,4,5,6-tetrahydropyrimidine derivative as a vitronectin inhibitor
US6849639B2 (en)	1999-12-14	2005-02-01	Amgen Inc.	Integrin inhibitors and their methods of use
EP1108721A1 (en) *	1999-12-15	2001-06-20	Aventis Pharma Deutschland GmbH	Thienylalanine derivatives as inhibitors of cell adhesion
AU2207001A (en) *	1999-12-24	2001-07-09	Smithkline Beecham Plc	Novel compounds and process
FR2808798A1 (fr) *	2000-05-09	2001-11-16	Hoechst Marion Roussel Inc	Nouveaux derives antagonistes du recepteur de la vitronectine
FR2847254B1 (fr)	2002-11-19	2005-01-28	Aventis Pharma Sa	Nouveaux derives antagonistes du recepteur de la vitronectine, leur procede de preparation, leur application comme medicaments et les compositions pharmaceutiques les refermant
ES2530056T3 (es) *	2004-03-24	2015-02-26	Shire Orphan Therapies Gmbh	Nuevos compuestos para la inhibición de la angiogénesis y su uso
FR2870541B1 (fr)	2004-05-18	2006-07-14	Proskelia Sas	Derives de pyrimidines antigonistes du recepteur de la vitronectine
GB0412553D0 (en)	2004-06-04	2004-07-07	Univ Aberdeen	Therapeutic agents for the treatment of bone conditions
UA87854C2 (en)	2004-06-07	2009-08-25	Мерк Энд Ко., Инк.	N-(2-benzyl)-2-phenylbutanamides as androgen receptor modulators
FR2873585B1 (fr) *	2004-07-27	2006-11-17	Aventis Pharma Sa	Nouvelles formulations galeniques de principes actifs
GB0705400D0 (en)	2007-03-21	2007-05-02	Univ Aberdeen	Therapeutic compounds andm their use
GB0817207D0 (en)	2008-09-19	2008-10-29	Pimco 2664 Ltd	therapeutic apsac compounds and their use
GB0817208D0 (en)	2008-09-19	2008-10-29	Pimco 2664 Ltd	Therapeutic apsap compounds and their use
GB201311361D0 (en)	2013-06-26	2013-08-14	Pimco 2664 Ltd	Compounds and their therapeutic use
ES2864079T3 (es)	2014-05-30	2021-10-13	Pfizer	Derivados de carbonitrilo como moduladores selectivos del receptor de andrógenos
LT3262028T (lt)	2014-12-17	2022-01-10	Pimco 2664 Limited	N-(4-hidroksi-4-metil-cikloheksil)-4-fenil-benzensulfonamido ir n-(-4-hidroksi-4-metil-cikloheksil)-4-(2-piridil)-benzensulfonamido junginiai ir jų terapinis panaudojimas
WO2023275715A1 (en)	2021-06-30	2023-01-05	Pfizer Inc.	Metabolites of selective androgen receptor modulators

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WO1997021726A1 (en) *	1995-12-08	1997-06-19	Hoechst Marion Roussel	Agents for promoting bone formation

1999
- 1999-01-16 JP JP2000528545A patent/JP2002501054A/ja not_active Abandoned
- 1999-01-16 AU AU25181/99A patent/AU752882B2/en not_active Ceased
- 1999-01-16 HR HR20000493A patent/HRP20000493A2/hr not_active Application Discontinuation
- 1999-01-16 PL PL99341871A patent/PL341871A1/xx unknown
- 1999-01-16 CA CA002318221A patent/CA2318221A1/en not_active Abandoned
- 1999-01-16 TR TR2000/02160T patent/TR200002160T2/xx unknown
- 1999-01-16 UA UA2000084983A patent/UA63990C2/uk unknown
- 1999-01-16 CN CNB998040894A patent/CN1177832C/zh not_active Expired - Fee Related
- 1999-01-16 HU HU0100520A patent/HUP0100520A3/hu unknown
- 1999-01-16 NZ NZ505613A patent/NZ505613A/xx unknown
- 1999-01-16 IL IL13742399A patent/IL137423A0/xx unknown
- 1999-01-16 EP EP99904789A patent/EP1049677A1/en not_active Withdrawn
- 1999-01-16 WO PCT/EP1999/000242 patent/WO1999037621A1/en not_active Ceased
- 1999-01-16 BR BR9907735-3A patent/BR9907735A/pt not_active IP Right Cessation
- 1999-01-16 ID IDW20001407A patent/ID26219A/id unknown
- 1999-01-16 SK SK1063-2000A patent/SK10632000A3/sk unknown
- 1999-01-16 AP APAP/P/2000/001863A patent/AP1269A/en active
- 1999-01-16 KR KR1020007008041A patent/KR20010034319A/ko not_active Abandoned
- 1999-01-16 EA EA200000785A patent/EA003102B1/ru not_active IP Right Cessation
- 1999-01-16 YU YU47200A patent/YU47200A/sh unknown
- 1999-01-22 ZA ZA9900476A patent/ZA99476B/xx unknown
- 1999-01-29 AR ARP990100244A patent/AR014456A1/es not_active Application Discontinuation
- 1999-04-30 TW TW088100862A patent/TWI247742B/zh active
2000
- 2000-07-21 NO NO20003765A patent/NO318795B1/no unknown
- 2000-07-21 BG BG104630A patent/BG104630A/xx unknown

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WO1995032710A1 (en) *	1994-05-27	1995-12-07	Merck & Co., Inc.	Compounds for inhibiting osteoclast-mediated bone resorption
WO1997021726A1 (en) *	1995-12-08	1997-06-19	Hoechst Marion Roussel	Agents for promoting bone formation

Also Published As

Publication number	Publication date
WO1999037621A1 (en)	1999-07-29
IL137423A0 (en)	2001-07-24
ZA99476B (en)	1999-08-05
AP2000001863A0 (en)	2000-09-30
AR014456A1 (es)	2001-02-28
JP2002501054A (ja)	2002-01-15
TWI247742B (en)	2006-01-21
CN1293662A (zh)	2001-05-02
BG104630A (en)	2001-04-30
NO20003765L (no)	2000-09-25
HUP0100520A1 (hu)	2001-07-30
KR20010034319A (ko)	2001-04-25
YU47200A (sh)	2002-11-15
CN1177832C (zh)	2004-12-01
PL341871A1 (en)	2001-05-07
BR9907735A (pt)	2000-10-17
TR200002160T2 (tr)	2001-07-23
EA003102B1 (ru)	2002-12-26
UA63990C2 (uk)	2004-02-16
EP1049677A1 (en)	2000-11-08
HUP0100520A3 (en)	2002-11-28
NZ505613A (en)	2002-11-26
SK10632000A3 (sk)	2001-02-12
AU752882B2 (en)	2002-10-03
NO318795B1 (no)	2005-05-09
EA200000785A1 (ru)	2001-02-26
CA2318221A1 (en)	1999-07-29
AU2518199A (en)	1999-08-09
HRP20000493A2 (en)	2001-06-30
NO20003765D0 (no)	2000-07-21
ID26219A (id)	2000-12-07

Publication	Publication Date	Title
US6313119B1 (en)	2001-11-06	Sulfonamide derivatives as inhibitors of bone resorption and as inhibitors of cell adhesion
US6492356B1 (en)	2002-12-10	Acylguanidine derivatives as inhibitors of bone resorption and as vitronectin receptor antagonists
AU752882B2 (en)	2002-10-03	Novel sulfonamide derivatives as inhibitors of bone resorption and as inhibitors of cell adhesion
US6660728B2 (en)	2003-12-09	Thienyl substituted acylguanidines as inhibitors of bone resorption and vitronectin receptor antagonists
CA2371789C (en)	2009-04-14	Novel guanidine derivatives as inhibitors of cell adhesion
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