AU615711B2 - (cycloalkylamino)methylenebis(phosphonic acid) and medicines containing the same as an active ingredient - Google Patents

(cycloalkylamino)methylenebis(phosphonic acid) and medicines containing the same as an active ingredient Download PDF

Info

Publication number: AU615711B2
Authority: AU; Australia
Prior art keywords: methylenebis; phosphonic acid; lower alkyl; compound; cycloalkylamino
Prior art date: 1988-01-20
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.): Ceased

Application number

AU28670/89A

Other languages

English (en)

Other versions

AU2867089A (en

Inventor

Tetsushi Abe

Yasuo Isomura

Shuichi Sakamoto

Makoto Takeuchi

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Yamanouchi Pharmaceutical Co Ltd

Original Assignee

Yamanouchi Pharmaceutical Co Ltd

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.)

1988-01-20

Filing date

1989-01-20

Publication date

1991-10-10

1989-01-20 Application filed by Yamanouchi Pharmaceutical Co Ltd filed Critical Yamanouchi Pharmaceutical Co Ltd

1989-07-20 Publication of AU2867089A publication Critical patent/AU2867089A/en

1991-10-10 Application granted granted Critical

1991-10-10 Publication of AU615711B2 publication Critical patent/AU615711B2/en

2009-01-20 Anticipated expiration legal-status Critical

Status Ceased legal-status Critical Current

Links

125000006310 cycloalkyl amino group Chemical group 0.000 title claims abstract description 10
MBKDYNNUVRNNRF-UHFFFAOYSA-N medronic acid Chemical compound OP(O)(=O)CP(O)(O)=O MBKDYNNUVRNNRF-UHFFFAOYSA-N 0.000 title claims description 10
239000004480 active ingredient Substances 0.000 title claims description 8
239000003814 drug Substances 0.000 title description 8
229940079593 drug Drugs 0.000 title description 7
150000003839 salts Chemical class 0.000 claims abstract description 17
125000000217 alkyl group Chemical group 0.000 claims abstract description 13
229940078581 Bone resorption inhibitor Drugs 0.000 claims abstract description 4
239000003435 antirheumatic agent Substances 0.000 claims abstract 2
150000001875 compounds Chemical class 0.000 claims description 54
LWRDQHOZTAOILO-UHFFFAOYSA-N incadronic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)NC1CCCCCC1 LWRDQHOZTAOILO-UHFFFAOYSA-N 0.000 claims description 16
239000000203 mixture Substances 0.000 claims description 16
239000002253 acid Substances 0.000 claims description 13
208000006386 Bone Resorption Diseases 0.000 claims description 12
230000024279 bone resorption Effects 0.000 claims description 11
238000000034 method Methods 0.000 claims description 9
125000005907 alkyl ester group Chemical group 0.000 claims description 8
230000002401 inhibitory effect Effects 0.000 claims description 8
-1 (cycloheptylamino)- Chemical group 0.000 claims description 6
208000037147 Hypercalcaemia Diseases 0.000 claims description 6
206010003246 arthritis Diseases 0.000 claims description 6
230000000148 hypercalcaemia Effects 0.000 claims description 6
208000030915 hypercalcemia disease Diseases 0.000 claims description 6
239000008194 pharmaceutical composition Substances 0.000 claims description 5
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
230000003110 anti-inflammatory effect Effects 0.000 claims description 3
230000003356 anti-rheumatic effect Effects 0.000 claims description 2
230000002917 arthritic effect Effects 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
230000002757 inflammatory effect Effects 0.000 claims description 2
239000003981 vehicle Substances 0.000 claims description 2
101100111947 Arabidopsis thaliana CYP72C1 gene Proteins 0.000 claims 1
101100439244 Glycine max CHI2-A gene Proteins 0.000 claims 1
208000025747 Rheumatic disease Diseases 0.000 claims 1
101150071577 chi2 gene Proteins 0.000 claims 1
239000003112 inhibitor Substances 0.000 claims 1
230000000552 rheumatic effect Effects 0.000 claims 1
150000002148 esters Chemical class 0.000 abstract description 3
229910052739 hydrogen Inorganic materials 0.000 abstract description 2
239000001257 hydrogen Substances 0.000 abstract description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract 1
229940124346 antiarthritic agent Drugs 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
241000700159 Rattus Species 0.000 description 13
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
108090000445 Parathyroid hormone Proteins 0.000 description 12
239000011575 calcium Substances 0.000 description 11
238000001819 mass spectrum Methods 0.000 description 11
239000000243 solution Substances 0.000 description 11
102100036893 Parathyroid hormone Human genes 0.000 description 10
210000000988 bone and bone Anatomy 0.000 description 10
238000006243 chemical reaction Methods 0.000 description 10
210000002966 serum Anatomy 0.000 description 10
239000007924 injection Substances 0.000 description 9
238000002347 injection Methods 0.000 description 9
239000000047 product Substances 0.000 description 9
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 8
238000004458 analytical method Methods 0.000 description 8
229910052791 calcium Inorganic materials 0.000 description 8
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
229940122361 Bisphosphonate Drugs 0.000 description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
150000004663 bisphosphonates Chemical class 0.000 description 6
238000001816 cooling Methods 0.000 description 6
CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 6
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 6
238000012360 testing method Methods 0.000 description 6
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
LXCYSACZTOKNNS-UHFFFAOYSA-N diethoxy(oxo)phosphanium Chemical compound CCO[P+](=O)OCC LXCYSACZTOKNNS-UHFFFAOYSA-N 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
238000001543 one-way ANOVA Methods 0.000 description 4
238000007920 subcutaneous administration Methods 0.000 description 4
239000000126 substance Substances 0.000 description 4
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
108091003079 Bovine Serum Albumin Proteins 0.000 description 3
208000009386 Experimental Arthritis Diseases 0.000 description 3
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
210000004369 blood Anatomy 0.000 description 3
239000008280 blood Substances 0.000 description 3
229940098773 bovine serum albumin Drugs 0.000 description 3
239000002775 capsule Substances 0.000 description 3
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
201000010099 disease Diseases 0.000 description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
230000000694 effects Effects 0.000 description 3
238000001914 filtration Methods 0.000 description 3
WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 3
210000002758 humerus Anatomy 0.000 description 3
230000007062 hydrolysis Effects 0.000 description 3
238000006460 hydrolysis reaction Methods 0.000 description 3
229960000905 indomethacin Drugs 0.000 description 3
239000008101 lactose Substances 0.000 description 3
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 3
239000002504 physiological saline solution Substances 0.000 description 3
239000008213 purified water Substances 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
238000010992 reflux Methods 0.000 description 3
239000007787 solid Substances 0.000 description 3
230000008961 swelling Effects 0.000 description 3
GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 3
KGRVJHAUYBGFFP-UHFFFAOYSA-N 2,2'-Methylenebis(4-methyl-6-tert-butylphenol) Chemical compound CC(C)(C)C1=CC(C)=CC(CC=2C(=C(C=C(C)C=2)C(C)(C)C)O)=C1O KGRVJHAUYBGFFP-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
229920002261 Corn starch Polymers 0.000 description 2
102000003982 Parathyroid hormone Human genes 0.000 description 2
239000002671 adjuvant Substances 0.000 description 2
208000020538 atrophic muscular disease Diseases 0.000 description 2
125000004432 carbon atom Chemical group C* 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
239000008112 carboxymethyl-cellulose Substances 0.000 description 2
239000008120 corn starch Substances 0.000 description 2
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
239000008187 granular material Substances 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
230000002723 inhibitory effect on hypercalcemia Effects 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
210000003141 lower extremity Anatomy 0.000 description 2
235000019359 magnesium stearate Nutrition 0.000 description 2
OJWJPSDEEWTQIZ-UHFFFAOYSA-N n-[bis(diethoxyphosphoryl)methyl]cycloheptanamine Chemical compound CCOP(=O)(OCC)C(P(=O)(OCC)OCC)NC1CCCCCC1 OJWJPSDEEWTQIZ-UHFFFAOYSA-N 0.000 description 2
239000000199 parathyroid hormone Substances 0.000 description 2
229960001319 parathyroid hormone Drugs 0.000 description 2
230000003389 potentiating effect Effects 0.000 description 2
238000002360 preparation method Methods 0.000 description 2
206010039073 rheumatoid arthritis Diseases 0.000 description 2
238000010898 silica gel chromatography Methods 0.000 description 2
239000002904 solvent Substances 0.000 description 2
238000003756 stirring Methods 0.000 description 2
ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 2
238000010998 test method Methods 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 2
206010065687 Bone loss Diseases 0.000 description 1
101150041968 CDC13 gene Proteins 0.000 description 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
101001135770 Homo sapiens Parathyroid hormone Proteins 0.000 description 1
101001135995 Homo sapiens Probable peptidyl-tRNA hydrolase Proteins 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
208000010191 Osteitis Deformans Diseases 0.000 description 1
208000001132 Osteoporosis Diseases 0.000 description 1
208000027868 Paget disease Diseases 0.000 description 1
ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
241000700157 Rattus norvegicus Species 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 1
UNLQCNUHOMXEEC-UHFFFAOYSA-N [(cyclobutylamino)-phosphonomethyl]phosphonic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)NC1CCC1 UNLQCNUHOMXEEC-UHFFFAOYSA-N 0.000 description 1
UGPXWDIZFKGVEG-UHFFFAOYSA-N [(cyclopropylamino)-phosphonomethyl]phosphonic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)NC1CC1 UGPXWDIZFKGVEG-UHFFFAOYSA-N 0.000 description 1
230000003187 abdominal effect Effects 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
239000003905 agrochemical Substances 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
230000000202 analgesic effect Effects 0.000 description 1
230000001754 anti-pyretic effect Effects 0.000 description 1
239000002221 antipyretic Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
244000052616 bacterial pathogen Species 0.000 description 1
BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
229960003773 calcitonin (salmon synthetic) Drugs 0.000 description 1
235000019994 cava Nutrition 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000007810 chemical reaction solvent Substances 0.000 description 1
WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
239000013078 crystal Substances 0.000 description 1
125000000753 cycloalkyl group Chemical group 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
VXVVUHQULXCUPF-UHFFFAOYSA-N cycloheptanamine Chemical compound NC1CCCCCC1 VXVVUHQULXCUPF-UHFFFAOYSA-N 0.000 description 1
125000006547 cyclononyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
239000012153 distilled water Substances 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
210000002683 foot Anatomy 0.000 description 1
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239000004009 herbicide Substances 0.000 description 1
210000000548 hind-foot Anatomy 0.000 description 1
102000058004 human PTH Human genes 0.000 description 1
150000002430 hydrocarbons Chemical group 0.000 description 1
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239000004615 ingredient Substances 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
208000027202 mammary Paget disease Diseases 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
230000001394 metastastic effect Effects 0.000 description 1
206010061289 metastatic neoplasm Diseases 0.000 description 1
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
NIQQIJXGUZVEBB-UHFFFAOYSA-N methanol;propan-2-one Chemical compound OC.CC(C)=O NIQQIJXGUZVEBB-UHFFFAOYSA-N 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
239000011707 mineral Substances 0.000 description 1
239000012046 mixed solvent Substances 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
239000002674 ointment Substances 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
239000006187 pill Substances 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
239000000843 powder Substances 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
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230000000630 rising effect Effects 0.000 description 1
108010068072 salmon calcitonin Proteins 0.000 description 1
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210000004872 soft tissue Anatomy 0.000 description 1
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OGBMKVWORPGQRR-UMXFMPSGSA-N teriparatide Chemical compound C([C@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](N)CO)C(C)C)[C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CNC=N1 OGBMKVWORPGQRR-UMXFMPSGSA-N 0.000 description 1
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Classifications

- 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
- A61K31/66—Phosphorus compounds
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3839—Polyphosphonic acids
- C07F9/3873—Polyphosphonic acids containing nitrogen substituent, e.g. N.....H or N-hydrocarbon group which can be substituted by halogen or nitro(so), N.....O, N.....S, N.....C(=X)- (X =O, S), N.....N, N...C(=X)...N (X =O, S)
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4025—Esters of poly(thio)phosphonic acids
- C07F9/405—Esters of poly(thio)phosphonic acids containing nitrogen substituent, e.g. N.....H or N-hydrocarbon group which can be substituted by halogen or nitro(so), N.....O, N.....S, N.....C(=X)- (X =O, S), N.....N, N...C(=X)...N (X =O, S)

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Molecular Biology (AREA)
Biochemistry (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Physical Education & Sports Medicine (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicinal Preparation (AREA)
Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

AU28670/89A 1988-01-20 1989-01-20 (cycloalkylamino)methylenebis(phosphonic acid) and medicines containing the same as an active ingredient Ceased AU615711B2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
JP63-11656		1988-01-20
JP1165688		1988-01-20

Publications (2)

Publication Number	Publication Date
AU2867089A AU2867089A (en)	1989-07-20
AU615711B2 true AU615711B2 (en)	1991-10-10

Family

ID=11784011

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
AU28670/89A Ceased AU615711B2 (en)	1988-01-20	1989-01-20	(cycloalkylamino)methylenebis(phosphonic acid) and medicines containing the same as an active ingredient

Country Status (14)

Country	Link
US (2)	US4970335A (2)
EP (1)	EP0325482B1 (2)
KR (1)	KR970005179B1 (2)
CN (1)	CN1022630C (2)
AT (1)	ATE74361T1 (2)
AU (1)	AU615711B2 (2)
CA (1)	CA1339805C (2)
DE (1)	DE68901097D1 (2)
DK (1)	DK174744B1 (2)
ES (1)	ES2032105T3 (2)
GR (1)	GR3004461T3 (2)
HU (1)	HU202243B (2)
IE (1)	IE60477B1 (2)
PH (1)	PH26819A (2)

Families Citing this family (48)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA1339805C (en) *	1988-01-20	1998-04-07	Yasuo Isomura	(cycloalkylamino)methylenebis(phosphonic acid) and medicines containing the same as an active
IE912115A1 (en) *	1990-06-25	1992-01-01	Takeda Chemical Industries Ltd	Bisphosphonic acid derivatives, their production and use
US5073339A (en) *	1990-08-23	1991-12-17	W. R. Grace & Co. - Conn	Method of inhibiting corrosion and scale formation in aqueous systems
IE914417A1 (en) *	1990-12-19	1992-07-01	Takeda Chemical Industries Ltd	Bisphosphonic acid derivatives, their production and use
US5350743A (en) *	1991-02-07	1994-09-27	Kaken Pharmaceutical Co., Ltd.	Bisphosphonic acid derivatives, as bone resorption inhibitors
CA2102303A1 (en) *	1991-06-19	1992-12-20	Roy Allen Johnson	Dialkyl (dialkoxyphosphinyl) methyl phosphates as anti-inflammatory agents
EP0522576A3 (en) *	1991-07-12	1993-07-14	Hoechst Aktiengesellschaft	Aminoethane-1,1-bisphosphonic acids and aminoethane-1,1-alkylphospinic/phosphonic acids, process of their preparation and their use
EP0541037A3 (en) *	1991-11-06	1997-02-26	Takeda Chemical Industries Ltd	Squalene synthetase inhibitory composition and use thereof
US5391743A (en) *	1992-05-29	1995-02-21	Procter & Gamble Pharmaceuticals, Inc.	Quaternary nitrogen-containing phosphonate compounds, pharmaceutical compositions, and methods of treating abnormal calcium and phosphate metabolism and methods of treating and preventing dental calculus and plaque
US5358941A (en)	1992-12-02	1994-10-25	Merck & Co., Inc.	Dry mix formulation for bisphosphonic acids with lactose
US6406714B1 (en)	1992-12-02	2002-06-18	Merck & Co., Inc.	Dry mix formulation for bisphosphonic acids
US6399592B1 (en)	1992-12-23	2002-06-04	Merck & Co., Inc.	Bishphosphonate/estrogen synergistic therapy for treating and preventing bone loss
FR2703590B1 (fr) *	1993-04-05	1995-06-30	Sanofi Elf	Utilisation de derives d'acide bisphosphonique pour la preparation de medicaments destines a favoriser la reparation osseuse .
US5854227A (en) *	1994-03-04	1998-12-29	Hartmann; John F.	Therapeutic derivatives of diphosphonates
US20010007863A1 (en)	1998-06-18	2001-07-12	Merck & Co., Inc.	Wet granulation formulation for bisphosphonic acids
WO1996039107A1 (en)	1995-06-06	1996-12-12	Merck & Co., Inc.	Bisphosphonate cement composition to prevent aseptic loosening of orthopedic implant devices
US20030096760A1 (en) *	1997-03-10	2003-05-22	Smithklinebeecham Corporation	Method of antagonizing the human SRC SH2 domain
IT1303672B1 (it)	1998-07-28	2001-02-23	Nicox Sa	Sali nitrati di farmaci attivi nei disordini ossei
AR024462A1 (es)	1999-07-01	2002-10-02	Merck & Co Inc	Tabletas farmaceuticas
US6682718B1 (en) *	1999-11-25	2004-01-27	Yamanouchi Pharmaceutical Co., Ltd.	Remedies for periodontosis
US6677320B2 (en)	2000-01-20	2004-01-13	Hoffmann-La Roches Inc.	Parenteral bisphosphonate composition with improved local tolerance
RU2294203C2 (ru) *	2001-12-21	2007-02-27	Дзе Проктер Энд Гэмбл Компани	Способ лечения костных нарушений
US20050070504A1 (en) *	2001-12-21	2005-03-31	The Procter & Gamble Co.	Risedronate compositions and their methods of use
CA2472578A1 (en) *	2002-01-24	2003-07-31	Yissum Research Development Company Of The Hebrew University Of Jerusalem	Anti-cancer combination and use thereof
RU2387451C2 (ru)	2002-05-10	2010-04-27	Ф.Хоффманн-Ля Рош Аг	Бисфосфоновые кислоты, предназначенные для лечения и профилактики остеопороза
JP2005534653A (ja) *	2002-06-06	2005-11-17	メルクフロストカナダアンドカンパニー	眼及び骨疾患の治療に於いてｅｐ４受容体作動薬として使用するための１，５−二置換イミダゾリジン−２−オン誘導体
CA2495917A1 (en) *	2002-08-28	2004-03-11	Merck Frosst Canada & Co.	Oxazolidin-2-one and thiazolidin-2-one derivatives for use as ep4 receptor agonists in the treatment of glaucoma
HRP20041013B1 (hr)	2002-12-20	2013-10-25	F. Hoffmann - La Roche Ag	Formulacija visoke doze ibandronata
CN1839114A (zh)	2003-08-21	2006-09-27	默克弗罗斯特加拿大有限公司	组织蛋白酶半胱氨酸蛋白酶抑制剂
WO2005027921A1 (en) *	2003-09-19	2005-03-31	Pfizer Products Inc.	Pharmaceutical compositions and methods comprising combinations of 2-alkylidene-19-nor-vitamin d derivatives and a bisphosphonate
US20050261250A1 (en) *	2004-05-19	2005-11-24	Merck & Co., Inc.,	Compositions and methods for inhibiting bone resorption
NZ551118A (en)	2004-05-24	2010-09-30	Warner Chilcott Co Llc	Enteric solid oral dosage form of bisphosphonate containing a chelating agent
UA87854C2 (en)	2004-06-07	2009-08-25	Мерк Энд Ко., Инк.	N-(2-benzyl)-2-phenylbutanamides as androgen receptor modulators
AU2006302797B2 (en)	2005-03-02	2012-02-02	Merck Canada Inc.	Composition for inhibition of cathepsin K
BRPI0606280A2 (pt) *	2005-03-17	2009-06-09	Elan Pharma Int Ltd	composições de bisfosfonato nanoparticulado
JP2011517313A (ja)	2007-12-11	2011-06-02	ビアメトファーマシューティカルズ，インク．	金属結合部分を標的化部分と組み合わせて使用する金属酵素阻害剤
EP2222636B1 (en)	2007-12-21	2013-04-10	Ligand Pharmaceuticals Inc.	Selective androgen receptor modulators (sarms) and uses thereof
US20090181138A1 (en)	2008-01-11	2009-07-16	David Howard	Process for producing precooked bacon slices
FR2954320B1 (fr)	2009-12-17	2012-06-15	Cll Pharma	Composition pharmaceutique orale suprabiodisponible contenant un acide biphosphonique ou un de ses sels
US8791162B2 (en)	2011-02-14	2014-07-29	Merck Sharp & Dohme Corp.	Cathepsin cysteine protease inhibitors
GB201200868D0 (en)	2012-01-19	2012-02-29	Depuy Int Ltd	Bone filler composition
WO2015051479A1 (en)	2013-10-08	2015-04-16	Merck Sharp & Dohme Corp.	Cathepsin cysteine protease inhibitors
CN105593230B (zh)	2013-10-08	2018-07-06	默沙东公司	组织蛋白酶半胱氨酸蛋白酶抑制剂
WO2015120580A1 (en)	2014-02-11	2015-08-20	Merck Sharp & Dohme Corp.	Cathepsin cysteine protease inhibitors
PL407922A1 (pl)	2014-04-16	2015-10-26	Wrocławskie Centrum Badań Eit + Spółka Z Ograniczoną Odpowiedzialnością	Nowe bisfosfoniany i ich zastosowanie
ES2864079T3 (es)	2014-05-30	2021-10-13	Pfizer	Derivados de carbonitrilo como moduladores selectivos del receptor de andrógenos
WO2020214834A1 (en)	2019-04-19	2020-10-22	Ligand Pharmaceuticals Inc.	Crystalline forms and methods of producing crystalline forms of a compound
WO2023275715A1 (en)	2021-06-30	2023-01-05	Pfizer Inc.	Metabolites of selective androgen receptor modulators

Citations (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE2037586A1 (de) *	1970-07-29	1972-02-03	Henkel & Cie GmbH, 4000 Düsseldorf	Gipsmassen
JPH01231980A (ja) *	1988-03-10	1989-09-18	Ishikawajima Harima Heavy Ind Co Ltd	管内作業用ピグ

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE1958123C3 (de) *	1969-11-19	1978-09-28	Henkel Kgaa, 4000 Duesseldorf	Verfahren zur Herstellung von 1 -Aminoalkan-1,1 -diphosphonsäuren oder deren Salzen
DE2104476C2 (de) *	1971-02-01	1983-12-01	Henkel KGaA, 4000 Düsseldorf	Verfahren zur Verhinderung von Ausfällungen in Wasser oder wäßrigen Lösungen
DE3540150A1 (de) *	1985-11-13	1987-05-14	Boehringer Mannheim Gmbh	Neue diphosphonsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel
CA1339805C (en) *	1988-01-20	1998-04-07	Yasuo Isomura	(cycloalkylamino)methylenebis(phosphonic acid) and medicines containing the same as an active

1989
- 1989-01-16 CA CA000588341A patent/CA1339805C/en not_active Expired - Fee Related
- 1989-01-19 PH PH38068A patent/PH26819A/en unknown
- 1989-01-20 ES ES198989300560T patent/ES2032105T3/es not_active Expired - Lifetime
- 1989-01-20 IE IE18389A patent/IE60477B1/en not_active IP Right Cessation
- 1989-01-20 DK DK198900243A patent/DK174744B1/da not_active IP Right Cessation
- 1989-01-20 KR KR1019890000568A patent/KR970005179B1/ko not_active Expired - Lifetime
- 1989-01-20 AT AT89300560T patent/ATE74361T1/de not_active IP Right Cessation
- 1989-01-20 DE DE8989300560T patent/DE68901097D1/de not_active Expired - Fee Related
- 1989-01-20 CN CN89101539A patent/CN1022630C/zh not_active Expired - Lifetime
- 1989-01-20 HU HU89230A patent/HU202243B/hu not_active IP Right Cessation
- 1989-01-20 AU AU28670/89A patent/AU615711B2/en not_active Ceased
- 1989-01-20 EP EP89300560A patent/EP0325482B1/en not_active Expired - Lifetime
- 1989-01-23 US US07/300,350 patent/US4970335A/en not_active Expired - Lifetime
1990
- 1990-07-10 US US07/551,434 patent/US5041428A/en not_active Expired - Lifetime
1992
- 1992-04-29 GR GR920400827T patent/GR3004461T3/el unknown

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE2037586A1 (de) *	1970-07-29	1972-02-03	Henkel & Cie GmbH, 4000 Düsseldorf	Gipsmassen
JPH01231980A (ja) *	1988-03-10	1989-09-18	Ishikawajima Harima Heavy Ind Co Ltd	管内作業用ピグ

Also Published As

Publication number	Publication date
US5041428A (en)	1991-08-20
CN1035829A (zh)	1989-09-27
EP0325482A1 (en)	1989-07-26
DE68901097D1 (de)	1992-05-07
IE60477B1 (en)	1994-07-13
DK24389D0 (da)	1989-01-20
ATE74361T1 (de)	1992-04-15
KR970005179B1 (ko)	1997-04-14
GR3004461T3 (2)	1993-03-31
EP0325482B1 (en)	1992-04-01
US4970335A (en)	1990-11-13
AU2867089A (en)	1989-07-20
KR890011601A (ko)	1989-08-21
DK174744B1 (da)	2003-10-13
PH26819A (en)	1992-11-05
CA1339805C (en)	1998-04-07
CN1022630C (zh)	1993-11-03
ES2032105T3 (es)	1993-01-01
DK24389A (da)	1989-07-21
HUT50841A (en)	1990-03-28
IE890183L (en)	1989-07-20
HU202243B (en)	1991-02-28

Publication	Publication Date	Title
AU615711B2 (en)	1991-10-10	(cycloalkylamino)methylenebis(phosphonic acid) and medicines containing the same as an active ingredient
EP0354806B1 (en)	1995-11-02	Heterocyclic bisphosphonic acid derivatives
EP0252505B1 (de)	1992-09-16	1-Hydroxy-3-(N-methyl-N-propylamino)propan-1,1-diphosphonsäure; Verfahren zu dessen Herstellung und diese Verbindung enthaltende Arzneimittel
EP0282320B1 (en)	1991-12-11	Bisphosphonic acid derivatives and medicines containing the same
US5013725A (en)	1991-05-07	Pharmaceutical compositions substituted aminomethylenebis(phosphonic acid) derivatives
RU2079504C1 (ru)	1997-05-20	Новые производные бисфосфоновой кислоты и способ их получения
EP0563107A1 (en)	1993-10-06	Novel methylenebisphosphonic acid derivatives
JPH03503643A (ja)	1991-08-15	Ｎ‐複素環プロピリデン‐１，１‐ビスホスホン酸、その製法および薬剤組成物
AU615886B2 (en)	1991-10-17	Novel bicyclic diphosphonate compounds, pharmaceutical compositions, and methods for treating abnormal calcium and phosphate metabolism
JP3883137B2 (ja)	2007-02-21	ピリジルビスホスホン酸エステルよりなる治療用活性薬剤
CN1040110C (zh)	1998-10-07	新的含无环脒基团的二膦酸衍生物及基制备方法以及含该物的药用组合物
IL113246A (en)	2004-08-31	Bisphosphonates and pharmaceutical compositions containing them
JPH07291983A (ja)	1995-11-07	ベンゾピラン誘導体およびそれを含んでなる医薬