US5036058A
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US
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N-substituted aminoalkanediphosphonic acids
Assignee: Novartis Corp
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Filing: 1990-02-16
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Granted: 1991-07-30
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Expires: 2010-02-16
Abstract
Abstract Compounds of the formula I ##STR1## in which R 1 is an aromatic radical, n is 0, 1, 2 or 3, X is an oxy group, a thio group which can be oxidized or an imino group which is unsubstituted or has aliphatic substituents, alk 1 and alk 2 are identical or different divalent aliphatic radicals, and R 2 is hydrogen or a monovalent aliphatic radical and salts thereof have properties which regulate calcium metabolism and can be employed for the treatment of diseases connected with disturbances in this metabolism. They are prepared, for example, by reacting a compound of the formula ##STR2## in which X 3 is carboxyl with a phosphorylating agent and hydrolysing the primary product.
Inventors
- 👤 Knut A. Jaeggi
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-29 16:37
CPC Classifications
C; C07; C07F; C07F9/00; C07F9/02; C07F9/28; C07F9/38; C07F9/3804; C07F9/3839; C07F9/3873; A; A61; A61P; A61P19/00; A61P19/08; A61P19/10; A61P3/00; A61P3/12; A61P3/14; A61P35/00; A61P43/00
Claims Analysis
Total Claims: 30
Claim 1
Independent Claim
84 words
A compound of the formula I ##STR18## wherein R 1 is a phenyl, naphthyl, imidazolyl, thiazolyl, oxazolyl, pyridyl, pyrimidinyl or pyridazinyl radical which is unsubstituted or monosubstituted, disubstituted or trisubstituted by lower alkyl, lower alkoxy, lower alkylenedioxy, hydroxyl, halogen and/or trifluoromethyl, n is 0, 1, 2 or 3, X is oxy, thio, sulfinyl, sulfonyl, imino or lower alkylimino, alk 1 is lower alkylene, R 2 is hydrogen, lower alkyl or lower alkenyl and alk 2 is lower alkylene or a pharmaceutically acceptable salt thereof.
Claim 2
Dependent Claim
84 words
A compound of the formula I ##STR18## wherein R 1 is a phenyl, naphthyl, imidazolyl, thiazolyl, oxazolyl, pyridyl, pyrimidinyl or pyridazinyl radical which is unsubstituted or monosubstituted, disubstituted or trisubstituted by lower alkyl, lower alkoxy, lower alkylenedioxy, hydroxyl, halogen and/or trifluoromethyl, n is 0, 1, 2 or 3, X is oxy, thio, sulfinyl, sulfonyl, imino or lower alkylimino, alk 1 is lower alkylene, R 2 is hydrogen, lower alkyl or lower alkenyl and alk 2 is lower alkylene or a pharmaceutically acceptable salt thereof.
Claim 3
Dependent Claim
105 words
A compound according to claim 1 of the formula I in which R 1 is a phenyl radical which is unsubstituted or monosubstituted or disubstituted by C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylenedioxy, hydroxyl, halogen having an atomic number up to and including 35 and/or trifluoromethyl, n is 0, 1 or 2, X is oxy, thio, sulfonyl, imino or C 1 -C 4 alkylimino, alk 1 is C 2 -C 6 alkylene, R 2 is hydrogen or C 1 -C 4 alkyl and alk 2 is C 2 -C 4 alkylene, or a pharmaceutically acceptable salt thereof.
Claim 4
Dependent Claim
119 words
A compound according to claim 1 of the formula I in which R 1 is a pyridyl or pyrimidinyl radical which is unsubstituted or substituted by C 1 -C 4 alkyl and/or phenyl which is unsubstituted or monosubstituted or disubstituted by C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylenedioxy, hydroxyl, halogen having an atomic number up to and including 35 and/or trifluoromethyl, n is 0, 1 or 2, X is oxy, thio, imino or C 1 -C 4 alkylimino, alk 1 is C 2 -C 6 alkylene, R 2 is hydrogen or C 1 -C 4 alkyl and alk 2 is C 2 -C 4 alkylene, or a pharmaceutically acceptable salt thereof.
Claim 5
Dependent Claim
93 words
A compound according to claim 1 of the formula I in which R 1 is phenyl which is unsubstituted or substituted by C 1 -C 4 alkyl, C 1 -C 4 alkoxy, hydroxyl, halogen having an atomic number up to and including 35 or trifluoromethyl, or R 1 is unsubstituted pyridyl or pyrimidinyl, n is 0, X is oxy, thio, sulfonyl, imino or methylimino, alk 1 is C 2 -C 6 alkylene, R 2 is hydrogen or C 1 -C 4 alkyl and alk 2 is ethylene, or a pharmaceutically acceptable salt thereof.
Claim 6
Dependent Claim
80 words
A compound according to claim 1 of the formula I in which R 1 is phenyl which is unsubstituted or substituted by C 1 -C 4 alkyl, C 1 -C 4 alkoxy or halogen having an atomic number up to and including 35, n is 0, X is oxy or thio, alk 1 is C 2 -C 4 alkylene, R 2 is C 1 -C 3 alkyl or hydrogen and alk 2 is ethylene, or a pharmaceutically acceptable salt thereof.
Claim 7
Dependent Claim
82 words
A compound according to claim 1 of the formula I in which R 1 is pyridyl or pyrimidinyl which is unsubstituted or substituted by C 1 -C 4 alkyl or phenyl, n is 0, X is imino which is unsubstituted or substituted by C 1 -C 4 alkyl, or is oxy or thio, alk 1 is C 2 -C 4 alkylene, R 2 is C 1 -C 3 alkyl or hydrogen and alk 2 is ethylene, or a pharmaceutically acceptable salt thereof.
Claim 8
Dependent Claim
16 words
A compound as claimed in claim 1 being 3-[N-(3-Phenoxypropyl)-N-methylamino]-1-hydroxypropane-1,1-diphosphonic acid or a pharmaceutically acceptable salt thereof.
Claim 9
Dependent Claim
16 words
A compound as claimed in claim 1 being 3-{N-[2-(4-Methoxyphenoxy)-ethyl]-amino}-1-hydroxypropane-1,1-diphosphonic acid or a pharmaceutically acceptable salt thereof.
Claim 10
Dependent Claim
16 words
A compound as claimed in claim 1 being 3-[N-(2-Phenoxyethyl)-N-methylamino]-1-hydroxypropane-1,1-diphosphonic acid or a pharmaceutically acceptable salt thereof.
Claim 11
Dependent Claim
16 words
A compound as claimed in claim 1 being 3-[N-(2-Phenylthioethyl)-N-methylamino]-1-hydroxypropane-1,1-diphosphonic acid or a pharmaceutically acceptable salt thereof.
Claim 12
Dependent Claim
16 words
A compound as claimed in claim 1 being 3-[N-(3-Phenoxypropyl)amino]-1-hydroxypropane-1,1-diphosphonic acid or a pharmaceutically acceptable salt thereof.
Claim 13
Dependent Claim
16 words
A compound as claimed in claim 1 being 3-[N-(3-Phenylthiopropyl)-N-methylamino]-1-hydroxypropane-1,1-diphosphonic acid or a pharmaceutically acceptable salt thereof.
Claim 14
Dependent Claim
14 words
A compound as claimed in claim 1 being 3-{N-[3-(4-Chlorophenoxy)propyl]-N-methylamino-1-hydroxypropane-1,1-diphosphonic acid or a salt thereof.
Claim 15
Dependent Claim
16 words
A compound as claimed in claim 1 being 3-[N-(3-(4-Methoxyphenoxy)propylamino]-1-hydroxypropane-1,1-diphosphonic acid or a pharmaceutically acceptable salt thereof.
Claim 16
Dependent Claim
16 words
A compound as claimed in claim 1 being 3-[N-(4-(Phenylthiobutyl)-N-methylamino]-1-hydroxypropane-1,1-diphosphonic acid or a pharmaceutically acceptable salt thereof.
Claim 17
Dependent Claim
16 words
A compound as claimed in claim 1 being 3-{N-[2-(3-Trifluoromethylphenylamino)-ethyl]-N-methylamino}-1-hydroxypropane-1,1-diphosphonic acid or a pharmaceutically acceptable salt thereof.
Claim 18
Dependent Claim
16 words
A compound as claimed in claim 1 being 3-{N-[3-(2-Pyridylamino)-propyl]-N-methylamino}-1-hydroxypropane-1,1-diphosphonic acid or a pharmaceutically acceptable salt thereof.
Claim 19
Dependent Claim
16 words
A compound as claimed in claim 1 being 3-{N-[3-(2-Pyrimidinyl)-propyl]-N-methylamino}-1-hydroxypropane-1,1-diphosphonic acid or a pharmaceutically acceptable salt thereof.
Claim 20
Dependent Claim
16 words
A compound as claimed in claim 1 being 3-[N-(3-Benzosulfonyl)-ethyl]-N-methylamino]-1-hydroxypropane-1,1-diphosphonic acid or a pharmaceutically acceptable salt thereof.
Claim 21
Dependent Claim
16 words
A compound as claimed in claim 1 being 3-{N-[3-(4-Methoxyphenoxy)-propyl]-N-methylamino}-1-hydroxypropane-1,1-diphosphonic acid or a pharmaceutically acceptable salt thereof.
Claim 22
Dependent Claim
16 words
A compound as claimed in claim 1 being 3-{N-[3-(3-Methylphenoxy)-propyl]-N-methylamino}-1-hydroxypropane-1,1-diphosphonic acid or a pharmaceutically acceptable salt thereof.
Claim 23
Dependent Claim
16 words
A compound as claimed in claim 1 being 3-{N-[3-(4-Fluorophenoxy)-propyl]-N-methylamino}-1-hydroxypropane-1,1-diphosphonic acid or a pharmaceutically acceptable salt thereof.
Claim 24
Dependent Claim
16 words
A compound as claimed in claim 1 being 3-[N-(4-(Phenoxybutyl)-N-methylamino]-1-hydroxypropane-1,1-diphosphonic acid or a pharmaceutically acceptable salt thereof.
Claim 25
Dependent Claim
16 words
A compound as claimed in claim 1 being 3-[N-(6-(Phenoxyhexyl)-N-methylamino]-1-hydroxypropane-1,1-diphosphonic acid or a pharmaceutically acceptable salt thereof.
Claim 26
Dependent Claim
16 words
A compound as claimed in claim 1 being 3-{N-[2-(4-Chlorophenoxy)-ethyl]-N-methylamino}-1-hydroxypropane-1,1-diphosphonic acid or a pharmaceutically acceptable salt thereof.
Claim 27
Dependent Claim
16 words
A compound as claimed in claim 1 being 3-{{N-{3-[N'-(Pyrid-2-yl)-N'-ethylamino]-propyl}-N-ethylamino}}-1-hydroxypropane-1,1-diphosphonic acid or a pharmaceutically acceptable salt thereof.
Claim 28
Dependent Claim
16 words
A compound as claimed in claim 1 being 3-{N-[2-(2-Hydroxyphenoxy)-ethyl]-N-methylamino}-1-hydroxypropane-1,1-diphosphonic acid or a pharmaceutically acceptable salt thereof.
Claim 29
Dependent Claim
36 words
A pharmaceutical formulation containing an effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof for the regulation of calcium metabolism in warm-blooded animals together with customary pharmaceutical adjuncts and excipients.
Claim 30
Dependent Claim
49 words
Method of treatment of inflammatory processes of the joints, degenerative processes in articular cartilage, osteoporosis, periodontitis, hyperparathyroidism and calcium deposits in blood vessels and prosthetic implants comprising administering a compound according to claim 1 or a pharmaceutically acceptable salt thereof to a warm-blooded animal in need of such treatment.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1994-07-29 | 1995-01-28 | 1995-07-30 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1998-07-29 | 1999-01-28 | 1999-07-30 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2002-07-29 | 2003-01-28 | 2003-07-30 | $7700.00 | Window Closed / Lapsed |