US4689432A
Expired / Lapsed
US
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Chelators whose affinity for calcium is decreased by illumination
Assignee: University of California
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Filing: 1984-09-07
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Granted: 1987-08-25
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Expires: 2004-09-07
Abstract
Abstract The present invention discloses a group of calcium chelating compounds which have a descreased affinity for calcium following illumination. These new compounds contain a photolabile nitrobenzyl derivative coupled to a tetracarboxylate Ca2+ chelating parent compound having the octacoordinate chelating groups characteristic of EGTA or BAPTA. In a first form, the new compounds are comprised of a BAPTA-like chelator coupled to a single 2-nitrobenzyl derivative, which in turn is a photochemical precursor of a 2-nitrosobenzophenone. In a second form, the new compounds are comprised of a BAPTA-like chelator coupled to two 2-nitrobenzyl derivatives, themselves photochemical prcursors of the related 2-nitrosobenzophenones. The present invention also discloses a novel method for preparing 1-hydroxy- or 1-alkoxy-1-(2-nitroaryl)-1-aryl methanes. Methanes of this type are critical to the preparation of, or actually constitute, the photolabile Ca2+ chelating compounds disclosed and claimed herein.
Inventors
- 👤 Roger Y. Tsien
- 👤 Grzegorz Grynkiewicz
- 👤 Akwasi Minta
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-08 00:31
CPC Classifications
G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/84; C; C07; C07D; C07D317/00; C07D317/08; C07D317/44; C07D317/46; C07D317/48; C07D317/62; Y; Y10; Y10S; Y10S424/00; Y10S424/06
Claims Analysis
Total Claims: 18
Claim 1
Independent Claim
277 words
A chemical compound having the general formula: ##STR10## and the pharmaceutically acceptable non-toxic salts and esters thereof wherein: A is --NO 2 or --H; R 1 is selected from the group comprised of --H (unless R 2 is also H), --CH 3 , --F, --Cl, and --Br; R 2 is selected from the group comprised of --H (unless R 1 is also H), --CH 3 , --F, --Cl, --Br, C 1 -C 4 alkoxy; R 3 , R 4 and R 5 are independently --H, OH, NR 6 R 7 , or alkoxy, or R 3 and R 4 together are --OCH 2 O-- or --OCH 2 CH 2 O-- and R 5 is --H, OH, NR 6 R 7 , or alkoxy, or R 4 and R 5 together are --OCH 2 O-- or OCH 2 CH 2 O-- and R 3 is --H, OH, NR 6 R 7 , or alkoxy; X is selected from the group comprised of --OH, alkoxy, --Cl, --Br, --NR 6 R 7 , --OCOCH 3 , --OCOCF 3 , --OCOCH 2 NH 2 , --OPO 3 H, and --OSO 2 CH 3 ; R 6 and R 7 are independently --H, methyl or ethyl; D is O, N, NH, or N alkyl; Q is a double bond when D is N and a single bond otherwise; R 8 is H and R 9 is H or R 8 and R 9 , together with heteroatom D, the carbon adjacent R 8 , and the phenyl ring adjacent to R 9 , form a quinoline ring system (D═N, Q═double bond); and W is --H, --OH, or --NHR 6 , or alkoxy.
Claim 2
Dependent Claim
277 words
A chemical compound having the general formula: ##STR10## and the pharmaceutically acceptable non-toxic salts and esters thereof wherein: A is --NO 2 or --H; R 1 is selected from the group comprised of --H (unless R 2 is also H), --CH 3 , --F, --Cl, and --Br; R 2 is selected from the group comprised of --H (unless R 1 is also H), --CH 3 , --F, --Cl, --Br, C 1 -C 4 alkoxy; R 3 , R 4 and R 5 are independently --H, OH, NR 6 R 7 , or alkoxy, or R 3 and R 4 together are --OCH 2 O-- or --OCH 2 CH 2 O-- and R 5 is --H, OH, NR 6 R 7 , or alkoxy, or R 4 and R 5 together are --OCH 2 O-- or OCH 2 CH 2 O-- and R 3 is --H, OH, NR 6 R 7 , or alkoxy; X is selected from the group comprised of --OH, alkoxy, --Cl, --Br, --NR 6 R 7 , --OCOCH 3 , --OCOCF 3 , --OCOCH 2 NH 2 , --OPO 3 H, and --OSO 2 CH 3 ; R 6 and R 7 are independently --H, methyl or ethyl; D is O, N, NH, or N alkyl; Q is a double bond when D is N and a single bond otherwise; R 8 is H and R 9 is H or R 8 and R 9 , together with heteroatom D, the carbon adjacent R 8 , and the phenyl ring adjacent to R 9 , form a quinoline ring system (D═N, Q═double bond); and W is --H, --OH, or --NHR 6 , or alkoxy.
Claim 3
Dependent Claim
227 words
A chemical compound having the general formula: ##STR11## and the pharmaceutically acceptable non-toxic salts and esters thereof wherein: A is --NO 2 or --H; R 3 , R 4 and R 5 are independently --H, OH, NR 6 R 7 , or alkoxy, or R 3 and R 4 together are --OCH 2 O-- or --OCH 2 CH 2 O-- and R 5 is --H, OH, NR 6 R 7 , or alkoxy, or R 4 and R 5 together are --OCH 2 O-- or --OCH 2 CH 2 O-- and R 3 is --H, OH, NR 6 R 7 , or alkoxy; X is selected from the group comprised of --OH, alkoxy, --Cl, --Br, --NR 6 R 7 , --OCOCH 3 , --OCOCF 3 , --OCOCH 2 NH 2 , --OPO 3 H, and --OSO 2 CH 3 ; R 6 and R 7 are independently --H, methyl or ethyl; D is O, N, NH, or N alkyl; Q is a double bond when D is N and a single bond otherwise; R 8 is H and R 9 is H or R 8 and R 9 , togehter with heteroatom D, the carbon adjacent to R 8 , and the phenyl ring adjacent to R 9 , form quinoline ring system (D═N, Q═double bond); and W is --H, --OH, or NHR 6 , or alkoxy.
Claim 4
Dependent Claim
227 words
A chemical compound having the general formula: ##STR11## and the pharmaceutically acceptable non-toxic salts and esters thereof wherein: A is --NO 2 or --H; R 3 , R 4 and R 5 are independently --H, OH, NR 6 R 7 , or alkoxy, or R 3 and R 4 together are --OCH 2 O-- or --OCH 2 CH 2 O-- and R 5 is --H, OH, NR 6 R 7 , or alkoxy, or R 4 and R 5 together are --OCH 2 O-- or --OCH 2 CH 2 O-- and R 3 is --H, OH, NR 6 R 7 , or alkoxy; X is selected from the group comprised of --OH, alkoxy, --Cl, --Br, --NR 6 R 7 , --OCOCH 3 , --OCOCF 3 , --OCOCH 2 NH 2 , --OPO 3 H, and --OSO 2 CH 3 ; R 6 and R 7 are independently --H, methyl or ethyl; D is O, N, NH, or N alkyl; Q is a double bond when D is N and a single bond otherwise; R 8 is H and R 9 is H or R 8 and R 9 , togehter with heteroatom D, the carbon adjacent to R 8 , and the phenyl ring adjacent to R 9 , form quinoline ring system (D═N, Q═double bond); and W is --H, --OH, or NHR 6 , or alkoxy.
Claim 5
Dependent Claim
13 words
The compound of claim 1 wherein said tetraacetic acid esters are alpha-acyloxyalkyl esters.
Claim 6
Dependent Claim
12 words
The compound of claim 3 wherein said alpha-acyloxyalkyl esters are acetoxymethyl esters.
Claim 7
Dependent Claim
10 words
The compound of claim 1 wherein R 2 is methyl.
Claim 8
Dependent Claim
13 words
The compound of claim 1 wherein D═O and R 8 ═R 9 ═H.
Claim 9
Dependent Claim
13 words
The compound of claim 2 wherein said tetraacetic acid esters are alpha-acyloxyalkyl esters.
Claim 10
Dependent Claim
12 words
The compound of claim 7 wherein said alpha-acyloxyalkyl esters are acetoxymethyl esters.
Claim 11
Dependent Claim
10 words
The compound of claim 2 wherein R 2 is methyl.
Claim 12
Dependent Claim
13 words
The compound of claim 2 wherein D═O and R 8 ═R 9 ═H.
Claim 13
Dependent Claim
5 words
The compound 1-(2-amino-5-(1-methoxy-1-(2-nitrophenyl)methyl)-phenoxy)-2-(2'-amino-5'-methylphenoxy)ethane-N,N,N',N' tetraacetic acid.
Claim 14
Dependent Claim
5 words
The compound 1-(2-amino-5-(1-methoxy-1-(2-nitrophenyl)methyl)-phenoxy)-2-(2'-amino-5'-methylphenoxy)ethane-N,N,N',N' tetraacetic acid.
Claim 15
Dependent Claim
4 words
The compound 1-(2-amino-5-(1-methoxy-1-(2-nitro-4,5-methylenedioxyphenyl)methyl)-phenoxy)-2-(2'-amino-5'-methylphenoxy)-ethane-N,N,N',N'-tetraacetic acid.
Claim 16
Dependent Claim
4 words
The compound 1-(2-amino-5-(1-methoxy-1-(2-nitro-4,5-methylenedioxyphenyl)methyl)-phenoxy)-2-(2'-amino-5'-methylphenoxy)-ethane-N,N,N',N'-tetraacetic acid.
Claim 17
Dependent Claim
5 words
The compound 1-(2-amino-5-(1-methoxy-1-(2,6-dinitro-3-methoxyphenyl))methylphenoxy)-2-(2'-amino-5'-methylphenoxy)-ethane,N,N,N',N' tetraacetic acid.
Claim 18
Dependent Claim
5 words
The compound 1-(2-amino-5-(1-methoxy-1-(2,6-dinitro-3-methoxyphenyl))methylphenoxy)-2-(2'-amino-5'-methylphenoxy)-ethane,N,N,N',N' tetraacetic acid.
References Cited (Backward Citations)
No citation records indexed.
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1990-08-24 | 1991-02-23 | 1991-08-25 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1994-08-24 | 1995-02-23 | 1995-08-25 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1998-08-24 | 1999-02-23 | 1999-08-25 | $7700.00 | Window Closed / Lapsed |