US4171244A — Enzyme-bound-polyidothyronine

Claim 1

Independent Claim 117 words

An ENZ-bound-ligand of the formula ##STR13## wherein: ENZ is an enzyme reversibly inhibited by ligand selected from the group consisting of malate dehydrogenase and triose phosphate isomerase; a is 0 or 1; n is on the average at least one and not more than about 10; X and Y are the same or different and are chalcogen or amino; D is hydrogen or an alkyl group of from 1 to 6 carbon atoms; Z is 3,5-diiodo-4-(3',5'-diodo-4'-hydroxyphenoxy-1')phenyl-1; and A is a bond or an organic divalent group of from 1 to 12 carbon atoms and 0 to 6 heteroatoms which are oxygen, sulfur or nitrogen, the total number of heterofunctionalities being in the range of 0 to 4.

Claim 2

Dependent Claim 117 words

An ENZ-bound-ligand of the formula ##STR13## wherein: ENZ is an enzyme reversibly inhibited by ligand selected from the group consisting of malate dehydrogenase and triose phosphate isomerase; a is 0 or 1; n is on the average at least one and not more than about 10; X and Y are the same or different and are chalcogen or amino; D is hydrogen or an alkyl group of from 1 to 6 carbon atoms; Z is 3,5-diiodo-4-(3',5'-diodo-4'-hydroxyphenoxy-1')phenyl-1; and A is a bond or an organic divalent group of from 1 to 12 carbon atoms and 0 to 6 heteroatoms which are oxygen, sulfur or nitrogen, the total number of heterofunctionalities being in the range of 0 to 4.

Claim 3

Dependent Claim 12 words

An ENZ-bound-ligand according to claim 1 wherein ENZ is triose phosphate isomerase.

Claim 4

Dependent Claim 12 words

An ENZ-bound-ligand according to claim 1, wherein said dehydrogenase is malate enzyme.

Claim 5

Dependent Claim 80 words

An ENZ-bound-ligand according to claim 3, wherein n is 1 to 8, D is an alkyl group of from 1 to 3 carbon atoms, and A is an aliphatic organic divalent radical of from 1 to 10 carbon atoms having from 0 to 2 heteroatoms in the chain between the non-oxo-carbonyl groups which are oxygen and nitrogen and are present as oxy, tertiary amino or amido and having a total of 0 to 4 heteroatoms which are oxygen or nitrogen.

Claim 6

Dependent Claim 59 words

An ENZ-bound-ligand according to claim 1, wherein n is on the average of from 1 to 8, X and Y are chalcogen, D is an alkyl group of from 1 to 6 carbon atoms, and A is an aromatic group of from 6 to 8 carbon atoms having from 0 to 4 heteroatoms which are oxygen, nitrogen, and sulfur.

Claim 7

Dependent Claim 143 words

An MDH-bound-ligand reversibly inhibited by said ligand and of the formula ##STR14## wherein: MDH is malate dehydrogenase; n 1 is on the average in the range of about 1 to 8; X 1 and Y 1 are the same or different and are oxygen, sulfur or imino; p, q and r are each 0 or 1; s is 0 to 2; α and γ are hydrocarbon groups of from 1 to 8 carbon atoms, β is oxy, thio, sufonyl or alkylamino, wherein the alkyl group is of from 1 to 3 carbon atoms, with the proviso that β is amino or alkylamino when p is 0; δ is ##STR15## wherein T 1 is hydrogen or lower alkyl of from 1 to 3 carbon atoms; Z is 3,5-diiodo-4-(3',5'-diiodo-4'-hydroxyphenoxy-1') phenyl-1; and D is hydrogen or an alkyl group of from 1 to 6 carbon atoms.

Claim 8

Dependent Claim 143 words

An MDH-bound-ligand reversibly inhibited by said ligand and of the formula ##STR14## wherein: MDH is malate dehydrogenase; n 1 is on the average in the range of about 1 to 8; X 1 and Y 1 are the same or different and are oxygen, sulfur or imino; p, q and r are each 0 or 1; s is 0 to 2; α and γ are hydrocarbon groups of from 1 to 8 carbon atoms, β is oxy, thio, sufonyl or alkylamino, wherein the alkyl group is of from 1 to 3 carbon atoms, with the proviso that β is amino or alkylamino when p is 0; δ is ##STR15## wherein T 1 is hydrogen or lower alkyl of from 1 to 3 carbon atoms; Z is 3,5-diiodo-4-(3',5'-diiodo-4'-hydroxyphenoxy-1') phenyl-1; and D is hydrogen or an alkyl group of from 1 to 6 carbon atoms.

Claim 9

Dependent Claim 30 words

An MDH-bound-ligand according to claim 6, wherein s is 0, beta is alkylamino, alpha and gamma are from 1 to 3 carbon atoms, p, q and r are all one.

Claim 10

Dependent Claim 31 words

An MDH-bound-ligand according to claim 6, wherein beta is oxy, alpha and gamma are from 1 to 3 carbon atoms, s is 0, and p, q and r are all one.

Claim 11

Dependent Claim 13 words

An MDH-bound-polyiodothyronine having from 1 to 10 thyroxine groups bound to said MDH.

Claim 12

Dependent Claim 13 words

An MDH-bound-polyiodothyronine having from 1 to 10 thyroxine groups bound to said MDH.

Claim 13

Dependent Claim 16 words

An MDH-bound-polyidothyronine according to claim 9, having from 2 to 6 thyroxine groups bound to MDH.

Claim 14

Dependent Claim 58 words

An MDH-bound-thyroxine reversibly inhibited by said thyroxine having on the average from about 1 to 10 thyroxines of the formula ##STR16## bonded at the amino group to MDH by a non-oxo-carbonyl group including the nitrogen and sulfur analogs thereof; wherein: D is hydrogen or an alkyl group of from 1 to 6 carbon atoms; and Z is 3,5-diiodo-4-(3',5'-diiodo-4'-hydroxyphenoxy-1')phenyl-1.

Claim 15

Dependent Claim 58 words

An MDH-bound-thyroxine reversibly inhibited by said thyroxine having on the average from about 1 to 10 thyroxines of the formula ##STR16## bonded at the amino group to MDH by a non-oxo-carbonyl group including the nitrogen and sulfur analogs thereof; wherein: D is hydrogen or an alkyl group of from 1 to 6 carbon atoms; and Z is 3,5-diiodo-4-(3',5'-diiodo-4'-hydroxyphenoxy-1')phenyl-1.

Claim 16

Dependent Claim 41 words

An MDH-bound-polyiodothyronine reversibly inhibited by said polyiodothyronine of the formula MDH--(COCH.sub.2 (CH.sub.2).sub.t Z).sub.n l wherein; t is 0 or 1; n 1 is on the average in the range of 1 to 10; Mdh is malate dehydrogenase; and Z is 3,5-diiodo-4-(3',5'-diiodo-4'-hydroxyphenoxy-1')phenyl-1.

Claim 17

Dependent Claim 41 words

An MDH-bound-polyiodothyronine reversibly inhibited by said polyiodothyronine of the formula MDH--(COCH.sub.2 (CH.sub.2).sub.t Z).sub.n l wherein; t is 0 or 1; n 1 is on the average in the range of 1 to 10; Mdh is malate dehydrogenase; and Z is 3,5-diiodo-4-(3',5'-diiodo-4'-hydroxyphenoxy-1')phenyl-1.

Claim 18

Dependent Claim 107 words

A TIM-bound-polyiodothyronine reversibly inhibited by said polyiodothyronine of the formula ##STR17## wherein TIM is triose phosphate isomerase; a is 0 or 1; n is on the average at least one and not more than about 10; X and Y are the same or different and are chalcogen or imino; D is hydrogen or an alkyl group of from 1 to 6 carbon atoms; Z is 3,5-diiodo-4-(3',5',-diiodo-4'-hydroxyphenoxy-1')phenyl-1; and A is a bond or an organic divalent group of from 1 to 12 carbon atoms and 0 to 6 heteroatoms which are oxygen, sulfur or nitrogen, the total number of heterofunctionalities being in the range of 0 to 4.

Claim 19

Dependent Claim 107 words

A TIM-bound-polyiodothyronine reversibly inhibited by said polyiodothyronine of the formula ##STR17## wherein TIM is triose phosphate isomerase; a is 0 or 1; n is on the average at least one and not more than about 10; X and Y are the same or different and are chalcogen or imino; D is hydrogen or an alkyl group of from 1 to 6 carbon atoms; Z is 3,5-diiodo-4-(3',5',-diiodo-4'-hydroxyphenoxy-1')phenyl-1; and A is a bond or an organic divalent group of from 1 to 12 carbon atoms and 0 to 6 heteroatoms which are oxygen, sulfur or nitrogen, the total number of heterofunctionalities being in the range of 0 to 4.

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	1982-10-15	1983-04-16	1983-10-16	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	1986-10-15	1987-04-16	1987-10-16	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	1990-10-15	1991-04-16	1991-10-16	$7700.00	Window Closed / Lapsed

Enzyme-bound-polyidothyronine

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