US4618598A
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Method of regulating hormone function or release
Assignee: Duke University
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Filing: 1982-04-12
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Granted: 1986-10-21
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Expires: 2002-04-12
Abstract
Abstract A synthetic hormone complex comprising means for binding to the surface of a cell and means for altering second messenger mobilization by the cell. One form of the synthetic hormone complex functions as an antagonist with specific binding affinity for a cell receptor, said hormone in combination with a calcium ion channel inhibitor. Another synthetic hormone complex functioning as an Agonist comprising two or more molecules of a hormone having specific binding affinity for a cell receptor wherein a spacer binding the hormones is 10 to 300 angstroms in length. A method of regulating hormones or other regulatory factors comprising contacting a synthetic hormone complex with a cell surface or internal receptor thereby altering the incorporation of second messenger molecules thereby regulating the physiological function of the cell.
Inventors
- 👤 P. Michael Conn
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-29 16:01
CPC Classifications
C; C07; C07K; C07K7/00; C07K7/04; C07K7/23; A; A61; A61K; A61K38/00; Y; Y10; Y10S; Y10S930/00; Y10S930/01; Y10S930/13
Claims Analysis
Total Claims: 30
Claim 1
Independent Claim
111 words
A synthetic gonadotropin releasing hormone conjugate, which functions as a gonadotropin releasing hormone agonist and consists of (a) gonadotropin releasing hormone or a biologically active analog thereof which comprises a D-lysine at the 6 position of gonadotropin releasing hormone to which another said gonadotropin releasing hormone or gonadotropin releasing hormone analog is covalently bound via a covalent spacer, wherein said spacer comprises a C 1 to C 20 hydrocarbon chain and said spacer is from 10-300 Å in length, thereby producing a dimer, and (b) wherein said dimer is bound via a gonadotropin releasing hormone antibody to another of said dimer to produce said conjugate having gonadotropin releasing hormone agonistic activity.
Claim 2
Dependent Claim
111 words
A synthetic gonadotropin releasing hormone conjugate, which functions as a gonadotropin releasing hormone agonist and consists of (a) gonadotropin releasing hormone or a biologically active analog thereof which comprises a D-lysine at the 6 position of gonadotropin releasing hormone to which another said gonadotropin releasing hormone or gonadotropin releasing hormone analog is covalently bound via a covalent spacer, wherein said spacer comprises a C 1 to C 20 hydrocarbon chain and said spacer is from 10-300 Å in length, thereby producing a dimer, and (b) wherein said dimer is bound via a gonadotropin releasing hormone antibody to another of said dimer to produce said conjugate having gonadotropin releasing hormone agonistic activity.
Claim 3
Dependent Claim
15 words
The conjugate of claim 1, wherein said dimer comprises 2 molecules of gonadotropin releasing hormone.
Claim 4
Dependent Claim
14 words
The conjugate of claim 1, wherein said dimer comprises 2 molecules of said analog.
Claim 5
Dependent Claim
83 words
A synthetic gonadotropin releasing hormone conjugate, which functions as a gonadotropin releasing hormone antagonist and consists of gonadotropin releasing hormone covalently bound via a covalent spacer, which comprises a C 1 to C 20 hydrocarbon chain, wherein said spacer is from 10-300 Å in length, to a synthetic calcium ion channel inhibitor selected from the group consisting of methoxy-[3-[[2-(3,4-Dimethoxyphenyl)ethyl]-methylamino]propyl]-3,4-dimethoxy-α-(1-methylethyl)benzeneacetonitrile; 5-((3,4-dimethoxyphenethyl)methylamino-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile; 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylic acid dimethyl ester; 1,4-dihydro-2,6-dimethyl-4-(2-isothiocyanatophenyl)-3,5-pyridinedicarboxylic acid dimethyl ester; 1-[bis(4-fluorophenyl)methyl]-4-(3-phenyl-2-propenyl)piperazine; 1-(diphenylmethyl)-4-(3-phenyl-2-propenyl)-piperazine; bis(2-propoxyethyl)-1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)-3,5-pyridine-dicarboxylate; N-(1-methyl-2-phenylethyl)-γ-phenylbenzenepropanamine; and cis-(+)-3-(acetyloxy)-5-(2-(dimethylamino)ethyl)-2,3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one, wherein said conjugate exhibits gonadotropin releasing hormone antagonistic activity.
Claim 6
Dependent Claim
83 words
A synthetic gonadotropin releasing hormone conjugate, which functions as a gonadotropin releasing hormone antagonist and consists of gonadotropin releasing hormone covalently bound via a covalent spacer, which comprises a C 1 to C 20 hydrocarbon chain, wherein said spacer is from 10-300 Å in length, to a synthetic calcium ion channel inhibitor selected from the group consisting of methoxy-[3-[[2-(3,4-Dimethoxyphenyl)ethyl]-methylamino]propyl]-3,4-dimethoxy-α-(1-methylethyl)benzeneacetonitrile; 5-((3,4-dimethoxyphenethyl)methylamino-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile; 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylic acid dimethyl ester; 1,4-dihydro-2,6-dimethyl-4-(2-isothiocyanatophenyl)-3,5-pyridinedicarboxylic acid dimethyl ester; 1-[bis(4-fluorophenyl)methyl]-4-(3-phenyl-2-propenyl)piperazine; 1-(diphenylmethyl)-4-(3-phenyl-2-propenyl)-piperazine; bis(2-propoxyethyl)-1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)-3,5-pyridine-dicarboxylate; N-(1-methyl-2-phenylethyl)-γ-phenylbenzenepropanamine; and cis-(+)-3-(acetyloxy)-5-(2-(dimethylamino)ethyl)-2,3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one, wherein said conjugate exhibits gonadotropin releasing hormone antagonistic activity.
Claim 7
Dependent Claim
14 words
The conjugate of claim 4, wherein said synthetic calcium ion channel inhibitor is methoxy-[3-[[2-(3,4-Dimethoxyphenyl)ethyl]-methylamino]propyl]-3,4-dimethoxy-α-(1-methylethyl)benzeneacetonitrile.
Claim 8
Dependent Claim
14 words
The conjugate of claim 4, wherein said synthetic calcium ion channel inhibitor is 5-((3,4-dimethoxyphenethyl)methylamino-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile.
Claim 9
Dependent Claim
17 words
The conjugate of claim 4, wherein said synthetic calcium ion channel inhibitor is 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylic acid dimethyl ester.
Claim 10
Dependent Claim
17 words
The conjugate of claim 4, wherein said synthetic calcium ion channel inhibitor is 1,4-dihydro-2,6-dimethyl-4-(2-isothiocyanatophenyl)-3,5-pyridinedicarboxylic acid dimethyl ester.
Claim 11
Dependent Claim
14 words
The conjugate of claim 4, wherein said synthetic calcium ion channel inhibitor is 1-[bis(4-fluorophenyl)methyl]-4-(3-phenyl-2-propenyl)piperazine.
Claim 12
Dependent Claim
14 words
The conjugate of claim 4, wherein said synthetic calcium ion channel inhibitor is 1-(diphenylmethyl)-4-(3-phenyl-2-propenyl)-piperazine.
Claim 13
Dependent Claim
14 words
The conjugate of claim 4, wherein said synthetic calcium ion channel inhibitor is bis(2-propoxyethyl)-1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)-3,5-pyridine-dicarboxylate.
Claim 14
Dependent Claim
14 words
The conjugate of claim 4, wherein said synthetic calcium ion channel inhibitor is N-(1-methyl-2-phenylethyl)-γ-phenylbenzenepropanamine.
Claim 15
Dependent Claim
14 words
The conjugate of claim 4, wherein said synthetic calcium ion channel inhibitor is cis-(+)-3-(acetyloxy)-5-(2-(dimethylamino)ethyl)-2,3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one.
Claim 16
Independent Claim
133 words
A method of stimulating the release of lutinizing hormone in a mammal, which comprises: administering to said mammal a therapeutically effective amount a synthetic gonadotropin releasing hormone conjugate, which functions as a gonadotropin releasing hormone agonist and consists of (a) gonadotropin releasing hormone or a biologically active analog thereof which comprises a D-lysine at the 6 position of gonadotropin releasing hormone to which another said gonadotropin releasing hormone or gonadotropin releasing hormone analog is covalently bound via a covalent spacer, wherein said spacer comprises a C 1 to C 20 hydrocarbon chain and said spacer is from 10-300 Å in length, thereby producing a dimer, and (b) wherein said dimer is bound via a gonadotropin releasing hormone antibody to another of said dimer to produce said conjugate having gonadotropin releasing hormone agonistic activity.
Claim 17
Independent Claim
133 words
A method of stimulating the release of lutinizing hormone in a mammal, which comprises: administering to said mammal a therapeutically effective amount a synthetic gonadotropin releasing hormone conjugate, which functions as a gonadotropin releasing hormone agonist and consists of (a) gonadotropin releasing hormone or a biologically active analog thereof which comprises a D-lysine at the 6 position of gonadotropin releasing hormone to which another said gonadotropin releasing hormone or gonadotropin releasing hormone analog is covalently bound via a covalent spacer, wherein said spacer comprises a C 1 to C 20 hydrocarbon chain and said spacer is from 10-300 Å in length, thereby producing a dimer, and (b) wherein said dimer is bound via a gonadotropin releasing hormone antibody to another of said dimer to produce said conjugate having gonadotropin releasing hormone agonistic activity.
Claim 18
Dependent Claim
15 words
The method of claim 14, wherein said dimer comprises 2 molecules of gonadotropin releasing hormone.
Claim 19
Dependent Claim
14 words
The method of claim 14, wherein said dimer comprises 2 molecules of said analog.
Claim 20
Independent Claim
106 words
A method of inhibiting the release of lutinizing hormone in a mammal, which comprises: administering to said mammal a therapeutically affective amount of a synthetic gonadotropin releasing hormone conjugate, which functions as a gonadotropin releasing hormone antagonist and consists of gonadotropin releasing hormone covalently bound via a covalent spacer, which comprises a C 1 to C 20 hydrocarbon chain, wherein said spacer is from 10-300 Å in length, to a synthetic calcium ion channel inhibitor selected from the group consisting of methoxy-[3-[[2-(3,4-Dimethoxyphenyl)ethyl]-methylamino]propyl]-3,4-dimethoxy-α-(1-methylethyl)benzeneacetonitrile; 5-((3,4-dimethoxyphenethyl)methylamino)-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile; 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylic acid dimethyl ester; 1,4-dihydro-2,6-dimethyl-4-(2-isothiocyanatophenyl)-3,5-pyridinedicarboxylic acid dimethyl ester; 1-[bis(4-fluorophenyl)methyl]-4-(3-phenyl-2-propenyl)piperazine; 1-(diphenylmethyl)-4-(3-phenyl-2-propenyl)-piperazine; bis(2-propoxyethyl)-1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)-3,5-pyridine-dicarboxylate; N-(1-methyl-2-phenylethyl)-γ-phenylbenzenepropanamine; and cis-(+)-3-(acetyloxy)-5-(2-(dimethylamino)ethyl)-2,3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one, wherein said conjugate exhibits gonadotropin releasing hormone antagonistic activity.
Claim 21
Independent Claim
106 words
A method of inhibiting the release of lutinizing hormone in a mammal, which comprises: administering to said mammal a therapeutically affective amount of a synthetic gonadotropin releasing hormone conjugate, which functions as a gonadotropin releasing hormone antagonist and consists of gonadotropin releasing hormone covalently bound via a covalent spacer, which comprises a C 1 to C 20 hydrocarbon chain, wherein said spacer is from 10-300 Å in length, to a synthetic calcium ion channel inhibitor selected from the group consisting of methoxy-[3-[[2-(3,4-Dimethoxyphenyl)ethyl]-methylamino]propyl]-3,4-dimethoxy-α-(1-methylethyl)benzeneacetonitrile; 5-((3,4-dimethoxyphenethyl)methylamino)-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile; 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylic acid dimethyl ester; 1,4-dihydro-2,6-dimethyl-4-(2-isothiocyanatophenyl)-3,5-pyridinedicarboxylic acid dimethyl ester; 1-[bis(4-fluorophenyl)methyl]-4-(3-phenyl-2-propenyl)piperazine; 1-(diphenylmethyl)-4-(3-phenyl-2-propenyl)-piperazine; bis(2-propoxyethyl)-1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)-3,5-pyridine-dicarboxylate; N-(1-methyl-2-phenylethyl)-γ-phenylbenzenepropanamine; and cis-(+)-3-(acetyloxy)-5-(2-(dimethylamino)ethyl)-2,3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one, wherein said conjugate exhibits gonadotropin releasing hormone antagonistic activity.
Claim 22
Dependent Claim
14 words
The method of claim 17, wherein said synthetic calcium ion channel inhibitor is methoxy-[3-[[2-(3,4-Dimethoxyphenyl)ethyl]-methylamino]propyl]-3,4-dimethoxy-α-(1-methylethyl)benzeneacetonitrile.
Claim 23
Dependent Claim
14 words
The method of claim 17, wherein said synthetic calcium ion channel inhibitor is 5-((3,4-dimethoxyphenethyl)methylamino-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile.
Claim 24
Dependent Claim
17 words
The method of claim 17, wherein said synthetic calcium ion channel inhibitor is 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylic acid dimethyl ester.
Claim 25
Dependent Claim
17 words
The method of claim 17, wherein said synthetic calcium ion channel inhibitor is 1,4-dihydro-2,6-dimethyl-4-(2-isothiocyanatophenyl)-3,5-pyridinedicarboxylic acid dimethyl ester.
Claim 26
Dependent Claim
14 words
The method of claim 17, wherein said synthetic calcium ion channel inhibitor is 1-[bis(4-fluorophenyl)methyl]-4-(3-phenyl-2-propenyl)piperazine.
Claim 27
Dependent Claim
14 words
The method of claim 17, wherein said synthetic calcium ion channel inhibitor is 1-(diphenylmethyl)-4-(3-phenyl-2-propenyl)-piperazine.
Claim 28
Dependent Claim
14 words
The method of claim 17, wherein said synthetic calcium ion channel inhibitor is bis(2-propoxyethyl)-1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)-3,5-pyridine-dicarboxylate.
Claim 29
Dependent Claim
14 words
The method of claim 17, wherein said synthetic calcium ion channel inhibitor is N-(1-methyl-2-phenylethyl)-γ-phenylbenzenepropanamine.
Claim 30
Dependent Claim
14 words
The method of claim 17, wherein said synthetic calcium ion channel inhibitor is cis-(+)-3-(acetyloxy)-5-(2-(dimethylamino)ethyl-2,3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one.
References Cited (Backward Citations)
No citation records indexed.
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1989-10-20 | 1990-04-21 | 1990-10-21 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1993-10-20 | 1994-04-21 | 1994-10-21 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1997-10-20 | 1998-04-21 | 1998-10-21 | $7700.00 | Window Closed / Lapsed |