IL257470B2 - Telomerase Activating Compounds for Use in Fertility and Related Applications - Google Patents
Telomerase Activating Compounds for Use in Fertility and Related ApplicationsInfo
- Publication number
- IL257470B2 IL257470B2 IL257470A IL25747018A IL257470B2 IL 257470 B2 IL257470 B2 IL 257470B2 IL 257470 A IL257470 A IL 257470A IL 25747018 A IL25747018 A IL 25747018A IL 257470 B2 IL257470 B2 IL 257470B2
- Authority
- IL
- Israel
- Prior art keywords
- compound
- represented
- formula
- subject
- alkoxy
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 32
- 230000035558 fertility Effects 0.000 title claims description 11
- 108010017842 Telomerase Proteins 0.000 title description 15
- 230000003213 activating effect Effects 0.000 title description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 125000001188 haloalkyl group Chemical group 0.000 claims description 9
- 230000001737 promoting effect Effects 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- 125000005055 alkyl alkoxy group Chemical group 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 230000002710 gonadal effect Effects 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 230000036512 infertility Effects 0.000 claims 2
- 208000000509 infertility Diseases 0.000 claims 2
- 231100000535 infertility Toxicity 0.000 claims 2
- 208000017701 Endocrine disease Diseases 0.000 claims 1
- 208000026350 Inborn Genetic disease Diseases 0.000 claims 1
- 244000089486 Phragmites australis subsp australis Species 0.000 claims 1
- 208000006994 Precancerous Conditions Diseases 0.000 claims 1
- 208000030172 endocrine system disease Diseases 0.000 claims 1
- 230000002708 enhancing effect Effects 0.000 claims 1
- 230000004720 fertilization Effects 0.000 claims 1
- 208000016361 genetic disease Diseases 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 230000002028 premature Effects 0.000 claims 1
- 230000010009 steroidogenesis Effects 0.000 claims 1
- -1 arylalkylenesulfonyl Chemical group 0.000 description 33
- 125000003118 aryl group Chemical group 0.000 description 12
- 125000001072 heteroaryl group Chemical group 0.000 description 9
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 150000001299 aldehydes Chemical class 0.000 description 6
- 125000003342 alkenyl group Chemical group 0.000 description 6
- 125000002877 alkyl aryl group Chemical group 0.000 description 6
- 125000005213 alkyl heteroaryl group Chemical group 0.000 description 6
- 125000004414 alkyl thio group Chemical group 0.000 description 6
- 125000000304 alkynyl group Chemical group 0.000 description 6
- 150000001408 amides Chemical class 0.000 description 6
- 125000003710 aryl alkyl group Chemical group 0.000 description 6
- 125000001769 aryl amino group Chemical group 0.000 description 6
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 6
- 125000005110 aryl thio group Chemical group 0.000 description 6
- 125000004104 aryloxy group Chemical group 0.000 description 6
- 125000003178 carboxy group Chemical class [H]OC(*)=O 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 125000000753 cycloalkyl group Chemical group 0.000 description 6
- 125000004663 dialkyl amino group Chemical group 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 125000003106 haloaryl group Chemical group 0.000 description 6
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 description 6
- 150000002576 ketones Chemical class 0.000 description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 6
- 125000002023 trifluoromethyl group Chemical class FC(F)(F)* 0.000 description 6
- 102100032938 Telomerase reverse transcriptase Human genes 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 150000001204 N-oxides Chemical class 0.000 description 3
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 3
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 3
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 description 3
- 229910052785 arsenic Inorganic materials 0.000 description 3
- RQNWIZPPADIBDY-UHFFFAOYSA-N arsenic atom Chemical compound [As] RQNWIZPPADIBDY-UHFFFAOYSA-N 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 229910052732 germanium Inorganic materials 0.000 description 3
- GNPVGFCGXDBREM-UHFFFAOYSA-N germanium atom Chemical compound [Ge] GNPVGFCGXDBREM-UHFFFAOYSA-N 0.000 description 3
- 210000002503 granulosa cell Anatomy 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 125000004043 oxo group Chemical group O=* 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 229940127557 pharmaceutical product Drugs 0.000 description 3
- 229910052710 silicon Inorganic materials 0.000 description 3
- 239000010703 silicon Substances 0.000 description 3
- 108091035539 telomere Proteins 0.000 description 3
- 210000003411 telomere Anatomy 0.000 description 3
- 102000055501 telomere Human genes 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 210000000287 oocyte Anatomy 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 230000021595 spermatogenesis Effects 0.000 description 2
- 241000206602 Eukaryota Species 0.000 description 1
- 102000006771 Gonadotropins Human genes 0.000 description 1
- 108010086677 Gonadotropins Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 108091081062 Repeated sequence (DNA) Proteins 0.000 description 1
- 108010081734 Ribonucleoproteins Proteins 0.000 description 1
- 102000004389 Ribonucleoproteins Human genes 0.000 description 1
- 206010046764 Uterine atrophy Diseases 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 231100000502 fertility decrease Toxicity 0.000 description 1
- 230000008303 genetic mechanism Effects 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 210000002149 gonad Anatomy 0.000 description 1
- 239000002622 gonadotropin Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 239000000203 mixture Chemical class 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 210000001082 somatic cell Anatomy 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 231100001042 uterine atrophy Toxicity 0.000 description 1
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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
-
- 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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
- A61K31/055—Phenols the aromatic ring being substituted by halogen
-
- 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
- A61K31/075—Ethers or acetals
- A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
- A61K31/09—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon having two or more such linkages
-
- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4025—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
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- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Reproductive Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
BGU7384IL2 TELOMERASE ACTIVATING COMPOUNDS FOR USE IN FERTILITY ANDRELATED APPLICATIONS FIELD OF THE INVENTION id="p-1" id="p-1" id="p-1" id="p-1" id="p-1" id="p-1" id="p-1" id="p-1" id="p-1"
id="p-1"
[001] The present invention is directed to use of a series of compounds and compositions comprising the same for treating diseases, disorders and/or conditions related to fertility and preserving same and conditions related to same.
BACKGROUND OF THE INVENTION id="p-2" id="p-2" id="p-2" id="p-2" id="p-2" id="p-2" id="p-2" id="p-2" id="p-2"
id="p-2"
[002] Telomerase is a ribonucleoprotein responsible for the elongation of repetitive DNA structure in the chromosome ends of eukaryotes - the Telomeres, which shorten every cell division due to the "end replication problem". Telomerase is composed of two major subunits, the catalytic subunit telomerase reverse transcriptase (TERT) and an RNA component (TR) which serves as a template for telomere elongation. Telomerase expression is essential for proliferative cells. One of the major genetic mechanisms determining cell proliferative capacity is the maintenance of telomeres by the enzyme telomerase. id="p-3" id="p-3" id="p-3" id="p-3" id="p-3" id="p-3" id="p-3" id="p-3" id="p-3"
id="p-3"
[003] Telomerase activity has been detected in human germ cells, such as in the ovary and expressed in intensively dividing cells and tissues which have the capacity of regeneration. Decrease in fertility among TERT deficient animal models and TR deficient female mice have shown uterine atrophy, which indicates dysfunction of granulosa cells. During the development of oocytes, folliculogenesis is accompanied by significant proliferation of granulosa cells. id="p-4" id="p-4" id="p-4" id="p-4" id="p-4" id="p-4" id="p-4" id="p-4" id="p-4"
id="p-4"
[004] Most somatic cells contain low or undedicated expression of telomerase but during the spermatogenesis process telomerase is active and its catalytic subunit TERT is expressed, as well. id="p-5" id="p-5" id="p-5" id="p-5" id="p-5" id="p-5" id="p-5" id="p-5" id="p-5"
id="p-5"
[005] Beyond the above, little is known about the role of telomerase and its subunits in developing gonads, for example, in oocytes and granulosa cells or in spermatogenesis. Still less is understood in terms of the differential impact of telomerase activating compounds and treatment or recovery of fertility.
BGU7384IL2 SUMMARY OF THE INVENTION id="p-6" id="p-6" id="p-6" id="p-6" id="p-6" id="p-6" id="p-6" id="p-6" id="p-6"
id="p-6"
[006] In one embodiment, this invention provides a method of promoting, improving, recovering or restoring fertility in a subject in need thereof, comprising contacting a gonadal or fertility-associated cell or tissue with a compound represented by the structure of formula I: R R I 5 wherein Z is carbon, nitrogen, phosphor, arsenic, silicon or germanium; R1 to R9 are the same or different, H, D, OH, halogen, nitro, CN, nitrileamido, amidosulfide, amino, aldehyde, substituted ketone, -COOH, ester, trifluoromethyl, amide, substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, arylalkyl, alkylaryl, arylsulfonyl, arylalkylenesulfonyl, alkoxy, alkylalkoxy, haloalkyl, alkylhaloalkyl, haloaryl, aryloxy, amino, monoalkylamino, dialkylamino, alkylamido, arylamino, arylamido. alkylthio, arylthio, heterocycloalkyl, alkylheterocycloalkyl, heterocycloalkylalkyl, heteroaryl, hetroarylalkyl, alkylheteroaryl; or R3, R4, or R7, forms a fused cycloalkyl, heterocycloalkyl, aromatic or heteroaromatic ring with the main aromatic ring; and R10 is nothing, H, D, OH, halogen, oxo, nitro, CN, nitrileamido, amidosulfide, amino, aldehyde, substituted ketone, -COOH, ester, trifluoromethyl, amide, substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, arylalkyl, alkylaryl, arylsulfonyl, arylalkylenesulfonyl, alkoxy, haloalkyl, haloaryl, cycloalkyl, alkylcycloalkyl, aryloxy, monoalkylamino, dialkylamino, alkylamido, arylamino, arylamido, alkylthio, arylthio, heterocycloalkyl, alkylheterocycloalkyl, heterocycloalkylalkyl, heteroaryl, hetroarylalkyl, alkylheteroaryl; or its isomer, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, crystal or any combination thereof. id="p-7" id="p-7" id="p-7" id="p-7" id="p-7" id="p-7" id="p-7" id="p-7" id="p-7"
id="p-7"
[007] In some embodiments, this invention provides for the use of a compound represented by BGU7384IL2 the structure of formula I: R R IR8 wherein Z is carbon, nitrogen, phosphor, arsenic, silicon or germanium; R1 to R9 are the same or different, H, D, OH, halogen, nitro, CN, nitrileamido, amidosulfide,amino, aldehyde, substituted ketone, -COOH, ester, trifluoromethyl, amide, substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, arylalkyl, alkylaryl, arylsulfonyl, arylalkylenesulfonyl, alkoxy, alkylalkoxy, haloalkyl, alkylhaloalkyl, haloaryl, aryloxy, amino, monoalkylamino, dialkylamino, alkylamido, arylamino, arylamido. alkylthio, arylthio, heterocycloalkyl, alkylheterocycloalkyl, heterocycloalkylalkyl, heteroaryl, hetroarylalkyl, alkylheteroaryl; or R3,R4, or R7, forms a fused cycloalkyl, heterocycloalkyl, aromatic or heteroaromatic ring with the main aromatic ring; and R10 is nothing, H, D, OH, halogen, oxo, nitro, CN, nitrileamido, amidosulfide, amino, aldehyde, substituted ketone, -COOH, ester, trifluoromethyl, amide, substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, arylalkyl, alkylaryl, arylsulfonyl, arylalkylenesulfonyl, alkoxy, haloalkyl, haloaryl, cycloalkyl, alkylcycloalkyl, aryloxy, monoalkylamino, dialkylamino, alkylamido, arylamino, arylamido, alkylthio, arylthio, heterocycloalkyl, alkylheterocycloalkyl, heterocycloalkylalkyl, heteroaryl, hetroarylalkyl, alkylheteroaryl; or its isomer, pharmaceutically acceptable salt, pharmaceutical product, hydrate, N-oxide, crystal or any combination thereof for promoting, improving, recovering or restoring fertility in a subject in need thereof. id="p-8" id="p-8" id="p-8" id="p-8" id="p-8" id="p-8" id="p-8" id="p-8" id="p-8"
id="p-8"
[008] According to these aspects and in some embodiments, such method and/or use promoting, improving, recovering or restoring fertility in a subject beneficially modulates gonadotropin expression or steroid hormone expression in terms of timing or quantity or a combination thereof, or in some embodiments, improves follicle maturation in terms of timing or3 BGU7384IL2 quantity or a combination thereof, or in some embodiments, improves sperm quantity, quality, motility or a combination thereof, or any combination of same. id="p-9" id="p-9" id="p-9" id="p-9" id="p-9" id="p-9" id="p-9" id="p-9" id="p-9"
id="p-9"
[009] In other embodiments, this invention provides a method of promoting, improving, recovering or restoring function to gonadal cells or tissues in a subject in need thereof, comprising contacting a gonadal or fertility-associated cell or tissue with a compound represented by the structure of formula I: R R IR8 wherein Z is carbon, nitrogen, phosphor, arsenic, silicon or germanium; R1 to R9 are the same or different, H, D, OH, halogen, nitro, CN, nitrileamido, amidosulfide,amino, aldehyde, substituted ketone, -COOH, ester, trifluoromethyl, amide, substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, arylalkyl, alkylaryl, arylsulfonyl, arylalkylenesulfonyl, alkoxy, alkylalkoxy, haloalkyl, alkylhaloalkyl, haloaryl, aryloxy, amino, monoalkylamino, dialkylamino, alkylamido, arylamino, arylamido. alkylthio, arylthio, heterocycloalkyl, alkylheterocycloalkyl, heterocycloalkylalkyl, heteroaryl, hetroarylalkyl, alkylheteroaryl; or R3, R4, or R7, forms a fused cycloalkyl, heterocycloalkyl, aromatic or heteroaromatic ring with the main aromatic ring; and R10 is nothing, H, D, OH, halogen, oxo, nitro, CN, nitrileamido, amidosulfide, amino, aldehyde, substituted ketone, -COOH, ester, trifluoromethyl, amide, substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, arylalkyl, alkylaryl, arylsulfonyl, arylalkylenesulfonyl, alkoxy, haloalkyl, haloaryl, cycloalkyl, alkylcycloalkyl, aryloxy, monoalkylamino, dialkylamino, alkylamido, arylamino, arylamido, alkylthio, arylthio, heterocycloalkyl, alkylheterocycloalkyl, heterocycloalkylalkyl, heteroaryl, hetroarylalkyl, alkylheteroaryl; or its isomer, pharmaceutically BGU7384IL2 acceptable salt, pharmaceutical product, hydrate, N-oxide, crystal or any combination thereof. id="p-10" id="p-10" id="p-10" id="p-10" id="p-10" id="p-10" id="p-10" id="p-10" id="p-10"
id="p-10"
[010] In other embodiments, this invention provides for the use of a compound represented by the structure of formula I: r3 r4R5 R6
Claims (13)
1. A compound represented by the structure of formula I: Z R RR R RRR RR R I wherein Z is carbon; R1 to R9 are the same or different, H, D, OH, halogen, alkoxy, alkylalkoxy, haloalkyl, alkylhaloalkyl,; and R 10 is H, D, or unsubstituted alkyl; or a compound represented by the structure of formula XVI: P CHO OCH OCHXVI or its isomer or pharmaceutically acceptable salt or any combination thereof for use in promoting, improving, recovering or restoring fertility in a subject in need thereof.
2. A compound represented by the structure of formula I: 257,470/ Z R RR R RRR RR R I wherein Z is carbon; R1 to R9 are the same or different, H, D, OH, halogen, alkoxy, alkylalkoxy, haloalkyl, alkylhaloalkyl, and R 10 is nothing, H, D unsubstituted alkyl; or a compound represented by the structure of formula XVI: P CHO OCH OCHXVI or its isomer or pharmaceutically acceptable salt or any combination thereof for use in promoting, improving, recovering or restoring function to gonadal cells or tissues in a subject in need thereof.
3. A compound represented by the structure of formula I: 257,470/ Z R RR R RRR RR R I wherein Z is carbon; R1 to R9 are the same or different, H, D, OH, halogen, alkoxy, alkylalkoxy, haloalkyl, alkylhaloalkyl; and R 10 is nothing, H, D, or unsubstituted alkyl; or a compound represented by the structure of formula XVI: P CHO OCH OCHXVI or its isomer or pharmaceutically acceptable salt or any combination thereof for use in promoting, enhancing or improving a fertility-associated cell or tissue yield as part of an in vitro fertilization protocol.
4. The compound for use of any one of claims 1-3, wherein said compound is represented by the structure of formula IV: 257,470/ RR HOROH R ROHR R IV wherein R1, R3, R4, R6, R7, R9 and R10 are as described above.
5. The compound for use of any one of claims 1-4, wherein said compound is represented by the structure of formula VI: RHO OH OH R' R' R' R' R' R' VI wherein R1’, R3’, R4’, R6’ R7’, and R9’ are the same or different comprising halogen, or alkoxy; and R10 is as described above.
6. The compound for use of any one of claims 1-5, wherein said compound is represented by the structure of formula XIII: 10 257,470/ HO OH OH EtO EtO OEt OEt OEt OEtXIII.
7. The compound for use of any one of claims 1-4, wherein said compound is represented by the structure of formula XIV: BrHO Br BrOH Br OHBr Br
8. The compound for use of any one of claims 1-4, wherein said compound is represented by the structure of formula XV: HO OH OHXV.
9. The compound for use of any one of claims 1-3, wherein said compound is represented by the structure of formula XVI: XIV. 257,470/ P CHO OCH OCHXVI.
10. The compound for use of any one of claims 1-4, wherein said compound is represented by the structure of the following formula: OCH Br HCO Br OCHBr Br Br Br CHBrOMol. Wt.: 821.81 .
11. The compound for use of any one of claims 1- 0 1 , wherein a cell or tissue in a subject is brought into contact with a pharmaceutical composition comprising said compound.
12. The compound for use according to claim 1 1, wherein said cell or tissue is isolated from or within a subject having a cancerous or precancerous condition, suffering from an endocrine disorder that negatively impacts steroidogenesis, suffering from infertility or predisposed to infertility, or suffering from a genetic disorder or other disorder causing premature failure of a gonadal cell or tissue.
13. The compound for use of any one of claims 1-12, wherein said subject is undergoing AIF, GIF or IVF. For the Applicant WOLFF, BREGMAN AND GOLLER By:
Priority Applications (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IL257470A IL257470B2 (en) | 2018-02-11 | 2018-02-11 | Telomerase Activating Compounds for Use in Fertility and Related Applications |
| CN201880024446.4A CN110505872A (en) | 2017-02-12 | 2018-02-12 | Telomerase activation compound for fertility and related application |
| US16/485,416 US11857516B2 (en) | 2017-02-12 | 2018-02-12 | Telomerase activating compounds for use in fertility and related applications |
| PCT/IL2018/050161 WO2018146689A1 (en) | 2017-02-12 | 2018-02-12 | Telomerase activating compounds for use in fertility and related applications |
| CA3053309A CA3053309C (en) | 2017-02-12 | 2018-02-12 | Telomerase activating compounds for use in fertility and related applications |
| AU2018218003A AU2018218003B2 (en) | 2017-02-12 | 2018-02-12 | Telomerase activating compounds for use in fertility and related applications |
| EP18709084.0A EP3579824A1 (en) | 2017-02-12 | 2018-02-12 | Telomerase activating compounds for use in fertility and related applications |
| US18/456,178 US20240180851A1 (en) | 2017-02-12 | 2023-08-25 | Telomerase activating compounds for use in fertility and related applications |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IL257470A IL257470B2 (en) | 2018-02-11 | 2018-02-11 | Telomerase Activating Compounds for Use in Fertility and Related Applications |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| IL257470A IL257470A (en) | 2018-03-29 |
| IL257470B1 IL257470B1 (en) | 2023-08-01 |
| IL257470B2 true IL257470B2 (en) | 2023-12-01 |
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| IL257470A IL257470B2 (en) | 2017-02-12 | 2018-02-11 | Telomerase Activating Compounds for Use in Fertility and Related Applications |
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| Country | Link |
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| IL (1) | IL257470B2 (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008149345A2 (en) * | 2007-06-04 | 2008-12-11 | Ben-Gurion University Of The Negev Research And Development Authority | Tri-aryl compounds and compositions comprising the same |
| WO2015068156A1 (en) * | 2013-11-05 | 2015-05-14 | Ben-Gurion University Of The Negev Research And Development Authority | Compounds for the treatment of diabetes and disease complications arising from same |
-
2018
- 2018-02-11 IL IL257470A patent/IL257470B2/en unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008149345A2 (en) * | 2007-06-04 | 2008-12-11 | Ben-Gurion University Of The Negev Research And Development Authority | Tri-aryl compounds and compositions comprising the same |
| WO2015068156A1 (en) * | 2013-11-05 | 2015-05-14 | Ben-Gurion University Of The Negev Research And Development Authority | Compounds for the treatment of diabetes and disease complications arising from same |
Non-Patent Citations (2)
| Title |
|---|
| NOVEL TELOMERASE-INCREASING COMPOUND IN MOUSE BRAIN DELAYS THE ONSET OF AMYOTROPHIC LATERAL SCLEROSIS, ", 31 December 2012 (2012-12-31) * |
| OXIDATIVE STRESS PROTECTION BY NOVEL TELOMERASE ACTIVATORS IN MESENCHYMAL STEM CELLS DERIVED FROM HEALTHY AND DISEASED INDIVIDUALS, ", 31 December 2013 (2013-12-31) * |
Also Published As
| Publication number | Publication date |
|---|---|
| IL257470A (en) | 2018-03-29 |
| IL257470B1 (en) | 2023-08-01 |
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