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Chemical compound
NC 45-0095 is a synthetic nonsteroidal selective estrogen receptor modulator (SERM) which was under development by Novo Nordisk for the treatment of postmenopausal osteoporosis but was never marketed.[1] [2] [3] [4] [5] It is a partial agonist of the estrogen receptor (IC50 (for binding inhibition) = 9.5 nM; EC50 = 13 nM) with mixed estrogenic and antiestrogenic activity, and shows full estrogenic activity in bone and uterus (Emax (relative to moxestrol , in Ishikawa endometrial cancer cell line ) = 105%).[1] [4] The compound is a pyrrolo indolizine derivative .[1] [2] Its development was discontinued by 2003.[5]
See also [ edit ]
References [ edit ]
^ a b c Jørgensen AS, Jacobsen P, Christiansen LB, Bury PS, Kanstrup A, Thorpe SM, Bain S, Naerum L, Wassermann K (February 2000). "Synthesis and pharmacology of a novel pyrrolo[2,1,5-cd] indolizine (NNC 45-0095), a high affinity non-steroidal agonist for the estrogen receptor". Bioorg. Med. Chem. Lett . 10 (4): 399–402. doi :10.1016/S0960-894X(00)00015-9 . PMID 10714509 .
^ a b Sharma, Vikas; Kumar, Vipin (2014). "Indolizine: a biologically active moiety". Medicinal Chemistry Research . 23 (8): 3593–3606. doi :10.1007/s00044-014-0940-1 . ISSN 1054-2523 . S2CID 2643469 .
^ Wallace OB, Richardson TI, Dodge JA (2003). "Estrogen receptor modulators: relationships of ligand structure, receptor affinity and functional activity". Curr Top Med Chem . 3 (14): 1663–82. doi :10.2174/1568026033451727 . PMID 14683521 .
^ a b Atta-ur- Rahman; Allen B. Reitz (10 December 2010). Frontiers in Medicinal Chemistry . Bentham Science Publishers. pp. 206–. ISBN 978-1-60805-205-9 .
^ a b "NNC 450095 - AdisInsight" .
External links [ edit ]
ER
Agonists
Steroidal: 2-Hydroxyestradiol
2-Hydroxyestrone
3-Methyl-19-methyleneandrosta-3,5-dien-17β-ol
3α-Androstanediol
3α,5α-Dihydrolevonorgestrel
3β,5α-Dihydrolevonorgestrel
3α-Hydroxytibolone
3β-Hydroxytibolone
3β-Androstanediol
4-Androstenediol
4-Androstenedione
4-Fluoroestradiol
4-Hydroxyestradiol
4-Hydroxyestrone
4-Methoxyestradiol
4-Methoxyestrone
5-Androstenediol
7-Oxo-DHEA
7α-Hydroxy-DHEA
7α-Methylestradiol
7β-Hydroxyepiandrosterone
8,9-Dehydroestradiol
8,9-Dehydroestrone
8β-VE2
10β,17β-Dihydroxyestra-1,4-dien-3-one (DHED)
11β-Chloromethylestradiol
11β-Methoxyestradiol
15α-Hydroxyestradiol
16-Ketoestradiol
16-Ketoestrone
16α-Fluoroestradiol
16α-Hydroxy-DHEA
16α-Hydroxyestrone
16α-Iodoestradiol
16α-LE2
16β-Hydroxyestrone
16β,17α-Epiestriol (16β-hydroxy-17α-estradiol)
17α-Estradiol (alfatradiol )
17α-Dihydroequilenin
17α-Dihydroequilin
17α-Epiestriol (16α-hydroxy-17α-estradiol)
17α-Ethynyl-3α-androstanediol
17α-Ethynyl-3β-androstanediol
17β-Dihydroequilenin
17β-Dihydroequilin
17β-Methyl-17α-dihydroequilenin
Abiraterone
Abiraterone acetate
Alestramustine
Almestrone
Anabolic steroids (e.g., testosterone and esters , methyltestosterone , metandienone (methandrostenolone) , nandrolone and esters , many others; via estrogenic metabolites)
Atrimustine
Bolandiol
Bolandiol dipropionate
Butolame
Clomestrone
Cloxestradiol
Conjugated estriol
Conjugated estrogens
Cyclodiol
Cyclotriol
DHEA
DHEA-S
ent -Estradiol
Epiestriol (16β-epiestriol, 16β-hydroxy-17β-estradiol)
Epimestrol
Equilenin
Equilin
ERA-63 (ORG-37663)
Esterified estrogens
Estetrol
Estradiol
Estramustine
Estramustine phosphate
Estrapronicate
Estrazinol
Estriol
Estrofurate
Estrogenic substances
Estromustine
Estrone
Etamestrol (eptamestrol)
Ethinylandrostenediol
Ethinylestradiol
Ethinylestriol
Ethylestradiol
Etynodiol
Etynodiol diacetate
Hexolame
Hippulin
Hydroxyestrone diacetate
Lynestrenol
Lynestrenol phenylpropionate
Mestranol
Methylestradiol
Moxestrol
Mytatrienediol
Nilestriol
Norethisterone
Noretynodrel
Orestrate
Pentolame
Prodiame
Prolame
Promestriene
RU-16117
Quinestradol
Quinestrol
Tibolone
Xenoestrogens: Anise -related (e.g., anethole , anol , dianethole , dianol , photoanethole )
Chalconoids (e.g., isoliquiritigenin , phloretin , phlorizin (phloridzin) , wedelolactone )
Coumestans (e.g., coumestrol , psoralidin )
Flavonoids (incl. 7,8-DHF , 8-prenylnaringenin , apigenin , baicalein , baicalin , biochanin A , calycosin , catechin , daidzein , daidzin , ECG , EGCG , epicatechin , equol , formononetin , glabrene , glabridin , genistein , genistin , glycitein , kaempferol , liquiritigenin , mirificin , myricetin , naringenin , penduletin , pinocembrin , prunetin , puerarin , quercetin , tectoridin , tectorigenin )
Lavender oil
Lignans (e.g., enterodiol , enterolactone , nyasol (cis -hinokiresinol) )
Metalloestrogens (e.g., cadmium )
Pesticides (e.g., alternariol , dieldrin , endosulfan , fenarimol , HPTE , methiocarb , methoxychlor , triclocarban , triclosan )
Phytosteroids (e.g., digitoxin (digitalis ), diosgenin , guggulsterone )
Phytosterols (e.g., β-sitosterol , campesterol , stigmasterol )
Resorcylic acid lactones (e.g., zearalanone , α-zearalenol , β-zearalenol , zearalenone , zeranol (α-zearalanol) , taleranol (teranol, β-zearalanol) )
Steroid -like (e.g., deoxymiroestrol , miroestrol )
Stilbenoids (e.g., resveratrol , rhaponticin )
Synthetic xenoestrogens (e.g., alkylphenols , bisphenols (e.g., BPA , BPF , BPS ), DDT , parabens , PBBs , PHBA , phthalates , PCBs )
Others (e.g., agnuside , rotundifuran )
Mixed (SERMs ) Antagonists
Coregulator-binding modulators: ERX-11
GPER
Agonists Antagonists Unknown