A 331440 dihydrochlorideH3 receptor antagonist,non-imidazole,high affinity CAS# 1049740-32-0 |
- KN-92 phosphate
Catalog No.:BCC1682
CAS No.:1135280-28-2
- KN-92 hydrochloride
Catalog No.:BCC1681
CAS No.:1431698-47-3
- Ivermectin
Catalog No.:BCC1251
CAS No.:70288-86-7
- A 438079 hydrochloride
Catalog No.:BCC1317
CAS No.:899431-18-6
- A 438079
Catalog No.:BCC1316
CAS No.:899507-36-9
Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
Cas No. | 1049740-32-0 | SDF | Download SDF |
PubChem ID | 16078942 | Appearance | Powder |
Formula | C22H29Cl2N3O | M.Wt | 422.39 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Solubility | Soluble to 100 mM in water and to 20 mM in DMSO | ||
Chemical Name | 4-[4-[3-[(3R)-3-(dimethylamino)pyrrolidin-1-yl]propoxy]phenyl]benzonitrile;dihydrochloride | ||
SMILES | CN(C)C1CCN(C1)CCCOC2=CC=C(C=C2)C3=CC=C(C=C3)C#N.Cl.Cl | ||
Standard InChIKey | XFPYVTSGYYMTFS-GHVWMZMZSA-N | ||
Standard InChI | InChI=1S/C22H27N3O.2ClH/c1-24(2)21-12-14-25(17-21)13-3-15-26-22-10-8-20(9-11-22)19-6-4-18(16-23)5-7-19;;/h4-11,21H,3,12-15,17H2,1-2H3;2*1H/t21-;;/m1../s1 | ||
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
||
About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
||
Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. |
Description | High affinity histamine H3 receptor antagonist (Ki values are 21.7 and 22.7 nM for rat and human H3 receptors, respectively). Exhibits selectivity for human H3 over H1, H2 and H4 receptors (Ki values are 2940, 14400 and >10000 nM respectively). Shown to reduce weight in a diet-induced obesity model. |
A 331440 dihydrochloride Dilution Calculator
A 331440 dihydrochloride Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 2.3675 mL | 11.8374 mL | 23.6748 mL | 47.3496 mL | 59.187 mL |
5 mM | 0.4735 mL | 2.3675 mL | 4.735 mL | 9.4699 mL | 11.8374 mL |
10 mM | 0.2367 mL | 1.1837 mL | 2.3675 mL | 4.735 mL | 5.9187 mL |
50 mM | 0.0473 mL | 0.2367 mL | 0.4735 mL | 0.947 mL | 1.1837 mL |
100 mM | 0.0237 mL | 0.1184 mL | 0.2367 mL | 0.4735 mL | 0.5919 mL |
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. |
Calcutta University
University of Minnesota
University of Maryland School of Medicine
University of Illinois at Chicago
The Ohio State University
University of Zurich
Harvard University
Colorado State University
Auburn University
Yale University
Worcester Polytechnic Institute
Washington State University
Stanford University
University of Leipzig
Universidade da Beira Interior
The Institute of Cancer Research
Heidelberg University
University of Amsterdam
University of Auckland
TsingHua University
The University of Michigan
Miami University
DRURY University
Jilin University
Fudan University
Wuhan University
Sun Yat-sen University
Universite de Paris
Deemed University
Auckland University
The University of Tokyo
Korea University
A-331440 is described here instead of A-331440 dihydrochloride. A-331440 is an antagonist of non-imidazole histamine H3 receptor with an IC50 value of 22.7 nM for human cortex histamine H3 [1].
Histamine, as a neurotransmitter, is important in homeostasis and physiology. In the CNS, histamine released has the potential to interact with H1, H2, H3 and possibly H4 receptors. All the receptors are G-protein coupled receptors [2].
In HEK 293 cells stably transfected with rat or human histamine H3 receptors, A-331440 was tested for its ability to antagonize increasing calcium mobilization in response to (R)-α-methylhistamine and showed pKb ± S.E.M. values of 7.38 ± 0.10 and 7.37 ± 0.29 for rat histamine H3 and human histamine H3, respectively [1].
In mice, treatment with A-331440 at a dose of 100 mg/kg resulted in piloerection and hypoactivity in the first 2 h, but diminished thereafter. In naive male CD-1 mice, administration with comparable doses of A-331440 i.p. also produced similar data. By day 28, mice treated with A-331440 at the intermediate dose weighed 35.7 ± 0.93 g with an average weight loss of 5.3 ± 0.99 g. The high dose of A-331440 (15 mg/kg, p.o., b.i.d.) produced a marked and sustained weight loss [1].
References:
[1]. Hancock AA, Bennani YL, Bush EN, et al. Antiobesity effects of A-331440, a novel non-imidazole histamine H3 receptor antagonist. European journal of pharmacology, 2004, 487(1): 183-197.
[2]. Hancock AA, Diehl MS, Faghih R, et al. In vitro Optimization of Structure Activity Relationships of Analogues of A-331440 Combining Radioligand Receptor Binding Assays and Micronucleus Assays of Potential Antiobesity Histamine H3 Receptor Antagonists. Basic & clinical pharmacology & toxicology, 2004, 95(3): 144-152.
- Naspm trihydrochloride
Catalog No.:BCC7476
CAS No.:1049731-36-3
- 8-Hydroxydigitoxigenin
Catalog No.:BCN5864
CAS No.:1049674-06-7
- Ethyl β-D-ribo-hex-3-ulopyranoside
Catalog No.:BCC8977
CAS No.:104953-08-4
- H-D-Val-OtBu.HCl
Catalog No.:BCC3146
CAS No.:104944-18-5
- Tranilast Sodium
Catalog No.:BCC4091
CAS No.:104931-56-8
- Borapetoside B
Catalog No.:BCN6593
CAS No.:104901-05-5
- dl-Aloesol
Catalog No.:BCN7265
CAS No.:104871-04-7
- (+)-Isopulegol
Catalog No.:BCN4975
CAS No.:104870-56-6
- NF 023
Catalog No.:BCC6985
CAS No.:104869-31-0
- NF 157
Catalog No.:BCC7367
CAS No.:104869-26-3
- UPF 1069
Catalog No.:BCC2213
CAS No.:1048371-03-4
- Germanicol acetate
Catalog No.:BCN7264
CAS No.:10483-91-7
- Cardiogenol C hydrochloride
Catalog No.:BCC7790
CAS No.:1049741-55-0
- PS 1145 dihydrochloride
Catalog No.:BCC7949
CAS No.:1049743-58-9
- 3-Acetoxy-4,7(11)-cadinadien-8-one
Catalog No.:BCN5865
CAS No.:104975-02-2
- Tacrolimus (FK506)
Catalog No.:BCC4952
CAS No.:104987-11-3
- Ascomycin(FK 520)
Catalog No.:BCC1370
CAS No.:104987-12-4
- Pallidol
Catalog No.:BCN3306
CAS No.:105037-88-5
- AST-1306 TsOH
Catalog No.:BCC4043
CAS No.:1050500-29-2
- GPR120 modulator 1
Catalog No.:BCC1599
CAS No.:1050506-75-6
- GPR120 modulator 2
Catalog No.:BCC1600
CAS No.:1050506-87-0
- 1-Ketoaethiopinone
Catalog No.:BCN3219
CAS No.:105062-36-0
- Ro 51
Catalog No.:BCC6157
CAS No.:1050670-85-3
- Moellendorffilin
Catalog No.:BCN3546
CAS No.:105099-87-4
Antiobesity effects of A-331440, a novel non-imidazole histamine H3 receptor antagonist.[Pubmed:15033391]
Eur J Pharmacol. 2004 Mar 8;487(1-3):183-97.
Histamine affects homeostatic mechanisms, including food and water consumption, by acting on central nervous system (CNS) receptors. Presynaptic histamine H(3) receptors regulate release of histamine and other neurotransmitters, and histamine H(3) receptor antagonists enhance neurotransmitter release. A-331440 [4'-[3-(3(R)-(dimethylamino)-pyrrolidin-1-yl)-propoxy]-biphenyl-4-carbonitrile] is a histamine H(3) receptor antagonist which binds potently and selectively to both human and rat histamine H(3) receptors (K(i)<==25 nM). Mice were stabilized on a high-fat diet (45 kcal % lard) prior to 28-day oral b.i.d. dosing for measurement of obesity-related parameters. A-331440 administered at 0.5 mg/kg had no significant effect on weight, whereas 5 mg/kg decreased weight comparably to dexfenfluramine (10 mg/kg). A-331440 administered at 15 mg/kg reduced weight to a level comparable to mice on the low-fat diet. The two higher doses reduced body fat and the highest dose also normalized an insulin tolerance test. These data show that the histamine H(3) receptor antagonist, A-331440, has potential as an antiobesity agent.
In vitro optimization of structure activity relationships of analogues of A-331440 combining radioligand receptor binding assays and micronucleus assays of potential antiobesity histamine H3 receptor antagonists.[Pubmed:15447739]
Basic Clin Pharmacol Toxicol. 2004 Sep;95(3):144-52.
A-331440 [4'-[3-(3(R)-(dimethylamino)-pyrrolidin-1-yl)-propoxy]-biphenyl-4-carbonitrile], a potent and selective antagonist of histamine H3 receptors, yielded positive results in an in vitro micronucleus assay, predictive of genotoxicity in vivo. Because this compound has highly favourable properties and potential as an antiobesity agent, new compounds of this general chemical class were sought that would retain or improve upon the high potency and selectivity of A-331440 for H3 receptors, but would lack the potential for genotoxicity obtained with that compound. Our working hypothesis was that the biphenyl rings in A-331440 might contribute to interactions with DNA and thereby predispose toward genotoxicity. Toward this end, several analogues were prepared, with substituents introduced onto the biaryl ring to alter the orientation, electronegativity, and polarity of this moiety, and were tested for their radioligand binding potency and selectivity and their propensity to induce genotoxicity in the in vitro micronucleus assay. Using this strategy, novel compounds were discovered that retained or improved upon the potency and selectivity of A-331440 for H3 receptors and were devoid of genotoxicity in vitro. Of these, the simple mono- and di-fluorinated analogues (A-417022 [4'-[3-[(3R)-3-(dimethylamino)-1-pyrrolidinyl]propoxy]-3'-fluoro-1,1'-biphenyl-4- carbonitrile] and A-423579 [4'-[3-[(3R)-3-(dimethylamino)-1-pyrrolidinyl]-propoxy]-3',5'-difluoro-1,1'-biphe nyl-4-carbonitrile], respectively) were found to bind to H3 receptors at least as potently as A-331440, while lacking genotoxicity in the micronucleus assay. The reason of the lack of genotoxicity of the fluorinated analogues is unclear, but is especially noteworthy in light of the general principle that fluorine and hydrogen are very similar in size. Therefore, these fluorinated analogues of A-331440 represented the most potent and potentially safest compounds for further evaluation as antiobesity leads. Preliminary findings with one of these examples, A-417022, in a mouse model of obesity are presented.