| Stereochemistry | ABSOLUTE |
| Molecular Formula | C45H58N10O13 |
| Molecular Weight | 947.0012 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 11 / 11 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(C)C[C@@H]1NC(=O)[C@@H]2CNC(=O)C[C@H](NC(=O)[C@H](CC(=O)N[C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3NC(C)=O)NC1=O)C(=O)N[C@@H](CC4=CNC5=C4C=CC=C5)C(=O)N[C@@H](CC6=CC=CC=C6)C(=O)N2
InChI
InChIKey=NGCNKEZHGRXHNL-WVWQGFTISA-N
InChI=1S/C45H58N10O13/c1-21(2)13-27-39(62)53-31(17-35(59)55-45-36(48-22(3)57)38(61)37(60)33(20-56)68-45)43(66)52-30-16-34(58)47-19-32(44(67)49-27)54-40(63)28(14-23-9-5-4-6-10-23)50-41(64)29(51-42(30)65)15-24-18-46-26-12-8-7-11-25(24)26/h4-12,18,21,27-33,36-38,45-46,56,60-61H,13-17,19-20H2,1-3H3,(H,47,58)(H,48,57)(H,49,67)(H,50,64)(H,51,65)(H,52,66)(H,53,62)(H,54,63)(H,55,59)/t27-,28-,29-,30-,31-,32-,33+,36+,37+,38+,45+/m0/s1
| Molecular Formula | C45H58N10O13 |
| Molecular Weight | 947.0012 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 11 / 11 |
| E/Z Centers | 1 |
| Optical Activity | UNSPECIFIED |
Menarini was developing oral nepadutant (MEN 11420), a potent and selective tachykinin neurokinin-2 receptor antagonist, for the treatment of infant colic. Nepadutant has been used in trials studying the treatment of colic, infantile colic, and infantile functional gastrointestinal disorders. MEN 11420 is a glycosylated derivative of the potent, selective, conformationally-constrained tachykinin NK2 receptor antagonist MEN 10627. MEN 11420 competitively bound with high affinity to the human NK2 receptor stably transfected in CHO cells, displacing radiolabelled [125I]-neurokinin A and [3H]-SR 48968 with Ki values of 2.5+/-0.7 nM (n = 6) and 2.6+/-0.4 nM (n = 3), respectively.
Originator
Approval Year
PubMed
Sample Use Guides
Infantile Colic: 0.1 - 0.5 mg/Kg as one single oral dose divided in three age strata (from 6 to 24 weeks old)
Route of Administration:
Oral
Nepadutant (MEN 11420) competitively bound with high affinity to the human NK2 receptor stably transfected in CHO cells, displacing radiolabelled [125I]-neurokinin A and [3H]-SR 48968 with Ki values of 2.5±0.7 nM (n=6) and 2.6±0.4 nM (n=3), respectively. In the rabbit isolated pulmonary artery and rat urinary bladder MEN 11420 potently and competitively antagonized tachykinin NK2 receptor-mediated contractions (pKB=8.6±0.07, n=10, and 9.0±0.04, n=12; Schild plot slope=−1.06 (95% c.l.=−1.3; −0.8) and −1.17 (95% c.l.=−1.3; −1.0), respectively). MEN 11420 produced an insurmountable antagonism at NK2 receptors in the hamster trachea and mouse urinary bladder. However, in both preparations, the effect of MEN 11420 was reverted by washout and an apparent pKB of 10.2±0.14, n= 9, and 9.8±0.15, n=9, was calculated in the hamster trachea and mouse urinary bladder, respectively.
