Devazepide

Devazepide
Clinical data
ATC code	none;
Identifiers
	IUPAC name N-(1-methyl-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl)-1H-indole-2-carboxamide;
CAS Number	103420-77-5 ;
PubChem CID	443375;
IUPHAR/BPS	878;
ChemSpider	391607 ;
UNII	JE6P7QY7NH;
KEGG	D02693 ;
ChEMBL	ChEMBL9506 ;
CompTox Dashboard (EPA)	DTXSID2046092 ;
ECHA InfoCard	100.208.547
Chemical and physical data
Formula	C25H20N4O2
Molar mass	408.461 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C(c2cc1ccccc1[nH]2)N[C@H]3/N=C(\c4ccccc4N(C3=O)C)c5ccccc5;
	InChI InChI=1S/C25H20N4O2/c1-29-21-14-8-6-12-18(21)22(16-9-3-2-4-10-16)27-23(25(29)31)28-24(30)20-15-17-11-5-7-13-19(17)26-20/h2-15,23,26H,1H3,(H,28,30)/t23-/m1/s1 ; Key:NFHRQQKPEBFUJK-HSZRJFAPSA-N ;
	(what is this?) (verify)

Devazepide^[1] (L-364,718, MK-329) is benzodiazepine drug, but with quite different actions from most benzodiazepines, lacking affinity for GABA_A receptors and instead acting as an CCK_A receptor antagonist.^[2] It increases appetite and accelerates gastric emptying,^[3]^[4] and has been suggested as a potential treatment for a variety of gastrointestinal problems including dyspepsia, gastroparesis and gastric reflux.^[5] It is also widely used in scientific research into the CCK_A receptor.^[6]^[7]

Synthesis

Devazepide is synthesised in a similar manner to other benzodiazepines.^[8]^[9]

References

^ US 4820834, Evans, Ben E.; Freidinger, Roger M. & Bock, Mark G., "Benzodiazepine analogs", published 1989-04-11, assigned to Merck & Co. Inc.
^ Hill DR, Woodruff GN (September 1990). "Differentiation of central cholecystokinin receptor binding sites using the non-peptide antagonists MK-329 and L-365,260". Brain Research. 526 (2): 276–83. doi:10.1016/0006-8993(90)91232-6. PMID 2257485. S2CID 23851131.
^ Cooper SJ, Dourish CT (December 1990). "Multiple cholecystokinin (CCK) receptors and CCK-monoamine interactions are instrumental in the control of feeding". Physiology & Behavior. 48 (6): 849–57. doi:10.1016/0031-9384(90)90239-z. PMID 1982361. S2CID 24850080.
^ Cooper SJ, Dourish CT, Clifton PG (January 1992). "CCK antagonists and CCK-monoamine interactions in the control of satiety". The American Journal of Clinical Nutrition. 55 (1 Suppl): 291S–295S. doi:10.1093/ajcn/55.1.291s. PMID 1728842.
^ Scarpignato C, Varga G, Corradi C (1993). "Effect of CCK and its antagonists on gastric emptying". Journal of Physiology, Paris. 87 (5): 291–300. doi:10.1016/0928-4257(93)90035-r. PMID 8298606. S2CID 23725376.
^ Weller A (July 2006). "The ontogeny of postingestive inhibitory stimuli: examining the role of CCK". Developmental Psychobiology. 48 (5): 368–79. doi:10.1002/dev.20148. PMID 16770766.
^ Savastano DM, Covasa M (October 2007). "Intestinal nutrients elicit satiation through concomitant activation of CCK(1) and 5-HT(3) receptors". Physiology & Behavior. 92 (3): 434–42. doi:10.1016/j.physbeh.2007.04.017. PMID 17531277. S2CID 5566756.
^ Evans BE, Rittle KE, Bock MG, DiPardo RM, Freidinger RM, Whitter WL, et al. (December 1988). "Methods for drug discovery: development of potent, selective, orally effective cholecystokinin antagonists". Journal of Medicinal Chemistry. 31 (12): 2235–46. doi:10.1021/jm00120a002. PMID 2848124.
^ EP 1492540, Jackson, Karen, "The use of devazepide as analgesic agent", published 2005-01-05, assigned to ML Laboratories plc

[1] US 4820834, Evans, Ben E.; Freidinger, Roger M. & Bock, Mark G., "Benzodiazepine analogs", published 1989-04-11, assigned to Merck & Co. Inc.

[2] Hill DR, Woodruff GN (September 1990). "Differentiation of central cholecystokinin receptor binding sites using the non-peptide antagonists MK-329 and L-365,260". Brain Research. 526 (2): 276–83. doi:10.1016/0006-8993(90)91232-6. PMID 2257485. S2CID 23851131.

[3] Cooper SJ, Dourish CT (December 1990). "Multiple cholecystokinin (CCK) receptors and CCK-monoamine interactions are instrumental in the control of feeding". Physiology & Behavior. 48 (6): 849–57. doi:10.1016/0031-9384(90)90239-z. PMID 1982361. S2CID 24850080.

[4] Cooper SJ, Dourish CT, Clifton PG (January 1992). "CCK antagonists and CCK-monoamine interactions in the control of satiety". The American Journal of Clinical Nutrition. 55 (1 Suppl): 291S–295S. doi:10.1093/ajcn/55.1.291s. PMID 1728842.

[5] Scarpignato C, Varga G, Corradi C (1993). "Effect of CCK and its antagonists on gastric emptying". Journal of Physiology, Paris. 87 (5): 291–300. doi:10.1016/0928-4257(93)90035-r. PMID 8298606. S2CID 23725376.

[6] Weller A (July 2006). "The ontogeny of postingestive inhibitory stimuli: examining the role of CCK". Developmental Psychobiology. 48 (5): 368–79. doi:10.1002/dev.20148. PMID 16770766.

[7] Savastano DM, Covasa M (October 2007). "Intestinal nutrients elicit satiation through concomitant activation of CCK(1) and 5-HT(3) receptors". Physiology & Behavior. 92 (3): 434–42. doi:10.1016/j.physbeh.2007.04.017. PMID 17531277. S2CID 5566756.

[8] Evans BE, Rittle KE, Bock MG, DiPardo RM, Freidinger RM, Whitter WL, et al. (December 1988). "Methods for drug discovery: development of potent, selective, orally effective cholecystokinin antagonists". Journal of Medicinal Chemistry. 31 (12): 2235–46. doi:10.1021/jm00120a002. PMID 2848124.

[9] EP 1492540, Jackson, Karen, "The use of devazepide as analgesic agent", published 2005-01-05, assigned to ML Laboratories plc

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

v t e Benzodiazepines
1,4-Benzodiazepines	2-Oxoquazepam 3-Hydroxyphenazepam Bromazepam BMS-906024* Camazepam Carburazepam Chlordiazepoxide Cinazepam Cinolazepam Clonazepam Cloniprazepam Clorazepate Cyprazepam Delorazepam Demoxepam Desmethylflunitrazepam Devazepide* Diazepam Diclazepam Difludiazepam Doxefazepam Elfazepam Ethyl carfluzepate Ethyl dirazepate Ethyl loflazepate Flubromazepam Fletazepam Fludiazepam Flunitrazepam Flurazepam Flutemazepam Flutoprazepam Fosazepam Gidazepam Halazepam Iclazepam Irazepine* Kenazepine Ketazolam Lorazepam Lormetazepam Lufuradom* Meclonazepam Medazepam Menitrazepam Metaclazepam Motrazepam N-Desalkylflurazepam Nifoxipam Nimetazepam Nitemazepam Nitrazepam Nitrazepate Nordazepam Nortetrazepam Oxazepam Phenazepam Pinazepam Pivoxazepam Prazepam Proflazepam Quazepam QH-II-66 Reclazepam RO4491533* Ro05-4082 Ro5-4864* Ro07-5220 Ro07-9749 Ro20-8065 Ro20-8552 SH-I-048A Sulazepam Temazepam Tetrazepam Tifluadom* Timelotem* Tolufazepam Triflunordazepam Tuclazepam Uldazepam
1,5-Benzodiazepines	Arfendazam Clobazam CP-1414S Lofendazam Triflubazam
2,3-Benzodiazepines*	Girisopam GYKI-52466 GYKI-52895 Nerisopam Talampanel Tofisopam
Triazolobenzodiazepines	Adinazolam Alprazolam Balovaptan* Bromazolam Clonazolam Estazolam Fluadinazolam Flualprazolam Flubromazolam Flunitrazolam Nitrazolam Phenazolam Pyrazolam Rilmazolam (active metabolite of Rilmazafone) Triazolam
Imidazobenzodiazepines	Bretazenil Climazolam EVT-201 FG-8205 Flumazenil GL-II-73 Imidazenil ¹²³I-Iomazenil L-655,708 Loprazolam Midazolam PWZ-029 Remimazolam Ro15-4513 Ro48-6791 Ro48-8684 Ro4938581 Sarmazenil SH-053-R-CH3-2′F
Oxazolobenzodiazepines	Cloxazolam Flutazolam Haloxazolam Mexazolam Oxazolam
Thienodiazepines	Bentazepam Clotiazepam Ro09-9212
Thienotriazolodiazepines	α-Hydroxyetizolam Apafant* Brotizolam Ciclotizolam Clotizolam Deschloroclotizolam Deschloroetizolam Etizolam Flubrotizolam Fluclotizolam Fluetizolam Israpafant* JQ1* Metizolam
Thienobenzodiazepines*	Olanzapine Telenzepine
Pyridodiazepines	Lopirazepam
Pyridotriazolodiazepines	Zapizolam
Pyrazolodiazepines	Razobazam* Ripazepam Zolazepam Zomebazam Zometapine*
Pyrrolodiazepines	Premazepam
Tetrahydroisoquinobenzodiazepines	Clazolam
Pyrrolobenzodiazepines*	Anthramycin
Benzodiazepine prodrugs	Alprazolam triazolobenzophenone Avizafone Rilmazafone
* atypical activity profile (not GABA_A receptor ligands)

Synthesis

See also

References