152665-84-4

Upstream product

• 109-04-6 2-bromo-pyridine 
• 1885-29-6 anthranilic acid nitrile 
• 621-84-1 O-benzyl carbamate 
• 153826-03-0 2--N^α-(benzyloxycarbonyl)glycinyl>-2'-aminobenzoyl>pyridine 
• 103711-23-5 α-<(tert-butyloxycarbonyl)amino>-N^α-(benzyloxycarbonyl)glycine 
• 124676-19-3 2-(benzotriazol-1-yl)-N-(benzyloxycarbonyl)glycine 
• 42471-56-7 2-(2-aminobenzoyl)pyridine 
• 1052665-90-3 {Amino-[2-(pyridine-2-carbonyl)-phenylcarbamoyl]-methyl}-carbamic acid benzyl ester 

Downstream Products

• 154064-10-5 [2-Oxo-1-(2-oxo-2-o-tolyl-ethyl)-5-pyridin-2-yl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl]-carbamic acid benzyl ester 
• 155488-25-8 N-((3R)-1-tert-Butylcarbonylmethyl-2,3-dihydro-2-oxo-5-(pyridin-2-yl)-1H-1,4-benzodiazepin-3-yl)-N'-(3-methylaminophenyl)urea 
• 155412-88-7 N-((3R)-1-tert-Butylcarbonylmethyl-2,3-dihydro-2-oxo-5-(pyridin-2-yl)-1H-1,4-benzodiazepin-3-yl)-N'-(3-aminophenyl)urea 

Relevant academic research and scientific papers

BENZODIAZEPINE DERIVATIVES AS CCK2/GASTRIN RECEPTOR ANTAGONISTS

The invention relates to benzodiazepine derivatives of formula (A) useful as CCK2/gastrin receptor antagonists, their preparation and their use in the treatment or prevention of disorders associated with CCK2/gastrin receptors, disorders caused by or associated with hypergastrinaemia, and gastric acid-related disorders.

(3R)-N-(1-(tert-butylcarbonylmethyl)-2,3-dihydro-2-oxo-5-(2-pyridyl)- 1H-1,4-benzodiazepin-3-yl)-N'-(3-(methylamino)phenyl)urea (YF476): A potent and orally active gastrin/CCK-B antagonist

A number of new 1,4-benzodiazepin-2-one-based gastrin/CCK-B receptor antagonists related to the archetypal analogue L-365,260, and more closely to the recently reported compound YM022, have been synthesized and evaluated for biological activity. The compounds were screened for their ability to inhibit the binding of [125I]CCK-8 to gastrin/CCK-B receptors prepared from rat brains and that of [3H]L-364,718 to CCK-A receptors from rat pancreas, and were shown to be potent and selective ligands for the gastrin/CCK-B receptor. Functional studies in vivo demonstrated the compounds to be antagonists of the receptor as evidenced by their ability to inhibit pentagastrin-induced gastric acid secretion in anesthetized rats. More extensive evaluation in viva included determination of ED50 values in the rat acid secretion model for selected compounds and an examination of the effect of these compounds on pentagastrin-induced gastric acid secretion in Heidenhain pouch dogs following oral and intravenous administration. Two compounds, i.e. (3R)-N- [1-[(tert-butylcarbonyl)methyl]-2,3-dihydro-2-oxo-5-(2-pyridyl)-1H-1,4- benzodiazepin-3-yl]-N'-[3-(methylamino)phenyl]urea, 15c (YF476), and (3R)-N- [1-[(tert-Butylcarbonyl)methyl]-2,3-dihydro-2-oxo-5-(2-pyridyl)-1H-1,4- benzodiazepin-3-yl]-N'-[3-(dimethylamino)phenyl]urea hydrochloride, 15d, showed potent dose-dependent effects in both models with the former showing excellent oral bioavailability and an ED50 of 21 nmol/kg po in dogs. 15e is currently under clinical investigation for the treatment of gastro-oesophagal reflux disease (GORD).

Synthesis and biological activity of 5-heteroaryl benzodiazepines: Analogues of YM022

A novel series of analogues of the potent gastrin/CCK-B receptor antagonist YM022 have been prepared which incorporate 5- and 6-membered heteroaromatic rings in the benzodiazepine 5-position. The 5-(2-pyridyl) derivatives in particular retained good in vitro and in vivo potency and one such compound 9i was shown to inhibit acid secretion after oral dosing in dogs. Improved bioavailability for 9i over the 5-phenyl analogue, 9h was demonstrated in rats.

Development of 1,4-Benzodiazepine Cholecystokinin Type B Antagonists

A series of 3-(arylureido)-5-phenyl-1,4-benzodiazepines, nonpeptidal antagonists of the peptide hormone cholecystokinin (CCK), are described.Derived by reasoned modification of the CCK-A selective 3-carboxamido-1,4-benzodiazepine, MK-329, this paper chronicles the development of potent, orally effective compounds in which selectivity for the CCK-B recebtor subtype was achieved.The principal lead structure that emerged from these studied is L-365,260, a compound which has been submitted for clinical evaluation.Details of the ability to modulate the receptor interactions of these benzodiazepines by appropriate structure modifications are discussed which imply the possibility of further refining the CCK-B receptor affinity and selectivity of this class of compounds.

Benzodiazepine analogs for treating panic syndrome and for directly inducing analgesia

From EXEMP_CLAIMS : 1. A pharmaceutical composition useful in treatment of panic disorder or other neurological disorders involving anxiety, comprising an effective amount of a CCK and/or gastrin antagonist compound of the formula: wherein: R1 is H, C1-6 linear or branched alkyl, X12-cycloalkyl, -X12COOR6, R2 is substituted or unsubstituted phenyl (wherein the substituents may be 1 or 2 of halo, loweralkyl, carboxyl, nitro or -CF3); -X12COOR6; 2-, 3-, 4-pyridyl; R4 and R5 are independently R6 or in combination with the N of the NR4R5 group form an unsubstituted or mono- or disubstituted, saturated or unsaturated, 4-7 membered heterocyclic ring, or benzofused 4-7 membered heterocyclic ring wherein said heterocyclic ring or said benzofused heterocyclic ring may contain a second heteroatom selected from 0 and NCH3 and the substituent(s) is/are independently selected from C1-4 alkyl; R6 is H, C1-6 straight or branched-chain alkyl or cycloalkyl; R7 is α- or β-naphthyl, substituted or unsubstituted phenyl (wherein the substitutents may be 1 to 2 of halo, -NO2, -OH,-NR4R5, loweralkyl, CF3, CN, COOR6, X12COOR6, X12OR6, or loweralkoxy), 2-, 3-, 4-pyridyl, R8 is H, loweralkyl, cycloloweralkyl, X12COOR6; X1 is H, -NO2, CF3, loweralkyl or halo; X2 and X3 are independently H, -NO2, OH, halo, loweralkyl, or loweralkoxy, X12COOR6, COOR6, or OX12COOR6; X4 is O, or NR8; X7 is O; X12 is C1-5 linear or branched chain alkyl, or the pharmaceutically acceptable salt thereof.