957130-49-3

Upstream product

• 939374-42-2 (+)-5-amino-1'-{[2-(trimethylsilyl)ethoxy]methyl}-1,3-dihydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one 
• 51832-31-6 4-amino-phthalic acid dimethyl ester 
• 610-27-5 4-nitrophthalic acid 
• 610-22-0 dimethyl 4-nitrophthalate 
• 3430-17-9 2-bromo-3-picoline 
• 1260403-53-9 dimethyl 4-(dibenzylamino)benzene-1,2-dicarboxylate 
• 1260403-54-0 [4-(dibenzylamino)-2-(hydroxymethyl)phenyl]methanol 
• 1235305-63-1 N-(tert-butyl)-3-methylpyridin-2-amine 
• 1260403-56-2 methyl tert-butyl(3-methylpyridin-2-yl)carbamate 
• 1321609-73-7 C₁₁H₁₃N₂O^(1-)*Li⁽¹⁺⁾ 
• 1246733-24-3 methyl 1-(tert-butyl)-2-hydroxy-1H-pyrrolo[2,3-b]pyridine-3-carboxylate 
• 1246647-79-9 C₁₃H₁₅N₂O₃^(1-)*K⁽¹⁺⁾ 
• 1260403-57-3 (R)-1’-(tert-butyl)-5-(dibenzylamino)-1,3-dihydrospiro[indene-2,3’-pyrrolo[2,3-b]pyridin]-2’(1’H)-one 
• 1260403-55-1 [2-(chloromethyl)-4-(dibenzylamino)phenyl]methanol hydro chloride 

Downstream Products

• 1059185-34-0 2-[5-(3,5-difluorophenyl)-3-ethyl-5-methyl-2,4-dioxoimidazolidin-1-yl]-N-[(2R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]acetamide 
• 1234507-37-9 2-[2-(3,5-difluorophenyl)-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl]-N-[(2R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]acetamide trifluoroacetate 
• 957118-49-9 [3H]-MK 3207 
• 1257387-50-0 2-((R)-3-(3,5-difluorophenyl)-5-oxo-8,11-dioxa-1,4-diazaspiro[5.6]dodecan-4-yl)-N-((R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl)acetamide 
• 1257388-14-9 tert-butyl 3-(3-methoxyphenyl)-5-oxo-4-(2-oxo-2-((R)-2'-oxo-1,1',2',3-tetrahydrospiro[inden-2,3'-pyrrolo[2,3-b]pyridin]-5-ylamino)ethyl)-8,11-dioxa-1,4-diazaspiro[5.6]dodecane-1-carboxylate 
• 1257387-61-3 (R)-tert-butyl 5-oxo-4-(2-oxo-2-((R)-2'-oxo-1,1',2',3-tetrahydrospiro[inden-2,3'-pyrrolo-[2,3-b]pyridin]-5-ylamino)ethyl)-3-phenyl-8,11-dioxa-1,4-diazaspiro[5.6]-dodecane-1-carboxylate 
• 1257388-36-5 2-(3-(4-fluorophenyl)-5-oxo-8,11-dioxa-1,4-diazaspiro[5.6]dodecan-4-yl)-N-((R)-2'-oxo-1,1',2',3-tetrahydrospiro[inden-2,3'-pyrrolo[2,3-b]pyridin]-5-yl)acetamide 
• 1257387-58-8 2-((R)-3-(3,5-difluorophenyl)-1-methyl-5-oxo-8,11-dioxa-1,4-diazaspiro[5.6]dodecan-4-yl)-N-((R)-2'-oxo-1,1',2',3-tetrahydrospiro[inden-2,3'-pyrrolo[2,3-b]pyridin]-5-yl)acetamide 
• 1257387-80-6 2-((3R)-3-(cycloheptylmethyl)-6-(3,5-difluorophenyl)-2-oxopiperazin-1-yl)-N-((R)-2'-oxo-1,1',2',3-tetrahydrospiro[inden-2,3'-pyrrolo[2,3-b]pyridin]-5-yl)acetamide 
• 1257387-53-3 2-((R)-3-(3,5-difluoro-phenyl)-5-oxo-12-oxa-1,4-diaza-dispiro[5.2.5.2]hexadecan-4-yl)-N-((R)-2'-oxo-1,1',2',3-tetrahydrospiro[inden-2,3'-pyrrolo[2,3-b]pyridin]-5-yl)acetamide 
• 1383733-39-8 (2R)-N-[(5R,6S,8S)-3-(2-hydroxypopan-2-yl)-5-methyl-6-phenyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-8-yl]-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridine]-5-carboxamide 
• 1383733-38-7 (2R)-N-{(5R,6S,8S)-5-methyl-6-phenyl-3-[1-(trifluoromethyl)cyclopropyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-8-yl}-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridine]-5-carboxamide 
• 1383733-33-2 (2R)-N-[(6S,8S)-6-(2,3-difluorophenyl)-3-(2,2,2-trifluoroethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-8-yl]-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridine]-5-carboxamide 
• 1383733-27-4 (2R)-N-[(6S,8S)-6-(2,3-difluorophenyl)-3-(2-methoxypopan-2-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-8-yl]-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridine]-5-carboxamide 

Relevant academic research and scientific papers

Discovery of a First-In-Class Small Molecule Antagonist against the Adrenomedullin-2 Receptor: Structure-Activity Relationships and Optimization

Class B G-protein-coupled receptors (GPCRs) remain an underexploited target for drug development. The calcitonin receptor (CTR) family is particularly challenging, as its receptors are heteromers comprising two distinct components: The calcitonin receptor-like receptor (CLR) or calcitonin receptor (CTR) together with one of three accessory proteins known as receptor activity-modifying proteins (RAMPs). CLR/RAMP1 forms a CGRP receptor, CLR/RAMP2 forms an adrenomedullin-1 (AM1) receptor, and CLR/RAMP3 forms an adrenomedullin-2 (AM2) receptor. The CTR/RAMP complexes form three distinct amylin receptors. While the selective blockade of AM2 receptors would be therapeutically valuable, inhibition of AM1 receptors would cause clinically unacceptable increased blood pressure. We report here a systematic study of structure-activity relationships that has led to the development of first-in-class AM2 receptor antagonists. These compounds exhibit therapeutically valuable properties with 1000-fold selectivity over the AM1 receptor. These results highlight the therapeutic potential of AM2 antagonists.

HETEROCYCLIC SPIRO-COMPOUNDS AS AM2 RECEPTOR INHIBITORS

Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof: wherein R1, R2, R4, R5, R6, R7, R8, R9, R10,Z, X1, X2, X3, L2, HET, n and q are as defined herein. The compounds are inhibitors of adrenomedullin receptor subtype 2 (AM2). Also disclosed are the compounds for use in the treatment of diseases modulated AM2, including proliferative diseases such as cancer; pharmaceutical compositions comprising the compounds; methods for preparing the compounds; and intermediates useful in the preparation of the compounds.

HETEROCYCLIC SPIRO-COMPOUNDS AS AM2 RECEPTOR INHIBITORS

Disclosed are compounds of the formula (I) and pharmaceutically acceptable salts thereof: wherein HET, R1, R2, R3, R4, R5, L, L1, X1, X2, X3 and q are as defined herein. The compounds are inhibitors of adrenomedullin receptor subtype 2 (AM2). Also disclosed are the compounds for use in the treatment of diseases modulated AM2, including proliferative diseases such as cancer; pharmaceutical compositions comprising the compounds; methods for preparing the compounds; and intermediates useful in the preparation of the compounds.

Piperidinone carboxamide indane CGRP receptor antagonists

The present invention is directed to piperidinone carboxamide indane derivatives which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

PYRIDINE CGRP RECEPTOR ANTAGONISTS

The present invention is directed to pyridine derivatives which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

ALIPHATIC SPIROLACTAM CGRP RECEPTOR ANTAGONISTS

The present invention is directed to aliphatic spirolactam derivatives which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which CGRP is involved, such as migraine. The invention is also directed to pharmaceutical\compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

PROCESS FOR MAKING CGRP RECEPTOR ANTAGONIST

The invention encompasses a novel process for making 2-[(8R)-8-(3,5-Difluorophenyl)-10-oxo-6,9-diazaspiro[4.5]dec-9-yl]-N-[(2R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]acetamide, which is a CGRP receptor antagonist useful for the treatment of migraine, using an asymmetric phase-transfer catalysis route. The invention also encompasses an efficient and practical synthesis of the (R)-acid intermediate, and generates the benzylic stereocenter in an enantioselective manner.

CGRP RECEPTOR ANTAGONISTS

Compounds of Formula (I) (wherein variables A1, A2, A3, ring-B, m, n, J, E1, E2, E3, R5, RPG and Y are as described herein), which are useful as antagonists of CGRP receptors, an

IMIDAZOLINONE DERIVATIVES AS CGRP RECEPTOR ANTAGONISTS

The present invention is directed to imidazolinone derivatives which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which CGRP is involved, such as migraine. The invention is also directed to pharmaceutical comp