183958-71-6

Basic information

• Product Name: 3(S)-3-Hydroxymethyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester
• Synonyms: 3(S)-3-Hydroxymethyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester;(S)-N-Boc-1,2,3,4-tetrahydro-3-isoquinolinylmethanol;(S)-2-Boc-1,3,4-trihydro-3-isoquinolinemethanol;(S)-N-Boc-1,2,3,4-tetrahydro-3-isoquinolinylmethanol,99%e.e.
• CAS NO: 183958-71-6
• Molecular Formula: C₁₅H₂₁NO₃
• Molecular Weight: 263.33214
• Mol File: 183958-71-6.mol

Chemical Properties

• Appearance: /
• CAS DataBase Reference: 3(S)-3-Hydroxymethyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: 3(S)-3-Hydroxymethyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester(183958-71-6)
• EPA Substance Registry System: 3(S)-3-Hydroxymethyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester(183958-71-6)

Safety Data

• Hazardous Substances Data: 183958-71-6(Hazardous Substances Data)

Upstream product

• 115962-35-1 (3S)-2-tert-butoxycarbonyl-1,2,3,4-tetrahydroisoquinole-3-carboxylic acid 
• 24424-99-5 di-tert-butyl dicarbonate 
• 252008-94-9 methyl (3S)-2-(tert-butoxycarbonyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylate 
• 74163-81-8 L-Tic-OH 
• 18881-17-9 (S)-3-hydroxymethyl-1,2,3,4-tetrahydroisoquinoline 
• 34619-03-9 tert-butyldicarbonate 

Downstream Products

• 357339-30-1 Boc-L-Tic-CH₂OBn 
• 140408-84-0 (S)-(-)-3-hydroxymethyl-1,2,3,4-tetrahydroisoquinoline hydrochloride 
• 869860-47-9 (3S)-(3-fluoro-phenoxymethyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester 
• 1415657-96-3 tert-butyl (S)-3-(((3-iodobenzyl)oxy)methyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate 
• 1415657-99-6 (S)-3-(((3-iodobenzyl)oxy)methyl)-1,2,3,4-tetrahydroisoquinoline 
• 1415657-97-4 tert-butyl ((S)-3-(3-hydroxyphenyl)-1-((S)-3-(((3-iodobenzyl)oxy)-methyl)-3,4-dihydroisoquinolin-2(1H)-yl)-1-oxopropan-2-yl)-carbamate 
• 1415657-98-5 tert-butyl ((S)-3-(1H-imidazol-4-yl)-1-((S)-3-(((3-iodobenzyl)oxy)-methyl)-3,4-dihydroisoquinolin-2(1H)-yl)-1-oxopropan-2-yl)-carbamate 
• 1415658-00-2 tert-butyl (S)-(3-(3-(((3-iodobenzyl)oxy)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)propyl)carbamate 
• 1415658-01-3 (S)-2-(3-hydroxyphenyl)-N-(3-(3-(((3-iodobenzyl)oxy)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)propyl)acetamide 
• 1415658-03-5 C₂₅H₂₉IN₄O₂ 

Relevant articles and documents

Cascade and RCM syntheses of chiral tricyclic alkaloids from (S)-1,2,3,4-tetrahydro isoquinoline carboxylic acid

Concise syntheses of novel chiral pyrroloazacyclo and chiral tricyclic isoquinoline alkaloids, starting from the readily available (S)-1,2,3,4-tetrahydroisoquinoline carboxylic acid methyl ester, by utilizing cascade spiro-to fused and RCM protocols, are

Discovery of tetrahydroisoquinoline-based CXCR4 antagonists

A de novo hit-to-lead effort involving the redesign of benzimidazole- containing antagonists of the CXCR4 receptor resulted in the discovery of a novel series of 1,2,3,4-tetrahydroisoquinoline (TIQ) analogues. In general, this series of compounds show good potencies (3-650 nM) in assays involving CXCR4 function, including both inhibition of attachment of X4 HIV-1IIIB virus in MAGI-CCR5/CXCR4 cells and inhibition of calcium release in Chem-1 cells. Series profiling permitted the identification of TIQ-(R)-stereoisomer 15 as a potent and selective CXCR4 antagonist lead candidate with a promising in vitro profile. The drug-like properties of 15 were determined in ADME in vitro studies, revealing low metabolic liability potential. Further in vivo evaluations included pharmacokinetic experiments in rats and mice, where 15 was shown to have oral bioavailability (F = 63%) and resulted in the mobilization of white blood cells (WBCs) in a dose-dependent manner.

PRMT5 INHIBITORS

The present invention provides a compound of Formula (I) or the pharmaceutically acceptable salts thereof, which are PRMT5 inhibitors.

PRMT5 INHIBITORS

The present invention provides a compound of Formula (I) or the pharmaceutically acceptable salts thereof, which are PRMT5 inhibitors.

TETRAHYDROISOQUINOLINES AS PRMT5 INHIBITORS

A compound of formula (I) wherein: n is 1 or 2; p is 0 or 1; R1a, R1b, R1c and R1d are independently selected from the group consisiting of H, halo, C1-4 alkoxy, C1-4 alkyl, C1-4 fluoroalkyl, C3-4 cycloalkyl, NH-C1-4 alkyl and cyano; R2a and R2b are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R2c and R2d are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R2e is H or Me; R3a and R3b are independently selected from H and Me; R4 is either H or Me; R5 is either H or Me; R6a and R6b are independently selected from H and Me; A is either (i) optionally substituted phenyl; (ii) optionally substituted naphthyl; or (iii) optionally substituted C5-12 heteroaryl; wherein when R2e is H, at least one of R1a, R1b, R1c and R1d is selected from C1-4 alkoxy, C2-4 alkyl, C1-4 fluoroalkyl, C3-4 cycloalkyl, NH-C1-4 alkyl and cyano.

TETRAHYDROISOQUINOLINES AS PRMT5-INHIBITORS

A compound of formula (I) wherein: n is 1 or 2; p is 0 or 1; R1a, R1b, R1c and R1d are independently selected from H, halo, methyl and methoxy; R2a and R2b are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R2c and R2d are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R2e is H or Me; R3a and R3b are independently selected from H and Me; R4 is either H or Me; R6a and R6b are independently selected from H and Me; X is either N or CH; R7 is selected from H and C1-4 alkyl; (a) one of R8a, R8b, R8c and R8d is selected from H, halo, C1-4 alkyl, C1-4 alkoxy, NHC1-4 alkyl; (b) another of R8a, R8b, R8c and R8d is selected from H, C1-4 alkyl, C1-4 fluoroalkyl, C3-6 cycloalkyl, C5-6 heteroaryl, C5-6 heteroaryl methyl, C4-6 heterocyclyl, C4-6 heterocyclyl methyl, phenyl, benzyl, halo, amido, amidomethyl, acylamido, acylamidomethyl, C1-4 alkyl ester, C1-4 alkyl ester methyl, C1-4 alkyl carbamoyl, C1-4 alkyl carbamoyl methyl, C1-4 alkylacyl, C1-4 alkylacyl methyl, phenylcarbonyl, carboxy, carboxymethyl, ether, amino, amino methyl, sulfonamido, sulfonamino, sulfone, sulfoxide, nitrile and nitrilemethyl; (c) the others of R8a, R8b, R8c and R8d are H.

BENZOPIPERIDINE DERIVATIVES AND THEIR USE IN THE TREATMENT OF CANCER AND HEMOGLOBINOPATHIES

A compound of formula I: (I) wherein: n is 1 or 2; p is 0 or 1; R1a, R1b, R1c and R1d are independently selected from H, halo, C1-4 alkyl, C1-4 fluoroalkyl, C3-4 cycloalkyl, C1-4 alkyloxy, NH-C1-4 alkyl and cyano; R2a and R2b are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R2c and R2d are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R2e is H or Me; R3a and R3b are independently selected from H and Me; R4 is either H or Me; R5 is either H or Me; R6a and R6b are independently selected from H and Me; A is either (IIa), where R7a is selected from N-linked N-containing C5-7 heterocycyl and (A); or (ii) (IIb), where X is selected from CH2, N H and O, one of R8a and R8b is selected from CI and ethoxy and the other of R8a and R8b is H.

3-OXA-8-AZABICYCLO[3.2.1]OCTANE DERIVATIVES AND THIER USE IN THE TREATMENT OF CANCER AND HEMOGLOBINOPATHIES

A compound of formula Ia, Ib, Ic or Id: wherein: n is 1 or 2;R N is H or Me; R1 is optionally one or more halo or methyl groups;R2a and R2b are independently selected from the group consisting of: (i) F; (ii) H;(iii) Me; and (iv) CH2 OH; R 2c and R 2d (if present) are independently selected from the group consisting of: (i) F; (ii) H;(iii) Me; and(iv) CH 2 OH;R 3a and R 3b are independently selected from H and Me; R 4a is selected from OH,-NH 2, -C(=O)NH 2, and -CH 2 OH; R 4b is either H or Me; R5 is either H or Me; m is 1 or 2; q is 0 or 1;R 11a, R 11b, R 11c and R 11d are independently selected from H, halo, C1-4 alkyl, C 1-4 fluoroalkyl, C 3-4 cycloalkyl, C 1-4 alkyloxy, NH-C 1-4 alkyl and cyano; R 12a and R 12b are independently selected from the group consisting of: (i) F; (ii) H;(iii) Me; and (iv) CH 2 OH; R 12c and R 12d are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH 2 OH;R 12e is H or Me; R 13a and R 13b are independently selected from H and Me; R 14 is either H or Me; R 16a and R 16b are independently selected from H and Me; R 6 is selected from H, OMe, and OEt.

TETRAHYDROISOQUINOLINE DERIVED PRMT5-INHIBITORS

A compound of formula I wherein: n is 1 or 2: p is 0 or 1; R1 is optionally one or more halo or methyl groups; R2a and R2b are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R2c and R2d are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R3a and R3b are independently selected from H and Me; R4 is either H or Me; R5 is either H or Me; R6a and R6b are independently selected from H and Me; A is either (i) optionally substituted phenyl; (ii) optionally substituted naphthyl; or (iii) optionally substituted C5-12 heteroaryl.

CHEMOKINE CXCR4 RECEPTOR MODULATORS AND USED RELATED THERETO

The disclosure relates to chemokine CXCR4 receptor modulators and uses related thereto. In certain embodiments, the disclosure relates to pharmaceutical compositions comprising compounds disclosed herein or pharmaceutically acceptable salts or prodrugs thereof. In certain embodiments, the compositions disclosed herein are used for managing CXCR4 related conditions, typically prevention or treatment of viral infections such as HIV or for managing cancer.