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PF-05387252

July 5, 2016 7:05 am / Leave a comment

PF-05387252

CAS 1604034-71-0

C₂₅H₂₇N₅O₂
MW	429.51418 g/mol

2-methoxy-3-[3-(4-methylpiperazin-1-yl)propoxy]-11H-indolo[3,2-c]quinoline-9-carbonitrile

IRAK4 inhibitor

Rheumatoid arthritis;
SLE

Preclinical

In the past decade there has been considerable interest in targeting the innate immune system in the treatment of autoimmune diseases and sterile inflammation. Receptors of the innate immune system provide the first line of defense against bacterial and viral insults. These receptors recognize bacterial and viral products as well as pro-inflammatory cytokines and thereby initiate a signaling cascade that ultimately results in the up-regulation of inflammatory cytokines such as TNFα, IL6, and interferons. Recently it has become apparent that self-generated ligands such as nucleic acids and products of inflammation such as HMGB1 and Advanced Glycated End-products (AGE) are ligands for Toll-like receptors (TLRs) which are key receptors of the innate immune system.

This demonstrates the role of TLRs in the initiation and perpetuation of inflammation due to autoimmunity.

Interleukin-1 receptor associated kinase (IRAK4) is a ubiquitously expressed serine/threonine kinase involved in the regulation of innate immunity. IRAK4 is responsible for initiating signaling from TLRs and members of the IL-1/18 receptor family. Kinase-inactive knock-ins and targeted deletions of IRAK4 in mice lead to reductions in TLR and IL-1 induced pro-inflammatory cytokines.^and 7 IRAK-4 kinase-dead knock-in mice have been shown to be resistant to induced joint inflammation in the antigen-induced-arthritis (AIA) and serum transfer-induced (K/BxN) arthritis models. Likewise, humans deficient in IRAK4 also display the inability to respond to challenge by TLR ligands and IL-1

However, the immunodeficient phenotype of IRAK4-null individuals is narrowly restricted to challenge by gram positive bacteria, but not gram negative bacteria, viruses or fungi. This gram positive sensitivity also lessens with age implying redundant or compensatory mechanisms for innate immunity in the absence of IRAK4.These data suggest that inhibitors of IRAK4 kinase activity will have therapeutic value in treating cytokine driven autoimmune diseases while having minimal immunosuppressive side effects. Additional recent studies suggest that targeting IRAK4 may be a viable strategy for the treatment of other inflammatory pathologies such as atherosclerosis.

Indeed, the therapeutic potential of IRAK4 inhibitors has been recognized by others within the drug-discovery community as evidenced by the variety of IRAK4 inhibitors have been reported to-date.^{12, 13, 14, 15 and 16} However, limited data has been published about these compounds and they appear to suffer from a variety of issues such as poor kinase selectivity and poor whole-blood potency that preclude their advancement into the pre-clinical models. To the best of our knowledge, no in vivo studies of IRAK4 inhibitors have been reported to-date in the literature. Herein we report a new class of IRAK4 inhibitors that are shown to recapitulate the phenotype observed in IRAK4 knockout and kinase-dead mice.

PAPER

Bioorganic & Medicinal Chemistry Letters (2014), 24(9), 2066-2072.

doi:10.1016/j.bmcl.2014.03.056

http://www.sciencedirect.com/science/article/pii/S0960894X14002832

Identification and optimization of indolo[2,3-c]quinoline inhibitors of IRAK4

^a Pfizer Global R&D, 445 Eastern Point Rd., Groton, CT 06340, USA
^b Pfizer Global R&D, 200 Cambridge Park Dr., Cambridge, MA 02140, USA
^c Pfizer Global R&D, 87 Cambridgepark Dr., Cambridge, MA 02140, USA
^d Pfizer Global R&D, 1 Burtt Rd., Andover, MA 01810, USA

Image for unlabelled figure

Abstract

IRAK4 is responsible for initiating signaling from Toll-like receptors (TLRs) and members of the IL-1/18 receptor family. Kinase-inactive knock-ins and targeted deletions of IRAK4 in mice cause reductions in TLR induced pro-inflammatory cytokines and these mice are resistant to various models of arthritis. Herein we report the identification and optimization of a series of potent IRAK4 inhibitors. Representative examples from this series showed excellent selectivity over a panel of kinases, including the kinases known to play a role in TLR-mediated signaling. The compounds exhibited low nM potency in LPS- and R848-induced cytokine assays indicating that they are blocking the TLR signaling pathway. A key compound (26) from this series was profiled in more detail and found to have an excellent pharmaceutical profile as measured by predictive assays such as microsomal stability, TPSA, solubility, and c log P. However, this compound was found to afford poor exposure in mouse upon IP or IV administration. We found that removal of the ionizable solubilizing group (32) led to increased exposure, presumably due to increased permeability. Compounds 26 and 32, when dosed to plasma levels corresponding to ex vivo whole blood potency, were shown to inhibit LPS-induced TNFα in an in vivo murine model. To our knowledge, this is the first published in vivo demonstration that inhibition of the IRAK4 pathway by a small molecule can recapitulate the phenotype of IRAK4 knockout mice.

CID 50992153.png

SYNTHESIS

////////PF-05387252, 1604034-71-0, PF 05387252, TLR signaling, Indoloquinoline, IRAK4, Kinase inhibitor, Inflammation, PRECLINICAL

N1(CCN(CC1)CCCOc3c(cc2c4nc5cc(ccc5c4cnc2c3)C#N)OC)C

CN1CCN(CC1)CCCOC2=C(C=C3C(=C2)N=CC4=C3NC5=C4C=CC(=C5)C#N)OC

PF-05388169

July 5, 2016 7:04 am / Leave a comment

PF-05388169

CAS 1604034-78-7, MF C₂₂ H₂₁ N₃ O₄

MW 391.42

11H-Indolo[3,2-c]quinoline-9-carbonitrile, 2-methoxy-3-[2-(2-methoxyethoxy)ethoxy]-

IRAK4 inhibitor

Rheumatoid arthritis;
SLE

Preclinical

PAPER

Bioorganic & Medicinal Chemistry Letters (2014), 24(9), 2066-2072.

http://www.sciencedirect.com/science/article/pii/S0960894X14002832

Identification and optimization of indolo[2,3-c]quinoline inhibitors of IRAK4

^a Pfizer Global R&D, 445 Eastern Point Rd., Groton, CT 06340, USA
^b Pfizer Global R&D, 200 Cambridge Park Dr., Cambridge, MA 02140, USA
^c Pfizer Global R&D, 87 Cambridgepark Dr., Cambridge, MA 02140, USA
^d Pfizer Global R&D, 1 Burtt Rd., Andover, MA 01810, USA

doi:10.1016/j.bmcl.2014.03.056

Image for unlabelled figure

SYNTHESIS

//////////PF-05388169, TLR signaling, Indoloquinoline, IRAK4, Kinase inhibitor, Inflammation, PRECLINICAL, 1604034-78-7

C(COC)OCCOc4c(cc3\C2=N\c1cc(ccc1/C2=C/Nc3c4)C#N)OC

PF-05387552

April 12, 2016 6:42 am / 1 Comment on PF-05387552

CID 50992153.png

PF-05387552

IRAK4

CAS 1604034-71-0

C₂₅ H₂₇ N₅ O₂

11H-Indolo[3,2-c]quinoline-9-carbonitrile, 2-methoxy-3-[3-(4-methyl-1-piperazinyl)propoxy]-

2-methoxy-3-[3-(4-methylpiperazin-1-yl)propoxy]-11H-indolo[3,2-c]quinoline-9-carbonitrile

Molecular Weight429.51

Molecular Formula:	C₂₅H₂₇N₅O₂
Molecular Weight:	429.51418 g/mol

Synthesis

PAPER

Bioorganic & Medicinal Chemistry Letters (2014), 24(9), 2066-2072

Bioorganic & Medicinal Chemistry Letters

Volume 24, Issue 9, 1 May 2014, Pages 2066–2072

Identification and optimization of indolo[2,3-c]quinoline inhibitors of IRAK4

^a Pfizer Global R&D, 445 Eastern Point Rd., Groton, CT 06340, USA

^b Pfizer Global R&D, 200 Cambridge Park Dr., Cambridge, MA 02140, USA
^c Pfizer Global R&D, 87 Cambridgepark Dr., Cambridge, MA 02140, USA
^d Pfizer Global R&D, 1 Burtt Rd., Andover, MA 01810, USA

doi:10.1016/j.bmcl.2014.03.056

http://www.sciencedirect.com/science/article/pii/S0960894X14002832?np=y

Herein we report the identification and optimization of a series of potent IRAK4 inhibitors. Representative examples from this series showed excellent selectivity over a panel of kinases, including the kinases known to play a role in TLR-mediated signaling. The compounds exhibited low nM potency in LPS- and R848-induced cytokine assays indicating that they are blocking the TLR signaling pathway.

A key compound (26) from this series was profiled in more detail and found to have an excellent pharmaceutical profile as measured by predictive assays such as microsomal stability, TPSA, solubility, and c log P. However, this compound was found to afford poor exposure in mouse upon IP or IV administration. We found that removal of the ionizable solubilizing group (32) led to increased exposure, presumably due to increased permeability. Compounds 26 and 32, when dosed to plasma levels corresponding to ex vivo whole blood potency, were shown to inhibit LPS-induced TNFα in an in vivo murine model.

To our knowledge, this is the first published in vivo demonstration that inhibition of the IRAK4 pathway by a small molecule can recapitulate the phenotype of IRAK4 knockout mice.

L. Nathan Turney L. Nathan Tumey, Ph.D., Principal Research Scientist, Pfizer Global R&D

REFERENCES

///////////TLR signaling, Indoloquinoline, IRAK4, Kinase inhibitor, Inflammation, PF-05387552, PF 05387552, 1604034-71-0

N#Cc3ccc4c5cnc2cc(OCCCN1CCN(C)CC1)c(OC)cc2c5nc4c3

ND 2158

April 11, 2016 7:21 am / Leave a comment

(2S)-2-hydroxy-3-[(3R)-12-{[(1r,4r)-4-(morpholin-4-yl)cyclohexyl]oxy}-7-thia-9,11-diazatricyclo[6.4.0.0²,⁶]dodeca-1(12),2(6),8,10-tetraen-3-yl]propanamide

S)-2-hydroxy-3-((R)-4-(((lr,4R)-4-morpholinocyclohexyl)oxy)-6,7-dihydro-5H-cyclopenta [4,5] thieno [2,3-d] pyrimidin-5-yl)propanamide

CAS 1388896-07-8

C₂₂ H₃₀ N₄ O₄ S

5H-Cyclopenta[4,5]thieno[2,3-d]pyrimidine-5-propanamide, 6,7-dihydro-α-hydroxy-4-[[trans-4-(4-morpholinyl)cyclohexyl]oxy]-, (αS,5R)-

Molecular Weight446.56

ND 2158

IRAK4, 446.2

C₂₂H₃₀N₄O₄S

Company	Nimbus Therapeutics LLC
Description	IL-1 receptor-associated kinase 4 (IRAK4) inhibitor
Molecular Target	Interleukin-1 receptor-associated kinase 4 (IRAK4)
Mechanism of Action	Interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor
Therapeutic Modality	Small molecule

ND-2158 is a potent and selective experimental inhibitor of IRAK4 described in patent WO2013106535 [2] and in a poster presented at the American College of Rheumatology meeting in 2012 (Abstract #1062 in Supplement: Abstracts of the American College of Rheumatology & Association of Rheumatology Health Professionals, Annual Scientific Meeting, November 9-4, 2012 Washington DC, Volume 64, Issue S10, Page S1-S1216).

PATENT

WO2013106535

http://www.google.com/patents/WO2013106535A1?cl=en

Figure imgf000085_0001

Figure imgf000086_0001

Scheme II

Example 88: (S)-l-((R)-4-(((lr,4R)-4-morpholinocyclohexyl)oxy)-6,7-dihydro- 5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-5-yl)butan-2-ol (1-64) and Example 89: (R)-l- ((R)-4-(((lr,4R)-4-morpholinocyclohexyl)oxy)-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-

Synthesis of compound 88.1. Note: For the preparation of the starting material compound 29.2, please see Example 29. A solution of

yl)cyclohexyl]oxy]-7-thia-9,l l-diazatricyclo[6.4.0.0[2,6]]dodeca-l(8),2(6),9,l l-tetraen-3- yl]ethan-l-ol (190 mg, 0.47 mmol, 1.00 equiv) in 10 mL of dichloromethane was added Dess- Martin periodinane at 0 °C in a water/ice bath under nitrogen. The resulting mixture was stirred for 2 h at room temperature. After completion of the reaction, the mixture was then diluted with saturated aqueous sodium bicarbonate and extracted with 3 x 30 mL of ethyl acetate. The combined organic layers were dried over sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1 :5 to 1 : 1) to afford 2-[(3Λ)-12-[[4-^ο 1ιο1ϊη-4-γ1)ογο1ο1ιβχγ1]οχγ]-7-ωΕ-9,11- diazatricyclo[6.4.0.0[2,6]]dodeca-l(8),2(6),9,l l-tetraen-3-yl]acetaldehyde (130 mg, 69%) as a colorless oil. MS (ES): m/z 402 [M+H]⁺.

Synthesis of Compound 1-64 and Compound 1-65. A solution of [(3i?)-12-[[4- (moφholin-4-yl)cyclohexyl]oxy]-7-thia-9,l l-diazatricyclo[6.4.0.0[2,6]]dodeca-l(8),2(6),9,l l- tetraen-3-yl]acetaldehyde (130 mg, 0.32 mmol, 1.00 equiv) in 5 mL of anhydrous THF was added bromo(ethyl)magnesium (1 M in THF, 0.62 mL, 2.0 equiv) dropwise at 0 °C under nitrogen. The resulting solution was stirred for 4 h at room temperature and then quenched by the addition of saturated aqueous NH₄CI and extracted with 3 x 50 mL of DCM/i-PrOH (3:1). The combined organic layers was dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product (150 mg) was purified by preparative HPLC under the following conditions (SHIMADZU): column: SunFire Prep C18, 19*150 mm 5um; mobile phase: water with 0.05% NH₄CO₃ and CH₃CN (6.0% CH₃CN up to 54.0% in 25 min); UV detection at 254/220 nm to afford (S)-l-((R)-4-(((lr,4R)-4-moφholinocyclohexyl)oxy)-6,7-dihydro-5H- cyclopenta[4,5]thieno[2,3-d]pyrimidin-5-yl)butan-2-ol (11.8 mg) and (R)-l-((R)-4-(((lr,4R)-4- mo holinocyclohexyl)oxy)-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-5-yl)butan- 2-ol (23.9 mg) as white solids.

Example 88 (1-64): MS: 432 (M+H)⁺. ¾ NMR (300 MHz, CDC1₃) S 8.47 (s, 2H), 5.24-5.20 (m, 1H), 3.75-3.58 (m, 5H), 3.06-2.93 (m, 2H), 2.70-2.61 (m, 4H), 2.28-1.98 (m, 3H), 1.59-1.41 (m, 10H), 1.28-1.23 (m, 2H),0.95-0.85 (m, 3H).

Example 89 (1-65): MS: 432 (M+H)⁺. ¾ NMR (300 MHz, CDC1₃) S 8.47 (s, 2H), 5.25 (m, 1H), 3.71-3.39 (m, 6H), 3.04-2.90 (m, 2H), 2.67-2.55 (m, 5H), 2.34-2.22 (m, 4H), 2.01- 1.81 (m, 3H), 1.64-1.39 (m, 7H), 0.94-0.92 (m, 3H).

WATCH OUT SYNTHESIS COMING…………

PATENT

WO 2014011906

https://www.google.co.in/patents/WO2014011906A2?cl=en

PATENT

WO-2014194242

https://www.google.com/patents/WO2014194242A2?cl=en

Example 49: Synthesis of Intermediate 49.1.

Image loading...

step 1 step 2

35.1 49.1 49.2 Image loading...

step 3 _{49 3}

] Intermediate 49.3 was prepared from 35.1 in a manner analogous to the synthesis of 36.3. Isolated 150 mg of a white solid in 57% overall yield. MS (ES): m/z 402 [M+H]⁺.

Example 50: Synthesis of Intermediate 50.4.

Image loading...

49.3 50.1 50.2

Image loading...

50.3 50.4

Intermediate 50.4 was prepared from 49.3 in a manner analogous to the synthesis of 1-25, except that HCl/MeOH rather than TBAF/THF was used in the second step. Isolated 124 mg of a white solid in 48% overall yield. MS (ES): m/z 447 [M+H]⁺. 1H NMR (400 MHz, CDCls): δ 8.46 (s, 1H), 5.28-5.25 (m, 1H), 4.17-4.06 (m, 51H), 3.74-3.72 (m, 5H), 3.37-2.98 (m, 2H), 2.72-2.28 (m, 10H), 2.11-2.08 (m, 2H), 1.79-1.46 (m, 5H).

Example 51: Synthesis of (S)-2-hydroxy-3-((R)-4-(((lr,4R)-4- morpholinocyclohexyl)oxy)-6,7-dihydro-5H-cyclopenta [4,5] thieno [2,3-d] pyrimidin-5- yl)propanamide (1-34) and Example 52: Synthesis of (R)-2-hydroxy-3-((R)-4-(((lr,4R)-4- morpholinocyclohexyl)oxy)-6,7-dihydro-5H-cyclopenta [4,5] thieno [2,3-d] pyrimidin-5- yl)propanamide (1-44)

Image loading...

The racemic 50.4 (1.6 g, 96.5% purity) was separated by Chiral-HPLC with the following conditions (Gilson G x 281): column: Chiralpak AD-H, 2*25 cm Chiral-P(AD-H); mobile phase: phase A: hex (O. P/oDEA) (HPLC grade), phase B: IPA (HPLC grade), gradient: 30% B in 9 min; flow rate: 20 mL/min; UV detection at 220/254 nm. The former fractions (tR = 4.75 min) were collected and evaporated under reduced pressure and lyophilized overnight to afford 1-44 (520 mg) with 100% ee as a white solid. And the latter fractions (tR = 5.82 min) were handled as the former fractions to give the desired 1-34 (510 mg) with 99.6%> ee as a white solid. The ee values of the two isomers were determined by the chiral-HPLC with the following conditions (SHIMADZU-SPD-20A): column: Chiralpak AD-H, 0.46*25 cm, 5um (DAICEL); mobile phase: hex (0.1% TEA): IPA = 85:15; UV detection at 254 nm. Flow rate: 1.0 mL/min. tR (1-44) = 7.939 min and tR (1-34) = 11.918 min.

[00431] Analytical data for 1-44: MS: (ES, m/z) 447 [M+H]⁺. 1H NMR (400 MHz, CD3OD+CDCI3): δ 8.47 (s, 1H), 5.32-5.22 (m, 1H), 4.08 (dd, 1H), 4.89-4.62 (m, 5H), 3.20-3.10 (m, 1H), 3.05-2.95 (m, 1H), 2.75-2.55 (m, 5H), 2.44-2.38 (m, 2H), 2.34-2.28 (m, 3H), 2.10 (d, 2H), 1.82-1.62 (m, 3H), 1.58-1.40 (m, 2H).

Analytical data for 1-34: MS: (ES, m/z) 447 [M+H]⁺. 1H NMR (400 MHz, CDC1₃): δ 8.46 (s, 1H), 5.32-5.22 (m, 1H), 4.15 (t, 1H), 3.73 (t, 4H), 3.59 (td, 1H), 3.19-3.08 (m, 1H), 3.02- 2.92 (m, 1H), 2.78-2.70 (m, 1H), 2.69-2.60 (m, 4H), 2.58-2.20 (m, 5H), 2.10 (d, 2H), 1.75-1.63 (m, 3H), 1.53-1.40 (m, 2H).

Paper

http://pubs.acs.org/doi/abs/10.1021/jm5016044

Recent Advances in the Discovery of Small Molecule Inhibitors of Interleukin-1 Receptor-Associated Kinase 4 (IRAK4) as a Therapeutic Target for Inflammation and Oncology Disorders

Miniperspective

Divya Chaudhary^†, Shaughnessy Robinson^‡, and Donna L. Romero^*^†

^†Nimbus Discovery, 25 First Street, Suite 404, Cambridge, Massachusetts 02141, United States

^‡Schrödinger Inc., 120 West Forty-Fifth Street, New York, New York 10036, United States

J. Med. Chem., 2015, 58 (1), pp 96–110

DOI: 10.1021/jm5016044

IRAK4, a serine/threonine kinase, plays a key role in both inflammation and oncology diseases. Herein, we summarize the compelling biology surrounding the IRAK4 signaling node in disease, review key structural features of IRAK4 including selectivity challenges, and describe efforts to discover clinically viable IRAK4 inhibitors. Finally, a view of knowledge gained and remaining challenges is provided.

78 Romero, D. L.; Robinson, S.; Wessel, M. D.; Greenwood, J. R. IRAK Inhibitors and Uses Thereof. WO201401902, January 16, 2014.
79.

Harriman, G. C.; Romero, D. L.; Masse, C. E.; Robinson, S.; Wessel, M. D.; Greenwood, J. R. IRAK Inhibitors and Uses Thereof. WO2014011911A2, January 16, 2014.
80.

Harriman, G. C.; Wester, R. T.; Romero, D. L.; Masse, C. E.; Robinson, R.; Greenwood, J. R. IRAK Inhibitors and Uses Thereof. WO2014011906A2, January 16, 2014

Patent ID	Date	Patent Title
US2013231328	2013-09-05	IRAK INHIBITORS AND USES THEREOF

PATENT

WO 2014194242

WO 2013106535

WO 2012097013

US20070155777 *	Feb 21, 2007	Jul 5, 2007	Amgen, Inc.	Antiinflammation agents
US20100041676 *		Feb 18, 2010	Hirst Gavin C	Kinase inhibitors
US20100143341 *	Jun 21, 2006	Jun 10, 2010	Develogen Aktiengesellschaft	Thienopyrimidines for pharmaceutical compositions
US20120015962 *		Jan 19, 2012	Nidhi Arora	PYRAZOLO[1,5a]PYRIMIDINE DERIVATIVES AS IRAK4 MODULATORS
US20120283238 *		Nov 8, 2012	Nimbus Iris, Inc.	Irak inhibitors and uses thereof

References
1. Chaudhary D, Robinson S, Romero DL. (2015) Recent Advances in the Discovery of Small Molecule Inhibitors of Interleukin-1 Receptor-Associated Kinase 4 (IRAK4) as a Therapeutic Target for Inflammation and Oncology Disorders. J. Med. Chem., 58 (1): 96-110. [PMID:25479567]
2. Harriman GC, Wester RT, Romero DL, Robinson S, Shelley M, Wessel MD, Greenwood JR, Masse CE, Kapeller-Libermann R. (2013) Irak inhibitors and uses thereof. Patent number: WO2013106535. Assignee: Nimbus Iris, Inc.. Priority date: 18/07/2013. Publication date: 10/01/2012.

References

1. Chaudhary D, Robinson S, Romero DL. (2015)
Recent Advances in the Discovery of Small Molecule Inhibitors of Interleukin-1 Receptor-Associated Kinase 4 (IRAK4) as a Therapeutic Target for Inflammation and Oncology Disorders.
J. Med. Chem., 58 (1): 96-110. [PMID:25479567]

2. Harriman GC, Wester RT, Romero DL, Robinson S, Shelley M, Wessel MD, Greenwood JR, Masse CE, Kapeller-Libermann R. (2013)
Irak inhibitors and uses thereof.
Patent number: WO2013106535. Assignee: Nimbus Iris, Inc.. Priority date: 18/07/2013. Publication date: 10/01/2012.

http://nimbustx.com/sites/default/files/uploads/posters/irak4_nimbus_acr_poster_2012_small.pdf

///////ND 2158, IRAK4, ND-2158, NIMBUS, 1388896-07-8

NC(=O)C(CC1CCc2c1c1c(ncnc1s2)OC1CCC(CC1)N1CCOCC1)O

C1CC(CCC1N2CCOCC2)OC3=C4C5=C(CCC5CC(C(=O)N)O)SC4=NC=N3

	DR ANTHONY MELVIN CR… on AZITHROMYCIN, アジスロマイシン;
	DR ANTHONY MELVIN CR… on BAY 1895344
	DR ANTHONY MELVIN CR… on ADAFOSBUVIR, адафосбувир , أدا…
	DR ANTHONY MELVIN CR… on AK 3280
	DR ANTHONY MELVIN CR… on Novobiocin, ノボビオシン;

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PF-05387252

Identification and optimization of indolo[2,3-c]quinoline inhibitors of IRAK4

Abstract

PF-05388169

Identification and optimization of indolo[2,3-c]quinoline inhibitors of IRAK4

PF-05387552

PF-05387552

Synthesis

Identification and optimization of indolo[2,3-c]quinoline inhibitors of IRAK4

ND 2158

WATCH OUT SYNTHESIS COMING…………

Recent Advances in the Discovery of Small Molecule Inhibitors of Interleukin-1 Receptor-Associated Kinase 4 (IRAK4) as a Therapeutic Target for Inflammation and Oncology Disorders

Miniperspective

SEARCH THIS BLOG

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PF-05387252

Identification and optimization of indolo[2,3-c]quinoline inhibitors of IRAK4

Abstract

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PF-05388169

Identification and optimization of indolo[2,3-c]quinoline inhibitors of IRAK4

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PF-05387552

PF-05387552

Synthesis

Identification and optimization of indolo[2,3-c]quinoline inhibitors of IRAK4

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ND 2158

WATCH OUT SYNTHESIS COMING…………

Recent Advances in the Discovery of Small Molecule Inhibitors of Interleukin-1 Receptor-Associated Kinase 4 (IRAK4) as a Therapeutic Target for Inflammation and Oncology Disorders

Miniperspective

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