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Extract from the Register of European Patents

EP About this file: EP3330256

EP3330256 - HETEROCYCLIC DERIVATIVE HAVING TrkA-INHIBITING ACTIVITY [Right-click to bookmark this link]
StatusNo opposition filed within time limit
Status updated on  22.04.2022
Database last updated on 01.01.2025
FormerThe patent has been granted
Status updated on  14.05.2021
FormerGrant of patent is intended
Status updated on  08.12.2020
FormerExamination is in progress
Status updated on  29.05.2020
FormerRequest for examination was made
Status updated on  04.05.2018
FormerThe international publication has been made
Status updated on  13.01.2017
Most recent event   Tooltip06.09.2024Lapse of the patent in a contracting state
New state(s): MT		published on 09.10.2024  [2024/41]
Applicant(s)For all designated states
Shionogi & Co., Ltd.
1-8, Doshomachi 3-chome
Chuo-ku
Osaka-shi, Osaka 541-0045 / JP
[2018/23]
Inventor(s)01 / YUKIMASA, Akira
c/o Shionogi&Co. Ltd.
1-1 Futabacho 3-chome
Toyonaka-shi Osaka 561-0825 / JP
02 / NAKAMURA, Kenichiroh
c/o Shionogi & Co., Ltd.
1-8, Doshomachi 3-chome
Chuo-ku
Osaka-shi Osaka 541-0045 / JP
03 / INAGAKI, Masanao
c/o Shionogi&Co. Ltd.
1-1 Futabacho 3-chome
Toyonaka-shi Osaka 561-0825 / JP
04 / KANO, Kazuya
c/o Shionogi&Co. Ltd.
1-1 Futabacho 3-chome
Toyonaka-shi Osaka 561-0825 / JP
05 / FUJIU, Motohiro
c/o Shionogi&Co. Ltd.
1-1 Futabacho 3-chome
Toyonaka-shi Osaka 561-0825 / JP
06 / YAMAGUCHI, Hiroki
c/o Shionogi&Co. Ltd.
1-1 Futabacho 3-chome
Toyonaka-shi Osaka 561-0825 / JP
07 / HATA, Kayoko
c/o Shionogi&Co. Ltd.
1-1 Futabacho 3-chome
Toyonaka-shi Osaka 561-0825 / JP
08 / INOUE, Takatsugu
c/o Shionogi&Co. Ltd.
1-8 Doshomachi 3-chome
Chuo-ku
Osaka-shi Osaka 541-0045 / JP
 [2018/23]
Representative(s)Vossius & Partner Patentanwälte Rechtsanwälte mbB
Siebertstrasse 3
81675 München / DE
[2018/23]
Application number, filing date16821422.906.07.2016
[2018/23]
WO2016JP69968
Priority number, dateJP2015013584407.07.2015         Original published format: JP 2015135844
JP2016000401013.01.2016         Original published format: JP 2016004010
[2018/23]
Filing languageJA
Procedural languageEN
PublicationType: A1 Application with search report
No.:WO2017006953
Date:12.01.2017
Language:JA
[2017/02]
Type: A1 Application with search report 
No.:EP3330256
Date:06.06.2018
Language:EN
[2018/23]
Type: B1 Patent specification 
No.:EP3330256
Date:16.06.2021
Language:EN
[2021/24]
Search report(s)International search report - published on:JP12.01.2017
(Supplementary) European search report - dispatched on:EP26.02.2019
ClassificationIPC:C07D231/38, A61K31/4155, A61K31/422, A61K31/433, A61K31/437, A61K31/4439, A61K31/454, A61K31/506, A61K31/519, A61P1/18, A61P13/08, A61P13/10, A61P17/00, A61P19/02, A61P25/02, A61P25/04, A61P29/00, A61P35/00, A61P37/08, C07D405/12
[2018/23]
CPC:
C07D405/14 (EP,US); A61K31/4155 (EP,US); A61K31/422 (EP,US);
A61K31/433 (EP,US); A61K31/437 (EP,US); A61K31/4439 (EP,US);
A61K31/454 (EP,US); A61K31/506 (EP,US); A61K31/519 (EP,US);
A61P1/18 (EP); A61P13/08 (EP); A61P13/10 (EP);
A61P17/00 (EP); A61P19/02 (EP); A61P25/00 (EP);
A61P25/02 (EP); A61P25/04 (EP); A61P29/00 (EP);
A61P35/00 (EP); A61P37/08 (EP); A61P43/00 (EP);
C07D231/38 (EP,US); C07D403/14 (EP,US); C07D405/12 (EP,US);
C07D413/14 (EP,US); C07D417/14 (EP,US); C07D471/04 (EP,US);
C07D487/04 (EP,US); C07D487/08 (EP,US); C07D491/048 (EP,US);
C07D491/056 (EP,US); C07D491/08 (EP,US); C07D491/107 (EP,US);
C07D498/04 (EP,US); C07F7/1804 (EP,US) (-)
Designated contracting statesAL,   AT,   BE,   BG,   CH,   CY,   CZ,   DE,   DK,   EE,   ES,   FI,   FR,   GB,   GR,   HR,   HU,   IE,   IS,   IT,   LI,   LT,   LU,   LV,   MC,   MK,   MT,   NL,   NO,   PL,   PT,   RO,   RS,   SE,   SI,   SK,   SM,   TR [2018/23]
Extension statesBANot yet paid
MENot yet paid
Validation statesMANot yet paid
MDNot yet paid
TitleGerman:HETEROZYKLISCHES DERIVAT MIT TRKA-HEMMENDER AKTIVITÄT[2021/24]
English:HETEROCYCLIC DERIVATIVE HAVING TrkA-INHIBITING ACTIVITY[2018/23]
French:DÉRIVÉ HÉTÉROCYCLIQUE À ACTIVITÉ INHIBITRICE CIBLANT TrkA[2018/23]
Former [2018/23]HETEROCYCLISCHE DERIVATE MIT TRKA-HEMMENDER AKTIVITÄT
Entry into regional phase12.01.2018Translation filed 
07.02.2018National basic fee paid 
07.02.2018Search fee paid 
07.02.2018Designation fee(s) paid 
07.02.2018Examination fee paid 
Examination procedure12.01.2018Date on which the examining division has become responsible
07.02.2018Examination requested  [2018/23]
16.09.2019Amendment by applicant (claims and/or description)
03.06.2020Despatch of a communication from the examining division (Time limit: M02)
10.08.2020Reply to a communication from the examining division
09.12.2020Communication of intention to grant the patent
16.04.2021Fee for grant paid
16.04.2021Fee for publishing/printing paid
16.04.2021Receipt of the translation of the claim(s)
Opposition(s)17.03.2022No opposition filed within time limit [2022/21]
Fees paidRenewal fee
11.07.2018Renewal fee patent year 03
15.07.2019Renewal fee patent year 04
14.07.2020Renewal fee patent year 05
Opt-out from the exclusive  Tooltip
competence of the Unified
Patent Court		 See the Register of the Unified Patent Court for opt-out data
Responsibility for the accuracy, completeness or quality of the data displayed under the link provided lies entirely with the Unified Patent Court.
Lapses during opposition  TooltipHU06.07.2016
AL16.06.2021
AT16.06.2021
CY16.06.2021
CZ16.06.2021
DK16.06.2021
EE16.06.2021
ES16.06.2021
FI16.06.2021
HR16.06.2021
IT16.06.2021
LT16.06.2021
LV16.06.2021
MC16.06.2021
MK16.06.2021
MT16.06.2021
NL16.06.2021
PL16.06.2021
RO16.06.2021
RS16.06.2021
SE16.06.2021
SI16.06.2021
SK16.06.2021
SM16.06.2021
IE06.07.2021
LU06.07.2021
BE31.07.2021
CH31.07.2021
LI31.07.2021
BG16.09.2021
NO16.09.2021
GR17.09.2021
IS16.10.2021
PT18.10.2021
[2024/41]
Former [2024/22]HU06.07.2016
AL16.06.2021
AT16.06.2021
CY16.06.2021
CZ16.06.2021
DK16.06.2021
EE16.06.2021
ES16.06.2021
FI16.06.2021
HR16.06.2021
IT16.06.2021
LT16.06.2021
LV16.06.2021
MC16.06.2021
MK16.06.2021
NL16.06.2021
PL16.06.2021
RO16.06.2021
RS16.06.2021
SE16.06.2021
SI16.06.2021
SK16.06.2021
SM16.06.2021
IE06.07.2021
LU06.07.2021
BE31.07.2021
CH31.07.2021
LI31.07.2021
BG16.09.2021
NO16.09.2021
GR17.09.2021
IS16.10.2021
PT18.10.2021
Former [2023/30]HU06.07.2016
AL16.06.2021
AT16.06.2021
CY16.06.2021
CZ16.06.2021
DK16.06.2021
EE16.06.2021
ES16.06.2021
FI16.06.2021
HR16.06.2021
IT16.06.2021
LT16.06.2021
LV16.06.2021
MC16.06.2021
NL16.06.2021
PL16.06.2021
RO16.06.2021
RS16.06.2021
SE16.06.2021
SI16.06.2021
SK16.06.2021
SM16.06.2021
IE06.07.2021
LU06.07.2021
BE31.07.2021
CH31.07.2021
LI31.07.2021
BG16.09.2021
NO16.09.2021
GR17.09.2021
IS16.10.2021
PT18.10.2021
Former [2023/29]HU06.07.2016
AL16.06.2021
AT16.06.2021
CZ16.06.2021
DK16.06.2021
EE16.06.2021
ES16.06.2021
FI16.06.2021
HR16.06.2021
IT16.06.2021
LT16.06.2021
LV16.06.2021
MC16.06.2021
NL16.06.2021
PL16.06.2021
RO16.06.2021
RS16.06.2021
SE16.06.2021
SI16.06.2021
SK16.06.2021
SM16.06.2021
IE06.07.2021
LU06.07.2021
BE31.07.2021
CH31.07.2021
LI31.07.2021
BG16.09.2021
NO16.09.2021
GR17.09.2021
IS16.10.2021
PT18.10.2021
Former [2022/36]AL16.06.2021
AT16.06.2021
CZ16.06.2021
DK16.06.2021
EE16.06.2021
ES16.06.2021
FI16.06.2021
HR16.06.2021
IT16.06.2021
LT16.06.2021
LV16.06.2021
MC16.06.2021
NL16.06.2021
PL16.06.2021
RO16.06.2021
RS16.06.2021
SE16.06.2021
SI16.06.2021
SK16.06.2021
SM16.06.2021
IE06.07.2021
LU06.07.2021
BE31.07.2021
CH31.07.2021
LI31.07.2021
BG16.09.2021
NO16.09.2021
GR17.09.2021
IS16.10.2021
PT18.10.2021
Former [2022/35]AL16.06.2021
AT16.06.2021
CZ16.06.2021
DK16.06.2021
EE16.06.2021
ES16.06.2021
FI16.06.2021
HR16.06.2021
LT16.06.2021
LV16.06.2021
MC16.06.2021
NL16.06.2021
PL16.06.2021
RO16.06.2021
RS16.06.2021
SE16.06.2021
SI16.06.2021
SK16.06.2021
SM16.06.2021
IE06.07.2021
LU06.07.2021
BE31.07.2021
CH31.07.2021
LI31.07.2021
BG16.09.2021
NO16.09.2021
GR17.09.2021
IS16.10.2021
PT18.10.2021
Former [2022/34]AL16.06.2021
AT16.06.2021
CZ16.06.2021
DK16.06.2021
EE16.06.2021
ES16.06.2021
FI16.06.2021
HR16.06.2021
LT16.06.2021
LV16.06.2021
MC16.06.2021
NL16.06.2021
PL16.06.2021
RO16.06.2021
RS16.06.2021
SE16.06.2021
SI16.06.2021
SK16.06.2021
SM16.06.2021
LU06.07.2021
BE31.07.2021
CH31.07.2021
LI31.07.2021
BG16.09.2021
NO16.09.2021
GR17.09.2021
IS16.10.2021
PT18.10.2021
Former [2022/29]AL16.06.2021
AT16.06.2021
CZ16.06.2021
DK16.06.2021
EE16.06.2021
ES16.06.2021
FI16.06.2021
HR16.06.2021
LT16.06.2021
LV16.06.2021
MC16.06.2021
NL16.06.2021
PL16.06.2021
RO16.06.2021
RS16.06.2021
SE16.06.2021
SI16.06.2021
SK16.06.2021
SM16.06.2021
LU06.07.2021
CH31.07.2021
LI31.07.2021
BG16.09.2021
NO16.09.2021
GR17.09.2021
IS16.10.2021
PT18.10.2021
Former [2022/26]AL16.06.2021
AT16.06.2021
CZ16.06.2021
DK16.06.2021
EE16.06.2021
ES16.06.2021
FI16.06.2021
HR16.06.2021
LT16.06.2021
LV16.06.2021
MC16.06.2021
NL16.06.2021
PL16.06.2021
RO16.06.2021
RS16.06.2021
SE16.06.2021
SK16.06.2021
SM16.06.2021
LU06.07.2021
CH31.07.2021
LI31.07.2021
BG16.09.2021
NO16.09.2021
GR17.09.2021
IS16.10.2021
PT18.10.2021
Former [2022/24]AT16.06.2021
CZ16.06.2021
DK16.06.2021
EE16.06.2021
ES16.06.2021
FI16.06.2021
HR16.06.2021
LT16.06.2021
LV16.06.2021
MC16.06.2021
NL16.06.2021
PL16.06.2021
RO16.06.2021
RS16.06.2021
SE16.06.2021
SK16.06.2021
SM16.06.2021
LU06.07.2021
CH31.07.2021
LI31.07.2021
BG16.09.2021
NO16.09.2021
GR17.09.2021
IS16.10.2021
PT18.10.2021
Former [2022/21]AT16.06.2021
CZ16.06.2021
DK16.06.2021
EE16.06.2021
ES16.06.2021
FI16.06.2021
HR16.06.2021
LT16.06.2021
LV16.06.2021
MC16.06.2021
NL16.06.2021
PL16.06.2021
RO16.06.2021
RS16.06.2021
SE16.06.2021
SK16.06.2021
SM16.06.2021
CH31.07.2021
LI31.07.2021
BG16.09.2021
NO16.09.2021
GR17.09.2021
IS16.10.2021
PT18.10.2021
Former [2022/18]AT16.06.2021
CZ16.06.2021
EE16.06.2021
ES16.06.2021
FI16.06.2021
HR16.06.2021
LT16.06.2021
LV16.06.2021
MC16.06.2021
NL16.06.2021
PL16.06.2021
RO16.06.2021
RS16.06.2021
SE16.06.2021
SK16.06.2021
SM16.06.2021
BG16.09.2021
NO16.09.2021
GR17.09.2021
IS16.10.2021
PT18.10.2021
Former [2022/10]AT16.06.2021
CZ16.06.2021
EE16.06.2021
ES16.06.2021
FI16.06.2021
HR16.06.2021
LT16.06.2021
LV16.06.2021
NL16.06.2021
PL16.06.2021
RO16.06.2021
RS16.06.2021
SE16.06.2021
SK16.06.2021
SM16.06.2021
BG16.09.2021
NO16.09.2021
GR17.09.2021
IS16.10.2021
PT18.10.2021
Former [2022/09]AT16.06.2021
CZ16.06.2021
ES16.06.2021
FI16.06.2021
HR16.06.2021
LT16.06.2021
LV16.06.2021
NL16.06.2021
RO16.06.2021
RS16.06.2021
SE16.06.2021
SK16.06.2021
SM16.06.2021
BG16.09.2021
NO16.09.2021
GR17.09.2021
PT18.10.2021
Former [2022/08]AT16.06.2021
CZ16.06.2021
ES16.06.2021
FI16.06.2021
HR16.06.2021
LT16.06.2021
LV16.06.2021
NL16.06.2021
RS16.06.2021
SE16.06.2021
SM16.06.2021
BG16.09.2021
NO16.09.2021
GR17.09.2021
Former [2022/07]AT16.06.2021
FI16.06.2021
HR16.06.2021
LT16.06.2021
LV16.06.2021
NL16.06.2021
RS16.06.2021
SE16.06.2021
SM16.06.2021
BG16.09.2021
NO16.09.2021
GR17.09.2021
Former [2021/51]FI16.06.2021
HR16.06.2021
LT16.06.2021
LV16.06.2021
RS16.06.2021
SE16.06.2021
BG16.09.2021
NO16.09.2021
GR17.09.2021
Former [2021/49]FI16.06.2021
HR16.06.2021
LT16.06.2021
LV16.06.2021
SE16.06.2021
BG16.09.2021
NO16.09.2021
GR17.09.2021
Former [2021/47]FI16.06.2021
LT16.06.2021
BG16.09.2021
Former [2021/46]FI16.06.2021
LT16.06.2021
Documents cited:Search[ID]WO2014078331  (ARRAY BIOPHARMA INC [US], et al) [ID] 1-18 * page 1, paragraph 1; example -; claim - *;
 [I]WO2015039334  (MERCK SHARP & DOHME [US], et al) [I] 1-18* page 1, line 5 - page 1, line 11; claim -; table - *;
 [X]  - NOE C R ET AL, "NOVEL THREE-ATOM 2'-5' LINKAGES IN ANTISENSE NUCLEOTIDES: SYNTHESIS AND PAIRING PROPERTIES OF DINUCLEOTIDES WITH A CARBOXYLIC ESTER LINKAGE", ARCHIV DER PHARMAZIE, WILEY VERLAG, WEINHEIM, (19950101), vol. 328, doi:10.1002/ARDP.19953281102, ISSN 0365-6233, page 743/744, XP000575533 [X] 1,2,6,9-11 * compound 13 *

DOI:   http://dx.doi.org/10.1002/ardp.19953281102
 [X]  - WOLFGANG NOTZ ET AL, "De Novo Synthesis of a Methylene-Bridged Neu5Ac-[alpha]-(2,3)-Gal C -Disaccharide", JOURNAL OF ORGANIC CHEMISTRY, (20010601), vol. 66, no. 12, doi:10.1021/jo015543l, ISSN 0022-3263, pages 4250 - 4260, XP055555570 [X] 1-3,5-11 * compound 24 *

DOI:   http://dx.doi.org/10.1021/jo015543l
 [X]  - KOSIOVA IVANA ET AL, "Synthesis of coumarin or ferrocene labeled nucleosides via Staudinger ligation", BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY, BIOMED CENTRAL, LONDON, GB, (20061130), vol. 2, no. 1, doi:10.1186/1860-5397-2-23, ISSN 1860-5397, page 23, XP021026870 [X] 1-3,5-11 * compounds 11a-11c *

DOI:   http://dx.doi.org/10.1186/1860-5397-2-23
 [X]  - KIYOHIKO KAWAI ET AL, "Excess Electron Transfer in DNA Studied by Pulse Radiolysis and [gamma]-Radiolysis of Naphthalimide and Iodouridine Modified ODN", JOURNAL OF PHYSICAL CHEMISTRY PART B: CONDENSED MATTER, MATERIALS, SURFACES, INTERFACES & BIOPHYSICAL, US, (20031101), vol. 107, no. 46, doi:10.1021/jp0346211, ISSN 1520-6106, pages 12838 - 12841, XP055556004 [X] 1-3,5-11 * compounds 4,5 *

DOI:   http://dx.doi.org/10.1021/jp0346211
 [X]  - HETING LI ET AL, "Synthesis of 2'-Amino-2'-deoxyuridine Modified by 1,8-Naphthalimide", SYNTHETIC COMMUNICATIONS, PHILADELPHIA, PA; US, (20060620), vol. 36, no. 14, doi:10.1080/00397910600631924, ISSN 0039-7911, pages 1933 - 1940, XP055555970 [X] 1-3,5-11 * compound 8a *

DOI:   http://dx.doi.org/10.1080/00397910600631924
 [X]  - ABOLFASL GOLISADE ET AL, "Improving an antitrypanosomal lead applying nucleophilic substitution on a safety catch linker", BIOORGANIC & MEDICINAL CHEMISTRY, GB, (20020101), vol. 10, no. 1, doi:10.1016/S0968-0896(01)00253-X, ISSN 0968-0896, pages 159 - 165, XP055556022 [X] 1-3,5-11 * compound 1e *

DOI:   http://dx.doi.org/10.1016/S0968-0896(01)00253-X
International search[X]JPH0196191  (TAIHO PHARMACEUTICAL CO LTD) [X] 1, 2, 7, 8, 10, 11, 16-19 * , claims; compound No.10 (Family: none) *;
 [X]WO0202525  (DU PONT PHARM CO [US]) [X] 1-5, 7-14, 16-19 * , claims; table 3, entry 146, 151, 320, 325, 494, 499, 668, 673, 842, 847 & JP 2004-517805 A & US 2003/0032654 A1 & EP 1296978 A1 & AU 7312901 A & CA 2413245 A & BR 111878 A & MX PA02012712 A & CN 1440402 A *;
 [X]JP2002507961  (Vertex Pharmaceuticals Inc.) [X] 1-3, 7, 8, 10, 16-19 * , claims 1, 6, 14, 16, 19, 23, 66 to 69 & WO 1997/022619 A2 claims 1, 6, 14, 16, 19, 23, 66 to 69 & JP 2003-137896 A & JP 2008-285493 A & US 6008217 A & US 5874424 A & EP 869967 A2 & NO 982597 A & AU 1522297 A & BR 9612258 A & CA 2239904 A & TW 200300761 A & CN 1229412 A & KR 10-2004-0096550 A & MX *;
 [X]WO03103677  (PROCTER & GAMBLE [US]) [X] 1-3, 7, 8, 10, 19 * , table III, No.181 to 240; table V, No.349 to 384 and many others & US 2004/0009966 A1 & EP 1511491 A1 & AU 2003237983 A *;
 [A]WO2012158413  (ARRAY BIOPHARMA INC [US], et al) [A] 1-19 * , claims; examples & JP 2014-514360 A & JP 2016-128500 A & US 2015/0166564 A1 & EP 2712358 A2 & CA 2835835 A & AU 2012256237 A & CN 103649076 A & KR 10-2014-0037872 A & MX 2013013342 A & TW 201249831 A *;
 [A]WO2014078417  (ARRAY BIOPHARMA INC [US], et al) [A] 1-19 * , claims; examples (Family: none) *;
 [A]WO2014078322  (ARRAY BIOPHARMA INC [US], et al) [A] 1-19* , claims; examples (Family: none) *;
 [X]WO2015035278  (SQUIBB BRISTOL MYERS CO [US]) [X] 1-3, 7, 8, 10, 16-19 * , claims; example 37 & EP 3044219 A1 & CN 105705501 A *;
 [X]WO2015039333  (MERCK SHARP & DOHME [US], et al) [X] 1-19 * , claims; compounds 3, 33 to 35; page 19, lines 1 to 19 & US 2016/0229850 A1 & WO 2015/042085 A2 & EP 3046553 A1 *;
 [X]  - WANG, YILI E et al., "Synthesis and evaluation of unsaturated caprolactams as interleukin-1β converting enzyme (ICE) inhibitors", Bioorganic & Medicinal Chemistry, (20070000), vol. 15, no. 3, pages 1311 - 1322, XP005823072 [X] 1-3, 7, 8, 10, 16-19 * , Compound 13, 25 *

DOI:   http://dx.doi.org/10.1016/j.bmc.2006.11.011
 [X]  - ELLIS, CHRISTOPHER D. et al., "Synthesis and evaluation of thiazepines as interleukin-1β converting enzyme (ICE) inhibitors", Bioorganic & Medicinal Chemistry Letters, (20060000), vol. 16, no. 18, pages 4728 - 4732, XP028596926 [X] 1-3, 7, 8, 10, 19 * , Compound 11, 13 *

DOI:   http://dx.doi.org/10.1016/j.bmcl.2006.07.016
 [X]  - GENG, HUI MIN et al., "Synthesis of the Revised Structure of Acortatarin A", European Journal of Organic Chemistry, (20140000), vol. 2014, no. 28, pages 6227 - 6241, XP055345485 [X] 1-3, 7, 8, 11, 19 * , Compound 36, 37 *

DOI:   http://dx.doi.org/10.1002/ejoc.201403000
 [X]  - CHENNAMADHAVUNI, DIVYA et al., "Tetrahedron Letters", Tetrahedron Letters, (20150000), vol. 56, no. 23, pages 3583 - 3586, XP055345488 [X] 1-3, 7, 8, 19 * , Compound 6aa-6ca *

DOI:   http://dx.doi.org/10.1016/j.tetlet.2015.02.133
 [X]  - BENSON, STEFAN et al., "Second-Generation Total Synthesis of Spirastrellolide F Methyl Ester: The Alkyne Route", Angewandte Chemie , International Edition, (20110000), vol. 50, no. 37, pages 8739 - 8744, XP055345490 [X] 1, 2, 7, 8, 10, 19 * , Compound 25 *

DOI:   http://dx.doi.org/10.1002/anie.201103270
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