ZA200401455B - Thienol[2,3-d]pyrimidines with combined LH and FSH agonistic activity. - Google Patents

Thienol[2,3-d]pyrimidines with combined LH and FSH agonistic activity. Download PDF

Info

Publication number: ZA200401455B
Authority: ZA; South Africa
Prior art keywords: composition; thieno; pyrimidine; substance; tert
Prior art date: 2001-09-04

Application number

ZA200401455A

Other languages

English (en)

Inventor

Robert Gerard Jules Ma Hanssen

Cornelis Marius Timmers

Original Assignee

Akzo Nobel Nv

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2001-09-04

Filing date

2004-02-23

Publication date

2004-11-19

2004-02-23 Application filed by Akzo Nobel Nv filed Critical Akzo Nobel Nv

2004-11-19 Publication of ZA200401455B publication Critical patent/ZA200401455B/en

Links

230000001270 agonistic effect Effects 0.000 title description 5
150000003230 pyrimidines Chemical class 0.000 title 1
150000001875 compounds Chemical class 0.000 claims description 29
239000000203 mixture Substances 0.000 claims description 21
238000000034 method Methods 0.000 claims description 19
150000003839 salts Chemical class 0.000 claims description 11
-1 (pyrrolidin-1-yl)-acetamido Chemical group 0.000 claims description 9
230000035558 fertility Effects 0.000 claims description 7
DDWBRNXDKNIQDY-UHFFFAOYSA-N thieno[2,3-d]pyrimidine Chemical class N1=CN=C2SC=CC2=C1 DDWBRNXDKNIQDY-UHFFFAOYSA-N 0.000 claims description 7
239000003814 drug Substances 0.000 claims description 6
239000008194 pharmaceutical composition Substances 0.000 claims description 6
238000004519 manufacturing process Methods 0.000 claims description 5
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
208000021267 infertility disease Diseases 0.000 claims description 3
AVKDUWXKFKONID-UHFFFAOYSA-N 5-amino-4-[3-[[2-(azetidin-1-yl)acetyl]amino]phenyl]-n-tert-butyl-2-methylsulfanylthieno[2,3-d]pyrimidine-6-carboxamide Chemical compound C=12C(N)=C(C(=O)NC(C)(C)C)SC2=NC(SC)=NC=1C(C=1)=CC=CC=1NC(=O)CN1CCC1 AVKDUWXKFKONID-UHFFFAOYSA-N 0.000 claims description 2
YIPQZUTVMXEUDX-UHFFFAOYSA-N 5-amino-n-tert-butyl-2-methylsulfanyl-4-[3-[(2-piperidin-1-ylacetyl)amino]phenyl]thieno[2,3-d]pyrimidine-6-carboxamide Chemical compound C=12C(N)=C(C(=O)NC(C)(C)C)SC2=NC(SC)=NC=1C(C=1)=CC=CC=1NC(=O)CN1CCCCC1 YIPQZUTVMXEUDX-UHFFFAOYSA-N 0.000 claims description 2
125000004432 carbon atom Chemical group C* 0.000 claims description 2
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UWTXKCMCTINMHD-UHFFFAOYSA-N 5-amino-n-tert-butyl-2-methylsulfanyl-4-[3-[(2-morpholin-4-ylacetyl)amino]phenyl]thieno[2,3-d]pyrimidine-6-carboxamide Chemical compound C=12C(N)=C(C(=O)NC(C)(C)C)SC2=NC(SC)=NC=1C(C=1)=CC=CC=1NC(=O)CN1CCOCC1 UWTXKCMCTINMHD-UHFFFAOYSA-N 0.000 claims 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
- A61P5/08—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH for decreasing, blocking or antagonising the activity of the anterior pituitary hormones

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Endocrinology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Reproductive Health (AREA)
Diabetes (AREA)
Gynecology & Obstetrics (AREA)
Pregnancy & Childbirth (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

ZA200401455A 2001-09-04 2004-02-23 Thienol[2,3-d]pyrimidines with combined LH and FSH agonistic activity. ZA200401455B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
EP01203327		2001-09-04

Publications (1)

Publication Number	Publication Date
ZA200401455B true ZA200401455B (en)	2004-11-19

Family

ID=8180876

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ZA200401455A ZA200401455B (en)	2001-09-04	2004-02-23	Thienol[2,3-d]pyrimidines with combined LH and FSH agonistic activity.

Country Status (28)

Country	Link
US (1)	US7317006B2 (de)
EP (1)	EP1427733B1 (de)
JP (1)	JP4262092B2 (de)
KR (1)	KR100900018B1 (de)
CN (1)	CN1246324C (de)
AR (1)	AR036407A1 (de)
AT (1)	ATE345345T1 (de)
AU (1)	AU2002337035B2 (de)
BR (1)	BR0211938A (de)
CA (1)	CA2456901C (de)
CY (1)	CY1106012T1 (de)
DE (1)	DE60216128T2 (de)
DK (1)	DK1427733T3 (de)
ES (1)	ES2275005T3 (de)
HR (1)	HRP20040202A2 (de)
HU (1)	HUP0401444A3 (de)
IL (1)	IL160084A0 (de)
IS (1)	IS2424B (de)
MX (1)	MXPA04002045A (de)
NO (1)	NO20040927L (de)
NZ (1)	NZ531340A (de)
PE (1)	PE20030439A1 (de)
PL (1)	PL368502A1 (de)
PT (1)	PT1427733E (de)
RU (1)	RU2298011C2 (de)
TW (1)	TWI228508B (de)
WO (1)	WO2003020726A1 (de)
ZA (1)	ZA200401455B (de)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6890923B2 (en) *	2002-12-16	2005-05-10	Astrazeneca Ab	Compounds
GB0315950D0 (en) *	2003-06-11	2003-08-13	Xention Discovery Ltd	Compounds
GB0525164D0 (en) *	2005-12-09	2006-01-18	Xention Discovery Ltd	Compounds
CN100430403C (zh) *	2006-10-13	2008-11-05	中国科学院上海有机化学研究所	3-芳基-5,6-取代噻吩并嘧啶-4-羰基-2-巯基乙腈、合成方法和用途
US20090118276A1 (en) *	2007-11-02	2009-05-07	Wyeth	Thienopyrimidines, thienopyridines, and pyrrolopyrimidines as b-raf inhibitors
TWI389913B (zh) *	2008-09-08	2013-03-21	Lg Life Sciences Ltd	并合雜環化合物
US8741259B2 (en) *	2008-10-20	2014-06-03	Marvin C. Gershengorn	Low molecular weight thyroid stimulating hormone receptor (TSHR) agonists
GB0905525D0 (en)	2009-03-31	2009-05-13	Univ Leiden	Compounds and uses
EA022553B1 (ru)	2010-01-22	2016-01-29	Байер Интеллектуэль Проперти Гмбх	Применение комбинации биологически активных веществ, набор и средство, содержащие комбинацию биологически активных веществ, для борьбы с вредителями животного происхождения и способ улучшения использования продукционного потенциала трансгенного растения
EP2563777A4 (de)	2010-04-08	2013-09-04	Us Health	Inverse agonisten und neutrale agonisten für den tsh-rezeptor
WO2016029375A1 (en)	2014-08-27	2016-03-03	The Procter & Gamble Company	Wearable article having elastic belt
WO2016029372A1 (en)	2014-08-27	2016-03-03	The Procter & Gamble Company	Wearable article having elastic belt
RU2619091C2 (ru) *	2015-10-13	2017-05-11	Министерство Промышленности И Торговли Рф	Цилиндрический термоэмиссионный катод
CN108883011B (zh)	2016-04-08	2021-05-07	宝洁公司	具有艺术作品的可穿着制品
AU2023282849A1 (en) *	2022-06-08	2025-01-09	Icahn School Of Medicine At Mount Sinai	Method of treating obesity with a luteinizing hormone receptor agonist

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ES2054784T3 (es)	1987-08-08	1994-08-16	Akzo Nv	Un metodo para la fabricacion de un implante.
TW564247B (en) *	1999-04-08	2003-12-01	Akzo Nobel Nv	Bicyclic heteraromatic compound

2002
- 2002-07-22 TW TW091116284A patent/TWI228508B/zh not_active IP Right Cessation
- 2002-08-29 NZ NZ531340A patent/NZ531340A/en unknown
- 2002-08-29 AU AU2002337035A patent/AU2002337035B2/en not_active Ceased
- 2002-08-29 PT PT02772230T patent/PT1427733E/pt unknown
- 2002-08-29 ES ES02772230T patent/ES2275005T3/es not_active Expired - Lifetime
- 2002-08-29 AT AT02772230T patent/ATE345345T1/de not_active IP Right Cessation
- 2002-08-29 KR KR1020047003095A patent/KR100900018B1/ko not_active Expired - Fee Related
- 2002-08-29 RU RU2004110042/04A patent/RU2298011C2/ru not_active IP Right Cessation
- 2002-08-29 HR HR20040202A patent/HRP20040202A2/hr not_active Application Discontinuation
- 2002-08-29 PL PL02368502A patent/PL368502A1/xx not_active Application Discontinuation
- 2002-08-29 WO PCT/EP2002/009647 patent/WO2003020726A1/en not_active Ceased
- 2002-08-29 BR BR0211938-2A patent/BR0211938A/pt not_active IP Right Cessation
- 2002-08-29 IL IL16008402A patent/IL160084A0/xx not_active IP Right Cessation
- 2002-08-29 EP EP02772230A patent/EP1427733B1/de not_active Expired - Lifetime
- 2002-08-29 CN CNB028172604A patent/CN1246324C/zh not_active Expired - Fee Related
- 2002-08-29 DE DE60216128T patent/DE60216128T2/de not_active Expired - Lifetime
- 2002-08-29 JP JP2003524996A patent/JP4262092B2/ja not_active Expired - Fee Related
- 2002-08-29 US US10/488,482 patent/US7317006B2/en not_active Expired - Lifetime
- 2002-08-29 MX MXPA04002045A patent/MXPA04002045A/es active IP Right Grant
- 2002-08-29 CA CA2456901A patent/CA2456901C/en not_active Expired - Fee Related
- 2002-08-29 DK DK02772230T patent/DK1427733T3/da active
- 2002-08-29 HU HU0401444A patent/HUP0401444A3/hu unknown
- 2002-09-02 AR ARP020103309A patent/AR036407A1/es unknown
- 2002-09-03 PE PE2002000840A patent/PE20030439A1/es not_active Application Discontinuation
2004
- 2004-01-29 IS IS7130A patent/IS2424B/is unknown
- 2004-02-23 ZA ZA200401455A patent/ZA200401455B/en unknown
- 2004-03-03 NO NO20040927A patent/NO20040927L/no not_active Application Discontinuation
2007
- 2007-02-13 CY CY20071100189T patent/CY1106012T1/el unknown

Also Published As

Publication number	Publication date
MXPA04002045A (es)	2004-07-08
US7317006B2 (en)	2008-01-08
AU2002337035B2 (en)	2008-04-24
WO2003020726A1 (en)	2003-03-13
EP1427733B1 (de)	2006-11-15
IL160084A0 (en)	2004-06-20
TWI228508B (en)	2005-03-01
KR20040029134A (ko)	2004-04-03
CA2456901A1 (en)	2003-03-13
IS7130A (is)	2004-01-29
KR100900018B1 (ko)	2009-06-01
HUP0401444A2 (hu)	2004-11-29
JP2005505555A (ja)	2005-02-24
PL368502A1 (en)	2005-04-04
NZ531340A (en)	2005-08-26
NO20040927L (no)	2004-03-03
DK1427733T3 (da)	2007-03-19
HRP20040202A2 (en)	2004-08-31
PT1427733E (pt)	2007-02-28
CN1246324C (zh)	2006-03-22
ES2275005T3 (es)	2007-06-01
US20040180873A1 (en)	2004-09-16
DE60216128D1 (de)	2006-12-28
RU2298011C2 (ru)	2007-04-27
HUP0401444A3 (en)	2008-05-28
ATE345345T1 (de)	2006-12-15
JP4262092B2 (ja)	2009-05-13
DE60216128T2 (de)	2007-09-27
BR0211938A (pt)	2004-09-21
CY1106012T1 (el)	2011-04-06
CN1551884A (zh)	2004-12-01
CA2456901C (en)	2011-01-04
AR036407A1 (es)	2004-09-08
EP1427733A1 (de)	2004-06-16
IS2424B (is)	2008-10-15
PE20030439A1 (es)	2003-05-17
RU2004110042A (ru)	2005-08-20

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US7317006B2 (en)	2008-01-08	Thieno[2,3-d]pyrimidines with combined LH and FSH agonistic activity
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