Download - CiVentiChem India Presentation - 2012.ppt
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
CiVentiChem (India) Private Limited
(Formerly Known as Indus BioSciences Private Limited)
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Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
• History• Business Overview• Services and Capabilities• Management Experience and Chemistry
Expertise• Chemistry Specialties & Capabilities• Bulk Projects Performed in Plant• Chemistry Experience
– Examples in Med. Chem & P R&D– Proprietary Building Blocks
• Facilities
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Highlights of Presentation
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
History• 1994 - Founded in RTP, North Carolina• 1999 – Expanded to Larger Laboratory• 2000 – Reached 12 Scientists at USA• 2001 – R&D Laboratories Opened in India with
5 Chemists• 2009 – Launch of our Plant in Hyderabad,
India• 2011 – cGMP Synthesis lab in RTP, NC, USA
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Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Business Overview• HQ: RTP, North Carolina• Services: Chemistry
– Discovery & Synthetic Chemistry, Process Development, Manufacturing & Analytical Services
• People: 80 Experienced Scientists & Admin• Facilities: USA and India
– RTP, North Carolina and Hyderabad, India– 50,000 Sq Ft Total Technical Facilities
• Customers: Around 150– including 10 of world Top 20 Pharma; 45 Biotechnology
Companies.• Integrated Management Systems
– ISO-9001-2008 (QMS), 14001-2004 (EMS) and 18001-2007 (OSHA)
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Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
BiologicalTarget
Screening Hits LaunchClinicalLeadsDrug
candidatePre -
clinical
ScreeningCompounds
CustomSynthesis
ParallelSynthesis
MedicinalChemistry
ManufacturingPilotPlant
ProcessScale -up
AssociatedChemistry
Peakdale Molecular Collaborators
-
BiologicalTarget
Screening Hits LaunchClinicalLeadsDrug
candidate
Pre -clinical
ScreeningCompounds
CustomSynthesis
ParallelSynthesis
MedicinalChemistry
ManufacturingPilotPlant
ProcessScale -up
AssociatedChemistry
CiVentiChem USA & India
CiVentiChem India
-
Our Role in Drug Development
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DEVELOPMENT CHEMISTRY
•Rapid Initial Scale-up to first Kg•Process Research & Development•Feasibility Studies•Pilot Development Manufacture•Manufacture Intermediatess & APIs•cGMP & Non-GMP Protocols
RESEARCH CHEMISTRY
•Medicinal Chemistry•Focused Libraries•Reference Standards & Metabolites•Lead Compounds & NCEs•Lead Optimization•Intermediates and Building Blocks available and in-stock
PRODUCTION CHEMISTRY
•Pilot Development Manufacture
•Process Research & Development
•Contract Manufacturing •Manufacture Intermediates & APIs
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Global Advantages
Flexibility of Choice… USA or India or BOTH !!
• Project Type• Deadline• Output Scale or Volume• Research Requirements• Expertise Requirements• Communication and Project Control• Lowest Cost
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Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Business Overview - Clients
• No. of clients – 150• No. of Pharma Clients – 10 (from world
top 20 Pharma Companies)• No. of Biotech Clients – 10 +• No. of Catalogue Companies – 5 +• No. of Fine Chemical Companies – 10
+
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Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Services and Capabilities
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Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Research Chemistry Services
• Medicinal Chemistry• Synthesis of Focused Libraries &
Analogues• Synthesis of Reference Standards &
Metabolites• Synthesis of Lead Compounds & NCEs• Lead Optimization & Parallel Synthesis• Novel Template Molecules Ready for
Purchase9
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Development/Manufacturing Services
• Rapid Initial Scale-up to 1st Kilogram• Route Scouting • Process Development & Optimization• Manufacture of Intermediates• API ready starting materials
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Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Management Experience
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Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Management Team
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Bhaskar Venepalli, Ph. DBhaskar Venepalli, Ph. DChief Executive OfficerChief Executive Officer
Professional ExperienceProfessional Experience
25 + Years experience in fine chemicals
including 13 Yrs experience in R&D, new
product development & Business
Management at Eastman Kodak-Eastman
Chemical Company
Expertise in CRAMS & Fine Chemicals
Founder of Civentichem in 1994 in USA
EducationEducation
Ph.D. from Osmania University,
Hyderabad (IND)
Post Doctoral Research at University of
Southampton (England) & Rockefeller
University, New York, (USA)
Vasu (Srinivas) Vasu (Srinivas) Chittineni, Ph. DChittineni, Ph. D
Chief Technical OfficerChief Technical Officer
Professional ExperienceProfessional Experience
20 + Years experience in synthetic
organic chemistry
Expertise in Complex Organic
Syntheses, Chiral & Carbohydrate
Chemistry
Co founder of Civentichem in 1994
EducationEducation
Ph.D. from Kakatiya University (IICT,
Hyderabad, INDIA)
Post Doctoral Research at Duke
University , NC, USA
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Management Team
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Venkataiah Sunku, Ph. DVenkataiah Sunku, Ph. DManaging DirectorManaging Director
Professional ExperienceProfessional Experience
30 + Years experience in pharma
including 8 Yrs experience as Director
R&D at Aurobindo Pharma (India)
Expertise in Process Development &
Plant Scale operations
Developed processes for 22 bulk drugs
& Transferred to Mfg Plants
EducationEducation
Ph.D. in Chemistry from Osmania
University, Hyderabad (INDIA).
6 Publications & Patents
Venu (Venugopal) Venu (Venugopal) Veeramaneni, Ph. DVeeramaneni, Ph. D
Head R&D and BD&PMHead R&D and BD&PM
Professional ExperienceProfessional Experience
18 Years experience in Drug Discovery
(Medicinal &Synthetic Organic
Chemistry. Including 11 yrs at Dr.
Reddy’s Discovery Research.
Expertise in Synthesis of NME’s &
Complex Organic Syntheses
EducationEducation
Ph.D. in Chemistry from JNTUniversity
(DRF, Hyderabad, INDIA)
25 Publications, Patents &
Presentations
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Research Team @ Civentichem India
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Hari Prasad Chittineni, Ph.D.Hari Prasad Chittineni, Ph.D.Section Head, Process DevelopmentSection Head, Process Development
14 Yrs Experience in Carbohydrate, Heterocyclic Chemistry including 4 Yrs in AVRA Synthesis Expertise in Process DevelopmentM.Sc. From Osmania UniversityPh.D. from JNT University 7 Publications & Patents
Venkat Laxman Rao Cilamkoti, Ph.D.Venkat Laxman Rao Cilamkoti, Ph.D.Section Head, Medicinal ChemistrySection Head, Medicinal Chemistry
16 Yrs experience in Multi Step Organic Synthesis including 8 Yrs in Dr Reddy’s Discovery Research Expertise in Medicinal & Small scale ChemistryM.Sc. From Osmania UniversityPh.D. from Osaka University, Japan 9 Publications & Patents
Vineel, Vineel, Ph.DPh.D
Group Leader
5 Yrs Exp in Sugar &
Chiral Chemistry.
Ph.D. from JUNTU
MamathaMamathaGroup Leader
8 Yrs Exp in Azaindole & Indazole Chemistry
M.Sc. from Osmania University
GopalGopal Group Leader
8 Yrs Exp in Process &
Scale Up Chemistry
M.Sc. from Osmania University
ShyamShyamGroup Leader
8 Yrs Exp in Med.
Chem. & Small Scale
M.Sc. from Osmania University
RC SekarRC SekarGroup Leader
8 Yrs Exp in Med.
Chem. & Small Scale
M.Sc. from Osmania University
RajithaRajithaGroup Leader
8 Yrs Exp in New
Building Blocks
M.Sc. from Osmania University
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Research Team @ Civentichem India
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Research Team @ Civentichem India
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Chemistry Expertise & Performance Matrix
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Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
• Sugar Molecules
• Chiral Catalysts and Reagents
• Reagents for peptide formation
• Novel Hetero cyclic compounds for supporting all the
stages in drug discovery.
• Pyrazoles, Isoxazole, Oxazoles, Pyrazines, Pyridazines,
Pyrimidines, Pyrrolopyrimidine, Azaindoles, Indazoles,
Piperidinopyrimidines and Heterocycles having Spiro
group
• Chiral Binaphthols & Boronic Acids18
Chemistry Specialties
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
• General Reactions - mg to Kg scale• Grignard Reactions – Up to 50 kg of Mg charge• Bromination – mg to multi Kg scale•Hydrogenation Reactions – 350L SS, 30 kg/cm²•Transition Metal Reactions
• Suzuki coupling (0.5Kg, 1Kg to 25Kg Scale)
• Buchwald-Hartwig Coupling (5g & 500g Scale)• Negishi coupling (150g & 250g)•Sonogashira reaction (1Kg Scale)• Stille coupling (10g Scale)
• Enzymatic Resolutions • Reactions in Aqueous medium • Phosgenations using triphosgene
Chemistry Capabilities
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Bulk Projects Performed in PlantS.No. Project Code Quantity No. of
StepsMonth of
completionRemarks/Key Chemistries
1 IB-205/151 45Kg 2 Oct, 2009 Iodination & amide formation
2 IB-205/284 120Kg 2 Nov, 2009 Indole Acylation
3 IB-150/011 425Kg & 415Kg
4 Jan & Oct 2010
Methylsulfonation & chlorination
4 IB-111/280 15Kg & 27Kg
3 Jan, 2010 Bromination & Phosphonate Chemistry
5 IB-111/291 15Kg & 27Kg
3 Jan, 2010 Bromination & Phosphonate Chemistry
6 IB-150/214 5Kg & 7Kg 7 Feb & Nov 2010
Cyclopropanation & Protection of Amine
7 IB-206/263 10Kg 1 Feb, 2010 Hydroxymethylation
8 IB-080/319 6Kg & 12Kg
2 March, 2010 Formyl pyrazoles
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Bulk Projects Performed in PlantS.No. Project Code Quantity No. of
StepsMonth of
completionRemarks/Key Chemistries
9 IB-206/320 21Kg/ 35Kg
4 March & July 2010
Amino acid Chemistry
10 IB-323/282 5Kg/30Kg 10 April & Nov 2010
Benzofuran formation, Suzuki coupling & Reduction
11 IB-323/086 7Kg 5 April 2010 Azaindole Chemistry & Catalytic hydrogenation
12 IB-206/263 10Kg/ 100Kg
1 April & june 2010
Hydroxymethylation
13 IB-313/275 3X100Kg 1 3 Times in 2010
Preparation Phase Transfer Catalyst
14 IB-150/333 15Kg 2 June, 2010 Nitration & etherification
15 IB-213/338 75Kg 2 June, 2010 Cyclopropanation
16 IB-150/014 24Kg 9 Sept, 2010 Nitration, Reduction and Migration
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Bulk Projects Performed in PlantS.No. Project Code Quantity No. of
StepsMonth of
completionRemarks/Key Chemistries
17 IB-080/293 10Kg 7 Oct, 2010 Azaindole Chemistry, Nitration & Bromination
18 IB-266/267 45Kg 3 Oct, 2010 Bromination & Selective Reduction
19 IB-036/206 10Kg / 100Kg
4 Oct, 2010 Grignard Reaction
20 IB-372/266 5Kg , 35Kg & 35Kg
2 Dec, 2010 & Feb, 2011
Bromination & Thiazole formation
21 BAL-PH 186Kg 2 Jan, 2011 Critical Reduction
22 IB-398/404 10Kg 3 Feb, 2011 Phosphonate Chemistry
23 IB-079/176 35Kg 1 Feb, 2011 Pyrazole formation
24 IB-373/399 48Kg 1 Feb, 2011 Cyclization
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Bulk Projects Performed in PlantS.No. Project Code Quantity No. of
StepsMonth of
completionRemarks/Key Chemistries
25 IB-416-205-3595
76Kg 3 April, 2011 Cyclization
26 IB-426-427-025
60Kg 4 June, 2011 Modified Reduction method to avoid expensive Pd
Charcoal
27 IB-147-150-3988
60Kg 5 July, 2011 Synthesized Starting Material instead of buying expensive
KSM
28 IB-455-150-5025
16Kg 4 July, 2011 Synthesized Starting Material instead of buying expensive
KSM
29 IB-407-150-5628
45Kg 10 July, 2011 Benzofuran formation, Suzuki coupling & Reduction
30 IB-232-450-4062
6Kg 5 July, 2011 Target is Very Useful KSM for Anti Viral APIs. And process
is performed in water
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Bulk Projects Performed in PlantS.No.
Project Code
Quantity
No. of
Steps
Month of completio
n
Remarks/Key Chemistries
31CVI-429-428-7024
30Kg 1 August, 2011
Salt preparation as per client’s typical specifications
32CVI-476-428-092
30Kg 1 August, 2011
Salt preparation as per client’s typical specifications
33CVI-431-428-7026
15Kg 1 August, 2011
Salt preparation as per client’s typical specifications
34CVI-431-428-7025
15Kg 1 August, 2011
Salt preparation as per client’s typical specifications
35IB-471-472-
088
10Kg & 25Kg
3 August, 2011 & Jan 2012
Handling of use amount of TFA (which is minimized to 30%)
36 CVI-432-150-5025
40Kg 5 November, 2011
Synthesized Starting Material instead of
buying expensive KSM
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Performance of our Research Team
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Quality and Integrated Management Systems
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Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
• CiVentiChem India has successfully obtained the following
certifications
• Currently follow Integrated Management Systems
• ISO-9001-2008 certification for Quality Management
Systems
• ISO-14001-2004 certification for Environmental
Management Systems
• ISO-18001-2007 certification for Occupational, Health and
Safety Management Systems (OSHA)
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ISO Certifications
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Chemistry Experience - Case Studies
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Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Route Scouting and Discovery Support Erlotinib Analogue
O
O
O
O N
N
HN
Erlotinib
Nitration
Reduction
Reduction
1 2 34
56
7
89
10
11 12
HO
HO
HO
HO
HO
OPh
O
OPh
O
O
OPh
O
NO2
O
HO
O
NO2
O
O
O
NO2O
O
O
O
NH2O
O
O
O
O N
N
OHO
O
O
O N
N
OH
H2N
EtOH
H2SO4O Br
O OTs
O
O
O
O N
N
Cl
H2N O
O
O
O N
N
HN
H2N
NNCO2Et
CO2Et CO2Et CO2Et
CO2EtCO2EtCO2Et
CO2H
N
N
NN N
Client wanted a compound with a reactive functional groupRe-designed the synthesis and delivered the product
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Med Chem Support/Route Scouting
C-imatinib analogue
N
O
N
O
N
N
NHN
4
2
6
N
N
N
NH2
Br
CO2H CO2H
Br
CO2H
N
N
NHN
7
N
N
NHN
18
1
3
5
14 15 16
O2N NO2
N
NO2 NH2
O
N
N
N
HN
N
NNH2
CO2H
N
NN
17
O
O
O O
N
N
NHN
O
N
N
NH2
HN
19
N
N
NHN
O
N
NHN
Imatinib
Client wanted analog with a reactive functional groupRe-designed the synthesis with a new route and delivered the product with NH2 and maleimido groups
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Med Chem Support-Focus Libraries
N
N
N
Ar OR1
R
Ar =
NH
O
Het
Het= Pyrazoles, Isoxazoles, Oxazoles, Piperidines, Piperazines, benzofurans & etc
OR1 = Alkyl, cyclopropyl, cyclobutyl & etc
R = Alkyls & Aryls
3-Alkyl/Aryloxy-4-Alkyl/Aryl-5-Aryl/Heteroaryl-4H-1,2,4-triazoles
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Med Chem Support-Focus Libraries
Ar =
Het= Pyrazoles, Isoxazoles, Oxazoles, Piperidines, Piperazines, benzofurans & etc
NO
NH2
Ar
Aryl/Hetero aryl
O
4-(1-Aryl/Heteroaryl-1,2,3,6-tetrahydropyridin-4-yl)benzamides
NN
NO2
NH
O
R1
R
R = Alkyl & ArylR1 = Substituted Aryls, heteroaryls,
cycloproppys and Pieridinyls
1-Alkyl/Aryl-4-nitro-N-Aryl/Heteroaryl-1H-pyrazole-3-carboxamide
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Med Chem Support-Focus Libraries
N
S
N
N
X
HNR
5-Halo-N-Aryl/heteroaryl/alkylimidazo[2,1-b][1,3,4]thiadiazol-2-amines
R = Alkyl/Aryl/Hetero aryls & etcX = Br & I
N
N
N
OO
R
O
R = Alkyls, Aryls & Hetero aryls
ethyl 2-(4/5-(Alkyl/Aryloxymethyl)-1H-1,2,3-triazol-1-yl)acetates
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Reference Standards for Med Chem Support
S
O
HN
NClHN
N
NMe
NN
HO
Dasatinib
O
O
O
O N
N
HN
ErlotinibN
N
NHN
HN O
N
N
Imatinib
N
N
Cl
O
NH
F
O
HN
SOMe
O
LapatinibHN
OEt N
CN
O
Cl
N
O
NNiratinib
N
N
NHN
O NH
N CF3N
NilotinibNH
NN
N
N
N
Pazopanib
SO2NH2
HNNH
ON
NH
F
OSunitinib
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Reference Standards for Med Chem Support
N N
HN
N N
OH
OO
GSK-3B-XI
HN
O OHO
F
F
O
O
O
Firatigrast/SB-683699/T-0047
N
HN
O OHO
F
F
N
O
O AJM - 300
HNNH
ON
NH
F
OSunitinib Analogue
NH
MeN N
O
O
O
Trequinsin
N
O
S
NHO
O
Pioglitazone
N
N
N
F Br
O
O
N
Vandetanib
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
New Route & Process Development
Hexahydrofuro[2,3-b]furan-3-ol moiety
O
O
OHHexahydrofuro[2,3-b]furan-3-ol
(Bisfuran Alcohol)
NHHO
O
N
O
O
O
SO
O
Brecanavir(GW640385)
OO
N
S
O
NHHO
O
N
O
O
O
H2N
S
OO
Darunavir(TMC-114)
HN
HO
O
N
O
O
O
H2N
SO
O
GS-9005
HNP
O
O
O
OO
NCE
Bis-THF alcohol -A Key intermediate in many antiviral drugsOur goal: Develop a new route for use in Med ChemThen develop a process for manufacturing
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
New Route & Process Development Hexahydrofuro[2,3-b]furan-3-ol moiety
CO2EtEtO2C
OH Br
LDA CO2Et
CO2Et
OHLAH
OH
HO
OH
HO
Acetone
PTSAO
O
O
MeO
Oxidation
CHO
OO
CSA
MeOH
O
MeO
O
O3 CSA
MeOH
O
O
HO
OH OH
Enantioselective Synthesis
Reported synthetic route
•Problems with enantiomeric purity•Scalability
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
New Route & Process Development Hexahydrofuro[2,3-b]furan-3-ol moiety
O OH OO
O
O OO
O
New Route Development to make chiral alchol
Process Development O
OH O
I
O
1) Cobaloxime
NaBH4/NaOH
CH2Cl2 / 0°C
O
O
O
2) NaIO4K2OsO2 (OH)4
O
O
HO
NaBH4O
O
HO
Enzymatic
ResolutionAcetylation(2) (4) (5)(1) NIS
(3)
O
O
AcO
Synthesis and Optical Resolution
Initial Goal:•Make small quantity to make 100 gm of API•After this is delivered, client wanted to file for IND, hence needed 10 Kg•No luxury of time as it was needed urgently•Brute forced the synthesis and delivered the product•Two enantiomers were separated by column chromatography
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
New Route & Process Development Hexahydrofuro[2,3-b]furan-3-ol moiety
Process Development – Objectives•Eliminate hazardous radical reactions•Avoid column purification of resolution mixture•Improve economics of API route- 12 step synthesis
Avoided column chromatography by developing a solid derivative that can be separated by filtration from resolution mixture
Preparation Bis THF Active Fragment
O
O
HO
O O
O
O
O N
O
O
NO O
O
N
O
O O
O
•Redesigned API route where this expensive chiral piece comes at penultimate step•In earlier synthesis it was used in second step-Thus improving economies by several fold•Made 500 gm of API with the route which is being used now
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
New Route & Process Developmentfor a key intermediate for API
potent farnesyl protein transferase (FPT) inhibitor
Inhibition of CholesterolSynthesis by Inhibiting
Squalene Synthase
BocNCO2H
O
O
N
Cl
OH
ON
O
O CO2Et
Br Br
Cl
N
O
NH
Piperidine-4-acetic acid is a key intermediate
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
New Route & Process Development Piperidine-4-acetic acid is a key intermediate
Lonarfanib
Br Br
Cl
N
O
NH
N
O N N
OO
N
OH
NH
OH
CO2Et CO2H
CO2Et
CO2Et
CO2Et
N
O
NO
O
OMs
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Process Development 4-(4-Chloro-pyrimidin-2-ylamino)-
benzonitrile for Anti Viral drugs
N
N
NH
N
Cl
NH
N
N
NH
N
Depivirin (TMC 120)
NH
N
N
N
NH
N
Rilpivirine (TMC 278)
O
N
NN
HN N
NH2Br
Etravirine (TMC 125)
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Process Development Synthesis of di-tert-butyl chloromethyl phosphateSynthesis of di-tert-butyl chloromethyl phosphate
for The Synthesis of ProdrugsProdrugs
OP
O
O
O Cl
HO P
O
OH
O N
N
F
FF
O
OCinnarizine prodrugantihistamine
O
NN
N
Cl
Loxapine prodrug
OHP
O
HO
O
F
FF
O
O
antipsychotic
N
S
N
NN
N
O
F
F
Ravuconazole (BMS-207147) Prodrug
OP
O
O
O
2Na
antifungal
NO
I
I
O
O
HOP
O
OH
O
F
FF
O
O Amiodarone Prodrug
antiarrhythmic agent
2NaN
NS NH
OO
OP
O OH
O
Water Soluble Prodrugs of Anthelmintic Benzimidazole
N
O
F
F
NH
O
S
N
HOPO
OH
O
Lu AA47070 ProdrugSelective hA2A Receptor Antagonist
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Innovative Chemistry- (+) Lactacystine
NH
O
OHOOHO
NH2
O
16 Steps
OHN
O
O
S
HN
O
OH
O
HO H
Isolated in 1991 by Omura et. Al from Steptomyces sp.
First non-protein neurotropic factor
Highly useful pharmacological tool
Lactone is key active component and acts by acylation of threonine residue
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Innovative ChemistryOrganic synthesis in Aqueous mediumWater as a solvent:Water as a solvent:
3,4-dihydro-2H-benzo[b]thiazine-3-ones 3,4-dihydro-2H-benzo[b]thiazine-3-ones 1,2,3,4-tetrahydro-2-quinoxalinones1,2,3,4-tetrahydro-2-quinoxalinones 2,6-dialkyl-3,5-dicarboxyl-1,4-dihydropyridines & others
NH
HN
O
R
1,2,3,4-tetrahydro-2-quinoxalinones
NH
S
O
R
3,4-dihydro-2H-benzo[b]thiazine-3-ones
NH
O
O
O
O
R
2,6-dialkyl-3,5-dicarboxyl-1,4-dihydropyridines
N
X N
R1
R2
R
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Summary of Chemistry Expertise
Medicinal Chemistry Support
New Route Development
Process Optimization
Innovative Chemistry
Reference Standards for Med Chem
Support
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Chemistry Experience Proprietary Building Blocks Developed at CiVentiChem
47
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Key building blocks for NCE’s 7-Azaindoles
Selective B-Raf inhibitors
Selective, ATP-competitive inhibitors of the mTOR
Selective Inhibitor of Aurora B/C Kinase
Active potent VEGFR-2 inhibitor
N N
NO
N O
OHN
HN
O N
N NH
RR1
R=4-Cl, Br, F, CN, OMe; 5-Cl, Br, F, I, CN, CHO, CO2Me 6-Cl, OHR1=3-Cl, Br, I, CN, CHO, CO2Me
N NH
NN HN
HN
OF
F
F
N NH
NN HN
HN
O
N
NNH
NH
NN
N N N
O
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Key building blocks for NCE’s 1H-Indazoles
Potent and Selective Inhibitors of Factor Xa
Potent TRPV1 Antagonist for
Pain Management (ABT-102)
Novel 5-HT6 Receptor Antagonists
Potent CDC7 inhibitors
N
NH
N
F
N
N
Me
O N
NH2
O
N
NH
NHN
Cl
O
N
N
S OO
N
H2N
N
HN
NHHN
O
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Azaindoles & (1H)-Indazoles
N NH
X = I
X
N NH
X
N NH
4,5,6,7-Azaindoles and Mono/DiSubstituted 7-Azaindole:
X = Cl, Br, I, CN & CHO
X = Cl, Br & OH
NH
N
4,5,6Azaindoles
N NH
YX
X
N NH
XY
X=Cl, Y=Cl, Br, I, CN. CHOX=Br, Y=Cl, I, CN, CHO
X=Br, Y=Cl, Br, I, CN. CHO
Substituted IH-Indazoles:
X=Br, CHO, CO2Me, CO2H, CH2NH2X = Br
NH
NNH
NNH
N
X X
X
NH
N
X
X= H, Cl, I, Br, CN & CO2H
NH
NX
Y
X=Br, CHO, CO2Me, Y=Cl, I
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Drug Intermediates in Bulk
N NH
XCl
NH
N
X
N NH
CO2H
NH
NH2
HCl
NH
N
RO2C
R = H, Me
NH
N
R = H, Me
RO2C
NCl Cl
O
N NH
X
NH
N
Br
N NH
X
N NH
BrX
X = Cl, I
OH
Br
O O
SO
O
NH2N
HNNH2
Ph
X = Cl, Br, IX = H, Br, I X = Cl, Br, I
X = Cl, Br
NH
N
Br
N
N NH
OH
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Pyrimidines
Aryl β-Keto & Diketo esters
O O
Y
O O
OEt
R=Cl, Br, F, I, Me, OMe, CF3, Y=OEt, CO2Et
R NH
O O
OEt
N
O O
OEt
O
O O
OEt
Aryl Beta Keto & Diketo Esters
R= Cl, Br, F, OMe, Me;
N
N
Cl
NH
RN
N
R
O
O
R1
N
N
R
O
O
R1
N
N
R
OO
R= Cl, Br, F, OMe, Me;R1=H, Me & Et
R= AlkylsR1=H, Me & Et
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Pyrazole Derivatives
Isoxazole Derivatves
N NH
O
O
R1
X
N NH
O
O
R1
X R
N NH
R
O
O
R1N N
H
X OO
R1
N NH
X OO
R1
R N NH
RO
OR1
X= Cl, Br, F, OMe, Me; R=H & Me, Et, Pr, iPrR1=H, Me & Et
X= Cl, Br, F, OMe, Me; R=H & Me, Et, Pr, iPrR1=H, Me & Et
R=H & Me, Et, Pr, iPr, CyPrR1=H, Me & Et
ON
R
O
O
R1
R= Cl, Br, F, OMe, Me; R1=H, Me & Et
NO
R= Alkyls & Substituted Aryls R1=H, Me
NO
R
R= Cl, Br, F, OMe, Me; R1=H, Me
H2N
R1
R
O
O
R1
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
2-Naphthol Derivatives (R & S Isomers)
Reagents & Catalysts
OH
OH
OMOM
OMOMOTs
OTsOAc
OAcOH
OH
Br
Br
NH
OH
R
R
R
RR-DPP & S-DPPR & S IsomersR=H & CF3
NH
O
R
R
R
RR & S IsomersR=H & CF3
Si N
O
O
O O
O
N
O
O
DSC
N
Co
N
N
N
O O
H
O OH
Py
Cobaloxime
N N
N
HNNH
O
O
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Facilities
55
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Facilities - India
Hyderabad, India
• Four Synthetic Laboratories • 6 Fume hoods in each lab
• Analytical Capabilities (HPLC, GC, LC-MS)
• Provide Competitive Large-Scale Production
• Provide Chemists (FTEs)• Access to Modern Library & Exceptional
Scientific Talent from National Labs 56
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Facilities - IndiaPlant - Equipment Configuration• Stainless Steel Reactors:
– 2000 L(1); 1600 L(2); 1000 L(1); – 500 L(2); 350 L(4) & 250 L (4)
• GL Reactors: – 2000 L(1); 1000 L(2); 630 L(1) &250 L(1)
• Autoclave (Hydrogenation) – 350 L(1) Yet to be installed and– 2.0 L(1) & 0.5 L(1)
• Auxiliary Filtration, Drying and Milling• Separate QC Laboratory and Documentation Center
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Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Manufacturing EquipmentSS316 Reactor SS316 Reactor 1200L1200L 2 No's2 No'sSS316 Reactor SS316 Reactor 1000L 1000L 1 No1 NoGlass Lined Reactor Glass Lined Reactor 1000L1000L 1 No1 NoSS316 Reactor SS316 Reactor 250L250L 2 No's2 No'sSS316 Reactor SS316 Reactor 350L350L 2 No's2 No'sSS316 Reactor SS316 Reactor 2000L2000L 1 No1 NoSS316 Reactor SS316 Reactor 500L500L 1 No1 NoGlass Lined ReactorGlass Lined Reactor 160L160L 2 No's2 No'sGlass Lined ReactorGlass Lined Reactor 250L250L 1 No1 NoGlass Lined ReactorGlass Lined Reactor 500L500L 1 No1 NoGlass Lined ReactorGlass Lined Reactor 1600L1600L 1 No1 NoCentrifuze SS316 Centrifuze SS316 36“36“ 1 No1 NoCentrifuze SS316Centrifuze SS316 24" 24" 1 No1 NoCentrifuze SS316Centrifuze SS316 18" 18" 1 No1 NoRotocone GL dryerRotocone GL dryer 250 L250 L 1 No1 NoRotocone SS316 dryerRotocone SS316 dryer 50 L50 L 1 No1 NoTray dryerTray dryer 12 trays12 trays 1 No1 NoVacuum Tray dryerVacuum Tray dryer 6 Tray6 Tray 1 No1 NoTray dryerTray dryer 24Tray24Tray 1 No1 NoSifterSifter 24“24“ 1 No1 NoMulti millMulti mill 25 Kg/Hr25 Kg/Hr 1 No1 NoSifterSifter 12“12“ 2 No's2 No'sMulti millMulti mill 10 Kg/Hr10 Kg/Hr 2 No's2 No'sCooling towerCooling tower 70 TR70 TR 1 No1 NoCooling towerCooling tower 30 TR30 TR 1No1NoVacuum Pumps Vacuum Pumps 300M300M33/Hr/Hr 4 No‘s4 No‘s
R&D , Stores and QCR&D Labs:R&D Labs:Fume HoodsFume Hoods 27 No’s27 No’s Cooling Tower 30TRCooling Tower 30TR 2 No’s2 No’s Vacuum Pumps 120M3/Hr Vacuum Pumps 120M3/Hr 4 No’s4 No’s Analytical Equipment:Analytical Equipment: HPLC (Quartanery & Gradient) HPLC (Quartanery & Gradient) 2 Nos 2 Nos Preparative HPLC, LCMS & GC - Preparative HPLC, LCMS & GC - 1 No Each1 No Each
Production Block
Utility Block Diesel Generator 180 KVA Diesel Generator 180 KVA 1 No1 NoOil Fired Boiler 1 Ton/Hr Oil Fired Boiler 1 Ton/Hr 1 No1 NoNN22 Generator 99.5 %, 5 m Generator 99.5 %, 5 m33/h/h 1 No1 NoDM Plant (with RO) 40 DM Plant (with RO) 40 mm33/Reg/Reg 1 No1 NoAir Compressor 70 CFM Air Compressor 70 CFM 1 No1 No
Corrosive Block FRP Reactor 2000L FRP Reactor 2000L 1 No1 No Glass Lined Reactor 1600 L Glass Lined Reactor 1600 L 1 No1 NoGlass Lined Reactor 630L Glass Lined Reactor 630L 1 No1 NoGlass Lined Reactor 100L Glass Lined Reactor 100L 1 No1 NoHydrogenator -SS316 -350L (25 Kg) Hydrogenator -SS316 -350L (25 Kg) 1 No1 NoBrine Compressor (-20 DEG) 15 TR Brine Compressor (-20 DEG) 15 TR 1 No1 NoCooling tower 165 TR Cooling tower 165 TR 1 No1 NoCentrifuze SS316 & halar coat 36“ Centrifuze SS316 & halar coat 36“ 1 No1 No
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
Analytical Facilities CiVentiChem, IndiaS. No. Name of the Instrument No. of instruments Make
1 HPLC With PDA detector 2 Agilent2 HPLC With VWD detector 1 Agilent3 HPLC with PDA Detector 1 Agilent4 Preparative HPLC 1 Agilent5 GC with FID Detector 2 Agilent6 LCMS 2 Agilent & Schimadzu7 Analytical Balance 2 Denver, Sartorius8 Ultrasonicator 2 PCi9 Digital PH-Meter 2 POLOMON & GLOBAL
10 Microprocessor PH-Meter 1 GLOBAL11 Conductivity & TDS Meter 1 GLOBAL12 Melting Range Apparatus 2 POLOMON13 Karl Fischer Apparatus 2 POLOMON14 Milli-Q Water purification
system2 Millipore
Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters
For inquiries, please contact:
Dr. Venugopal Rao VeeramaneniCiVentiChem India Limited[Formerly known as Indus BioSciences (P) Ltd.,]Plot No. 72/A, Part 2, Phase-I, I.D.A., Jeedimetla,Hyderabad, A.P. , India..
Tel : +91-40-23197766/67/68 Ext: 228; Fax : +91-40-23091692Mobile: +91-9030026010; e-mail : [email protected] www.civentichem.com
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